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Volume 26
Number 2
April 2013
Baylor University Medical Center Proceedings
Multipatient Studies
95
Model for the cost-efficient delivery of continuous quality cancer care: a
hospital and private-practice collaboration
163
166
Thermoregulatory catheter–associated inferior vena cava thrombus
168
J. L. Gierman, W. P. Shutze Sr., G. J. Pearl, M. L. Foreman, S. E. Hohmann, and W. P. Shutze Jr.
103
Impact of sham-controlled vertebroplasty trials on referral patterns at two
academic medical centers
High-intensity, occupation-specific training in a series of firefighters during
phase II cardiac rehabilitation
J. Adams, D. Cheng, and R. F. Berbarie
109
Morphological features of temporal arteritis
116
Quality of life of HIV/AIDS patients in a secondary health care facility,
Ilorin, Nigeria
W. C. Roberts, S. Zafar, and J. M. Ko
120
Timing and causes of death after injuries
J. Sobrino and S. Shafi
Volume 26, Number 2 • April 2013
Baylor University Medical Center, Dallas, Texas
124
Facts and principles learned at the 39th Annual Williamsburg Conference
on Heart Disease
M. M. Benjamin and W. C. Roberts
137
177
179
182
185
Editorials, Tributes, and Book Reviews
194
146
Lymphoma in the breast
Inflammatory breast cancer
K. Y. Ha, S. B. Glass, and L. Laurie
Pages 93–232
152
Plasmablastic lymphoma following transplantation
156
Recurrent acute inflammatory demyelinating polyradiculoneuropathy
following R-CHOP treatment for non-Hodgkin lymphoma
159
Endolymphatic sac tumor and otalgia
M. J. Van Vrancken, L. Keglovits, and J. Krause
J. J. Liang, P. P. Singh, and T. E. Witzig
M. Zarghouni, M. L. Kershen, L. Skaggs, A. Bhatki, S. C. Gilbert,
C. E. Gomez, and M. J. Opatowsky
To access Baylor’s physicians, clinical services, or
educational programs, contact the Baylor Physician
ConsultLine: 1-800-9BAYLOR (1-800-922-9567)
161
196
Tributes to Harold C. Urschel Jr., MD
A. U. Goldstein and M. A. Ramsay
199
Tribute to Elgin W. Ware Jr., MD
Steve Frost
200
Book review: Making Rounds with Oscar
James Marroquin
From the Editor
202
Facts and ideas from anywhere
William C. Roberts
Miscellany
94
158
165
167
187
192
193
212
215
Inguinal lymphadenopathy as the initial presentation of sarcoidosis
J. George, R. Graves, and R. Meador Jr.
Tributes to George E. Hurt Jr., MD
B. Allison, C. H. Scheihing, and W. C. Roberts
K. Y. Ha, J. C. Wang, and J. I. Gill
149
An underappreciated problem with auscultation
Allen B. Weisse
Charles Stewart Roberts
Case Studies
Diagnosis and management of delayed hemoperitoneum following
therapeutic paracentesis
M. J. Katz, M. N. Peters, J. D. Wysocki, and C. Chakraborti
J. I. Ewing, C. A. Denham, C. R. Osborne, N. B. Green, J. Divers, and J. E. Pippen Jr.
The debate on national health insurance . . . 80 years ago
Hepatitis C and recurrent treatment-resistant acute ischemic stroke
A. Saxsena, J. Tarsia, C. Dunn, A. Aysenne, B. Shah, and D. F. Moore
Invited commentary
144
The calcium-alkali syndrome
M. Arroyo, A. Z. Fenves, and M. Emmett
191
Thomas B. Gore
Persistent giant U wave inversion with anoxic brain injury
M. N. Peters, M. J. Katz, L. A. Howell, J. C. Moscona, T. A. Turnage, and P. Delafontaine
Our experience as a Health Volunteers Overseas–sponsored team in Huế,
Vietnam
A forgotten landmark medical study from 1932 by the Committee on the
Cost of Medical Care
A 21-year-old pregnant woman with congenital heart disease
D. Luke Glancy
Historical Studies
142
Congenitally bicuspid aortic valve in brothers: coarctation of the aorta with
a normally functioning aortic valve in one and no coarctation but severe
aortic stenosis in the other
S. Zafar and W. C. Roberts
174
S. I. Bello and I. K. Bello
Review Articles
Ascites with elevated protein content as the presenting sign of constrictive
pericardial disease
B. A. George, G. dePrisco, J. F. Trotter, A. C. Henry III, and R. C. Stoler
171
S. S. Lindsey, D. F. Kallmes, M. J. Opatowsky, E. A. Broyles, and K. F. Layton
106
Kayser-Fleischer rings of acute Wilson’s disease
A. M. Mantas, J. Wells, and J. Trotter
Y. M. Coyle, A. M. Miller, and R. S. Paulson
100
Levamisole-induced vasculitis
R. Abdul-Karim, C. Ryan, C. Rangel, and M. Emmett
231
Clinical research studies enrolling patients
Avocations: Photograph by Dr. Rosenthal
Avocations: Photograph by Dr. Hoppenstein
Avocations: Photograph by Dr. Khan
Baylor news
Reader comments
In memoriam
Selected published abstracts of Baylor researchers
2012 publications of the Baylor Health Care System medical
and scientific staff
Instructions for authors
www.BaylorHealth.edu/Proceedings
Indexed in PubMed, with full text available through PubMed Central
Baylor University Medical Center
Proceedings
The peer-reviewed journal of Baylor Health Care System, Dallas, Texas
Editor in Chief
William C. Roberts, MD
Associate Editor
Michael A. E. Ramsay, MD
Associate Editor
Andrew Z. Fenves, MD
Founding Editor
George J. Race, MD, PhD
Bradley R. Grimsley, MD
Joseph M. Guileyardo, MD
Carson Harrod, PhD
H. A. Tillmann Hein, MD
Daragh Heitzman, MD
Priscilla A. Hollander, MD, PhD
Ronald C. Jones, MD
Göran B. Klintmalm, MD, PhD
Sally M. Knox, MD
John R. Krause, MD
Joseph A. Kuhn, MD
Zelig H. Lieberman, MD
Jay D. Mabrey, MD
Michael J. Mack, MD
Gavin M. Melmed, JD, MBA, MD
Robert G. Mennel, MD
Dan M. Meyer, MD
Michael Opatowsky, MD
Joyce A. O’Shaughnessy, MD
Dighton C. Packard, MD
Gregory J. Pearl, MD
Robert P. Perrillo, MD
Daniel E. Polter, MD
Irving D. Prengler, MD
Chet R. Rees, MD
Randall L. Rosenblatt, MD
Lawrence R. Schiller, MD
W. Greg Schucany, MD
Jeffrey M. Schussler, MD
S. Michelle Shiller, DO
Craig T. Shoemaker, MD
Michael J. Smerud, MD
Marvin J. Stone, MD
C. Allen Stringer Jr., MD
William L. Sutker, MD
Gary L. Tunell, MD
Beverlee Warren, MA, MS
Wilson Weatherford, MD
Lawrence S. Weprin, MD
F. David Winter Jr., MD
Larry M. Wolford, DMD
Scott W. Yates, MD, MBA, MS
[email protected]
Editorial Board
Jenny Adams, PhD
W. Mark Armstrong, MD
Joanne L. Blum, MD, PhD
C. Richard Boland Jr., MD
Jennifer Clay Cather, MD
Evangeline T. Cayton, MD
Cristie Columbus, MD
Barry Cooper, MD
R. D. Dignan, MD
Gregory G. Dimijian, MD
Michael Emmett, MD
Giovanni Filardo, PhD
Adrian E. Flatt, MD
Dennis R. Gable, MD
D. Luke Glancy, MD
L. Michael Goldstein, MD
Paul A. Grayburn, MD
Editorial Staff
Managing Editor
Cynthia D. Orticio, MA, ELS
Administrative Liaison
JaNeene Jones, RN, FACHE
Residents/Fellows
Mina Benjamin, MD
Kyle Gummelt, DO
Brittany D. Shoemake, MD
Anumeha Tandon, MD
Design and Production
Aptara, Inc.
[email protected]
Baylor University Medical Center Proceedings (ISSN 0899-8280), a peer-reviewed
journal, is published quarterly (January, April, July, and October). Proceedings is
indexed in PubMed and CINAHL; the full text of articles is available both at www.
BaylorHealth.edu/Proceedings and www.pubmedcentral.nih.gov. The journal’s mission is to communicate information about the research and clinical activities, continuing education, philosophy, and history of the Baylor Health Care System.
Funding for the journal is provided by the following:
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Statements and opinions expressed in Proceedings are those of the authors and
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Subscriptions are offered free to libraries, physicians affiliated with Baylor, and
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Permission is granted to students and teachers to copy material herein for
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Copyright © 2013, Baylor University Medical Center. All rights reserved. Printed
in the United States of America on acid-free paper. Press date: March 8, 2013.
To access Baylor’s physicians, clinical services, or educational programs, contact
the Baylor Physician ConsultLine: 1-800-9BAYLOR (1-800-922-9567).
93
Clinical research studies enrolling patients through
Baylor Research Institute
Currently, Baylor Research Institute is conducting more than 800 research projects. Studies open to enrollment are listed in
the Table. To learn more about a study or to enroll patients, please call or e-mail the contact person listed.
Table. Clinical research studies conducted through Baylor Research Institute that are enrolling patients
Research area
Specific disease/condition
Contact information (name, phone number, and e-mail address)
Asthma and
pulmonary disease
Chronic obstructive pulmonary disease, asthma (adult)
Rose Boehm, RRT, RCP, AE-C
214-820-9772
[email protected]
Cancer
Breast, ovarian, endometrial, prostate, brain, lung,
bladder, colorectal, pancreatic, and head and neck
cancer; hematological malignancies, leukemia,
multiple myeloma, non-Hodgkin’s lymphoma;
melanoma vaccine
Grace Townsend
214-818-8472
[email protected]
Type 1 and type 2 diabetes, cardiovascular events
Kris Chionh
214-820-3416
[email protected]
Pancreatic islet transplantation
Kerri Purcell, RN
817-922-4640
[email protected]
Diabetes (Fort Worth)
Type 2
Theresa Cheyne, RN
817-922-2579
[email protected]
Gastroenterology
Crohn’s disease
Dallas Clinical Trials Office
214-820-9626
[email protected]
Heart and vascular
disease (Dallas)
Aortic aneurysms, coronary artery disease, hypertension, poor leg circulation, heart attack, heart disease,
congestive heart failure, angina, carotid artery disease,
familial hypercholesterolemia, surgical renal denerMerielle Boatman
vation for hypertension, diabetes in heart disease,
cholesterol disorders, heart valves, thoracotomy pain,
stem cells, critical limb ischemia
214-820-2273
[email protected]
Heart and vascular disease (Fort
Worth)
Atrial fibrillation, carotid artery stenting
Deborah Devlin
817-922-2575
[email protected]
Heart and vascular
disease (Plano)
Aneurysms; coronary artery disease; uncontrolled
hypertension; intermittent claudication; heart attack;
heart disease; heart valve repair and replacement;
critical limb ischemia; repair of AAA, TAA, and dissections with endografts; thoracic surgery leak repair;
atrial fibrillation; carotid artery disease; heart failure;
left atrial appendage and stroke; gene profiling
Natalie Settele, PA-C
469-814-4712
[email protected]
Hepatology
Liver disease
Shalundra Conwell
214-820-1731
[email protected]
HIV/AIDS
Bryan King, LVN
214-823-2533
[email protected]
Hepatitis C, hepatitis B
Shalundra Conwell
214-820-1731
[email protected]
Homocysteine and kidney disease, dialysis fistulas,
urine/protein disorders in cancer patients
Dallas Clinical Trials Office
214-820-9626
[email protected]
Stroke
Dion Graybeal, MD
214-820-4561
[email protected]
Multiple sclerosis
Annette Okai, MD
214-820-4655
[email protected]
Neurosurgery
Cerebral aneurysms
Kennith Layton, MD
214-827-1600
[email protected]
Rheumatology (9900 N. Central
Expressway)
Rheumatoid arthritis, psoriatic arthritis, lupus, gout,
ankylosing spondylitis
John J. Cush, MD
214-987-1253
Kathryn Dao, MD
214-987-1249
[email protected]
[email protected]
Bone marrow, blood stem cells
Grace Townsend
214-818-8472
[email protected]
Solid organs
Shalundra Conwell
214-820-1731
[email protected]
Weight management
Obesity
Kris Chionh
214-820-3416
[email protected]
Women’s health (Fort Worth)
Endometriosis and endometrial ablation
Theresa Cheyne, RN
817-922-2579
[email protected]
Diabetes (Dallas)
Infectious disease
Nephrology
Neurology
Transplantation
Baylor Research Institute is dedicated to providing the support and tools needed for successful clinical research. To learn more
about Baylor Research Institute, please contact Kristine Hughes at 214-820-7556 or [email protected].
94
Proc (Bayl Univ Med Cent) 2013;26(2):94
Model for the cost-efficient delivery of continuous quality
cancer care: a hospital and private-practice collaboration
Yvonne M. Coyle, MD, Alan M. Miller, MD, PhD, and R. Steven Paulson, MD, MBA
Cancer care is expensive due to the high costs of treatment and preventable utilization of resources. Government, employer groups, and
insurers are seeking cancer care delivery models that promote both
cost-efficiency and quality care. Baylor University Medical Center at
Dallas (BUMC), a large tertiary care hospital, in collaboration with Texas
Oncology, a large private oncology practice, established two independent
centers that function cooperatively within the Baylor Charles A. Sammons
Cancer Center, the Oncology Evaluation and Treatment Center (OETC)
and Infusion Center, to deliver urgent care and infusions after hours
to oncology patients. Quality measures based on evidence-based care
and cost-efficiency measures were implemented within these centers.
Ability to meet predetermined goals for these measures will be a guide
for implementing continuous quality and cost-efficiency interventions.
During the first two quarters of operations, 2023 patients received care
in the OETC (n = 423) and Infusion Center (n = 1600). The average
time spent in the OETC was 48% less than the time spent in the BUMC
emergency department (ED). Eighty-nine percent of the cancer center’s
patients who received urgent care at BUMC were referred to the OETC
for this care, instead of the BUMC ED. The hospital admission rate in
the OETC was 59% lower than it was in the BUMC ED, a high-volume
level I trauma center. The addition of the OETC and Infusion Center to
the cancer center holds promise for providing continuous quality cancer
care that is cost-efficient.
T
he ideal cancer care delivery model is coordinated to
provide comprehensive multidisciplinary services (1).
However, this type of care can be costly, not only with
respect to the high cost of treatment, but also related
to the preventable use of resources. Therefore, government,
employer groups, and insurers are seeking models for the delivery of quality cancer care that is cost-efficient. Oncologists
in private practice are in a unique position to take the lead in
defining treatment and operational standards for the delivery of
cancer care that is value based, with regards to cost and quality,
through collaborations with hospitals and insurers. This article
describes two independent centers—the Oncology Evaluation
and Treatment Center (OETC) and the Infusion Center—that
serve as a model for the delivery of continuous cancer quality
care to promote cost-efficiency. The centers were established
within the existing Baylor Charles A. Sammons Cancer Center
Proc (Bayl Univ Med Cent) 2013;26(2):95–99
through a joint collaboration of a hospital, Baylor University
Medical Center at Dallas (BUMC), and Texas Oncology, a large
statewide private oncology practice.
HISTORY OF THE BAYLOR CHARLES A. SAMMONS CANCER
CENTER
The cancer center opened in 1976 and is an integral part of
BUMC, a not-for-profit tertiary care hospital with 1025 beds
whose medical staff is composed of physicians in private practice. The BUMC campus includes a large-volume emergency
department (ED), designated as a Level I trauma center offering
the most comprehensive level of service to patients. Promoting multidisciplinary interaction among physicians from Texas
Oncology and other specialties housed at BUMC has been the
main concept underlying the organization and development
of a cancer center. The long-standing working relationship between BUMC and Texas Oncology dates back to 1972, when a
small private practice called the Medical Oncology Group was
developed to provide coverage and assistance with the growing
number of oncology consults at BUMC (2). Currently, Texas
Oncology leases space in the cancer center, further emphasizing the concept of collaboration between BUMC and Texas
Oncology.
Since the opening of the Sammons Cancer Center in 1976,
education and clinical and basic science cancer research has been
an important part of the center’s activities (3). Along with the
opening of the cancer center, a medical oncology fellowship
program, funded in part by Texas Oncology and by BUMC,
was established at BUMC the same year. In conjunction with
the training program, cancer research at the cancer center is
coordinated between BUMC and Texas Oncology. Texas Oncology is a part of the US Oncology Network. McKesson Specialty Health supports the US Oncology Network to advance
the science of oncology by providing the infrastructure to support innovative clinical trials and clinical care operations, as
From the Baylor Charles A. Sammons Cancer Center, Baylor University Medical
Center at Dallas (Coyle, Miller); and Texas Oncology, Dallas, Texas (Coyle, Miller,
Paulson).
Corresponding author: Yvonne M. Coyle, MD, Baylor Charles A. Sammons
Cancer Center, Medical Director, Oncology Evaluation and Treatment Center, 3410
Worth Street, Dallas, TX 75246 (e-mail: [email protected]).
95
well as to provide the technological solutions
to improve cancer clinical outcomes. The US
Oncology Network is one of the nation’s largest networks of community-based oncology
physicians, serving more than 850,000 cancer
patients annually.
The new facility for outpatient services at
the cancer center opened in 2011. BUMC
opened the Baylor T. Boone Pickens Cancer
Hospital in January 2012. Recognizing the
need to further integrate oncology patient
care at the cancer center to provide continuous quality care that promotes cost-efficiency,
BUMC, in collaboration with Texas Oncology,
opened the OETC and the Infusion Center in
March 2012.
Table 1. Oncology Evaluation and Treatment Center quality measures
Adult cancer supportive care
Outcome measure
Chemotherapy-related
breakthrough nausea and
vomiting
Treat with an additional antiemetic
agent from a different drug class
Palliative care consult
Hospital admissions for
Obtain palliative care consult if
intractable pain
pain is resistant to conventional
interventions or if there is a high
risk for poor pain control related to
one or more of the following:
• Neuropathic pain
• Incident or breakthrough pain
• Associated psychological and family distress
• Rapid escalation of opioid dosage
• History of drug or alcohol abuse
• Impaired cognitive function
ONCOLOGY EVALUATION AND TREATMENT
CENTER AND INFUSION CENTER MODEL
The OETC and the Infusion Center have Febrile neutropenia
a cooperative working relationship and are
housed side by side in an outpatient facility
located on the first floor of the cancer hospital.
The OETC provides urgent care after office
hours as well as scheduled procedures during
office hours to adult oncology patients of all
oncology physicians at BUMC, including Texas
Oncology physicians. The procedures scheduled
are diagnostic and therapeutic, such as thoracenteses, paracenteses, and lumbar punctures for the administration of intrathecal
chemotherapy, as well as to maintain adherence to prescheduled
clinical research testing, which may occur outside of normal
office hours. All acute care can be provided at the OETC, with
the exception of care required by patients who are transported
by emergency medical services or care for patients with acute
myocardial infarctions, cerebral vascular accidents, or trauma.
Therefore, if necessary, OETC patients may be transferred to
the BUMC ED, which is located in close proximity to the
cancer hospital and is accessible by an indoor connector. The
Infusion Center is open 24 hours a day 7 days a week to provide
oncology patients access to blood product transfusions, as well
as hydrating, chemotherapy, and biological therapy infusions.
Thus, interruptions in cancer care can be prevented by administering infusions that are due on weekends and holidays in the
Infusion Center, when private practice offices at the Sammons
Cancer Center are closed.
The OETC and Infusion Center are staffed with a medical
director under contract with BUMC, who is also a Texas Oncology physician, and a nurse manager employed by BUMC.
BUMC owns and operates the OETC and the Infusion Center
and owns the equipment therein, as well as employing the nursing staff within these two centers. Accordingly, BUMC bills
facility and technical fees. Providers that evaluate and treat the
patients in the OETC include Texas Oncology physicians and
internal medicine physicians, all of whom have BUMC medical
staff membership and admitting privileges, and these providers
96
Quality measure
Hospital admissions for
intractable nausea and
vomiting
• High risk: within 1 hour treat with • Hospital admissions for
febrile neutropenia
a broad-spectrum, antipseudomonal, bactericidal, antibiotic
• Hospital 30-day, all-cause,
regimen as initial empiric therapy
risk standardization
mortality rate following
• Low risk: treat with ciprofloxacin
febrile neutropenia
+ amoxicillin or ciprofloxacin +
hospitalization
clindamycin for penicillin-allergic
patients
bill for the related professional fees. Patients are referred to the
OETC by their oncology physicians. Patients in the OETC
may be transferred for services provided in the Infusion Center 24 hours a day, and patients in the Infusion Center can be
evaluated and treated after normal office hours by an OETC
provider, if necessary.
To promote efficient patient care, providers staffing the
OETC are able to access the Texas Oncology electronic medical
record, iKnowMed, developed by the US Oncology Network,
in addition to the BUMC electronic medical record, Eclipsys.
Evidence-based medicine is used as a guide to deliver quality
cancer supportive care in the OETC.
The most prevalent patient clinical problems evaluated and
treated in the OETC are used to periodically select quality measures derived from the National Comprehensive Cancer Network Guidelines for Cancer Supportive Care (4). Adherence to
clinical outcome-based quality of care measures for the OETC
is measured on a quarterly basis (Table 1) (5–7). As an indirect
measure of quality of care in the OETC, Press Ganey patient
satisfaction scores will be collected and analyzed quarterly (8).
The cost-efficiency measures were selected based on commonly
accepted business practices, as well as a review of the literature
(9, 10). These measures focus on health care utilization, staff,
facility, and ancillary service costs required to evaluate and treat
patients in the OETC, as well as the time that patients spend
in the OETC. Adherence to these measures will be reported
quarterly. Table 2 includes the current cost-efficiency measures
for the OETC. The cost-efficiency measure, mean cost per visit,
Volume 26, Number 2
Table 2. Oncology Evaluation and Treatment Center
cost-efficiency measures
•
•
•
•
•
•
Time spent in the OETC
OETC hospital admission rate
BUMC admission rate for oncology patients
BUMC Emergency Department admission rate for oncology patients
Average length of stay for oncology patients at BUMC
Mean cost per visit in the OETC
OETC indicates Oncology Evaluation and Treatment Center; BUMC, Baylor
University Medical Center at Dallas.
will be determined primarily based on nursing staff and provider
hourly wages, drug and supply costs, and ancillary service costs,
such as laboratory and radiology services. The cost per visit will
be adjusted for severity of illness. Quality improvement and
cost-efficiency interventions will be based on predetermined
goals for adherence to the quality and cost measures listed in
Tables 1 and 2.
Together, the OETC and Infusion Center provide patients
with continuous supportive cancer care to 1) promote favorable clinical outcomes, 2) support the successful completion of
clinical cancer research studies, and 3) reduce health care costs
by decreasing preventable and expensive health care utilization.
Within the OETC, health services research studies are being
conducted to further advance our knowledge of the most costefficient ways to deliver quality cancer care (11). The Figure
presents the model for the delivery of quality continuous cancer
care to promote cost-efficiency that we developed by incorporating the OETC and Infusion Center within our existing cancer
center infrastructure.
INITIAL UTILIZATION RESULTS
Between April and December 2012, the first two quarters of
operations of the OETC and Infusion Centers, a total of 2023
oncology patients received care: 423 in the OETC and 1600
in the Infusion Center. During the first quarter, we identified
visits to the BUMC ED if at least one cancer International Classification of Diseases, Ninth Revision, Clinical Modification
(ICD-9-CM) code was assigned for the care that was received
during one of these visits (12). Health care delivery data for the
first quarter of the OETC and Infusion Center operations are
as follows. The average time spent in the OETC (3 hours and
48 minutes) was 48% lower than it was for the time spent for
oncology patients in the BUMC ED (7 hours and 17 minutes).
Ninety percent of the cancer center’s patients who received urgent care at BUMC were referred to the OETC for this care,
instead of the BUMC ED. The hospital admission rate in the
OETC was 34%, compared with 83% for the BUMC ED.
DISCUSSION
Comprehensive and coordinated oncology care is necessary
to promote favorable clinical outcomes for oncology patients,
but it is costly. In a recent study, it was projected that the total cost of cancer care would be $173 billion by 2020, which
April 2013
Figure. Model for the cost-efficient delivery of continuous quality cancer care.
The Baylor Charles A. Sammons Cancer Center at Baylor University Medical
Center (BUMC) includes cancer center outpatient services, the Baylor T. Boone
Pickens Cancer Hospital, and the Oncology Evaluation and Treatment Center
(OETC) and Infusion Center.
represents a 39% increase from 2010 (13). As a result, costcontainment efforts by insurers have become commonplace.
These cost-containment efforts have resulted in lower reimbursement for drugs, as well as for evaluation and management
services, which is occurring in the face of rising costs for the new
technologies required for the treatment of cancer.
Coinciding with the decline in cancer care reimbursement
from insurers over the last decade, the delivery of cancer care
in the community setting decreased from 85% to 65% in
2012, correlating with a number of community-based oncologists entering into employment or management arrangements
with institutionally based programs in 2011 (14). Thus, it is
important for oncologists in community-based settings to be
engaged in developing models that promote the cost-efficient
delivery of quality cancer care due to the current trends in
health care economics. To provide direction for addressing this
issue, the Institute of Medicine recently convened a workshop
where its participants determined that the medical home concept should be considered when redesigning models of care
in oncology (15).
Because cancer is increasingly being viewed as a chronic
disease, the concept of the patient-centered medical home
(PCMH), a model that has been used mainly in the primary
care setting, is a viable option for use in the delivery of costefficient and quality cancer care. In the medical home model,
care is provided by a dedicated team of providers, and they
are reimbursed with an upfront fee and higher reimbursement
for episodes of care (15). An episode of care is a managed care
concept in which a single payment for health care services is
provided for a specific illness during a set time period (16).
The National Committee for Quality Assurance (NCQA) developed the standards for the primary care PCMH program
(17). The NCQA’s standards for the PCMH program require a
physician-led care team to direct disease management and care
coordination, to standardize care which is evidence-based, and
to promote patient disease management education (17). Results
Model for the cost-efficient delivery of continuous quality cancer care: a hospital and private-practice collaboration
97
indicate that the use of the PCMH model has a positive effect
on quality and cost, as well as satisfaction of the patient and
the clinical team (17).
In 2010, Consultants in Medical Oncology and Hematology (CMOH), a community-based single-specialty practice
in Philadelphia, became the first oncology practice recognized
by the NCQA as a level three PCMH program (18). Achievement at this level requires the highest level of expertise related
to patient communication, data tracking, care management,
self-management support, electronic prescribing, test tracking,
referral tracking, advanced electronic patient communications,
and performance metrics reporting and improvement (18). As
the result of CMOH implementing the PCMH model, ED
visits decreased by 68%, chemotherapy-related hospital admissions decreased by 51%, and length of hospital stay decreased
by 21% (14, 18). In addition, CMOH outpatient visits and
chemotherapy outpatient visits per patient per year decreased
by 22% and 12%, respectively (14, 18).
The US Oncology network launched its program, Innovent Oncology, in 2010 to improve the clinical management of
oncology patients receiving chemotherapy (19). The program
is supported by the US Oncology network and is offered at
all of the Texas Oncology sites. This program creates a link
between physicians and insurers by using evidence-based practice guidelines for the selection of chemotherapy, along with
patient support services and advance care planning to promote
favorable cost metrics and health care utilization patterns. The
clinical and cost outcomes included in Innovent Oncology are
chemotherapy-related hospitalizations and ED visits, length of
hospital stay, chemotherapy costs, end-of-life care including
hospice enrollment, death in a hospital, and chemotherapy administration within 2 to 4 weeks of death. Insurers make a single
payment for each patient enrolled in Innovent Oncology, and
they provide Innovent Oncology staff with access to program
enrollee health care utilization and financial data to calculate
the program’s clinical and cost outcomes. Initial results related
to implementation of the program are encouraging. Physician
adherence to the evidence-based practice guidelines for the selection of chemotherapy was 72%, which increased to over
80% for the most recent quarter (J. R. Hoverman, personal
communication, September 12, 2012). In addition, there was
a substantial decrease in the hospitalization costs for the first
100 patients enrolled in this program (19).
However, as important as CMOH and the Innovent Oncology program are in promoting the cost-efficient delivery of
quality cancer care within the private oncology practice setting,
we propose it is just as important to make interventions in the
emergency and urgent care settings to prevent avoidable health
care utilization. The need to develop interventions for reducing
avoidable inpatient and outpatient visits at all points of care
that are affordable, efficient, and of high quality is of further
importance since it is projected that there will be a shortage of
oncologists in the US by 2020 (13). This shortage in oncologists is due, in part, to the increase in the aging US population
among whom the cancer incidence is higher (13). Through the
combined efforts of an oncology group practice and hospital, the
98
OETC and Infusion Center was incorporated within the cancer
center, creating a model for the efficient delivery of continuous
quality care to help prevent the avoidable use of costly health
care resources.
Analysis of data from the first quarter of operations for
the OETC and Infusion Center provides evidence that we are
likely to achieve our goal of reducing preventable health care
utilization in a cost-efficient manner. A total of 2023 oncology
patients received care in the OETC and Infusion Center, and
90% of the cancer center’s patients who received urgent care at
BUMC were referred to the OETC for this care, instead of the
BUMC ED. The average time spent in the OETC was 48%
lower than the time spent for oncology patients in the BUMC
ED, as would be expected since the BUMC ED is a high-volume
Level I trauma center. Moreover, the hospital admission rate in
the OETC was 34%, which was more than 59% lower than it
was for the BUMC ED. Similarly, the hospital admission rate
in the OETC was almost 50% lower than what was recently
reported for oncology patients in the ED using a statewide
database in North Carolina (63.2%) (20). Furthermore, our
new initiatives for conducting health service research within
the OETC and Infusion Center hold promise for providing
our cancer center and others with results that will assist in developing new methods for effectively organizing, managing,
financing, and delivering quality cancer care.
An additional benefit related to establishing new models for
cancer care delivery that promote favorable cost-efficiency and
clinical outcomes is that more equitable medical insurance reimbursement contracts for both the payer and payee may be
negotiated for this type of center. This type of center also has
an infrastructure conducive to receiving bundled payments for
a defined episode of care (21). The bundled payment functions
as a tool of alignment between insurers and providers, which can
eliminate some of the unintended financial incentives that can lead
to fractured and inefficient care. Using the episode of care model
tied to bundled payments is a rapidly evolving movement by insurers to produce the best cost and clinical outcomes by decreasing
unwanted variations in the delivery of health care (22).
Given the growing public awareness of the need to redesign
the cancer delivery system, including government, physicians
and hospitals, and employer groups and insurers, a new health
care environment is developing that demands accountability
for the cost and quality of care. Consequently, it is critical for
oncologists to continue to take the lead in defining standards of
care for specific disease states and to collaborate with hospitals
and insurers when possible to develop systems for the delivery
of high-quality and cost-efficient cancer care.
Acknowledgments
We thank Kevin Croy, vice president and assistant general
counsel for the Baylor Health Care System, and JaNeene Jones,
chief operating officer for the Baylor Health Care System and
vice president for oncology services, for their critical review of
the manuscript regarding the working relationship between
Baylor University Medical Center and Texas Oncology at
the Baylor Charles A. Sammons Cancer Center; J. Russell
Volume 26, Number 2
Hoverman, MD, medical director for the US Oncology
Innovent Oncology program, for his critical review of the
manuscript and providing information regarding the status
of Innovent Oncology; Dighton Packard, MD, chairman of
the Department of Emergency Medicine at Baylor University Medical Center, for his critical review of the manuscript;
Kimberly Hanna, RN, the nurse manager for the Oncology
Evaluation and Treatment Center and Infusion Center, for
her critical review of the manuscript; and Margaret Hinshelwood, PhD, for her critical review of the manuscript along
with completing its formatting and producing the tables and
figure for the manuscript.
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Model for the cost-efficient delivery of continuous quality cancer care: a hospital and private-practice collaboration
99
Thermoregulatory catheter–associated inferior vena cava
thrombus
Joshua L. Gierman, MD, William P. Shutze Sr., MD, Gregory J. Pearl, MD, Michael L. Foreman, MD, Stephen E. Hohmann,
MD, and William P. Shutze Jr.
The use of thermoregulatory catheters (TRCs) in critically ill patients has
become increasingly popular. TRCs have been shown to be effective in
regulating patient body temperature with improved outcomes. Critically
ill patients, especially multitrauma patients and those with femoral catheters, are at high risk for deep vein thrombosis (DVT). Among patients for
whom chemical DVT prophylaxis is not an option, inferior vena cava (IVC)
filters are often placed prophylactically. The development of intravascular
ultrasound (IVUS) has allowed placement of IVC filters at the bedside for
patients who are too ill for transport to the operating room or cardiac
catheterization lab. After encountering several patients with occult DVT of
the IVC during bedside IVC filter placement, we performed a retrospective review to determine the incidence of DVT or pulmonary embolus
(PE) in patients who had been treated with a TRC at Baylor University
Medical Center at Dallas. Since 2008, IVC filters have been deployed
at the bedside with the use of IVUS at Baylor University Medical Center.
During that same time period, 83 patients had a TRC placed for either
intravascular warming or cooling during their resuscitation. Forty-seven
out of 83 patients who had a TRC placed survived their injuries. Ten of
47 patients (21%) were diagnosed with DVT or PE, and 6 of these 10
(60%) were found to have caval thrombus. We present this case series
as evidence that undiagnosed IVC thrombus associated with TRCs may
be higher than previously suspected, given that 5 out of 10 patients who
had IVUS of their IVC for prophylactic IVC filter placement, as well as one
patient diagnosed with PE, were found to have caval thrombus.
W
ithin the last 15 years, the use of thermoregulatory
catheters (TRCs) has gained popularity. They have
been used to induce hypothermia to improve outcomes in cases of cardiopulmonary arrest and to
reverse the harmful effects of hypothermia in the trauma patient
by providing a means for rapid rewarming (1–3). Over the last
3 years at our institution, the trauma service has been utilizing
the Alsius catheter and Coolguard Icy thermoregulatory system
to aid in resuscitation of hypothermic patients as well as in the
cooling of patients with fever and traumatic brain injury. During
that same period of time, the vascular surgery service has been
placing bedside inferior vena cava (IVC) filters in critically ill
patients using intravascular ultrasound (IVUS) (4, 5). Some of
the patients who had TRCs used during their hospital course
also had IVC filters placed either for prophylaxis or after a
100
diagnosis of deep venous thrombosis (DVT) or pulmonary
embolus (PE). Surprisingly, caval thrombus was found in several of these patients undergoing placement of an IVC filter
with IVUS. Currently, only one series has examined the risk of
iliofemoral DVT (6), and only one case has been reported of
vena cava thrombus associated with the use of a TRC (7). We
performed a retrospective review to examine whether trauma
patients who have been exposed to a TRC are at additional risk
for iliocaval DVT in addition to the risk of DVT associated
with femoral vein catheterization.
MATERIALS AND METHODS
Institutional review board approval was obtained for our
study. Patient records were obtained from the trauma registry at
Baylor University Medical Center at Dallas to identify patients
who had TRCs placed beginning in 2008. Catheterization lab
records were reviewed to identify patients receiving IVC filters
during the same time period. The Student’s t test was used for
statistical comparison of age and injury severity score (ISS).
RESULTS
Since 2008, 83 trauma patients have had a TRC placed as part
of their postinjury care: 47 of those patients, with an average age
of 41 years and an ISS of 20.9, survived their initial injuries, and
32 patients had no diagnosis of DVT/PE, nor were they selected
for prophylactic IVC filter placement. Fifteen of the 47 were
referred for IVC filter placement. Five of these 15 patients were
diagnosed with either DVT or PE prior to vascular referral. Four
patients received an IVC filter; of them, three underwent filter
placement under fluoroscopy, and the other patient who received
a filter secondary to PE had it placed with IVUS guidance. This
demonstrated a caval thrombus. The fifth patient was found to
have a femoral DVT and was treated with anticoagulation.
Ten patients underwent prophylactic placement or attempted placement of an IVC filter at bedside with IVUS, four of
whom were discovered to have IVC thrombus at the time of
From the Department of Surgery (Gierman, Shutze Sr., Pearl, Foreman, Hohmann),
Baylor University Medical Center at Dallas; and Texas Vascular Associates, Dallas,
Texas (Shutze Jr.).
Corresponding author: William P. Shutze Sr., MD, Texas Vascular Associates,
621 N. Hall Street, Suite 100, Dallas, Texas 75226 (e-mail: William.Shutze@
BaylorHealth.edu).
Figure 2. Intravascular ultrasound image depicting inferior vena cava
thrombus.
Figure 1. Diagnosis of DVT in patients receiving a thermoregulatory catheter.
DVT indicates deep vein thrombosis; IVC, inferior vena cava; IVUS, intravascular
ultrasound; PE, pulmonary embolus.
filter placement. A fifth patient was diagnosed with caval thrombus by IVUS, but had too extensive a thrombus to allow for
IVC filter placement. He was treated with anticoagulation. The
remaining five patients did not have caval thrombus detected
by IVUS (Figure 1).
The average age for patients with DVT, PE, or vena cava
thrombus was 28 years. This was less than the average age of
the overall group (41) but was not statistically different (P >
0.05). The ISS of the patients in the DVT, PE, or vena cava
thrombus subgroup was 33. This was much higher than in the
overall group (ISS = 21) treated with TRCs who survived their
initial injuries, and this difference reached statistical significance
(P = 0.039).
DISCUSSION
TRCs have been shown to be an effective clinical tool,
whether to improve outcomes when used for corporal cooling
after cardiac arrest or to efficiently reverse hypothermia (1–3).
However, there is little reported evidence addressing potential
complications. Specifically, the potential to form venous thromboembolism (VTE) has only been reported in one study (6) and
in a single case report (7).
The patient population examined in this study was at high
risk for DVT/VTE. Because of their associated injuries, most
of these patients could not receive chemical DVT prophylaxis.
Critical illness with contraindications to chemoprophylaxis carries a 7% DVT risk (8). DVT/VTE associated with femoral vein
catheters ranges from 10% to 25% (9, 10). In looking at our
April 2013
institutional experience with TRCs by the trauma service, we
found that the overall rate of DVT/VTE formation was 21%
(10/47). This is at the high end of the spectrum, but not out of
line with what has been previously published. A previous study
of DVT formation in patients with TRCs showed a 50% rate
of DVT formation (6).
We found occult caval thrombus in 60% of patients ultimately diagnosed with DVT. Given the high incidence of
occult caval DVT discovered at the time of prophylactic filter
placement, we feel that the 21.3% rate of DVT (specifically
caval DVT) in this study may be an underestimation. Only
10 of 47 patients underwent cavography or IVUS. The status
of the IVC was not evaluated in 32 of the 47 patients in this
series, and a significant number of caval DVT cases could have
gone undetected.
We did find a higher ISS in patients with DVT/PE (33
vs. 21, P = 0.039) compared to the overall group. This could
indicate that injury severity contributes to DVT formation.
However, we feel that this possibly represents a selection bias,
as the more critically ill patients are typically selected to receive prophylactic IVC filters. Only by studying every patient
receiving a TRC can the true rate of DVT and caval DVT be
determined and the effect of age and ISS be honestly assessed.
There are two points of concern regarding the DVT/VTE
associated with these catheters. The first is the fact that half of
the caval DVTs were found in asymptomatic patients. Therefore,
the actual rate of DVT formation could be as high as 50% in
our studied patient population (similar to the experience of
Simosa et al). Since 60% of patients having prophylactic IVC
filters placed were found to have IVC DVT, the use of TRCs
may increase the incidence of DVT significantly higher than
the baseline rates for critically ill patients who typically develop
DVT in the lower extremity veins or in the femoral vein if a
catheter has been placed there. The second point of concern is
101
that these proximal DVTs are much more dangerous, as they
are associated with a higher mortality rate when compared with
more distal DVTs (11). They are also less likely to be detected by
surveillance, symptoms, or noninvasive imaging. The increased
incidence of caval DVT with TRCs identified by our study is
therefore quite worrisome.
Although there has not been a comparison of IVUS and
venography for thrombotic occlusion, IVUS has been shown to
be more sensitive than venography in detecting nonthrombotic
lesions (12, 13). This increased sensitivity may translate to the
diagnosis of thrombotic lesions as well. Caval DVT in patients
from TRCs can be nonocclusive and attached to the wall of
the IVC and may not be obvious on venography. However,
IVUS readily identifies these clots (Figure 2). Notably, the three
patients in our series who had fluoroscopy only when having
their IVC filters placed could have had missed caval thrombus.
We believe that the use of IVUS during the placement of IVC
filters increased the sensitivity in identifying occult caval DVTs
in asymptomatic patients. Therefore, we recommend the use
of IVUS to detect occult DVT in patients with a history of
femoral TRCs.
3.
4.
5.
6.
7.
8.
9.
10.
11.
1.
2.
102
Taylor EE, Carroll JP, Lovitt MA, Petrey LB, Gray PE, Mastropieri CJ,
Foreman ML. Active intravascular rewarming for hypothermia associated
with traumatic injury: early experience with a new technique. Proc (Bayl
Univ Med Cent) 2008;21(2):120–126.
Diringer MN; Neurocritical Care Fever Reduction Trial Group. Treatment
of fever in the neurologic intensive care unit with a catheter-based heat
exchange system. Crit Care Med 2004;32(2):559–564.
12.
13.
Polderman KH. Application of therapeutic hypothermia in the ICU:
opportunities and pitfalls of a promising treatment modality. Part 1: Indications and evidence. Intensive Care Med 2004;30(4):556–575.
Garrett JV, Passman MA, Guzman RJ, Dattilo JB, Naslund TC. Expanding options for bedside placement of inferior vena cava filters with
intravascular ultrasound when transabdominal duplex ultrasound imaging
is inadequate. Ann Vasc Surg 2004;18(3):329–334.
Ebaugh JL, Chiou AC, Morasch MD, Matsumura JS, Pearce WH. Bedside
vena cava filter placement guided with intravascular ultrasound. J Vasc
Surg 2001;34(1):21–26.
Simosa HF, Petersen DJ, Agarwal SK, Burke PA, Hirsch EF. Increased
risk of deep venous thrombosis with endovascular cooling in patients with
traumatic head injury. Am Surg 2007;73(5):461–464.
Lau E, Bajzer C, Menon V. Inferior vena cava thrombus associated with
intravascular cooling catheter. Resuscitation 2010; 81(11):1457–1458.
Malinoski D, Ewing T, Patel MS, Jafari F, Sloane B, Nguyen B, Barrios
C, Kong A, Cinat M, Dolich M, Lekawa M, Hoyt DB. Risk factors for
venous thromboembolism in critically ill trauma patients who cannot
receive chemical prophylaxis. Injury 2011;10(1):1–6.
Joynt GM, Kew J, Gomersall CD, Leung VY, Liu EK. Deep venous
thrombosis caused by femoral venous catheters in critically ill adult patients. Chest 2000;117(1):178–183.
Trottier SJ, Veremakis C, O’Brien J, Auer AI. Femoral deep vein thrombosis associated with central venous catheterization: results from a prospective, randomized trial. Crit Care Med 1995;23(1):52–59.
Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M, Cattelan
AM, Polistena P, Bernardi E, Prins MH. The long-term clinical course of
acute deep venous thrombosis. Ann Intern Med 1996;125(1):1–7.
Neglén P, Raju S. Intravascular ultrasound scan evaluation of the obstructed vein. J Vasc Surg 2002;35(4):694–700.
Raju S, Neglen P. High prevalence of nonthrombotic iliac vein lesions
in chronic venous disease: a permissive role in pathogenicity. J Vasc Surg
2006;44(1):136–143.
Volume 26, Number 2
Impact of sham-controlled vertebroplasty trials on referral
patterns at two academic medical centers
Sara S. Lindsey, MD, David F. Kallmes, MD, Michael J. Opatowsky, MD, Elizabeth A. Broyles, RN,
and Kennith F. Layton, MD
Debate persists regarding the merit of vertebroplasty following publication
of blinded vertebroplasty trials in 2009, one of which was the Investigational
Vertebroplasty Efficacy and Safety Trial (INVEST). This study was performed
to determine whether referring physicians at two academic medical centers
were aware of the trial results and to assess if this awareness prompted
a change in their treatment of osteoporotic fractures. E-mail surveys were
distributed to physicians within the Mayo Clinic and Baylor Health Care
System (BHCS). Of 1390 surveys sent, 194 (14%) were returned. Results
showed that 92 of 158 respondents (58%) reported familiarity with INVEST;
66 of 92 (72%) agreed that INVEST changed their understanding of vertebroplasty efficacy; and 64 of 92 (70%) agreed that INVEST diminished
their enthusiasm to refer patients for vertebroplasty. However, 105 of 159
respondents (66%) felt vertebroplasty was an effective procedure in appropriate patients. Mayo physicians were more likely than BHCS physicians
to be aware of INVEST (73% vs 67%, P < .0001), respond that INVEST
changed their understanding of the appropriate treatment for osteoporotic
compression fractures (79% vs 57%, P = 0.026), view vertebroplasty less
favorably (45% vs 21%, P = 0.005), and treat osteoporotic compression
fractures with medical therapy/pain management alone (73% vs 48%,
P = 0.003). INVEST changed referring physicians’ understanding of the
role of vertebroplasty and diminished their willingness to refer osteoporotic
compression fracture patients; the impact varied by location.
results, whether their awareness of these results changed their
understanding of the efficacy of vertebroplasty and/or their management decisions for patients suffering from painful osteoporotic
fractures, and whether there were differences between the institutions regarding these research questions.
METHODS
Short e-mail surveys were distributed to physicians in a wide
range of specialties (Table) that commonly encounter patients
with osteoporotic compression fractures within the Mayo Clinic
system (Rochester, MN) and the Baylor Health Care System
(BHCS, Dallas–Fort Worth, TX). The survey was sent to all physicians with accessible e-mail addresses in these specialty areas, not
only to individual physicians who had previously referred patients
to interventional neuroradiology for vertebroplasty. Results were
collected from September to November 2010 and were analyzed
using Survey Monkey. Approval for this research was granted by
the institutional review board of Baylor Research Institute.
The survey asked participants about their familiarity with
the INVEST study, their understanding of the role of vertebroplasty for treatment of osteoporotic compression fractures, if the
Table. Respondents by subspecialty
T
he Investigational Vertebroplasty Safety and Efficacy Trial
(INVEST) (1) and a concurrent Australian vertebroplasty
trial (2) were published in the New England Journal of
Medicine in August 2009 and demonstrated equivalent
efficacy for vertebroplasty and a sham intervention for improvement in pain and function in osteoporotic compression fracture
patients. Despite extensive criticism (3–8), these studies created
controversy regarding the benefit and appropriateness of vertebral augmentation. Historically, the literature has shown positive
outcomes associated with thousands of vertebroplasty patients
(9, 10). Follow-up vertebroplasty studies have ensued (11, 12),
including a study from the Mayo Clinic, which documented a
statistically significant decline in referral volumes before and after
publication of the August 2009 sham-controlled studies (13). This
study was performed to determine whether referring physicians
at two academic medical centers, one of which (Mayo Clinic)
was the lead site for INVEST, were aware of the INVEST trial
Specialty
n
Specialty
n
Cardiology
4
Neurosurgery
5
Endocrinology
13
Orthopedic surgery
6
Family medicine
40
Pain management
6
Gastroenterology
7
Physical medicine
and rehabilitation
20
Hematology/oncology
9
Pulmonology
9
Internal medicine
51
Rheumatology
1
Neurology
14
Transplant medicine
5
From the Department of Radiology, Baylor University Medical Center at Dallas
(Lindsey, Opatowsky, Broyles, Layton); and the Mayo Clinic, Rochester, MN
(Kallmes).
Corresponding author: Sara Lindsey, MD, Department of Radiology, Baylor
University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246
(e-mail: [email protected]).
103
INVEST results changed their understanding of the treatment
for osteoporotic compression fractures or changed their referral
patterns for vertebroplasty, and how they were currently treating patients with painful osteoporotic compression fractures. In
addition to collecting information on respondents’ specialty, it
asked whether they had seen at least one patient during the last 18
months with an osteoporotic vertebral compression fracture.
Statistical analysis of the data was performed with chi-square
tests. Physicians were allowed to skip questions. Referring physicians were not queried regarding the Buchbinder et al trial (2) or
any of the other vertebral augmentation trials in our survey. No
incentives were offered for participation.
RESULTS
Surveys were distributed to 1390 clinicians with a collective response rate of 14% (194 participants). Overall, 92 of 158
respondents (58%) reported being familiar with INVEST (36
respondents did not answer this question), and 53 of these 92
respondents (58%) agreed and 13 (14%) strongly agreed that the
results of INVEST had changed their understanding of the efficacy of vertebroplasty (Figure 1); 51 (55%) agreed and 13 (14%)
strongly agreed that the study had diminished their enthusiasm
to refer patients for vertebroplasty (Figure 2). Cumulatively, 105
respondents (66%) felt that vertebroplasty was an effective procedure in appropriate patients, 52 respondents (33%) felt that
vertebroplasty was of limited efficacy, and 2 respondents (1.3%)
felt that the potential benefits of vertebroplasty were outweighed
by the risks of the procedure (Figure 3).
There was a statistically significant difference in the responses
between clinicians in the two geographic locations, with Mayo
physicians being more aware of the INVEST study (63 of 86
[73%] at Mayo vs 29 of 43 [67%] at BHCS; chi-square DF 1,
P < 0.001) and responding that INVEST had changed their
understanding of the appropriate treatment for osteoporotic compression fractures (Figure 1; 49 of 62 [79%] at Mayo vs 17 of
Figure 2. Respondents indicating that INVEST diminished their enthusiasm to
refer patients for vertebroplasty. Difference between Mayo and Baylor respondents: ␹2 (1, n = 92) = 0.82, P = 0.3662.
Figure 3. Respondents’ current view of vertebroplasty for treatment of osteoporotic compression fractures. Difference between Mayo and Baylor respondents:
␹2 (2, n = 159) = 10.76, P = 0.0046.
Figure 1. Respondents indicating that INVEST changed their understanding of
the role of vertebroplasty for treatment of osteoporotic compression fractures.
Difference between Mayo and Baylor respondents: ␹2 (1, n = 92) = 4.99,
P = 0.0255.
104
30 [57%] at BHCS, chi-square DF 1, P = 0.026). There was also
a statistically significant difference between clinicians in the two
locales in response to descriptions of their current understanding of vertebroplasty for treatment of osteoporotic compression
fractures, with Mayo clinicians viewing vertebroplasty less favorably than BHCS physicians (Figure 3; 39 of 87 [45%] at Mayo
vs 15 of 72 [21%] at BHCS, chi-square DF 2, P = 0.005). A
majority of respondents from both clinician groups indicated
that the INVEST results had diminished their willingness to refer
patients for vertebroplasty, although the difference between the
two respondent groups was not statistically significant for this
question (Figure 2; 45 of 62 [73%] at Mayo vs 19 of 30 [63%]
at BHCS, chi-square DF 1, P = 0.366). Mayo clinicians were
also statistically significantly more likely than BHCS clinicians
Volume 26, Number 2
considering all of the subsequent and ongoing clinical trials
investigating the efficacy of vertebroplasty.
Further research is needed to address the suggested flaws and
confounding factors and to clarify the appropriate treatment of
patients with osteoporotic compression fractures. The current
ambiguity surrounding vertebroplasty should prompt physicians
to enroll as many patients as possible into well-designed trials
to help generate data.
Acknowledgments
The authors thank Sunni Barnes, PhD, director of survey
research and clinical trials at BHCS.
1.
Figure 4. Respondents’ approach to treating most of their patients with painful osteoporotic compression fractures. Difference between Mayo and Baylor
respondents: ␹2 (1, n = 136) = 8.73, P = 0.0031.
to treat osteoporotic compression fracture patients with medical
therapy and pain management alone, rather than in combination
with vertebroplasty (Figure 4; 57 of 78 [73%] at Mayo vs 28 of
58 [48%] at BHCS, chi-square DF 1, P = 0.003).
2.
3.
4.
5.
DISCUSSION
This survey suggests that INVEST negatively influenced clinicians’ perceptions of and referral patterns for vertebroplasty for
treatment of painful osteoporotic compression fractures, similar
to the findings reported by Luetmer and Kallmes (13). It also
unveiled interesting geographic distinctions, as the survey results
varied significantly by location. Though a percentage of physicians
at both sites viewed vertebroplasty as an effective procedure in
appropriate patients (55% at Mayo vs 79% at BHCS), the referral/utilization rates of vertebral augmentation were notably lower
(27% at Mayo vs 52% at BHCS); the reason for this discrepancy
is likely multifaceted but was not determined by this survey.
This study sampled a relatively small population of physicians and included inherent bias by limiting the survey to two
predefined groups of physicians. The response rate was within
the previously published range for e-mail–based surveys, which
has been as low as 6% (14). Subgroup analysis by medical subspecialty was not performed due to the relatively small sample
size. The Mayo Clinic physicians were likely more aware of the
INVEST results since Mayo was the lead site in the original
multicenter trial. Peer-to-peer education and interactive discussions were proactively performed at the Baylor University
Medical Center campus to educate referring physicians about
the INVEST data and to encourage continued patient referrals to interventional neuroradiology. Generalization of these
two groups’ responses to the wider medical community may
not be entirely representative. Additionally, extrapolation of
this information to predict future trends in clinician demand
and referral patterns for vertebroplasty is shortsighted without
April 2013
6.
7.
8.
9.
10.
11.
12.
13.
14.
Kallmes DF, Comstock BA, Heagerty PJ, Turner JA, Wilson DJ,
Diamond TH, Edwards R, Gray LA, Stout L, Owen S, Hollingworth W,
Ghdoke B, Annesley-Williams DJ, Ralston SH, Jarvik JG. A randomized
trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med
2009;361(6):569–579.
Buchbinder R, Osborne RH, Ebeling PR, Wark JD, Mitchell P, Wriedt C,
Graves S, Staples MP, Murphy B. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med 2009;361(6):557–568.
Baerlocher MO, Munk PL, Liu DM, Tomlinson G, Badii M, Kee ST, Loh
CT, Hardy BW, Murphy KJ. Clinical utility of vertebroplasty: need for
better evidence. Radiology 2010;255(3):669–674.
Buchbinder R, Kallmes DF. Vertebroplasty: when randomized placebo-controlled trial results clash with common belief. Spine J 2010;10(3):241–243.
Buchbinder R, Osborne RH, Kallmes D. Invited editorial presents an accurate summary of the results of two randomised placebo-controlled trials
of vertebroplasty. Med J Aust 2010;192(6):338–341.
Clark WA, Diamond TH, McNeil HP, Gonski PN, Schlaphoff GP, Rouse
JC. Vertebroplasty for painful acute osteoporotic vertebral fractures: recent
Medical Journal of Australia editorial is not relevant to the patient group
that we treat with vertebroplasty. Med J Aust 2010;192(6):334–337.
Kallmes D, Buchbinder R, Jarvik J, Heagerty P, Comstock B, Turner J,
Osborne R. Response to “Randomized vertebroplasty trials: bad news or
sham news?” AJNR Am J Neuroradiol 2009;30(10):1809–1810.
Kallmes DF, Jarvik JG, Osborne RH, Comstock BA, Staples MP, Heagerty
PJ, Turner JA, Buchbinder R. Clinical utility of vertebroplasty: elevating
the evidence. Radiology 2010;255(3):675–680.
Layton KF, Thielen KR, Koch CA, Luetmer PH, Lane JI, Wald JT, Kallmes
DF. Vertebroplasty, first 1000 levels of a single center: evaluation of the outcomes and complications. AJNR Am J Neuroradiol 2007;28(4):683–689.
McGirt MJ, Parker SL, Wolinsky JP, Witham TF, Bydon A, Gokaslan
ZL. Vertebroplasty and kyphoplasty for the treatment of vertebral compression fractures: an evidenced-based review of the literature. Spine J
2009;9(6):501–508.
Brinjikji W, Comstock BA, Gray L, Kallmes DF. Local Anesthesia with
Bupivacaine and Lidocaine for Vertebral Fracture trial (LABEL): a report of
outcomes and comparison with the Investigational Vertebroplasty Efficacy and
Safety Trial (INVEST). AJNR Am J Neuroradiol 2010;31(9):1631–1634.
Klazen CA, Lohle PN, de Vries J, Jansen FH, Tielbeek AV, Blonk MC,
Venmans A, van Rooij WJ, Schoemaker MC, Juttmann JR, Lo TH, Verhaar
HJ, van der Graaf Y, van Everdingen KJ, Muller AF, Elgersma OE, Halkema
DR, Fransen H, Janssens X, Buskens E, Mali WP. Vertebroplasty versus
conservative treatment in acute osteoporotic vertebral compression fractures
(Vertos II): an open-label randomised trial. Lancet 2010;376(9746):1085–
1092.
Luetmer MT, Kallmes DF. Have referral patterns for vertebroplasty changed
since publication of the placebo-controlled trials? AJNR Am J Neuroradiol
2011;32(4):647–648.
Sheehan KB, McMillan SJ. Response variation in e-mail surveys: an exploration. J Advert Res 1999;39(4):45–54.
Impact of sham-controlled vertebroplasty trials on referral patterns at two academic medical centers
105
High-intensity, occupation-specific training in a series of
firefighters during phase II cardiac rehabilitation
Jenny Adams, PhD, Dunlei Cheng, PhD, and Rafic F. Berbarie, MD
Six male firefighters who were referred to phase II cardiac rehabilitation
after coronary revascularization participated in a specialized regimen
of high-intensity, occupation-specific training (HIOST) that simulated
firefighting tasks. During each session, the electrocardiogram, heart rate,
and blood pressure were monitored, and the patients were observed for
adverse symptoms. No patient had to discontinue HIOST because of
adverse arrhythmias or symptoms. For physicians who must make decisions about return to work, the information collected over multiple HIOST
sessions might be more thorough and conclusive than the information
gained during a single treadmill exercise stress test (the recommended
evaluation method).
F
irefighting is arduous and has one of the highest occupational fatality rates in the United States (1). Surprisingly,
coronary heart disease (CHD), not injury, is the number
one cause of on-duty deaths among firefighters (2). However, the vast majority of these firefighters were not previously
diagnosed with CHD and had uncontrolled risk factors (3).
Current recommendations state that firefighters with CHD
should be restricted from performing strenuous emergency duties (4). To our knowledge, there are no data regarding firefighters’ exercise tolerance following successful revascularization of
their CHD and hence no assessment of whether they are then
able to perform simulated firefighting tasks.
The National Fire Protection Agency, which promotes codes
and standards for fire safety worldwide, has proposed guidelines
for veteran firefighters who may want to return to work in
the presence of CHD. These guidelines include seven criteria,
four of which are clinical observations that can be obtained
from a patient history: 1) no angina, 2) no major coronary
artery stenosis (>70% of lumen), 3) normal left ventricular
ejection fraction, and 4) no persistent modifiable risk factor for
plaque rupture (i.e., tobacco use, hypertension, total cholesterol
>180 mg/dL, low-density lipoprotein cholesterol >100 mg/dL,
or glycated hemoglobin >7%). The other three criteria involve
observations made during an exercise stress test: 5) exercise
tolerance >12 metabolic equivalents (METs), 6) no exerciseinduced angina, and 7) no ischemia or ventricular arrhythmia
during exercise (with imaging) (5). However, treadmill exercise
stress tests are not always reliable predictors of performance in
106
activities that require both strength and endurance (6), such
as firefighting. Deciding whether a firefighter should return to
work on the basis of the results from a single treadmill exercise
stress test might be inadequate considering the unique specificity
and intensity of the job.
In a prior study of the exercise tolerance of firefighters, we
collected metabolic data on healthy subjects as they performed
simulated firefighting tasks on an obstacle course (7). We then
translated the study’s tasks, which required a mean level of 12
METs, into a telemetry-monitored program of high-intensity,
occupation-specific training (HIOST) within the cardiac rehabilitation (CR) program at our institution. Our goal was
to evaluate the firefighter-patient’s tolerance for performing
strenuous occupational tasks in repeated sessions, with the resulting information assisting the physician’s decision about the
patient’s physical potential for returning to work. Here, we
report data from the first six patients with CHD to undergo
this training.
PATIENT TRAINING
From June 2008 through May 2012, six male firefighters
were referred to outpatient phase II CR in Dallas, Texas, following revascularization of CHD, and they consented to participate in CR 3 days per week. CR staff gave them the option
of participating in HIOST or conventional CR; all selected
the HIOST option. The hospital’s institutional review board
approved the reporting of their data.
The patients’ demographic and clinical information is summarized in the Table. At enrollment, all six patients were on an
antiplatelet regimen and were taking lipid-lowering drugs and
beta-blockers. In addition, one was taking a nitrate and diuretic;
another was taking ranolazine for angina.
From the Cardiac Rehabilitation Department, Baylor Jack and Jane Hamilton
Heart and Vascular Hospital (Adams, Berbarie), the Institute for Health Care
Research and Improvement, Baylor Health Care System (Cheng), and the Division
of Cardiology, Department of Internal Medicine, Baylor University Medical Center
at Dallas and Baylor Hamilton Heart and Vascular Hospital (Berbarie). Dr. Cheng
is now with the Division of Biostatistics, The University of Texas School of Public
Health Dallas Regional Campus.
Corresponding author: Jenny Adams, PhD, Cardiac Rehabilitation Department,
Baylor Heart and Vascular Hospital, 411 N. Washington, Suite 3100, Dallas, TX
75246 (e-mail: [email protected]).
Table. Clinical characteristics of six male firefighters and the data from their high-intensity, occupation-specific training (HIOST)
sessions after coronary revascularization
Peak values during HIOST (mean ± SD)†
Pt. no.
(age, y)
EF
(%)
BMI
(kg/m2)
Additional
cardiac risk
factors*
1 (61)
65
32.4
DM, FHx, PI, STR
2 (54)
50
35.1
PI, SM, STR
–
CABG
34
26
147 ± 5
143 ± 12
68 ± 10
21,220 ± 1844
3 (48)
50
28.2
–
+
PCI
28
20
142 ± 13
168 ± 28
83 ± 14
24,160 ± 4879
4 (58)
55
26.3
FHx, PI, STR
+
PCI, CABG
24
20
141 ± 9
163 ± 31
69 ± 8
22,767 ± 4793
5 (51)
50
25.3
FHx
–
PCI, CABG
25
15
139 ± 8
167 ± 24
85 ± 8
23,494 ± 4368
6 (52)
NA
31.1
–
–
PCI
18
15
149 ± 9
202 ± 12
88 ± 10
29,958 ± 2744
MI
Type of
revasc.
–
PCI
No. of sessions
Total
HIOST
HR (bpm)
SBP
(mm Hg)
DBP
(mm Hg)
RPP‡
24
21
140 ± 13
174 ±17
84 ± 9
23,432 ± 3515
*Other than hypertension and hyperlipidemia (present in all six patients) and obesity (see BMI).
†Peak
heart rate recorded every session; peak blood pressure recorded a total of 73 times.
‡Calculated
for sessions during which peak heart rate and blood pressure were recorded.
BMI indicates body mass index; CABG, coronary artery bypass graft surgery; DBP, diastolic blood pressure; DM, diabetes mellitus; EF, ejection fraction; FHx, family history; HR, heart rate;
MI, myocardial infarction; NA, not available (pending follow-up); PCI, percutaneous coronary intervention; PI, physical inactivity; RPP, rate-pressure product (heart rate × systolic blood
pressure); SBP, systolic blood pressure; SM, smoking; STR, stress.
The patients were monitored by telemetry during exercise
training. Resting heart rate and blood pressure measurements
were taken before and after each session, and the patients performed warm-up and cool-down routines. A physician was in
the room and approved the exercise regimen. The patients participated in supervised endurance training (treadmill walking)
during several early sessions (the number varied per individual)
until their vital signs were found to respond appropriately to
exercise. At that juncture, the patients began the subsequent
HIOST sessions, which were specifically designed to mirror
the occupational tasks included in our prior study of healthy
firefighters (7).
During HIOST, no calculated target heart rate range was
used to restrict exercise intensity. Training was symptomlimited; patients were monitored for hypertension (blood
pressure >240/110 mm Hg), hypotension (systolic blood pressure decrease of ≥10 mm Hg), elevated rate-pressure product
(≥36,000), ventricular arrhythmias, ST depression, angina, dizziness, pain, shortness of breath, and perceived exertion.
The HIOST workouts were customized by incrementally
increasing cardiovascular intensity and weight loads over the
course of the CR program exercise sessions. The patients wore
weighted vests (10 to 55 pounds) as they completed the following occupation-specific tasks (Figure):
• Carrying a weighted box ranging from 11.5 to 50 pounds
(simulates carrying equipment)
• Climbing stairs carrying a 15- or 30-pound hose (simulates
carrying a high-rise hose pack to an upper-story location)
• Dragging a 50-, 95-, or 165-pound dummy (simulates removing a victim from a fire scene)
• Using a stair-climbing machine (simulates walking up
stairs)
• Pulling a 30- or 60-pound fire hose (simulates advancing a
hose)
April 2013
• Raising a pike pole weighing 5.5 to 15.4 pounds (simulates
removing debris from a ceiling)
• Hitting a tire for 20 to 60 seconds with a 9-pound sledgehammer (simulates forcible entry)
The six patients participated in a total of 153 sessions;
36 consisted of supervised endurance training and 117 were
HIOST. During each session, the peak exercise heart rate was
determined from the electrocardiogram. Peak blood pressure
was recorded a total of 73 times during HIOST, and the resulting rate-pressure product values were calculated (see the
Table).
None of the patients had to stop training because of adverse
arrhythmias or symptoms. Peak heart rates were likely blunted
by beta-blocker therapy, but all six patients were able to perform
firefighting tasks that mirrored the 12-MET activities from
the prior study. During exercise, their peak blood pressures
remained well below 240/110 mm Hg, the limit recommended
by established guidelines (8), and their rate-pressure product
values were below the 36,000 threshold (9).
DISCUSSION
The American College of Sports Medicine endorses using
specificity of training for cardiac patients who desire to return
to manual labor occupations (10). To our knowledge, this is the
first report of firefighters’ ability to perform occupation-specific
tasks following successful coronary revascularization.
The HIOST program has limitations. Because the CR setting lacks the danger and stress of actual fire suppression activities, the patients’ physiological responses during training
may not reflect their responses on the job at a fire scene. In
addition, the program cannot simulate many of the hazardous
work conditions that firefighters must face, including exposure
to smoke, carbon monoxide, fumes, and other chemicals (11);
heat stress (12); and high noise levels (13).
High-intensity, occupation-specific training in a series of firefighters during phase II cardiac rehabilitation
107
a
b
Acknowledgments
Grant support was provided by the Harry S.
Moss Heart Trust and the Baylor Health Care
System Foundation, Dallas, Texas, through the
Cardiovascular Research Review Committee and
in cooperation with the Baylor Heart and Vascular Institute. The authors thank the committee for their continued support of cardiovascular
rehabilitation research projects. Beverly Peters,
MA, ELS, a freelance medical editor, assisted
with manuscript development and preparation.
1. Fabio A, Ta M, Strotmeyer S, Li W, Schmidt E. Incidentlevel risk factors for firefighter injuries at structural fires.
J Occup Environ Med 2002;44(11):1059–1063.
2. Kales SN, Soteriades ES, Christophi CA, Christiani
DC. Emergency duties and deaths from heart disease
among firefighters in the United States. N Engl J Med
2007;356(12):1207–1215.
3. Kales SN, Soteriades ES, Christoudias SG, Christiani
DC. Firefighters and on-duty deaths from coronary
c
d
heart disease: a case control study. Environ Health
2003;2(1):14.
4. Soteriades ES, Smith DL, Tsismenakis AJ, Baur DM,
Kales SN. Cardiovascular disease in US firefighters: a
systematic review. Cardiol Rev 2011;19(4):202–215.
5. Hales T. Practical application of the NFPA 1582 Standard [presentation]. Quoted by Mittelman J. How to
reduce cardiovascular mortality in your fire department.
New England College of Occupational and Environmental Medicine (NECOEM) Reporter 2008;2(24):1–2, 5.
Available at http://www.necoem.org/newsletter_archive2.html; accessed January 11, 2013.
6. Åstrand P-O, Rodahl K, Dahl HA, Strømme SB. Textbook of Work Physiology: Physiological Bases of Exercise,
4th ed. Champaign, IL: Human Kinetics, 2003:346.
7. Adams J, Roberts J, Simms K, Cheng D, Hartman J,
Bartlett C. Measurement of functional capacity requirements to aid in development of an occupation-specific
rehabilitation training program to help firefighters
with cardiac disease safely return to work. Am J Cardiol
2009;103(6):762–765.
Figure. Four of the occupation-specific activities performed by firefighters while wearing a weighted 8. American Association of Cardiovascular and Pulmonary
vest: (a) after climbing stairs with a hose pack, (b) dragging a dummy, (c) using a stair-climbing
Rehabilitation. Guidelines for Cardiac Rehabilitation and
machine, and (d) hitting a tire with a sledgehammer.
Secondary Prevention Programs, 4th ed. Champaign, IL:
Human Kinetics, 2004:115.
9. Adams J, Cline MJ, Hubbard M, McCullough T, Hartman J. A new
Despite these limitations, HIOST allows patients to perparadigm for post-cardiac event resistance exercise guidelines. Am J Cardiol
form simulated firefighting tasks while their electrocardiogram,
2006;97(2):281–286.
10. American College of Sports Medicine. ACSM’s Guidelines for Exercise
blood pressure, and heart rate are monitored in a clinical setting,
Testing and Prescription, 8th ed. Philadelphia: Lippincott Williams &
providing information about exercise-induced angina, ischemia,
Wilkins, 2010:222.
and arrhythmias over multiple sessions. For physicians who
11. Carey MG, Thevenin BJ. High-resolution 12-lead electrocardiograms of
must make decisions about return to work, these findings might
on-duty professional firefighters: a pilot feasibility study. J Cardiovasc Nurs
be more thorough and conclusive than the information gained
2009;24(4):261–267.
12. Rossi R. Fire fighting and its influence on the body. Ergonomics
during a single treadmill exercise stress test.
2003;46(10):1017–1033.
13. Tubbs RL. Noise and hearing loss in firefighting. Occup Med
1995;10(4):843–856.
108
Volume 26, Number 2
William C. Roberts, MD, Saleha Zafar, MD, and Jo Mi Ko, BA
Although it varies from center to center, the frequency of temporal artery
biopsy in patients suspected of having temporal arteritis (TA) is relatively
small. Most commonly, patients suspected of having TA are placed on
prednisone for varying periods of time, and if symptoms disappear or
lessen the diagnosis is made. During a recent 13-year period at Baylor
University Medical Center at Dallas, 15 patients with TA had the diagnosis
of TA confirmed by histological examination of a biopsy of one temporal
artery. The length of the biopsied artery varied from 0.7 to 5.5 cm (mean
2.7). The 15 patients ranged in age from 68 to 94 years (mean 82,
median 85), and 11 (73%) were women. In 13 of the 15 patients (87%),
the lumen of the temporal artery was narrowed >95% in cross-sectional
area by the panarteritis, and the temporal artery was associated with
giant cells in 11 patients (73%). Large collections of erythrocytes were
present in the inflamed arterial walls in 5 patients (33%). All 15 patients
were treated with varying doses of prednisone with favorable response
in each. Eight patients (53%) died from 1 to 105 months (mean 52,
median 57) after biopsy of the temporal artery. We have neither positive
nor negative evidence that the TA played a role in the patients’ death.
Despite the present study and numerous others in the last 70 years, the
cause of TA remains a mystery.
I
n 1932 and in 1934, Bayard T. Horton, a vascular specialist
at the Mayo Clinic, and others (1, 2) reported two patients
with headache, scalp tenderness, weight loss, fever, and night
sweats, and histologic examination of one biopsied temporal
artery disclosed granulomatous panarteritis. Thereafter, the condition was called temporal arteritis (TA) by some and Horton’s
disease by others. In 1937, Horton and Magath (3) described
visual loss, jaw claudication, and elevated erythrocyte sedimentation rates in several additional patients with the disease.
According to Boes (4), Horton in 1942 was the first to give a
patient with TA Kendall’s adrenocorticoid extract (nonpure),
but apparently it had no effect on the patient’s disease. Shick
and colleagues (5), in 1950, also at the Mayo Clinic, reported
clinical improvement in two patients with TA using a pure
form of cortisone. The present study summarizes findings in
15 patients with TA seen at Baylor University Medical Center
at Dallas (BUMC) in the last 13 years and describes in detail
the various histological features in the temporal artery in these
patients.
METHODS
Cases coded as TA by the surgical pathology division of
the Department of Pathology of BUMC from 1997 through
2012 were retrieved. Fifteen such cases having biopsy of one
temporal artery were found. The paraffin blocks of the temporal
artery in each patient were retrieved and recut. The resulting
6-micron-thick sections were stained by both the hematoxylineosin method and by the Movat method, and the sections were
examined. The clinical records in each patient were retrieved
and examined in the BUMC record room, and pertinent findings were tabulated in each patient. Finally, the Social Security
Death Index was searched to determine how many of the 15
patients had died.
RESULTS
Pertinent findings in the 15 patients are summarized in
Tables 1 and 2. The 15 patients ranged in age from 68 to 94
years (mean 82) at the time of the temporal artery biopsy; 11
were women and 4 were men. The age at biopsy in all 15 patients
corresponded to the age at which symptoms and/or signs of TA
appeared. The symptoms at the time of temporal artery biopsy
are displayed for each patient in Table 1: headache in 12, visual
disturbance in 10, mastication pain in 7, and temporal artery
tenderness in 6. At the time of biopsy, the indirect systemic
arterial pressure was ≥140 mm Hg systolic and/or ≥90 mm
Hg diastolic in 11 patients (73%). The body mass index was
>25 kg/m2 in 8 of the 15 patients, but in none was it ≥30 kg/m2.
Anemia (hematocrit <35%) was present in 8 (57%) of the 14
patients in which the result of this test was available. The platelet
count was >250 mm3 in 9 of the 11 patients in whom it was
performed. The erythrocyte sedimentation rates were elevated
(>20 mm/hour) in all 10 patients where the results were available. The serum C-reactive protein was elevated in all 5 patients
in which it was done. One patient (#2) had an aortic aneurysm,
and one patient (#8) had had a stroke a few months before
From the Baylor Heart and Vascular Institute (Roberts, Zafar, Ko) and the
Departments of Pathology and Internal Medicine (Division of Cardiology) (Roberts),
Baylor University Medical Center at Dallas.
Corresponding author: William C. Roberts, MD, Baylor Heart and Vascular
Institute, 621 North Hall Street, Dallas, TX 75226 (e-mail: wc.roberts@
BaylorHealth.edu).
109
BMI indicates body mass index; BP, blood pressure; CRP, C-reactive protein; CS, cigarette smokers; ESR, erythrocyte sedimentation rate; H, headache; HCT, hematocrit; Hgb, hemoglobin; LC, leg claudication; MP, mastication pain; PR, polymyalgia
rheumatica; S/D, peak systole/end diastole; VD, visual disturbance; –, not done, not applicable, or no information.
60
19
26.2
6
281
4/13/2009
15
94
M
–
–
94
+
+
+
0
+
+
+
160/90
14.3
40.0
41
50
3
25.4
19
369
8/22/2008
14
83
M
–
–
83
0
0
+
0
0
0
0
115/70
9.9
29.5
103
60
60
4
–
29.8
25.1
–
–
–
57
258
–
32.0
–
–
11.0
110/70
155/95
+
0
+
+
0
0
0
+
+
0
+
0
+
0
68
81
–
68
3
–
M
M
13
68
9/9/2010
4/25/1998
12
81
60
24
–
q
90
2/10/2000
11
F
28
92
90
+
0
0
0
0
0
0
175/80
13.6
32.4
21.8
60
60
11
14
29.1
20.8
–
28
q
269
565
33.5
9.8
220/80
140/60
+
+
0
0
0
0
0
0
0
+
+
0
+
+
89
86
–
96
74
–
F
86
9/8/2004
89
3/26/2002
9
10
F
11.2
29.9
130
60
60
0.5
0.25
26.0
q
q
24.3
26
92
245
230
32.2
35.8
12.1
10.6
140/80
150/55
0
0
+
0
0
+
0
0
+
+
+
0
0
+
85
86
–
85
1
–
F
F
86
8
85
3/22/2001
11/22/2010
7
60
60
–
73
23.0
24.6
–
–
–
121
347
379
32.0
38.2
12.4
10.5
130/60
130/90
0
+
+
0
0
+
+
0
+
0
+
0
+
+
80
82
90
85
65
87
F
F
1/29/2002
6
82
11/21/2002
5
80
60
40
17
–
27.1
26.2
–
–
40.1
–
76
470
37.0
11.5
13.3
180/90
140/80
0
0
0
0
0
0
+
0
+
0
0
0
+
+
77
77
–
85
105
–
F
77
6/25/1997
10/23/2001
4
2
3
8/3/2001
1
F
331
8/6/1998
Patient
77
60
70
73
26
20.0
20.8
–
–
–
–
35.2
26.9
11.7
8.5
170/75
130/80
0
+
+
+
0
0
+
0
+
+
+
+
+
+
75
75
–
79
50
–
F
Date
of
biopsy
75
LC
PR
CS
VD
MP
H
Symptoms at time of biopsy
Sex
F
BMI
(kg/m2)
CRP
(mg/
dL)
ESR
(mm/
hr)
BP s/d
(mm Hg)
Hgb
(g/dL)
HCT
(%)
Platelet
count
(mm3)
Age at
symptom
onset
(yr)
Age
at
death
(yr)
Age
at
biopsy
(years)
75
Maximal
dose of
prednisone
(mg)
Minimal
time on
prednisone
(mo)
Temporal
artery
tenderness
Interval
from
biopsy to
death
(mo)
Table 1. Clinical and laboratory findings in the 15 patients with temporal arteritis confirmed by biopsy and treated with prednisone
110
biopsy. The length of the temporal artery biopsied ranged from 0.7 to 5.5
cm (mean 2.7); sample images and descriptions appear in Figures 1 to 9. In
13 of the 15 patients (87%), the lumen
of the temporal artery was narrowed
>95% in cross-sectional area. The temporal artery was associated with giant
cells in 11 patients (73%). All 15 patients received prednisone (maximal
dose 40–70 mg) for 0.25 to 73 months
(mean 22), and all had symptomatic
improvement, including 5 with loss or
virtual loss of symptoms.
DISCUSSION
It might seem a bit inappropriate in 2013 to report a series of only
15 patients with biopsy-proven TA
when others have reported such large
series of patients with biopsy-proven
TA (6–35). Gonzalez-Gay and colleagues (13, 19, 20, 25, 26, 28, 31),
for example, in 7 articles from 1998
to 2011 described anywhere from 161
to 255 patients with biopsy-proven
TA (called “giant cell arteritis” by the
authors), but none contained a photomicrograph of a temporal artery. Indeed, of the 30 studies presented in
Table 3 (6–35), only two included a
photomicrograph of a temporal artery, and in both only hematoxylineosin–stained sections had been used.
It is not possible to demonstrate the
locations of the panarteritis, i.e., how
much of the process involved the intima, media, and adventitia, without
an elastic tissue stain that readily identifies the internal and external elastic
membranes allowing clear demonstration of media, thus separating it
from the intima and adventitia. We
employed the Movat stain for this
purpose in our study (36).
We prefer the phrase “temporal
arteritis” to the phrase “giant cell arteritis” because giant cells are not seen
in all TA patients having biopsies of
the temporal arteries. Among our 15
patients, we found giant cells in only
11. Mahr and colleagues (37) suggested that finding giant cells in patients
with TA is determined in part by the
lengths of the temporal arteries examined. These authors examined surgical
Volume 26, Number 2
Table 2. Morphological findings in the 15 patients with biopsy-proven temporal arteritis
Cross-sectional
narrowing
Collection
of red
blood cells
in intima
Lymphocytes
Giant
cells
3
>95%
0
+++
++
11
2
>95%
+
+++
++
2.4
8
2
>95%
0
+++
++
4
2.0
8
2
>95%
+
+++
++
5
2.4
12
2
>95%
+
+++
++
6
0.7
3
2
>95%
0
+
0
7
2.6
8
2
51%–75%
+
+
0
8
2.2
4
2
>95%
0
+++
++
9
5.5
19
6
>95%
0
+++
++
10
3.0
8
4
>95%
0
+++
+
11
0.7
2
2
>95%
0
+
+
12
1.9
4
2
>95%
+
+++
++
13
2.1
6
3
>95%
0
+++
++
14
3.5
7
4
>95%
0
+++
0
15
3.0
7
3
51%–75%
0
+++
0
Length (cm) of
excised TA
Number of
histological
cross-sections
Maximal diameter
(mm) of crosssections
1
4.2
8
2
4.7
3
Patient
TA indicates temporal arteritis.
a
b
c
routine endeavor. A near universal observation in TA is a rapid, sometimes dramatic,
diminution or loss of symptoms after corticosteroid therapy has been initiated. If there
is not a quick symptomatic response, biopsy
e
d
can then be performed. There appears to be
little change in the histologic features of the
TA before corticosteroid therapy and up to
about 6 weeks after initiation of therapy
(10). A report by Guevara et al described
Figure 1. Patient 1. Various views of the temporal artery. (a) Movat-stained section (×40) showing relatively
intact media (pink), very thickened intima (green) with severe luminal narrowing, and severely thickened a positive biopsy after 6 months of predfibrous tissue of the adventitia (tan). (b) Hematoxylin-eosin (H&E)–stained section showing numerous inflam- nisone treatment (38). If a patient with
matory cells involving the outer intima, media, and inner adventitia (×100). (c) A close-up showing intimal suspected TA has a negative biopsy of the
granulomatous-type cells adjacent to the media with penetration of the media (H&E, ×400). (d) Another temporal artery, is it useful then to biopsy
view showing an inflamed nodule in brackets in the adventitia (H&E, ×40). (e) A close-up of that nodule the contralateral temporal artery? Accord(H&E, ×400).
ing to a study by Boyev and colleagues (18),
biopsy of one temporal artery in a patient
reports of temporal artery biopsies in 223 patients with TA and
with TA provides a 97% chance that the same findings would be
found that 164 (74%) of the reports mentioned the presence of
present in the contralateral temporal artery, so that the additional
giant cells. These authors also mentioned that a temporal artery
biopsy would rarely be useful diagnostically.
length of at least 0.5 cm was sufficient for diagnosis of TA. Our
On occasion, TA resolves without corticosteroid therapy.
smallest length among the patients was 0.7 cm. Among the
Horton et al, in their original two patients, described tempofour patients in whom we did not see giant cells, the lengths
rary remissions with relapses (1), and they later described seven
of the temporal artery biopsied were 0.7, 2.6, 3.0, and 3.5 cm;
additional patients in whom remission occurred without drug
the latter three lengths were among the longest in the patients
therapy months after diagnosis (3). Patients have been described
we studied.
where headaches and local symptoms have disappeared simply
Although the present study focuses on the histologic features
by removal of a portion of the temporal artery for diagnostic
of TA, one might reasonably ask if biopsy of this artery is a useful
purposes (39, 40).
April 2013
111
a
a
b
c
b
Figure 2. Patient 2. (a) A Movat-stained section (×100) of temporal artery with
severely narrowed lumen (within the green portion) of the intima with blood (red)
within the intimal plaque and marked disruption of the internal elastic membrane
(black). The adventitia is thickened by dense fibrous tissue (tan). (b) The same
section stained by hematoxylin-eosin (×100). (c) A close up of a portion of the
media showing numerous mononuclear cells (×400).
Figure 4. Patient 6. Two views of Movat-stained sections of the temporal artery
showing (a) virtual occlusion (×100) and (b) severe narrowing (×100). The internal elastic membrane (black) is interrupted and the quantity of fibrous tissue
in the adventitia is considerably less than in previously illustrated cases.
a
Figure 3. Patient 4. Movat-stained section (×40) of the temporal artery showing
near-total occlusion of the lumen, blood (red) within the intimal plaque, disruption
of the internal elastic membrane (black), and severely thickened adventitia by
dense fibrous tissue (tan). The absence of much lumen and the marked thickening of the adventitia by dense fibrous tissue makes these arteries, by external
palpation, quite firm and nodular.
b
c
Figure 5. Patient 8. (a) A Movat-stained section of the temporal artery showing
near occlusion of the lumen by fibrous tissue and mucopolysaccharide material
(green) and dense fibrous tissue causing considerable thickening of the adventitia.
(b) Hematoxylin-eosin stain (×40) of another section of the same artery showing
numerous inflammatory cells between the 8:00 and 11:00 positions. (c) Close-up
(×400) of a portion of the inflammatory cells.
112
Volume 26, Number 2
a
b
a
Figure 6. Patient 9. (a) View of a hematoxylin-eosin–stained section (×20) of
the temporal artery with virtual total occlusion of its lumen. The darkened area
represents collections of inflammatory cells. The adventitia is thickened by fibrous
tissue. (b) A close-up (×400) of a minute portion of the inflammatory infiltrates.
Granulomatous-type cells and a giant cell are visible.
a
Figure 9. Patient 13. (a) A Movat-stained section of the temporal artery (×40)
with severe luminal narrowing. The lumen in all sections in temporal arteritis tends
to be in the more central portion of the artery and not on the periphery, as it is in
typical atherosclerosis. (b) A close-up hematoxylin-eosin–stained section (×400)
shows several giant cells in the outer intima adjacent to the media. These cells
are lined up perpendicular to the smooth muscle cells in the media.
1.
2.
3.
4.
5.
b
6.
c
7.
8.
9.
10.
Figure 7. Patient 9. (a) A Movat-stained section (×40) of three branches of a
temporal artery with narrowing of each branch, marked disruption of the media
in two of the branches, and dense fibrous tissue in the adventitia. (b) A close-up
of a hematoxylin-eosin–stained section (×400) of a portion of the inflammatory
cells in the media. (c) Another hematoxylin-eosin stained section (×400) showing
giant cells among the collection of cells.
11.
12.
13.
a
b
14.
15.
Figure 8. Patient 10. A Movat-stained section of the temporal artery showing
(a) severe narrowing of the lumen (×100) and (b) less narrowing (×100). The
amount of adventitial fibrous tissue is considerable. Inflammatory cells are present
in the intima, media, and adventitia. The dark staining in the medial wall in part
b represents calcific deposits.
April 2013
b
16.
Horton BT, Magath TB, Brown GE. An undescribed form of arteritis of
the temporal vessels. Proc Staff Meet Mayo Clinic 1932;7:700–701.
Horton BT, Magath TB, Brown GE. Arteritis of the temporal vessels: a
previously undescribed form. Arch Intern Med 1934;53:400–409.
Horton BT, Magath TB. Arteritis of the temporal vessels: report of seven
cases. Proc Staff Meet Mayo Clinic 1937;12:548–553.
Boes CJ. Bayard Horton’s clinicopathological description of giant cell
(temporal) arteritis. Cephalalgia 2007;27(1):68–75.
Shick RM, Baggenstoss AH, Fuller BF, Polley HF. Effects of cortisone and
ACTH on periarteritis nodosa and cranial arteritis. Proc Staff Meet Mayo
Clin 1950;25(17):492–494.
Birkhead NC, Wagener HP, Shick RM. Treatment of temporal arteritis
with adrenal corticosteroids; results in fifty-five cases in which lesion was
proved at biopsy. J Am Med Assoc 1957;163(10):821–827.
Huston KA, Hunder GG, Lie JT, Kennedy RH, Elveback LR. Temporal
arteritis: a 25-year epidemiologic, clinical, and pathologic study. Ann
Intern Med 1978;88(2):162–167.
Graham E, Holland A, Avery A, Russell RW. Prognosis in giant-cell arteritis. Br Med J (Clin Res Ed) 1981;282(6260):269–271.
Nordborg E, Bengtsson BA. Death rates and causes of death in 284
consecutive patients with giant cell arteritis confirmed by biopsy. BMJ
1989;299(6698):549–550.
Achkar AA, Lie JT, Hunder GG, O’Fallon WM, Gabriel SE. How does
previous corticosteroid treatment affect the biopsy findings in giant cell
(temporal) arteritis? Ann Intern Med 1994;120(12):987–992.
Lie JT. Aortic and extracranial large vessel giant cell arteritis: a review
of 72 cases with histopathologic documentation. Semin Arthritis Rheum
1995;24(6):422–431.
Salvarani C, Gabriel SE, O’Fallon WM, Hunder GG. The incidence of
giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations
in a cyclic pattern. Ann Intern Med 1995;123(3):192–194.
González-Gay MA, Blanco R, Rodríguez-Valverde V, Martínez-Taboada
VM, Delgado-Rodriguez M, Figueroa M, Uriarte E. Permanent visual
loss and cerebrovascular accidents in giant cell arteritis: predictors and
response to treatment. Arthritis Rheum 1998;41(8):1497–1504.
Cid MC, Font C, Oristrell J, de la Sierra A, Coll-Vinent B, López-Soto
A, Vilaseca J, Urbano-Márquez A, Grau JM. Association between strong
inflammatory response and low risk of developing visual loss and other
cranial ischemic complications in giant cell (temporal) arteritis. Arthritis
Rheum 1998;41(1):26–32.
Duhaut P, Pinede L, Demolombe-Rague S, Loire R, Seydoux D, Ninet J,
Pasquier J; Groupe de Recherche sur l’Artérite à Cellules Géantes. Giant
cell arteritis and cardiovascular risk factors: a multicenter, prospective
case-control study. Arthritis Rheum 1998;41(11):1960–1965.
Duhaut P, Pinède L, Bornet H, Demolombe-Ragué S, Dumontet
C, Ninet J, Loire R, Pasquier J; Groupe de Recherche sur l’Artérite à
Cellules Géantes. Biopsy proven and biopsy negative temporal arteritis:
113
114
Volume 26, Number 2
3001
225
Walvick, 2011
Ninan, 2011
225
459
174
26
287
30
57
255
49
240
151
74
9
147
161
161
722
74
207
207
200
239
115
67
175
284
90
38
55
62/163
–
80/94
–
132/155
10/20
28/50
116/139
0/49
110/130
36/137
–
3/8
38/109
79/82
79/82
–
16/58
50/157
118/282
59/141
106/133
22/103
21/51
190/345
–
26/64
9/33
28/27
M/F
(78.2)
–
(74.2)
–
50–80+
– (77.5)
56–89 (74.6)
55–94 (75)
50–69 (64.1)
50–80+ (74)
50–80+
–
65–90 (75)
– (75)
50–80+ (75)
50–80+ (75)
–
50+ (72)
50+ (74.5)
50+ (74)
57–92 (74.5)
50+ (73.5)
50–80+
54–96 (69)
31–93 (71.7)
–
55–88
56–92 (75)
60–83
Age range
(mean)
14
9
14
19
27
6
18
25
9
23
50
11
–
22
18
18
28
36
6
6
16
21
42
25
3
10
10
25
6
Length
of study
(yr)
5.5
–
3.5
–
–
–
–
–
3
–
6.8
2
–
–
–
–
–
–
36
–
–
–
–
–
–
1
11
19
–
Followup
(yr)
ESR indicates erythrocyte sedimentation rate; F, female; M, male; TA, temporal arteritis; −, no information.
207
107
Zhou, 2009
Martinez-Lado, 2011
287
240
Gonzalez-Gay, 2005
Gonzalez-Gay, 2009
173
Salvarani, 2004
30
181
Hall, 2003
78
11
Ray-Chaudhur, 2002
Makkuni, 2008
174
Liozon, 2001
Narvaez, 2007
190
Gonzalez-Gay, 2001
49
190
Gonzalez-Gay, 2000
255
756
Boyev, 1999
Gonzalez-Gay, 2007
148
Brack, 1999
Larsson, 2006
292
Duhaut, 1999
125
Salvarani, 1995
400
72
Lie, 1995
200
535
Achkar, 1994
Duhaut, 1998
284
Nordborg, 1989
Cid, 1998
90
Graham, 1981
239
42
Huston, 1978
Gonzalez-Gay, 1998
55
Patients
(n)
Birkhead, 1957
First author,
year of publication
Biopsyproven
TA
(n)
–
12
71
0
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
1
–
–
–
–
–
–
7
3
1
–
Deaths
attributed
to TA
–
0
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
38
–
–
–
–
–
–
82
32
21
–
Deaths
(n)
–
81
92.7
–
–
78.5
94.4
–
–
93
–
–
66
90
93
93
–
–
88
–
82.7
94
–
96
63
–
81
96
–
Mean
ESR
values
(mm/hr)
–
–
11.7
–
–
–
11.4
–
–
11.7
–
–
–
11.3
11.8
11.8
–
–
15.6
–
12.2
–
–
–
–
–
–
11.5
–
Median
hemoglobin
values
(g/dl)
–
391,000
392,000
–
–
–
340,000
–
–
397,000
–
–
–
419,000
412,816
412,816
–
–
424,000
–
337,000
–
–
–
–
–
–
–
–
Median
platelet
count
(mm3)
–
–
36
–
138
12
16
89
–
21
–
–
5
58
–
42
–
18
20
–
28
64
–
–
–
–
55
17
21
Visual
loss
(n)
–
–
174
–
–
–
78
–
–
–
–
–
11
174
–
–
–
74
292
–
–
239
–
–
249
–
90
42
55
Received
corticosteroids
(n)
Table 3. Reported studies of patients with temporal arteritis confirmed by biopsy of the temporal artery
–
–
44.1
–
–
–
1
–
–
–
–
–
1.5
–
–
–
–
–
36
–
–
–
–
–
–
–
84
77
15
Maximal
length of
treatment
(mo)
–
–
71
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
18
11
–
Patients
that
relapsed
(n)
0
0
0
+
0
+
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Temporal
artery
photo
mics
–
–
–
26
–
–
–
–
–
–
–
–
7
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
Giant
cell
histology
(n)
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
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Brack A, Martinez-Taboada V, Stanson A, Goronzy JJ, Weyand CM.
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Boyev LR, Miller NR, Green WR. Efficacy of unilateral versus bilateral
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32.
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34.
35.
36.
37.
38.
39.
40.
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115
Quality of life of HIV/AIDS patients in a secondary health care
facility, Ilorin, Nigeria
Shakirat I. Bello, MPharm, and Ibrahim K. Bello, MPharm
This study evaluated the quality of life (QoL) and associated factors for
160 HIV/AIDS patients in Sobi Specialist Hospital, Ilorin, Nigeria. The
patients were assessed with the World Health Organization Quality of
Life Questionnaire-Short Version. Frequency distribution, percentages,
and means were employed for the statistical analysis of the results. The
mean age of the HIV/AIDS patients was 38.0 years; 70% were females,
55% were literates, more than three quarters were married, and one
third were businessmen/women. The overall mean scores for healthrelated QoL were 72 for the physical domain, 67 for the psychological
domain, 65 for the environment domain, and 47 for the social domain.
Significant differences were observed in all domains among patients
who had received 12 months of antiretroviral therapy compared with
those who had just begun therapy. Marital status, fewer pills, and
longer duration of therapy appeared to predict better QoL in this study.
The improved QoL in the physical, psychological, and environmental
domains is suggestive of the interventions offered to the patients by
the pharmacists in this setting.
T
he pandemic of HIV and AIDS has led to serious health
and socioeconomic challenges for more than two decades
(1). The epidemic has also facilitated the reemergence of
disease conditions such as pulmonary tuberculosis, which
cause physical and psychological damage and decreased quality
of life (QoL) (2, 3). Based on an overall national prevalence of
4.1%, it is estimated that in 2012, 3.6 million Nigerians were
living with HIV/AIDS, 2.5 million children were orphaned,
and about 1000 new cases of HIV were discovered daily (4).
With this alarming increase of the HIV/AIDS pandemic in developing countries and the limited accessibility and availability
of highly active antiretroviral therapy (HAART), the majority of HIV/AIDS patients continue to suffer with the disease,
with a serious impact on their QoL (5). Many HIV patients
battle numerous social problems such as stigma and depression,
which affect their QoL in terms of their physical, mental, and
social health (6). QoL is an indicator of not only how well an
individual functions in daily life, but also how the individual’s
perceptions of health status influence his or her life (7, 8).
In Nigeria, QoL has been found to be determined by education, income, family support, HIV serostatus, and patient age
(9). Further, a study reported higher QoL scores in the physical,
116
psychological, and environmental domains and a relatively lower
score in the social domain among HIV patients in Nigeria (10).
Mweemba et al (11) suggested that periodical assessment of QoL
of people living with HIV/AIDS is imperative for holistic care,
thereby ameliorating the symptoms of ill health. Such assessments are useful not only in documenting patients’ perceived
burden of chronic disease, but also in evaluating treatment effects
(12). This study was therefore conducted to assess QoL of HIV/
AIDS patients in Sobi Specialist Hospital, Ilorin, Nigeria.
METHODS
The study site was the HIV/AIDS treatment center, Sobi
Specialist Hospital, Ilorin, Kwara State. Sobi Specialist Hospital,
Ilorin is a secondary health care facility established in April 1985
by the Kwara State Government, located in the north central
part of Nigeria. The primary ethnic group of Kwara State is
Yoruba, with Nupe, Bariba, and Fulani as minorities. The facility provides health services for citizens in Kogi, Niger, Osun,
Oyo, and Ekiti States and other neighboring states in Nigeria.
The hospital receives referrals of HIV-positive patients from
surrounding private hospitals and primary health care centers.
The center was funded by Friends in Global Health and supported by the Kwara State Government. As at June 2011, the
clinic had registered 616 HIV/AIDS patients, of whom 554
were on HAART.
This cross-sectional study involved 160 patients selected
from the population of 616 HIV/AIDS-positive patients receiving services and care from Sobi Specialist Hospital, Ilorin, during the period of April to October 2011. Included in the sample
were known HIV/AIDS patients who were 18 years or older
and regularly refilled their prescriptions in the pharmacy unit of
the center. Newly diagnosed patients and children (less than 18
years) were excluded. At the time of drug refill, an information
sheet describing the significance of the study was presented to
the patients. Those who showed interest in participating were
asked to sign informed consent forms. Ethical approval for the
From the Department of Clinical Pharmacy and Pharmacy Practice, Faculty of
Pharmaceutical Sciences, University of Ilorin, Ilorin, Nigeria (S. Bello); and the
Department of Pharmacy, University of Ilorin Teaching Hospital, Ilorin, Nigeria
(I. Bello).
Corresponding author: Shakirat I. Bello (e-mail: [email protected]).
study was obtained from the Ethics and Research Committee
of Kwara State Ministry of Health, Ilorin.
The patients were interviewed using a pretested structured
questionnaire to obtain information on sociodemographic status
and treatment variables. During the interview, all drug therapy
problems encountered were identified, resolved, and prevented
through pharmacist intervention in collaboration with other
health care providers. Counseling, education, training, and information interventions on HIV/AIDS, drug adherence, good
nutrition, safe drinking water, and malaria prevention were also
offered to the patients on a monthly basis.
The English version of the World Health Organization
Quality of Life Questionnaire-Short Version (WHOQoLBREF) was used to assess the QoL of these patients. This questionnaire consists of 26 items in four domains. The physical
health domain, with seven items, assesses the impact of disease on the activities of daily living, dependence on medicinal
substances, fatigue, restricted mobility, presence of pain and
discomfort, sleep and rest, a lack of energy and initiative, and
perceived working capacity. The psychological well-being domain includes eight items that assess the patient’s thoughts
about body image and appearance, positive feelings, negative
feelings, self-esteem and personal beliefs, higher cognitive functions, spirituality, anxiety, suicide, and depression. The third
domain, social relationships, has three items that assess personal
relationships, social contacts, social support, and sexual activity. The final domain, environment, with eight items, assesses
areas such as freedom, quality of home environment, physical
safety and security, financial status, involvement in recreational
activity, health, and social care quality and accessibility. The
English version of the instrument was translated to the Yoruba
language (the main language understood by most patients);
the translated version was validated prior to administration
to participants.
The QoL of each patient was assessed monthly during drug
refill at the main pharmacy of the hospital. The participants
who could not read were interviewed, while literates completed
the questionnaire under the supervision of the researchers. Participants selected the number on a 5-point Likert-type scale
that best represented their opinion, based on their life over the
previous 4 weeks. In the scale, 1 indicated low and negative
perceptions, and 5 indicated high and positive perceptions,
which denoted better QoL.
Negatively worded items were reverse scored, and all scores
were checked for appropriate range (between 1 and 5). Descriptive statistics, including frequency, means, percentages,
minimum values, and maximum values, were calculated. Each
item contributed equally to the domain score. To transform
scores so that they were equivalent to those used for the WHOQOL-100, two steps were used. First, scores were converted to a
range between 4 and 20, comparable with the WHOQOL-100.
Second, these scores were multiplied by 5 so that the scores
were converted to a scale of 0 to 100, where 100 is the highest
health-related QoL. Student’s t test was used to analyze the
differences between the mean scores of QoL. P < 0.05 was set
as the level of statistical significance.
April 2013
RESULTS
A total of 160 eligible participants completed the questionnaires; most were married (76%) and female (70%). The mean
age of the participants was 38.0 years (range 18–53 years). The
modal age range was 31–40 years. Other participant demographics are shown in Table 1. Almost half of the patients were
on HAART for over 12 months and employed self-reminder
or alarm methods of medication-taking behavior (Table 2). A
fixed-dose combination of a zidovudine-based regimen was most
tolerated by the patients, and more than three quarters of the
patients were taking two pills daily (Table 3).
HIV-seropositive married women had the highest QoL
scores in all the domains compared to those with a different
marital status (Table 4). Among the patients included in the
present study, however, those on two pills per day of antiretroviral drugs had the best QoL in the four domains. There was
no significant difference in the QoL of patients in the various
domains when compared based on pill burden (Table 5).
When patients’ QoL was assessed with respect to duration
of antiretroviral therapy, patients who had received treatment
for over 12 months had higher QoL scores in the psychological
and social domains; the difference was statistically significant
for the psychological domain (Table 6). Table 7 reveals the
overall QoL of the patients. The highest mean score was observed in the physical domain followed by the psychological
and environmental domains, while the social domain had the
lowest score.
Table 1. Sociodemographic characteristics of 160 HIV/AIDS
patients in Sobi Specialist Hospital, Ilorin
Variables
Gender
Age (years)
Marital status
Education
Occupation
N (%)
Females
112 (70%)
Males
48 (30%)
18–30
46 (29%)
31–40
67 (42%)
41–50
38 (24%)
>50
9 (5%)
Single
19 (12%)
Married
121 (76%)
Widowed
12 (7%)
Divorced
8 (5%)
None
49 (31%)
Primary school
50 (31%)
Secondary school
38 (24%)
Tertiary
23 (14%)
Businessmen/women
58 (37%)
Public servants
25 (16%)
Self-employed
34 (20%)
Students
7 (4%)
Not employed
36 (23%)
Quality of life of HIV/AIDS patients in a secondary health care facility, Ilorin, Nigeria
117
Table 2. Treatment characteristics of 160 HIV/AIDS patients in
Sobi Specialist Hospital, Ilorin
Characteristics
Therapy initiation
period (months)
Patient’s
medication-taking
behavior
Drug
allergies
N (%)
Table 5. Antiretroviral pill burden and quality of life scores of
160 HIV/AIDS patients
Domain
2 pills
4 pills
6 pills
P value
3–5
15 (9%)
Physical
73
72
71
0.022
6–8
18 (11%)
Psychological
67
64
65
0.048
9–12
60 (37%)
Social
47
44
43
0.242
>12
67 (42%)
Environmental
67
66
64
0.006
Use of alarm/self-reminder
71 (44%)
Family/clinic counselor
5 (3%)
Daily routine
16 (10%)
All of the above
68 (43%)
Cotrimoxazole
43 (27%)
Chloroquine
64 (40%)
Tetracycline
5 (3%)
Nevirapine
16 (10%)
Efavirenz
5 (3%)
None
27 (17%)
Table 3. Number of antiretroviral drugs taken per day by 160
HIV/AIDS patients
Drugs
Table 6. Antiretroviral therapy duration and quality of life
scores of 160 HIV/AIDS patients
Domain
3–5 mo
6–8 mo
9–11 mo
≥12 mo
P value
Physical
69
71
71
70
0.033
Psychological
62
60
64
68
<0.017
Social
44
45
46
48
0.008
Environmental
64
64
65
63
0.453
Table 7. Distribution of transformed quality of life scores obtained
from WHOQoL-BREF questionnaire for 160 HIV/AIDS patients
Domain
Mean scores
(transformed
0–100)
Minimum
domain
Maximum
domain
2 (1%)
Physical
72
43
80
15 (9%)
Psychological
67
43
87
Pills per day (n)
N (%)
Fixed-dose combination (AZT + 3TC + NVP)
2
98 (61%)
Lose dose (AZT + 3TC + NVP )
6
Combined (AZT + 3TC) + EFV
3
Combined (FTC + TDF) + NVP
3
5 (4%)
Social
47
20
60
Combined (FTC + TDF) + EFV
2
24 (15%)
Environment
65
47
80
Combined (FTC + TDF) + LPV/r
5
2 (1%)
Combined (AZT + 3TC) + LPV/r
6
12 (8%)
3TC + ABC + NVP
6
2 (1%)
AZT indicates zidovudine; 3TC, lamivudine; NVP, nevirapine; EFV, efavirenz; FTC, emtricitabine;
TDF, tenofovir; LPV, lopinavir; LPV/r, ritonavir-boosted lopinavir; ABC, abacavir.
Table 4. Marital status and quality of life scores of 160 HIV/
AIDS patients
Domain
Single
Physical
70
Married Divorced Widowed
72
71
71
P value
0.032
Psychological
66
69
66
67
0.355
Social
45
48
46
45
0.011
Environmental
64
65
62
61
0.428
DISCUSSION
The present study showed the prevalence of HIV infection
among all age groups but with the highest prevalence for those
in their 30s followed by those 18 to 30 years. This is consistent
with the findings of Bankole et al (13) and Khan et al (14), who
118
WHOQoL-BREF indicates World Health Organization Quality of Life Questionnaire-Short
Version.
reported that people within the age bracket of 15 to 24 years
were vulnerable to HIV, while those in their 30s were most
susceptible (15, 16). The demographic profile of the participants
also showed the predominance of the female gender, which is
consistent with other studies. Kelly et al (17) showed that 60%
of those living with HIV/AIDS are women. In contrast, in the
USA, 87% of the patients are men (18).
Patients who are more educated can better understand
the disease state and the instructions given on drug usage,
which invariably enhances their QoL. Almost one third of this
study population had received no formal education. Patients on
HAART for a longer duration, however, had higher QoL in this
study. By this time, patients had perceived medications as part
of their daily routine and had also developed coping strategies to
overcome the adverse effects of HAART that might have affected
their QoL. In line with this work was a study conducted by
Mannheimer et al (19), who reported significant improvement
in QoL after 1 to 4 months of treatment with antiretroviral
therapy, and this improvement persisted at 12 months.
Volume 26, Number 2
In this study, patients on a lower pill regimen had better
QoL. The explanation is probably related to fewer side effects,
fewer tablets to swallow, and a smaller container (easy to convey
and a pocket-friendly package). This study confirms the findings
of Jack et al (20) that improvements in overall evaluations of
QoL occurred for patients on a single daily dose.
The present study showed better QoL among married HIV/
AIDS patients than for unmarried women. It is believed that the
physical, emotional, and social support the married women received from their partners likely led to improved QoL. Evidence
has shown that support from sources outside the family cannot
compensate for what is missing in the family (21). Consistent
with the present work was a study reported by Nojomi et al (22)
that marital status had a significant effect on patients’ QoL. In
contrast, Pedram et al (23) showed that marital status had no
significant association with any domain of QoL.
Overall, however, the social domain showed the lowest score
of the four QoL domains in this study. The social domain was
affected by societal discrimination and stigmatization, as well
as HIV/AIDS’ influences on patients’ sexual desire, personal
relationships, and family life. In line with this study was that
of Fatiregun et al (24) in Kogi State, Nigeria, who reported a
lower QoL in the social relationship domain. The better scores
observed in the other three domains—physical, psychological,
and environmental—could be attributed to pharmacists’ impact
through comprehensive and consistent counseling on patients’
antiretroviral drugs and education on their disease state.
RECOMMENDATION
HIV/AIDS has affected many lives. Therefore, health care
providers and other stakeholders should strengthen their efforts
by addressing its social consequences to enhance QoL.
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Quality of life of HIV/AIDS patients in a secondary health care facility, Ilorin, Nigeria
119
Justin Sobrino, MD, and Shahid Shafi, MD, MPH
Currently, long-term outcomes are significant because health care system
changes will likely lead to a single payment for each occurrence of care,
including readmissions—the “bundled payment” system. Therefore, it is
essential to understand the outcomes of trauma patients discharged alive
from trauma centers. This article reviews the current knowledge base
on the timing and causes of deaths after trauma. The trimodal mortality
model (immediate deaths, early deaths, and late deaths) is utilized as the
early research describing trimodal distribution is discussed. Also covered
is the successive work as trauma systems matured, showing a shift toward a bimodal distribution with a decline in late deaths. Finally, studies
of long-term outcomes are highlighted. Deaths occurring within minutes
or a few hours of injury are largely unchanged, which underscores the
enormity of injuries to the central nervous and cardiovascular systems.
Late deaths caused by multiple organ failure and sepsis have declined
considerably, however. Also, the causes of death in this patient population
remain constant. Lastly, a considerable number of deaths after discharge
may be due to nontraumatic causes.
S
urvival to discharge has long been the primary endpoint
for research and quality improvement in trauma (1, 2).
More recent studies have begun assessing long-term
outcomes such as complications, costs, readmissions,
and survival after discharge (3–11). We have recently shown
that over a period of 1 year after the initial injury, about half
of the deaths occur within the first 30 days but the rest occur
afterward (12). It is important to understand the outcomes of
trauma patients discharged alive from trauma centers. Baker
et al and Trunkey defined timing of trauma deaths as a trimodal distribution in urban environments in the United States
(13, 14). However, the development and maturation of regionalized trauma networks in the 1970s and 1980s have shifted
the epidemiology of trauma patients and patterns of mortality.
Subsequent research has shown a decline in deaths late after
trauma, indicating that the trimodal concept may no longer
be accurate in urban trauma environments (12, 15–18). A
confounding factor is inconsistent time intervals chosen by
researchers to define the timing of deaths (18–20). Herein,
we review the existing knowledge on timing and causes of
deaths after trauma. We use the trimodal mortality model to
cover the early research describing the trimodal distribution,
120
the subsequent work as trauma systems matured, and studies
of long-term outcomes.
TIMING OF DEATHS
The first peak in the classic trimodal model of trauma mortality is immediate death occurring within minutes of the injury.
These patients are declared dead on the scene or die shortly after
arrival to the hospital. In most published reports, these include
deaths at the scene, deaths occurring within 1 hour of arrival
to the hospital, and all deaths in the emergency department.
These deaths are generally a consequence of severe and likely
nonsurvivable injuries. The seminal works of Baker et al and
Trunkey in the 1970s showed that 64% and 53%, respectively,
of trauma deaths occurred on the scene, with the patients not
even transported to a hospital (13, 14). Figure 1 displays a
summary of studies evaluating immediate deaths (12, 13, 15,
16, 18, 19, 21–24). This recognition led to rapid development
of regionalized trauma systems in the United States, led by the
work of Dr. Cowley in Maryland (25, 26). The primary purpose of regionalized integrated care was rapid transportation
of patients from the scene to definitive care. It is interesting
Figure 1. Studies reviewing immediate deaths (12, 13, 15, 16, 18, 19, 21–24).
From the Institute for Health Care Research and Improvement, Baylor Health
Care System, Dallas, Texas.
Corresponding author: Shahid Shafi, MD, MPH, Baylor Health Care System,
1600 W. College Street, Suite LL 10, Grapevine, TX 76052 (e-mail: shahid.
[email protected]).
to note in Figure 1 that despite all the progress in emergency
medical services and trauma systems, prehospital care, injury
prevention, and automotive safety, the proportion of deaths
occurring immediately after injury has remained unchanged
over time, at 50% to 60%.
The second peak in the trimodal distribution is early
deaths, defined as deaths within hours of arrival to the hospital. In most published reports, early deaths include deaths
within 24 hours of arrival to a trauma center, excluding immediate deaths. These deaths are also a consequence of severe
injuries, but the patients arrive at the hospital alive and are
potentially treatable with prompt definitive care. Trunkey estimated this group to include approximately 30% of deaths
(14). Figure 2 depicts a range of studies evaluating early deaths
(12, 13, 15, 16, 19). Again, the proportion of deaths in this
group has remained relatively unchanged over time, at 25%
to 30% of all trauma deaths.
In Trunkey’s original description of the trimodal distribution, 20% of trauma deaths were “late deaths,” defined as those
occurring days to weeks after the injury among patients who
survived the initial insult (14). In most reports, this category
includes deaths occurring after the first 24 hours and all other
in-hospital deaths. Figure 3 displays studies evaluating late
deaths (12, 13, 15, 16, 19, 22–24). In contrast to the first two
Figure 2. Studies reviewing early deaths (12, 13, 15, 16, 19).
Figure 3. Studies reviewing late deaths (12, 13, 15, 16, 19, 22–24).
April 2013
categories, there has been a definite and dramatic drop in late
deaths over time. In the most recent study by Gunst and colleagues, this group included only 9% of deaths (12).
Deaths among trauma patients after discharge have largely
remained overlooked in the trauma literature. This is due in
large part to the difficulty of follow-up in the trauma patient
population. First, regionalized trauma networks often mean
that patients are transported farther from home for their initial
episode of care at designated trauma centers. Second, trauma
patients are typically younger individuals who are more mobile
in pursuit of work or education. However, several studies have
shown that trauma patients have an increased risk of mortality
after discharge. Follow-up methods have varied, but the most
commonly used are trauma registries, hospital databases, and
patient records from single institutions. Combined with a lack
of communication between medical record systems, single-institution studies are likely to miss patients who pursue follow-up
care closer to home at a different hospital. In order to capture
higher percentages of the study population, particularly over
longer periods of time, telephone interviews or mail surveys
are commonly utilized. More recently, trauma researchers have
employed vital statistics records and Social Security data as a
means of capturing high percentages of patients while also obtaining cause-of-death data (27–29).
In a study of data from 1991 to 1993, Mullins et al reported
an in-hospital mortality rate of 12.1 per 100,000 for trauma
deaths. This increased to 14.1 per 100,000 when including patients who died within 30 days of discharge (30). Among injured
Medicare patients discharged to home, the 30-day mortality
ranged from 1.9% to 2.3% (31). In 2004, Clark and colleagues
reported that among injured Medicare patients, 30-day mortality
was 7.5% compared with 3.7% in-hospital mortality (6). In 2006,
MacKenzie et al reported a case fatality rate for in-hospital deaths
of 7.6%, which remained stable for 30 days but increased to
10.4% at 1 year (32). In 2008, Gorra et al reported 30-day mortality rates of 4.2% to 5.4% among injured Medicare patients
discharged to a long-term care facility (31). A 2010 study by Claridge and colleagues reported a mortality rate of 3.6% at 30 days,
4.1% at 90 days, 5.5% at 1 year, and 8.1% over the entire study
period (33). In 2011, Davidson et al demonstrated 9.8% mortality at 1 year and 16% 3-year cumulative mortality (34). The
multiinstitutional prospective National Study on Costs and Outcomes of Trauma evaluated patients up to 1 year after discharge.
In this study, MacKenzie et al reported an in-hospital mortality
rate of 21.3%, but a further 2.6% were dead at 3 months, and an
additional 2.2% were dead by 12 months (35). Similarly, in 2005,
Wright and colleagues reported a 5-year mortality rate of 22.1%
in trauma patients admitted to an intensive care unit during their
initial hospitalization (36). In 2011, Timmers et al reported a
1-year mortality rate of 17%, which increased to 29% between
6 and 11 years (37). Finally, our recently published study utilizing Social Security data showed that almost half of the deaths in
trauma patients occurred after discharge from the trauma center
(27). All these studies are consistent in their findings that the risk
of death among trauma patients remains elevated for months to
years afterward.
121
Table. Causes of death by timing category
Immediate and early
deaths
Brain injury
Hemorrhage
Late deaths
Postdischarge
Infection
Multiple-organ failure
Brain injury
Hemorrhage
Cardiovascular disease
Second major trauma
Neurologic disease
Malignancy
CAUSES OF DEATH
Several studies have investigated the causes of death in trauma
patients. Baker et al found that brain injury accounted for a
majority of deaths, at 50% (13). Heart or aortic injury (17%),
hemorrhage (12%), sepsis (10%), lung injury (6%), burn (3%),
and liver injury (2%) accounted for the remainder. The majority
of patients with major cardiac, vascular, or liver injury died of
hemorrhage. Shackford and colleagues also found that head injury
was the most common cause of death, and when combined with
spinal cord injury, neurologic injuries were responsible for 49% of
deaths (24). On autopsy, secondary brain injury, defined as diffuse
cerebral edema; herniation; or cerebral necrosis due to hypoxia,
hypotension, or cerebral edema that followed the primary injury
was present in just over half of neurotrauma cases. Almost a third
(31%) of victims died of hemorrhage in the chest, the abdomen,
or both cavities. Other causes of death included asphyxia in 6%,
cardiac arrest in 4%, sepsis in 3%, and pneumonia in 2%. The
Table lists the most common causes of death for each time interval. Immediate and early deaths are considered together, given
the similar etiologies.
In Trunkey and Lim’s initial case series in 1972, 45% of the
patients in the immediate death category died of irreversible brain
injury, such as lacerations of the brain, brain stem, or spinal cord,
and 35% died due to hemorrhage resulting from injuries to the
heart, aorta, liver, lungs, and pelvic fractures (21). Similarly,
Meislin et al showed that for death within 1 hour of injury, 46%
were neurologic injuries and 31% were due to circulatory collapse
resulting from hemorrhage (19). Likewise, work from Sauaia et
al showed that among those dead on the scene, 42% died from
central nervous system injuries, 39% from exsanguination, and
7% from organ failure (18). These studies are consistent in reporting that the two most common causes of immediate deaths are
head injuries and hemorrhage.
The cause of early trauma deaths is similar to that of immediate deaths and likely represents less catastrophic injuries
or better prehospital care and shorter transport times to trauma
centers. As described by Trunkey and Lim, the causes of death
in this group include major internal hemorrhages of the head,
respiratory system, or abdominal organs or multiple minor injuries resulting in severe blood loss (21). Sauaia et al reported that
among trauma deaths within 48 hours of injury, exsanguination
was the most common cause (51%) due to injuries to the liver,
heart, or major blood vessels (7). This was particularly true
for patients with penetrating injuries. Central nervous system
injury was the second most common cause of death, including
122
brain lacerations, contusions, and subdural hemorrhages (18).
Meislin et al showed that neurologic injuries and circulatory
collapse or hemorrhage accounted for over 80% of early deaths
(19). Baker and colleagues showed that most of the deaths due
to head injuries were within the first 2 days after injury (13).
Trunkey reported that 80% of late deaths in the hospital
were due to infections or multiple organ failure (14). Similarly,
Baker found that 78% of deaths after 7 days were due to sepsis
and multiple organ failure (13). Cowley indicated that the most
common causes of death in this group were overwhelming infection and irreversible head injuries (26). Sauaia et al reported
that for deaths occurring after 1 week postinjury, organ failure
claimed the majority of patients (61%) (18). More recently,
Meislin et al reported that for the group dying within 24 to
48 hours, 45% died of neurologic injury, 42% of circulatory
collapse or hemorrhage, and 9% of multiple organ failure (19).
Similarly, for the group dying 2 days to 3 weeks after injury,
48% died of neurologic injury, 35% of circulatory collapse or
hemorrhage, and 16% of multiple organ failure. These studies
indicate that head injuries and hemorrhage remain important
causes of death among patients who survive the first 24 hours,
but multiple organ failure becomes more prominent with the
passage of time.
Causes of death after discharge from trauma centers are less
well studied. This is due, in part, to the difficulties of followup. Mullins evaluated cause-of-death codes reported on death
certificates for injured patients who died of nontraumatic causes
during their hospital stay and within 30 days after discharge (30).
Of 1174 postdischarge deaths, 15% were due to neoplasms, 12%
to cerebrovascular disease, 11% to cardiovascular disease, 11%
to ischemic heart disease, 9% to chronic obstructive pulmonary
disease, and 8% to acute myocardial infarction. Another 20%
were due to a myriad of other causes. In a German study, Probst
and colleagues described in-hospital and postdischarge causes
of death for trauma patients (38). While in-hospital causes of
death mirrored those previously discussed, postdischarge deaths
included cardiovascular disease in 23%, a second major trauma
in 19%, neurologic disease in 16%, suicide in 10%, and malignancies in 6%. Furthermore, trauma patients had increased
mortality compared with the general population during the first
year after injury. The mortality rates were more closely approximated during years 2 to 10 after injury. Claridge and colleagues
classified deaths as trauma related in 33%, possibly related in
23%, and unrelated in 44% (33). Additionally, mortality after
discharge was more likely trauma related in younger patients.
The authors found that most deaths within the first year after
injury were attributable to trauma, after which chronic diseases
increased mortality. These studies indicate that postdischarge
deaths among trauma patients are related to common chronic
diseases within the population. However, the impact of injuries
on the outcome of these chronic diseases remains unknown.
CONCLUSION
Three important conclusions can be drawn from this review.
First, deaths occurring within minutes or a few hours of injury
are largely unchanged, reflecting the devastating nature of injures
Volume 26, Number 2
to the central nervous and cardiovascular systems. Late deaths
due to multiple organ failure and sepsis, however, have declined
dramatically. Second, the causes of death in this patient population, i.e., those with severe head injuries and hemorrhage, remain
persistent. Finally, a large number of deaths in trauma patients
that occur after discharge may be related to nontraumatic causes.
Reasons for the increased risk of death from nontraumatic causes
after discharge need to be studied further.
Acknowledgment
The authors wish to thank Kelli R. Trungale, MLS, ELS,
for editorial assistance.
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123
Facts and principles learned at the 39th Annual Williamsburg
Conference on Heart Disease
Mina M. Benjamin, MD, and William C. Roberts, MD
T
he December 2012 Williamsburg Conference on Heart
Disease in Williamsburg, Virginia, was the 39th such
annual conference to be held in that city. The conference
has been directed by one of the authors (WCR) since
1972. The conference provides 16.5 hours of continuing medical education category one credit, and nearly all of the speakers
are nationally and internationally recognized. It is one of the 2
longest-running cardiology courses. Its unique feature is that
each presentation is 90 minutes, which allows the speakers time
to discuss more than one topic and to answer questions from
enrollees. This article summarizes the proceedings of the 2012
conference.
SOME FACTS AND PRINCIPLES LEARNED AFTER SPENDING
50 YEARS INVESTIGATING CORONARY HEART DISEASE
William C. Roberts, MD, Executive Director, Baylor Heart
and Vascular Institute; Dean, A. Webb Roberts Center for
Continuing Medical Education, Baylor University Medical Center, Dallas, Texas; and Editor in Chief, The American Journal of Cardiology and the Baylor University Medical Center
Proceedings
Although the same blood flows through both arteries and
veins, atherosclerosis affects only the arteries. The arterial
system can be subdivided into various regions—coronary,
carotid, cerebral, renal, peripheral (arm and leg), and aorta—
and one region may cause symptoms of organ ischemia or
discomfort and the other regions may be clinically silent.
Nevertheless, when one region contains considerable amounts
of atherosclerotic plaque such that it produces symptoms
or discomfort in that region, necropsy studies have demonstrated that large quantities of atherosclerotic plaque also are
present in the other regions. In other words, atherosclerosis
is a systemic disease. To demonstrate this principle, detailed
studies of the coronary arteries in patients with large abdominal aneurysms and/or peripheral limb ischemia so severe that
amputation was required disclosed atherosclerotic plaque
in every 5-mm segment of each of the 4 major epicardial
coronary arteries (right, left main, left anterior descending,
left circumflex). The quantity was so severe that a large portion (about 33%) of the length of the four major coronary
arteries had plaques that narrowed the lumens >75% in crosssectional area (1, 2).
124
Multiple necropsy studies have shown that when any particular arterial region produces symptoms of organ ischemia
(or discomfort in the case of abdominal aortic aneurysm), the
atherosclerotic process in that region is diffuse and severe—i.e.,
there are no “skip areas” where a 5-mm-long arterial segment
does not contain atherosclerotic plaque (3). Multiple necropsy
studies of each 5-mm-long segment of the 4 major epicardial
coronary arteries in a variety of coronary subsets (those with
acute myocardial infarction, stable and unstable angina pectoris,
healed myocardial infarction with and without chronic heart
failure, and sudden coronary death) have demonstrated that
about a third of the entire lengths of the 4 major coronary arteries is narrowed >75% in cross-sectional area by atherosclerotic
plaque alone (3, 4).
There appears to be a common belief that atherosclerotic
plaques consist mainly of lipid material. Several studies have
examined the composition of atherosclerotic coronary plaques
at necropsy in patients with fatal coronary heart disease (5–8).
The studies traced out the various components of plaques from
each 5-mm-long segment of each of the 4 major coronary arteries, and fibrous tissue was by far the dominant component
of coronary plaques, comprising about 70%, while lipids comprised about 10%; calcium, about 10%; and miscellaneous,
the other 10%. Fibrous tissue also was the dominant component of plaques in saphenous veins used for aortocoronary
bypass grafts. That the predominant component of coronary
plaques is fibrous tissue is probably advantageous for percutaneous coronary intervention (PCI) because that procedure
works simply by cracking plaques and not by compressing
them to the side.
Studying atherosclerosis at necropsy or after endarterectomy
has convinced Roberts that the only real long-term therapy for
the Western world’s number one disease is prevention. Although
the Framingham investigators and others have convinced most
physicians and the lay public that atherosclerosis is a multifactorial disease, Roberts is convinced that the disease has a
From the Departments of Internal Medicine (Benjamin, Roberts) and Pathology
(Roberts), and the Baylor Heart and Vascular Institute (Roberts), Baylor University
Medical Center at Dallas.
Institute, 621 North Hall Street, Suite H030, Dallas, TX 75246 (e-mail: wc.roberts@
baylorhealth.edu).
Table 1. The differences between carnivores and herbivores
Features
Carnivore
Herbivore
Teeth
Sharp
Flat
Intestine
Short (3 × BL)
Long (12 × BL)
Fluids
Lap
Sip
Cooling
Pant
Sweat
Appendages
Claws
Hands or hoofs
Vitamin C
Self-made
Diet
BL indicates body length.
Figure 1. The atherosclerotic risk factors showing that the only factor required
to cause atherosclerosis is cholesterol.
Table 2. Drug treatment guidelines of the Adult Treatment
Panel of the National Cholesterol Education Program (2004) to
decrease risk
LDL (mg/dL)
Other RF
Goal
single cause, namely cholesterol, and that the other so-called
>190
≤1
<160
atherosclerotic risk factors are only contributory at most (9–13).
>160
>1
<130
As shown in Figure 1, most of the risk factors do not in themselves cause atherosclerosis.
>130
HA
<100 (<70)
Th ere are in Roberts’ opinion 4 facts supporting the
HA indicates heart attack; LDL, low-density lipoprotein cholesterol; RF, risk factor.
contention that atherosclerosis is a cholesterol problem: 1) Atherosclerosis is easily produced experimentally in herbivores (monkeys, rabbits) by giving
had an atherosclerotic event, who have diabetes mellitus, or
them diets containing large quantities of cholesterol
who are at an extremely high risk of developing an athero(egg yolks) or saturated fat (animal fat). Indeed, atherosclerosis
sclerotic event (e.g., homozygous or heterogeneous familial
is one of the easiest diseases to produce experimentally, but
hypercholesterolemia). Roberts’ guidelines, in contrast, are dithe recipient must be an herbivore. It is not possible to prorected at preventing atherosclerotic plaques, and when they are
duce atherosclerosis in carnivores (tigers, lions, dogs, etc.). In
prevented atherosclerotic risk is negated. The only requirement
contrast, it is not possible to produce atherosclerosis simply
is an LDL-C <50 mg/dL.
by raising a rabbit’s blood pressure or blowing cigarette smoke
Statins, at least in Roberts’ view, are the finest cardioin its face for an entire lifetime. 2) Atherosclerotic plaques convascular drug ever created (released in the USA in 1987)
tain cholesterol. 3) Societies with high average cholesterol levels
(14). Table 3 displays the equivalent doses of six statins, their
have higher event rates (heart attacks, etc.) than societies with
average reductions in total cholesterol and LDL-C, and the
much lower average cholesterol levels. 4) When serum cholesterol
additional LDL-C–lowering effect when ezetimibe is added
levels (especially the low-density lipoprotein cholesterol [LDL-C]
to a statin (15).
level) are lowered (most readily, of course,
by statin drugs), atherosclerotic events fall
Table 3. Dosing of six statin drugs, their relative efficacy and effects on cholesterol,
accordingly and the lower the level, the
and the effect of adding ezetimibe
fewer the events (“less is more”). Although
most humans consider themselves carniEquivalent dose (mg)
vores or at least omnivores, basically we
E (10 mg)
Total
humans have characteristics of herbivores
R (C) A (L)
S (Z)
P (P) L (M)
F (L)
L TC
L LDL
L LDL
LDL L
(Table 1).
1.25
5
10
20
20
40
22%
27%
18%
45%
The Adult Treatment Panel of the Na2.5
10
20
40
40
80
27%
34%
18%
52%
tional Cholesterol Education Program
5
20
40
80
80
–
32%
41%
14%
55%
has provided guidelines for whom to treat
10
40
80
–
–
–
37%
48%
12%
60%
with cholesterol-altering drugs. The latest
(2004) guidelines are summarized in Table
20
80
–
–
–
–
42%
55%
10%
65%
2. The guidelines are aimed entirely at re40
–
–
–
–
–
45%
62%
10%
72%
ducing the risk of atherosclerotic events.
R indicates rosuvastatin (C, Crestor); A, atorvastatin (L, Lipitor); S, simvastatin (Z, Zocor); P, pravastatin (P, PravaLowering the LDL-C goal from <100 to
chol); L, lovastatin (M, Mevacor); F, fluvastatin (L, Lescol); TC, total cholesterol; LDL, low-density lipoprotein
<70 mg/dL is recommended by the comcholesterol; E, ezetimibe.
mittee only in patients who have already
April 2013
Facts and principles learned at the 39th Annual Williamsburg Conference on Heart Disease
125
ASSESSING THE BENEFIT OF THERAPY THAT RAISES HIGHDENSITY LIPOPROTEIN CHOLESTEROL
William E. Boden, MD, Chief of Medicine, Stratton VA Medical
Center, Vice-Chairman of Medicine, Albany Medical Center, and
Professor of Medicine, Albany Medical College, Albany, New York
All the major primary and secondary prevention statin studies have shown an average of 25% cardiovascular risk reduction
at 5 years, which means that 75% of the cardiovascular events
were not prevented during this time period. Statins act mainly
on LDL-C, with much less effect on triglycerides or high-density
lipoprotein cholesterol (HDL-C). Fibrates act mainly on triglycerides, reducing it 30% to 35% with a slight increase in HDL-C
and only a minor effect on LDL-C (16). In the FIELD study
(17), fenofibrate did not significantly reduce coronary events
in 9775 patients vs placebo. In the ACCORD trial (18), the
combination of fenofibrate and simvastatin did not reduce the
rate of fatal cardiovascular events, nonfatal myocardial infarction (MI), or nonfatal stroke, compared with simvastatin alone
in 5518 high-risk patients with diabetes mellitus. Niacin raises
HDL-C by 30% to 35%, has a lesser effect on triglycerides
than fibrates, and reduces LDL-C by 15% to 20%. Niacin also
increases LDL particle size, from a small, dense pattern B to
the larger nonatherogenic pattern A (19). In the Framingham
study (20), LDL-C and HDL-C were independent risk factors
of coronary heart disease (CHD). A patient with an LDL-C of
220 and HDL-C of 45 mg/dL had a similar risk to a patient
with an LDL-C of 100 and HDL-C of 25 mg/dL. Statins had
a maximal relative risk reduction in cardiovascular events of
about 30% (21), niacin about 20% (22), and fibrates 23% (16).
Although the National Cholesterol Education Program Adult
Treatment Panel III guidelines (23) stated that low HDL-C is
an independent risk factor for coronary artery disease (CAD)
morbidity and mortality, the panel concluded that the risk reduction documented by controlled clinical trials is not sufficient
to warrant setting a specific HDL-C goal.
Several surrogate marker studies (24–26) demonstrated
slowing or even regression of arterial narrowing with niacin. The
ARBITER 6-HALTS (26) trial was terminated early on the basis
of a prespecified interim analysis showing superiority of niacin
over ezetimibe for change in carotid thickness. Major adverse
cardiac events occurred at a significantly lower incidence in the
niacin (1.2%) vs the ezetimibe group (5.5%). In a metaanalysis
of the 14 niacin studies including 2682 patients taking 1 to
3 g/day of niacin and 3934 controls, niacin decreased the rate
of progression of atherosclerosis by 41% and decreased carotid
intima thickness by 17 μm/year.
In the Coronary Drug Project (27), immediate-release
niacin (3 g/day) reduced the incidence of CHD death/MI by
14%, nonfatal MI by 26%, and stroke/transient ischemic attacks by 21% after 5 years. There was also a 50% reduction in
the need for coronary bypass surgery. In the VA-HIT study (28),
gemfibrozil reduced CHD death/MI by 22% vs placebo after
5 years. These patients did not take statins, and the benefit was
attributed to a decrease in triglycerides (–31%) and an increase
in HDL-C (+6%), as there was no significant change in LDL-C.
It took 2 years in the VA-HIT trial for a considerable benefit
126
to be evident with treatment, quite different from the time
course seen with statins, where event reduction is seen as early as
2 weeks after institution of treatment.
Several single-center trials demonstrated the benefits of adding niacin to other cholesterol-lowering drugs. In the Familial
Atherosclerosis Treatment Study (FATS) (29, 30), 126 men with
known CHD were randomized to receive conventional therapy
or lovastatin plus colestipol or niacin (4 g/day). All patients
had a coronary angiogram at baseline. After 2.5 years, coronary narrowing in patients on conventional therapy progressed,
while it regressed in the treatment group. Multivariate analysis
showed that increasing HDL-C correlated independently with
the regression of disease. The HDL Atherosclerosis Treatment
Study (HATS) (31) was a 3-year trial of 160 patients with CHD
whose HDL-C averaged 31 mg/dL and LDL-C, 125 mg/dL.
Patients were administered either niacin (mean dose 2.4 g/day)
plus simvastatin (mean dose 13 mg/day) or placebo for 3 years.
In the group receiving niacin plus simvastatin, LDL-C levels
decreased 42% and HDL-C increased 26%. The combination
of niacin and simvastatin reduced CHD events by about 75%.
There was a slight regression in coronary narrowing with simvastatin plus niacin but progression in all other groups. Both
FATS and HATS were single-center studies with relatively small
numbers of patients. Pooled data from 28 different lipid trials (32) showed that there was an aggregation of benefit from
adding different cholesterol-altering medicines. Data from the
4S (33), CARE (34), WOSCOPS (35), and LIPID (36) trials
demonstrated that a 1% decrease in LDL-C was associated with
a 1% decrease in CHD events. A 1% increase in HDL-C was
associated with a 3% decrease in events, as seen in HELSINKI
(37), AFCAPS/TexCAPS (38), and VA-HIT.
The results from the Coronary Drug Project, VA-HIT, and
HATS constituted the base for a large, multicenter trial assessing
the outcomes for niacin. The AIM-HIGH (39) study was conducted mainly to investigate whether the residual risk associated
with low levels of HDL-C in patients with established CHD
(whose LDL-C therapy was optimized with statins ± ezetimibe)
would be mitigated with extended-release niacin vs placebo. The
patients were >45 years of age with CHD, cerebrovascular disease, or peripheral arterial disease and dyslipidemia (HDL-C
<40 for men, <50 for women; triglycerides 150–400; LDL-C
<180 mg/dL). A total of 3414 patients were randomized to receive
extended-release niacin (1.5 to 2 g/day) or placebo. All patients
received simvastatin (40 to 80 mg/day) plus ezetimibe (10 mg/
day) (if needed) to maintain an LDL-C of 40 to 80 mg. (The
placebo tablets had a small amount of niacin, 200 mg/2 g, to
produce similar side effects as in the treatment group.) Patients
on statins (94%) had a mean baseline LDL-C of 71 mg/dL.
The trial was stopped after a mean follow-up period of 3 years
due to a lack of efficacy. There was also an increased incidence
of ischemic strokes in the niacin arm (n = 29) vs the placebo
arm (n = 18). At study termination, HDL-C had increased from
35 to 42 mg/dL, LDL-C had decreased from 74 to 62 mg/dL,
and triglycerides had decreased from 164 to 120 mg/dL. In both
the Coronary Drug Project and VA-HIT, in the prestatin era,
niacin and gemfibrozil increased HDL and lowered triglycerides
Volume 26, Number 2
and also decreased cardiovascular events, but baseline triglycerides
and LDL-C were significantly higher than in AIM-HIGH. It
appears that the addition of niacin did not work in this population, possibly because these patients had been well treated with
statins and the HDL-C had increased to 38 mg/dL in the placebo
arm, changes that might have minimized event rate differences
between the treatment and placebo groups.
The HPS 2-THRIVE trial began in 2004 and is expected
to be finished by 2013. It enrolled 25,000 patients with CAD
or diabetes mellitus from the UK, Scandinavia, and China.
Patients were randomized to simvastatin 40 mg or simvastatin
plus extended-release niacin/laropiprant. The use of ezetimibe is
allowed. There is no target LDL-C level or attempt to equalize
LDL-C levels between groups.
COCAINE-ASSOCIATED MYOCARDIAL ISCHEMIA AND
INFARCTION
L. David Hillis, MD, Professor and Chair, Department of
Medicine, Dan F. Parman Distinguished Chair of Medicine, The
University of Texas Health Science Center at San Antonio, San
Antonio, Texas
Five million Americans use cocaine daily, 1 million are addicted to it, and 5000 use it for the first time each day. Possible
mechanisms of cocaine-induced myocardial ischemia include
increased myocardial oxygen demand with severe CAD and
decreased myocardial oxygen supply due to coronary arterial
vasospasm (40) and/or coronary arterial thrombosis. ␣-Blockers
abolish the coronary vasoconstrictor effect of cocaine, while
␤-blockers augment it (41). Cocaine-induced vasoconstriction
is more pronounced in coronary arterial segments narrowed
by atherosclerosis (42). The time course of cocaine-induced
vasoconstriction parallels the blood concentration of cocaine
following intranasal administration, after which a second “wave”
of vasoconstriction parallels the increasing blood concentrations of cocaine’s major metabolites and occurs as the blood
concentration of cocaine is decreasing (43). The deleterious
effects of cocaine on myocardial oxygen supply and demand are
exacerbated by concomitant cigarette smoking. This combination substantially increases the metabolic requirement of the
heart for oxygen but simultaneously decreases the diameter of
diseased coronary arterial segments (44). The combination of
intranasal cocaine and intravenous ethanol causes an increase in
the determinants of myocardial oxygen demand. The combination also causes a concomitant increase in epicardial coronary
arterial diameter (45). Morphine can reverse cocaine-induced
coronary arterial vasoconstriction (46). Sublingual nitroglycerin
(47) 0.4 to 0.8 mg and intravenous verapamil (48) also reverse
the coronary vasoconstrictive effect of cocaine, while intravenous labetalol has no effect (49). The mechanism of cocaineinduced vasospasm and its aggravating and relieving factors are
summarized in Figure 2.
CORONARY ARTERY BYPASS GRAFTING—2012
L. David Hillis, MD
Coronary artery bypass grafting (CABG) is superior to
medical therapy for eliminating angina pectoris (50). CABG,
April 2013
Figure 2. The mechanism of cocaine-induced coronary vasospasm, aggravating
factors, and treatment. CAD indicates coronary artery disease; Ca, calcium.
however, does not prevent MIs (51, 52). CABG is superior to
medical therapy in improving survival only in patients with left
main CAD, in those with 3-vessel CAD and left ventricular (LV)
ejection fraction (EF) <50%, and in those with 2- or 3-vessel
CAD with significant narrowing of the proximal left anterior
descending coronary artery. In the VA COOPERATIVE study
(53), the survival of patients with 1, 2, and 3-vessel CAD with
a normal LVEF (medical therapy vs CABG) was 87% vs 82%,
82% vs 77%, and 68% vs 61% at 5, 7, and 11 years, respectively,
while the survival of patients with 3-vessel CAD and LVEF
<50% was (medical therapy [n = 97] vs CABG [n = 71]) 66%
vs 83%, 52% vs 78%, and 38% vs 50% at 5, 7, and 11 years,
respectively. In the STICH trial (54), a total of 1212 patients
with an EF < 35% and CAD amenable to CABG were randomly
assigned to medical therapy alone (n = 602) or medical therapy
plus CABG (n = 610). At 5 years, death from any cause was
41% in the medical therapy arm and 36% in the CABG group
(insignificant), and the rate of hospitalization for heart failure
was 54% vs 48%. Patients assigned to CABG, as compared
with those assigned to medical therapy alone, had lower rates
of death from cardiovascular causes. Compared with patients
who have CABG, those who have PCI are more likely to require
another revascularization procedure in the next 12 months (45),
and rates of major adverse cardiac or cerebrovascular events at
12 months were significantly higher in the PCI group (18% vs
12% for CABG), in large part because of an increased rate of
repeat revascularization (13% vs 6%).
The determinants of peri-CABG mortality include age
(peri-CABG mortality markedly increases above 70 years) (55),
LV systolic function, comorbid conditions (chronic obstructive
pulmonary disease, diabetes mellitus, azotemia, obesity), extracardiac vascular disease, left main CAD, previous thoracotomy
(mortality of the first sternotomy 3% vs 7% for subsequent
sternotomies), and gender (1.9% in men vs 4.5% in women in
CASS [n = 6630] and 2.6% in men vs 5.3% in women in the
Texas Heart Institute [n = 22,284] registry).
There was no significant difference in 30-day death, MI,
stroke, or renal failure requiring dialysis between patients
127
undergoing CABG off-pump or on-pump in a large trial involving
79 centers in 19 countries randomizing 4752 patients. Offpump CABG reduced rates of transfusion, reoperation for perioperative bleeding, respiratory complications, and acute kidney
injury but also resulted in an increased risk of early revascularization (56).
CARDIOPULMONARY RESUSCITATION AND PUBLIC-ACCESS
DEFIBRILLATION
Richard L. Page, MD, George R. and Elaine Love Professor,
Chair, Department of Medicine, University of Wisconsin School
of Medicine and Public Health, Madison, Wisconsin
The 2010 American Heart Association guidelines (57)
place a strong emphasis on delivering high-quality chest compressions. Rescuers should push hard to a depth of at least 2
inches (5 cm) at a rate of at least 100 compressions per minute, allow full chest recoil, and minimize interruptions in chest
compressions. Rescuers also should provide ventilation using a
compression:ventilation ratio of 30:2. Longer periods of resuscitation are associated with better outcomes. Goldberger et al (58)
studied 64,339 subjects with cardiac arrest in US hospitals. The
median duration of resuscitation was 12 minutes in survivors
vs 20 minutes in nonsurvivors. The survival to discharge was
related to hospital duration of resuscitation.
The PAD trial (59) evaluated automated external defibrillator (AED) use vs conventional cardiopulmonary resuscitation (CPR) in 1000 US sites. There were more survivors to
hospital discharge in the units assigned to have volunteers
trained in CPR plus the use of AEDs (30 survivors among 128
arrests) than there were in the units assigned to have volunteers
trained only in CPR. Weisfeldt et al (60) reported 13,769
out-of-hospital arrests where 32% received CPR but no AED
before paramedics arrived and 2.1% had an AED placed before
paramedics arrived. The survival to hospital discharge was
9% with CPR only, 24% with AED application, and 38%
with AED shock delivery. Page et al reported early results of
the first use of the AEDs by a US airline between 1997 and
1999. Of 200 events (mean age 58 years), ventricular fibrillation (VF) was present in 16 patients. All VF episodes were
recognized (sensitivity 100%) and shock delivered in 15 of
16. First shock success was 100%. Six of 15 patients receiving
shocks for VF survived to hospital discharge (40%). Valenzuela
et al (61) published a study where casino officers were trained
in the use of AEDs. The first 148 patients were reported: 105
(71%) had VF and 59% survived to hospital discharge. There
was a significant difference in survival between defibrillation
used before and after 3 minutes of the arrest (26/35 [74%]
vs 27/55 [49%]).
MANAGEMENT OF VALVULAR HEART DISEASE
Robert O. Bonow, MD, Goldberg Distinguished Professor
of Cardiology, Director, Center for Cardiovascular Innovation,
Northwestern University Feinberg School of Medicine, Chicago,
Illinois
Only 0.3% of the guidelines for valvular heart disease are at
evidence level A, i.e., based on high-quality randomized clinical
128
trial or metaanalysis, while 70% are at evidence level C, i.e.,
based on expert consensus (62).
Mitral regurgitation (MR). The current guidelines for treatment of severe chronic primary (degenerative) MR recommend
mitral valve surgery in symptomatic patients (class I), patients
with LVEF <0.6 and LV end systolic dimension 50 to 55 mm
(class I), asymptomatic patients with atrial fibrillation (class
Ia), and asymptomatic patients with pulmonary artery systolic
pressure >50 mm Hg at rest or >60 mm Hg with exercise (class
Ia). Management of asymptomatic severe MR with preserved
EF remains controversial.
The mortality of severe asymptomatic MR varies markedly
among different studies. Maurice et al (63) studied 456 patients
with MR (EF 70 ± 8%): the 5-year mortality rate with severe
MR was 42%, while that of moderate MR was 33%. In contrast,
Rosenhek et al reported 0% 5-year mortality in 132 patients
with severe asymptomatic MR (64); Grigioni and coworkers
(65) reported 14% 5-year mortality in 394 patients with severe
MR who were followed for an average of 3.9 years; and Kang
et al (66) reported 5% 7-year mortality among 286 patients with
severe MR and preserved EF who were treated medically.
In a retrospective review of outcomes of 13,614 patients
having elective surgery for MR between 2000 and 2003 in 575
North American centers (67), the hospital procedural volume
was associated with higher frequency of valve repair, higher
frequency of prosthetic valve usage in older patients, and lower
adjusted operative mortality. There was variation among cardiologists as to the degree of knowledge and adherence to the
guidelines about the timing of referral to surgery. In a survey
in 2007, among 319 responders, LVEF was rated as extremely
important in referral decisions by 71% of those who completed
the surveys and moderately important by 26%. In asymptomatic
patients, EF of 50% to 60% was correctly identified as a trigger
for surgery by 57% of cardiologists, while only 16% of cardiologists correctly referred New York Heart Association (NYHA)
class II patients with normal LV function (68).
Ischemic MR is managed differently from primary MR.
Detection and quantification of ischemic MR provide major
information for risk stratification and clinical decision making
in the chronic post-MI phase (69). The mitral annulus clip is an
evolving technique for treatment of functional MR. Treatment
with the clip device in 51 severely symptomatic cardiac resynchronization therapy (CRT) nonresponders with functional MR
was feasible, safe, and demonstrated improved functional class,
increased LVEF, and reduced ventricular volumes in about 70%
of these study patients (70).
Aortic stenosis (AS). The current guidelines do not recommend aortic valve replacement (AVR) in patients with severe
asymptomatic AS. The producibility of symptoms or hypotension with exercise is currently a class IB indication, according
to the American College of Cardiology and American Heart
Association. In 123 adults with asymptomatic AS, event-free
survival—with endpoints defined as death (n = 8) or aortic valve
surgery (n = 48)—was 93%, 62%, and 26% at 1, 3, and 5 years,
respectively (71). The likelihood of remaining alive without valve
replacement at 2 years was only 21% for a jet velocity >4.0 m/s
Volume 26, Number 2
at entry, compared with 66% for a velocity of 3.0 to 4.0 m/s and
84% for a jet velocity <3.0 m/s. In another series of 128 patients
with asymptomatic severe AS (72), event-free survival—with
the endpoint defined as death (8 patients) or AVR necessitated
by the development of symptoms (59 patients)—was 67%,
56%, and 33% at 1, 2, and 4 years, respectively. Rosenhek
et al also reported a series of 116 asymptomatic patients (73)
with very severe AS, defined by a peak aortic jet velocity ≥5.0
m/s. Event-free survival was 64%, 36%, 25%, 12%, and 3% at
1, 2, 3, 4, and 6 years, respectively. Patients with a peak aortic
jet velocity ≥5.5 m/s had an event-free survival of 44%, 25%,
11%, and 4% at 1, 2, 3, and 4 years, respectively. Early elective valve replacement surgery should therefore be considered
in these patients. The current guidelines recommend AVR in
patients with a high likelihood for rapid progression (calcification) and/or very severe AS (maximum velocity >5 m/s, mean
gradient >60 mm Hg, AV area <0.6 cm2) (class IB).
Exercise-stress echocardiography is very useful for risk stratification of true asymptomatic patients with AS (74). N-terminal
beta natriuretic peptide (75) independently predicts symptomfree survival, and preoperative N-terminal beta natriuretic peptide independently predicts postoperative outcome with regard
to survival, symptomatic status, and LV function. The STS score
(76) is more suitable than the EuroSCORE (77) for estimating
the perioperative mortality associated with AVR.
Transcatheter aortic valve implantation (TAVI) is an emerging
technique with enormous potential (78). The PARTNER trial
(79) investigators concluded that TAVI is superior to medical
therapy in patients who are not fit for AVR and that TAVI is
equivalent to surgical AVR in high-risk patients. In patients with
severe AS and depressed LV systolic function, TAVI is associated
with better LVEF recovery compared with surgical AVR (80). In
200 patients undergoing surgical AVR and 83 patients undergoing TAVI for severe AS (AV area ≤1 cm2) with LVEF ≤50%,
patients who underwent TAVI had better recovery of LVEF compared with those who underwent surgical AVR (ΔLVEF, 14%
vs 7%). Stroke and paravalvular regurgitation remain concerns
with TAVI. The average hospital mortality for TAVI was 9%
(13.0% for low-volume centers vs 6% for high-volume centers).
The broad application of TAVI presents challenges for patient
selection and the need for dedicated expert heart valve centers.
The goal in AS patients is to operate late enough in the natural history to justify the risk of intervention and early enough to
prevent irreversible ventricular dysfunction, pulmonary hypertension, and/or chronic arrhythmias and sudden death.
OPERATIVE TREATMENT OF CARDIOVASCULAR DISEASE
Charles S. Roberts, MD, Trident Health, Hospital Corporation
of America, Charleston, South Carolina
CABG remains the standard of care for patients with 3-vessel
or left main CAD, since the use of CABG, as compared with
PCI, results in lower rates of the combined endpoint of major
adverse cardiac events or cerebrovascular events at 1 year (81).
For patients with less severe CAD, symptom severity and noninvasive test results are used to stratify patients into one of two
groups: those who will benefit from immediate revascularization
April 2013
and those in whom an initial trial of aggressive medical therapy
alone may be safely attempted. In patients without the highestrisk CAD who require revascularization because of unacceptable
symptoms or because of noninvasive test results indicating a high
risk of failure of medical therapy, PCI with drug-eluting stents
and CABG appear to result in similar rates of death and MI.
Therefore, the choice depends largely upon how effectively the
lesions can be treated with PCI and upon the patient’s feelings
about the temporary disability and the slightly increased stroke
risk associated with CABG vs the increased risk of repeat revascularization with PCI (82). Stroke predictors from prospective data
collected on 4941 patients undergoing cardiac surgery included
history of stroke and hypertension, older age, systolic hypertension, bronchodilator and diuretic use, high serum creatinine,
surgical priority, great vessel repair, use of inotropic agents after
cardiopulmonary bypass, and total CABG time (83).
Carotid endarterectomy (CEA). CEA currently remains the
first choice of revascularization therapy for an asymptomatic
carotid lesion in most centers (84). The Society for Vascular Surgery appointed a committee of experts to formulate
evidence-based clinical guidelines for the management of carotid
stenosis. In formulating clinical practice recommendations, the
committee used systematic reviews to summarize the best available evidence and the GRADE scheme to grade the strength
of recommendations (GRADE 1 for strong recommendations;
GRADE 2 for weak recommendations) and rate the quality of
evidence (high, moderate, low, and very low quality) (85). The
following therapies had both GRADE 1 recommendation and
high quality of evidence:
• Medical therapy for symptomatic patients with <50%
stenosis
• Medical therapy for asymptomatic patients with <60%
stenosis
• CEA for symptomatic patients with ≥50% stenosis
• CEA for asymptomatic patients with ≥60% stenosis
Concomitant carotid and coronary artery surgery is safe
and effective, particularly in preventing ipsilateral stroke, and
neutralizes the impact of unilateral carotid stenosis on early
and late stroke (86). In the US, patients who undergo carotid
artery stenting and CABG have significantly decreased inhospital stroke rates compared with patients undergoing CEA
and CABG, but the in-hospital mortality is similar. Carotid
artery stenting may provide a safer carotid revascularization
option for patients who require CABG (87).
Surgical treatment of peripheral artery disease. Invasive therapy
in peripheral artery disease is indicated for critical limb ischemia
(ankle brachial index <0.4), not for claudication, unless it is
disabling. The long-term results of the Bypass vs Angioplasty in
Severe Ischemia of the Leg (BASIL) trial favor surgery rather than
angioplasty if there is a good vein and the patient is fit (88).
THORACIC AORTIC ANEURYSMS: DIAGNOSIS AND TREATMENT
Randolph P. Martin, MD, Medical Director, Cardiovascular
Imaging, Chief, Structural and Valvular Heart Disease, Piedmont
Heart Institute; Professor Emeritus of Medicine, Emory University
School of Medicine, Atlanta, Georgia
129
Thoracic aortic aneurysms (TAA). Each year, 30,000 to 60,000
deaths occur due to TAA. Thus, in the USA, they are the 18th
most common cause of death and the 15th most common cause
of death in individuals >65 years of age. TAAs are increasing
in incidence. TAA is a virulent condition but an indolent process, growing slowly at ~0.1 cm per year. The use of an imaging technique to estimate true aortic size is confounded by its
obliquity and asymmetry; thus, multiple imaging techniques
may be required (89). Surgical intervention is indicated before
TAAs reach 5.5 cm in diameter. A diameter of 5.0 cm may be
the cut-off for patients with Marfan syndrome, a bicuspid aorta,
or a family history of aortic dissection.
Aortic dissection occurs in a circadian and diurnal pattern,
with predominance in winter months and early morning. Aortic
dissections also occur around the time of extreme physical exertion or emotional distress. The frequency of aortic dissection or
through-and-through rupture increases sharply when the ascending aortic diameter reaches 6.0 cm (34% lifetime risk of rupture
or dissection) and 7.0 cm in descending thoracic aorta.
The Marfan syndrome. Marfan syndrome occurs due to a
mutation of the fibrillin-1 gene. Patients with Marfan syndrome
have a 50% risk of developing aortic dissection in their lifetime.
About 5% of all TAAs are due to Marfan syndrome. TAAs in
Marfan syndrome patients grow rapidly (>0.5 cm per year). A
family history of aortic dissection may prompt earlier operative intervention at a diameter <5.0 cm. Pregnant patients with
Marfan syndrome are at increased risk for aortic dissection if
aortic diameter exceeds 4.0 cm.
Loeys-Deitz syndrome. Loeys-Deitz syndrome occurs due to
mutations in the TGFBR1 and TGFBR2 genes. Patients have
skeletal features of Marfan syndrome but with distinct cranial
features, including craniosynostosis. Other features include hypertelorism, translucent skin and veins, arterial tortuosity, and
aneurysms. Aortic repair should be done at aortic diameters
<5.0 cm in patients with Loeys-Deitz syndrome.
Osteoarthritis syndrome. Osteoarthritis syndrome is an autosomal dominant disorder (SMAD3 mutations) responsible
for 2% of familial TAA dissections. The main features of the
disease include early onset of osteoarthritis (the usual reason for
patients seeking medical attention), mild craniofacial abnormalities, and tortuosities throughout the arterial tree—mostly
the intracranial, iliac, abdominal, and thoracic aorta—leading to
aneurysms. Patients have a substantial mortality and a high risk
of aortic rupture and dissection with mildly dilated aortas.
Penetrating atherosclerotic ulcers. Atherosclerotic lesions may
ulcerate (penetrating the internal elastic lamina) and produce
hematomas within the media (90% in the descending thoracic
aorta). They appear as a mushroom-like outpouching of the
aortic lumen with overhanging edges.
Pseudoaneurysm of the thoracic aorta. Pseudoaneurysms occur
in the descending thoracic aorta due to deceleration or torsional
trauma. They can also occur after aortic root or aortic valve
surgery, catheter-based interventions, or penetrating trauma.
Takayasu’s aortitis. Takayasu’s aortitis (90), a chronic inflammatory vasculitis involving the ascending aorta and carotid,
renal, and subclavian arteries, is rare (1–2 cases/million) and
130
of unknown etiology. It affects women more than men (with a
ratio of 9:1) and usually begins in the second or third decade
of life. Takayasu’s aortitis produces intimal fibroproliferation
that results in segmental stenosis, occlusion, dilatation, and
aneurysm formation. It is the only aortitis that causes stenosis
and occlusion. Takayasu’s aortitis is more prevalent in women
of Asian descent, and 90% of the cases occur in patients <30
years of age. In its inflammatory stage, patients present with
low-grade fever, tachycardia, pain adjacent to the inflamed arteries (carotodynia), and easy fatigability. Carotid and cervical
bruits are often present. The systemic stage can be followed in
5 to 20 years by an occlusive stage. Neurologic symptoms are
present in 80% of patients.
SEVERE BUT ASYMPTOMATIC AORTIC STENOSIS
Randolph P. Martin, MD
Severe AS is undertreated. More than 50% of patients with
echocardiographic findings of severe AS are not referred for
further evaluation for AVR. In the Euro Heart Survey (91),
36% of patients already had significant symptoms at the time
of evaluation for AVR: 47% were NYHA class III/IV and 8%
were NYHA class IV and had LV dysfunction at the time of
surgery. Studies of severe asymptomatic AS suggest that a third
of the patients will become symptomatic within 2 years. Within
4 to 5 years, two thirds have either had an AVR or died. The risk
for sudden death is about 1% per year. Kang et al (92) showed
a risk of sudden cardiac death of 1.7% per year in those with
aortic velocity >5.0 m/sec.
The assessment of AS severity should be based on valve morphology: calcium, peak jet velocity, mean gradient, aortic valve
area, LVEF, LV wall strain, LV wall fibrosis, and beta natriuretic
peptide. These parameters should be integrated with presenting
symptoms and response to exercise stress testing. The predictors of
poor outcome in asymptomatic severe AS are a resting peak transvalvular velocity of 5.0 to 5.5 m/sec (73, 93), densely calcified
aortic valve, valve area <0.75 cm2 (94), mean gradient >50 mm
Hg, abnormal LVEF, beta natriuretic peptide, and abnormal
exercise test (defined as failure of systolic blood pressure to rise
or a fall in systolic blood pressure, symptoms, or ST-segment depression with exercise). The echocardiographic predictors of poor
outcome in AS also include the degree of valve calcium (95). The
degree of valve calcium is not influenced by hemodynamic conditions, which is useful in low flow states. A computed tomography
calcium score >1650 AU has 80% sensitivity and specificity for
severe AS. Exercise stress testing can uncover symptoms in >40%
of “asymptomatic severe AS” patients. Only 20% of patients who
have positive stress tests are alive, symptom-free, without AVR
at 24 months vs 85% with a negative test.
SYSTEMIC HYPERTENSION
William H. Frishman, MD, the Barbara and William Rosenthal Professor and Chairman, Department of Medicine, New York
Medical College; Director of Medicine, Westchester Medical Center,
Valhalla, New York
In older adults, hypertension is characterized by an elevated systolic blood pressure with normal or low diastolic blood
Volume 26, Number 2
pressure, due to age-associated stiffening of the large arteries.
Hypertension prevalence increases markedly with age; ~60% of
the population has hypertension by age 60 and ~65% of men
and ~75% of women have hypertension by 70 years (96). In the
Framingham Study (97), hypertension eventually developed in
>90% of subjects with normal blood pressure at age 55 years.
Throughout middle and old age, usual blood pressure is strongly
and directly related to vascular (and overall) mortality, without
any evidence of a threshold down to at least 115/75 mm Hg (98).
Numerous randomized trials have shown substantial reductions
in cardiovascular events in cohorts of patients 60 to 79 years old
with antihypertensive drug therapy, though the effect on all-cause
mortality has been modest. In HYVET, antihypertensive therapy
reduced all-cause mortality in people ≥80 years old by 21% at
1.8-year follow-up. Those randomized to indapamide vs placebo
had a 30% nonsignificant decrease in fatal/nonfatal stroke, 39%
significant decrease in fatal stroke, 21% significant decrease in
all-cause mortality, 23% insignificant decrease in cardiovascular
death, and 64% significant decrease in heart failure.
Although the optimal blood pressure treatment goal in the
elderly has not been determined, a therapeutic target <140/90 mm
Hg in persons aged 65 to 79 years and a systolic blood pressure
of 140 to 145 mm Hg, if tolerated, in persons aged ≥80 years
is reasonable. The further lowering of diastolic blood pressure
below 60 mm Hg may lead to coronary insufficiency and myocardial ischemic manifestations.
ALTERNATIVE MEDICINE FOR THE HEART
William H. Frishman, MD
About 50% of patients seek an alternative sort of medicine,
which is defined as any practice that is put forward as having
the healing effects of medicine, but is not based on evidence
gathered by the scientific method. The placebo effects on blood
pressure, arrhythmia (e.g., decrease in premature ventricular
complexes), heart failure symptoms (increase in EF of 5% to
20%–30% of patients) and angina pectoris (about 50% of patients) have been noticed in every cardiovascular trial. Patients
also develop common adverse effects to placebo drugs (99). No
megavitamin, mineral, or nutraceutical has shown an evidencebased effect on cardiovascular disease. Most trials evaluating
homeopathy have shown no benefit on cardiovascular diseases
(100). Chelation therapy has theoretical benefits but had no
effect on CAD in clinical trials (101). Neither masked prayer
nor music, imagery, or touch therapy significantly improved
clinical outcomes after elective catheterization or PCI (102).
There are some conditions in which herbal medicines are used
as cardiovascular treatments. Several adverse cardiovascular
reactions have been observed with herbal medicines used for
other indications. Also, several herbs have potential and documented interactions with warfarin (103).
Age, magnitude of LV hypertrophy, EF, presence of atrial
fibrillation, LV obstruction, apical aneurysm, and other cardiovascular risk factors all contribute to the outcome of patients
with hypertrophic cardiomyopathy (HC). Morbidity in patients
with HC includes sudden death, progressive heart failure, or
the development of atrial fibrillation and stroke. The incidence
of sudden death is proportional to the LV wall thickness; its
incidence is only 0.2%/year in patients diagnosed after the age
of 60 years. In a multicenter study of 670 low-risk HC patients,
the incidence of sudden death was 0.6%/year. The Bethesda
Conference recommended that athletes with an unequivocal
diagnosis of HC should not participate in most competitive
sports, with the possible exception of those of low intensity.
This recommendation includes those athletes with or without
symptoms and with or without LV outflow obstruction.
Drugs provide only a modest protection from sudden death
in HC. A report of 506 patients showed that the implantable
cardioverter defibrillator (ICD) intervened appropriately to
abort ventricular tachycardia/fibrillation in 20% of patients
over an average follow-up period of only 3.7 years, at a rate of
about 4% per year in those patients implanted prophylactically,
and often with considerable delays of up to 10 years (104). Appropriate device discharges for ventricular tachycardia/ventricular fibrillation occur with similar frequency in patients with 1,
2, or ≥3 noninvasive risk markers. In a study of 1101 patients
with HC, the risk of progression to NYHA class III or IV or
death specifically from heart failure or stroke was greater among
patients with obstruction (relative risk: 4.4) (105). About 70%
of HC patients have LV outflow obstruction either at rest (37%)
or with provocation (33%).
Ommen and colleagues (106) evaluated 1337 consecutive
HC patients: 289 patients had surgical myectomy; 228 had LV
outflow obstruction without operation; and 820 had nonobstructive HC. Mean follow-up duration was 6 ± 6 years. Their
1-, 5-, and 10-year overall survival after myectomy was 98%,
96%, and 83%, respectively, which did not differ from that of
patients with nonobstructive HC or from the general US population matched for age and gender. Compared with nonoperated obstructive HC patients, myectomy patients experienced
superior survival free from all-cause mortality (98%, 96%, and
83% vs 90%, 79%, and 61%, respectively), HC-related mortality, and sudden cardiac death.
Different cardiology societies in the US and Europe recommend surgical myectomy as the gold standard in HC patients
rather than alcohol septal ablation. Several issues remain with
alcohol septal ablation: whether the outflow gradient/symptom
relief is long-lasting; the relatively high rate of repeat procedures
(25%); failure to obliterate the high gradients; and the fact that
myectomy after failed ablations is difficult. The infarct/scar produced by ablation also may predispose patients to sudden death.
HYPERTROPHIC CARDIOMYOPATHY AND PREVENTING SUDDEN
DEATH IN THE YOUNG
Barry J. Maron, MD, Director, Hypertrophic Cardiomyopathy
Center, Minneapolis Heart Institute Foundation, Minneapolis,
Minnesota
HEART FAILURE GUIDELINES
Clyde W. Yancy, MD, Professor of Medicine, Chief, Division of
Cardiology, Northwestern University Feinberg School of Medicine,
and Associate Director, Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Chicago, Illinois
April 2013
131
There is a substantial variation among cardiologists in
conformity with quality treatment measures for heart failure
patients (107). Fonarow et al (108) reported 15,177 patients
with reduced LVEF (≤35%) and chronic heart failure or postMI. The mortality rate at 24 months was 22%. Angiotensinconverting enzyme inhibitor or angiotensin receptor blocker
use, ␤-blocker use, anticoagulant therapy for atrial fibrillation,
CRT, ICDs, and heart failure education for eligible patients
were each independently associated with improved 24-month
survival, whereas aldosterone antagonist use was not. Each 10%
improvement in guideline-recommended composite care was
associated with a 13% lower odds of 24-month mortality. The
adjusted odds for mortality risk for patients with conformity
to each measure was 38% lower than for those whose care did
not conform for one or more measures.
The 2013 heart failure guidelines are expected to include
changes in the areas of CRT, LV assist device, the role of reduced
dietary sodium intake, and evidence-proven methods to reduce
readmissions.
Cardiac resynchronization therapy. The REVERSE (109)
trial was designed to determine if CRT ± ICD modified disease
progression over 12 months in patients with asymptomatic and
mildly symptomatic heart failure and ventricular dyssynchrony.
Patients were in NYHA class II or I (previously symptomatic), normal sinus rhythm, QRS ≥ 120 ms, LVEF ≤ 40%, LV
end diastolic diameter ≥ 55 mm, without bradycardia, with
or without ICD indication, on optimal medical therapy. All
patients received CRT and then were randomized to have the
device either on or off. Beginning at 1 year in the US and 2
years in Europe, all patients with CRT ON underwent yearly
follow-up over 5 years. The heart failure clinical composite
response endpoint indicated 16% worsening with CRT-ON
compared with 21% worsening with CRT-OFF. Patients assigned to CRT-ON experienced a greater improvement in LV
end-systolic volume index (–18.4 mL/m2 vs –1.3 mL/m2) and
other measures of LV remodeling. Time to first heart failure
hospitalization was significantly delayed in CRT-ON (hazard
ratio: 0.47). The investigators concluded that CRT produced
sustained reverse remodeling accompanied by low mortality
and need for heart failure hospitalization. The benefits of CRT
persisted, indicating that CRT attenuates disease progression
in mildly symptomatic heart failure patients with wide QRS
over at least 5 years. REVERSE, however, was underpowered to
show mortality benefit and there was no long-term comparator.
The RAFT (110) and MADI CRT (111) trials also showed the
benefit of CRT in mild to moderate heart failure with short
follow-up periods.
Left ventricular assist device. Several clinical studies (112–
115) have shown improved survival with LV assist devices compared to medical therapy for advanced heart failure. The LV
assist devices have not been shown to be cost effective.
Salt restriction in systolic heart failure. Taylor et al (116) performed a Cochrane database review and identified 7 randomized
controlled trials (3 in normotensives, 2 in hypertensives, 1 in a
mixed population of normo- and hypertensives, and 1 in heart
failure) with follow-up of at least 6 months comparing restricted
132
dietary salt intake or advice to reduce salt intake to control/no
intervention in adults, and reported mortality or cardiovascular
disease morbidity data. All-cause mortality and cardiovascular
mortality for both normotensives and hypertensives were not
reduced compared with the control group. In heart failure patients, salt restriction significantly increased all-cause death.
Dinicolantonio and colleagues (117) analyzed 6 randomized
controlled trials comparing low-sodium diets (1.8 g/day) with
a higher-sodium diet (2.8 g/d) in 2747 patients with systolic
heart failure. The low-sodium diet significantly increased allcause mortality, sudden death, death due to heart failure, and
heart failure readmissions.
Heart failure readmission rates. Hernandez et al studied a
population that included 30,136 patients from 225 hospitals
(118). Patients who were discharged from hospitals with higher
early follow-up rates had a lower risk of 30-day readmission.
The proper planning for transition of care and early outpatient
follow-up was the only evidence-proven method of decreasing
readmission rates for heart failure patients.
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Volume 26, Number 2
Our experience as a Health Volunteers Overseas–sponsored
team in Huế, Vietnam
James I. Ewing, MD, Claude A. Denham, MD, Cynthia R. Osborne, MD, Nathan B. Green, DO, Josephine Divers, RN,
and John E. Pippen Jr., MD
A group from Texas Oncology and Baylor Charles A. Sammons Cancer
Center traveled to Huế, Vietnam, as part of Health Volunteers Overseas.
From February 21 to March 6, 2012, five Baylor Sammons medical
oncologists and an oncology nurse worked with a medical oncologist
and a surgeon at the Huế College of Medicine and Pharmacy, suggesting approaches based on available resources. The two groups worked
together to find optimal solutions for the patients. What stood out the
most for the Baylor Sammons group was the Huế team’s remarkable
work ethic, empathy for patients, and treatment resourcefulness. The
Baylor Sammons group also identified several unmet needs that could
potentially be addressed by future volunteers in Huế, including creation of
an outpatient hospice program, establishment of breast cancer screening, modernization of the pathology department, instruction in and better
utilization of pain management, better use of clinic space, and the teaching of oncology and English to medical students. There was a mutual
exchange of knowledge between the two medical teams. The Baylor
Sammons group not only taught but also learned how to take good care
of patients with limited resources.
A
group of health care professionals from Baylor Charles
A. Sammons Cancer Center at Dallas traveled to Vietnam from February 21 to March 6, 2012, to work
alongside local caregivers and introduce new concepts,
teach new techniques, and identify needs that can be addressed
on follow-up trips. The team from Baylor Dallas consisted of
two experts in breast cancer (Drs. John Pippen and Cynthia
Osborne), two general medical oncologists (Drs. Claude Denham and Nate Green, a former medical oncology fellow who
now practices in Lincoln, Nebraska), a second-year oncology
fellow (Dr. James Ewing), and an oncology nurse (Josie Divers,
RN) (Figure 1). After a formal application was made to the Accreditation Council for Graduate Medical Education, Dr. Ewing
received fellowship credit for the time spent in Vietnam.
Planning for the trip began when physicians of the Baylor
Sammons Cancer Center and Texas Oncology were contacted by
Health Volunteers Overseas (HVO), a not-for-profit organization dedicated to improving the availability and quality of health
care in developing countries through the training and education of local health care providers. HVO works with numerous
professional medical societies to develop training programs for
Figure 1. Our team in front of the oncology clinic. Left to right: Dr. Osborne and
Josie Divers (front row) and Drs. Pippen, Green, Denham, and Van Cau (back
row). Not pictured: Dr. Ewing.
a wide range of specialties. In its quarter century of existence,
HVO has sent over 4000 volunteers to places around the world
and has completed close to 8000 assignments.
The International Cancer Corps (ICC) of the American
Society of Clinical Oncology (ASCO) began partnering with
HVO in 2010, with the goal of having highly qualified health
care professionals provide relevant, realistic training that focuses
on oncologic diseases and health conditions relevant to the geographic area, so this knowledge can be disseminated to other
health care providers in the area. The first ICC site chosen was
Tegucigalpa, Honduras; the second, Addis Ababa, Ethiopia;
and the third, Huế, Vietnam.
Huế is a city in central Vietnam that serves as the capital
city of the Thua Thien-Huế province. It was once the ancient
imperial capital of the Nguyến Lords, who were rulers of what is
now Southern and Central Vietnam. In the 1800s, still under the
rule of the Nguyến Lords, it became the capital of all of Vietnam.
Due to its location near the border of North and South Vietnam,
From the Baylor Charles A. Sammons Cancer Center (Ewing, Denham, Osborne,
Pippen), Baylor University Medical Center at Dallas; Texas Oncology, PA, Dallas,
Texas (Denham, Osborne, Divers, Pippen); and Southeast Nebraska Cancer
Center, Lincoln, Nebraska (Green).
Corresponding author: John E. Pippen Jr., MD, FACP, Baylor Charles A. Sammons
Cancer Center, 3410 Worth Street, Suite 400, Dallas, TX 75246 (e-mail: John.
[email protected]).
137
this South Vietnamese city was a site of intense fighting in the
Vietnam War, especially during the Tết Offensive of 1968. Now
a peaceful large city bisected by the Sông Húóng (Perfume) River
(Figure 2), Huế is home to approximately 950,000 residents and
the Huế College of Medicine and Pharmacy (Figure 3). The facility was founded in 1957 and has trained over 12,000 graduates in
medicine, pharmacy, dentistry, and allied health professions. It has
an annual enrollment of over 1000 students, with almost 4000
undergraduates studying various health-related fields on campus
at any given time. The college serves the central area of Vietnam,
whose population is approximately 20 million people.
Since Vietnam is a developing country, a large percentage of the
patients served by the college have limited financial means, with the
average monthly wage reported to be US $185 last year (1). Many
of the patients travel 30 miles or more by bicycle or motorcycle
to get to the clinic for an appointment with a doctor. Both the
medical school and hospital are run by the government.
THE CLINIC
Working within the college’s oncology clinic were the Vietnamese hosts, Dr. Nguyen Van Cau, a medical oncologist, and
Dr. Phung Phuong, a surgeon. Dr. Van Cau had one oncology
fellow who helped with patient care. At least 10 nurses and
other assistants also staffed the clinic. The clinic was an airconditioned building built in the 1980s. The first floor housed
the Gamma Knife center, and the upper floors housed the clinics
and inpatient hospital rooms. The equipment was not new, but
it was functional. Dr. Phuong, a surgeon by training, had dual
roles, as he planned, mapped, and operated the Gamma Knife,
in addition to operating and serving as a clinical professor at the
medical school. Dr. Van Cau’s office (where most of the patients
were seen) was located on the second floor, and this is where
we spent most of our time. In addition to Dr. Van Cau’s office,
there was a room for the nursing staff to meet and do charting,
a room to prepare the chemotherapy, and another room storing medications. In the chemotherapy preparation room, there
was a ventilation hood with a small hole cut in the back wall. A
small fan took air from the hood and sent it outside. Most basic
chemotherapy drugs and antiemetics were available.
The pathology department was on site as well. The department was small and simple, with processing and microscope
work done in the same room. Several basic immunohistochemical stains were available for breast cancer, although Ki-67, an
immunostain used as a measure of the proliferation index in
a
b
Figure 2. Scenes from Huế, Vietnam: (a) flower vendors and (b) motorbikes.
138
Figure 3. Our first view of the Huế, College of Medicine and Pharmacy.
breast tumor specimens, was not routinely used. The oncologists
did not generally review the pathology themselves, but relied
on written or verbal reports by the pathologists. The pathology
reports did not always clearly establish orientation and distance
of the tumor from surgical margins. This was one issue we addressed during our stay in Huế.
We were able to observe a number of patients undergo treatment during our visit, including a patient with a hepatoma who
was being mapped prior to radiation therapy. Additionally, a
patient with brain cancer was treated while we were there. The
machine was old and was shut down one day by a water leak;
however, the oncology team in the clinic did remarkably well
with the tools they had available.
The gap in wealth in Vietnam is extreme. Those with connections to the communist leaders live quite well, with the rest of the
population living in severe poverty. Most drugs and health care are
subsidized by the Vietnamese government; however, there is an
exception with trastuzumab for HER2-positive breast cancer. This
drug is completely unsubsidized, but we did see one patient elect
to add it to her adjuvant treatment, at a cost of over US $8000
per month. Obviously, not many in Vietnam can afford this
treatment. Rituximab is partially subsidized by the government
and is for patients who can afford the large copayments. Thus,
during our trip we did see one patient with non-Hodgkin’s lymphoma treated with R-CHOP (rituximab, cyclophosphamide,
doxorubicin, vincristine, and prednisolone), but most patients
were treated with CHOP or CHOP-E (etoposide), regimens
inferior to R-CHOP, for diffuse large B-cell lymphoma. Dr. Van Cau was able to order almost
any chemotherapy drug on the World Health
Organization (WHO) list.
The patients were treated in four rooms, each
of which had five beds. As we went from room
to room, the patients were quiet, well mannered,
and did not ask a lot of questions. Both male and
female patients were in the same rooms with no
concern for privacy. If there were more patients
than beds, the patients shared a bed, with one at
each end (Figure 4). Each room had five to 10
Volume 26, Number 2
Figure 4. Dr. Denham visiting with some of the oncology patients staying in the
inpatient rooms in the clinic.
patients in it. Services such as food, water, and bedding were not
provided. Attentive family members took care of these needs.
Patients could stay overnight in the clinic if they had special
needs or if their treatment took several days. Several nurses were
present after hours if there were problems. The clinic was located
a few feet from the hospital itself. Dr. Van Cau would usually go
to see consults in the hospital in the late afternoon and would
direct patients back to the clinic after discharge.
Just as patient confidentiality was not a concern in the inpatient rooms, neither was it a concern in the clinic, which seemed
unusual coming from our culture. As many as four breast cancer
patients might be in the same room at the same time for their
follow-up visit. Each disrobed and was examined in turn, which
was viewed as perfectly normal by patients and staff. In talking
to patients, it seemed that they only saw the doctor for a very
brief visit, lasting less than 5 minutes. There was generally little
discussion with the physician; rather, most discussions were
among the physicians, who then made a declaration of when the
patient’s next follow-up visit should be. This was followed by a
flurry of stamping a stack of documents, which were then passed
back to the patients. Patients seemed to be in charge of holding
their own records, and many would come in with their scans
and radiology films in hand. Computed tomography images and
ultrasound were locally available and performed quickly for the
outpatients. The quality of the images was quite good. Most lab
tests were available. The subsidized cost to the patient was about
US $40. Positron emission tomography imaging required a trip
to Ho Chi Minh City or Hanoi, if the patient had the means
to pay for it. Bone marrow transplantation also required going
to one of the same two larger cities in Vietnam. Otherwise,
oncology treatments were performed in Huế.
Once the team settled in to work at the clinic, we found an
interesting and challenging mix of cases. One breast cancer case
involved a 34-year-old woman, 11 weeks pregnant, who presented with a left subareolar breast mass and a palpable axillary
node. Dr. Van Cau, as well as the rest of us, encouraged her to
keep the baby, but her husband was adamant that the pregnancy
be terminated. The patient already had four children, and her
husband said he could not take care of another child. We also
April 2013
saw a 59-year-old Catholic nun who recently had a mastectomy
for a T2N1M0 estrogen receptor–positive, HER2-negative breast
cancer. After deciding chemotherapy was needed, she was treated
with a combination of epirubicin and paclitaxel. This is the adjuvant chemotherapy regimen of choice for all breast cancer
patients deemed to be in need of chemotherapy. The decision
of whether or not to use adjuvant chemotherapy was hindered
somewhat by the lack of availability of Ki-67 staining. Tests such
as Oncotype DX were not used, largely due to cost.
Other types of cancer reflected what would be expected in
a busy oncology clinic, with a tendency toward tobacco-related
and gastric malignancies. Breast cancer and other malignancies
seemed to present at a more advanced stage. This is likely related,
at least in part, to the lack of screening or effective primary or
secondary prevention programs. We were also surprised by the
relative youth of the majority of the patients. Today, according
to a 2010 WHO report, Vietnam is among the countries with
the highest smoking rates in the world, with a prevalence of
more than 45% in men aged 18 years or older (2). Several of the
physicians we worked with were smokers themselves. Smoking
among health care providers was found to have a prevalence
>40%. Further efforts towards primary prevention are definitely
needed. The high prevalence of smoking and cervical cancer
relay the need for better primary prevention in Vietnam.
Several patients we saw showed the need for a linear accelerator, which has been used for over 50 years for external
beam radiation treatments for cancer. There were several local
recurrences of cancer that likely could have been prevented if
standard radiation treatment was given either concurrently with
or after chemotherapy. One such patient was a young woman
with a painful vaginal recurrence of a rectal cancer. The cancer
involved the posterior vaginal wall, and the tumor was exuding
from the vagina and causing significant pain and bleeding. As
stated earlier, the only radiation treatment available in the Huế
Oncology Clinic is in the form of Gamma Knife radiosurgery.
Access to other types of radiation treatments would have allowed
treatment of a much wider range of cancers.
PALLIATIVE CARE
The lack of palliative care and hospice represents a great
need for the people of Huế and is a topic we can explore much
more with the medical staff on a subsequent trip. The use of
long-acting narcotics was much more uneven between patients.
Patients who were at the end stage of their cancer and experiencing a lot of pain could come back to the clinic and receive
injections of morphine. Conversely, one of the clinic nurses
could go out to the patient if he or she was nearby. Death was
a topic not generally discussed with patients. When I asked one
of the fellows if she ever told patients that cancer would end
their life, the question was met with a surprised look and an
emphatic “no, never!” The family was told to “be prepared for
anything.” Unfortunately, the “anything” families are prepared
for does not usually include death.
The differences in palliative care and hospice practices between our two countries were best represented by a patient we
saw the first day while rounding on the inpatient service. The
Our experience as a Health Volunteers Overseas–sponsored team in Huế, Vietnam
139
patient was a 54-year-old man with a metastatic high-grade
sarcoma. He had been diagnosed with a high-grade rhabdosarcoma of his leg 7 months previously. At the time of diagnosis,
surgery was advised but the patient refused. Unfortunately, his
malignancy progressed despite extensive anthracycline-based
chemotherapy. He had been at the hospital since the time of
diagnosis and his tumor had grown rapidly, extending from his
right knee to above his hip in a circumferential manner. Moreover, he had severe pain and extensive pulmonary metastatic
disease. We saw this patient once again several days later, during
our next rounding. In talking with one of the fellows, we learned
the patient had not been told his tumor would progress and
eventually take his life. With help from the fellow in interpreting, we spoke with the patient, who was from a local village,
about 30 km from Huế. He and his wife had four children;
both of his sons lived with him. He worked in a shoe factory
prior to his sarcoma diagnosis. His sister was staying with him
to cook and take care of him in the hospital until he “gets better
from his tumor.” At that time, his cancer had progressed while
on chemotherapy and he was only on intravenous fluids and
supportive medications. We found this patient had a real lack
of insight and unrealistic expectations regarding his condition,
but we were informed that often patients are not told they are
going to die from their disease. We discussed through an interpreter with the patient about his diagnosis and how his tumor
would continue to grow and likely ultimately take his life. He
stated he definitely wanted to be home when he passed. Our
conversation was relatively short by American standards, but
the patient seemed to take the news well. He thanked us and
smiled when we moved on with our rounds. When rounding
the following day, we were told he was to be discharged that
day to go home to be with family.
AN ONCOLOGY FELLOW’S PERSPECTIVE
In October 2011, I was asked by Dr. John Pippen, a member
of the clinical faculty, if I would like to travel to Huế, Vietnam,
to volunteer with a group from ASCO for 2 weeks. Dr. Pippen
put together an incredible team for the trip. It took me all of
two seconds to say, “Yes, let’s do this!”
During my first week, I was fortunate to locate the Englishspeaking club. On our third day I met a unique group of medical
students who gathered weekly to practice their English skills.
We reviewed core oncology and hematology skills, including
how to evaluate a peripheral blood smear. During our time
together, we talked extensively about the system of medicine in
our two countries, medical training, oncology, and many other
topics. I learned that in Vietnam all medical schools are run by
the government. Due to the influence of their political system,
every medical school has its own Communist Party committee.
Typically, the dean or head of the department is appointed by
the Communist Party committee.
In addition to learning medicine, medical students are
taught Marx’s philosophy (during the first few years), Ho Chi
Minh’s philosophy, as well as the history of the Communist
Party. Upon completion of 6 years of medical school, graduates have several options. Most begin work as general doctors.
140
Many engage in self-study or attend conferences to become
specialists without a formalized system of training. For the more
competitive 10% to 15% of new physicians, another option is
to pursue postgraduate education through the academic track
or the clinical track of study. The academic track is designed
for those who will teach at a medical school or university. The
clinical track is what Dr. Thi, a trainee with Dr. Van Cau, was
doing. This program consisted of 3 years in residency training, similar to a US residency program. Admission to these
postgraduate programs was highly competitive and required
an entrance exam along with an interview.
From the students I learned that health care services in Vietnam are often paid for on a cash basis, despite a national health
insurance program, known as “Bao Hiem Y Te.” The national
plan has two types of health care insurance: obligatory and
voluntary. Obligatory insurance is the plan for people who are
currently working, and it is paid for by a combination of employer and employee contributions. Voluntary insurance is for
those not belonging to the obligatory section, such as students
or those out of work. This insurance still may require a fee, but it
is much less. All children under 6 years of age have free medical
insurance in Vietnam; however, access to medical services varies
greatly based on geography and socioeconomic factors.
I was told by some that patients who pay cash usually receive
more attention and better care; however, we saw no evidence of
this in our experience in the clinic. I met with the English club
several times on my trip. I continue to correspond with one of
the fourth-year medical students whose goal is to pursue a career
in oncology. Overall it was an incredibly rewarding opportunity
for me as an oncology fellow, and I believe that many of the lessons and experiences we shared with our Vietnamese colleagues
will be integrated into their everyday practice. I think that we
were able to learn much from the resourcefulness and ingenuity
of Dr. Van Cao and his team, and I am looking forward to a
future return trip to the site.
TRAVEL-RELATED ISSUES FOR THE VOLUNTEER
Several minor obstacles, other than just the lengthy air
travel, must be overcome to successfully navigate Vietnam. In
addition to a valid passport, a tourist visa must be obtained.
For a stay longer than 4 weeks, visitors require a different class
of visa. Since there are a limited number of Vietnamese consulates in the US, it is easiest to employ a travel service to obtain
the tourist visa, which is valid for one entry into Vietnam. The
total expense for the visa is around $300. In-country travel is
inexpensive, owing to the strength of the dollar relative to the
Vietnamese currency. In addition to completion of the necessary paperwork, travel to a developing country requires some
advance medical preparations. Vietnam is an area known to
be endemic for malaria, so DEET-containing insect repellant
is recommended. If traveling outside of urban areas, malaria
prophylaxis is advised. Other common-sense travel precautions
should be followed, including drinking bottled water, avoiding
salad items that may have been washed with tap water, and using sufficient sunscreen, a huge task even for a well-practiced
group from Texas.
Volume 26, Number 2
IDENTIFICATION OF NEEDS
There are opportunities to make a positive impact on subsequent trips to the Huế College of Medicine and Pharmacy.
Below is a partial list of opportunities.
1. Modernization of the pathology department. In breast and
other cancers, the orientation of the specimens was not
always known, and on some specimens it appeared as if
cancer was at the margins. The Ki-67 tumor marker test
needs to be added to the breast cancer immunohistochemical analysis panel to better gauge the proliferative status
of a tumor. A visiting pathologist could go a long way in
making sure basic protocols are in place to improve their
diagnostic capabilities.
2. Instruction in the use of long-acting oral pain medicines
and further instruction on WHO’s pain relief ladder. In
addition to managing the pain of cancer patients, managing the side effects of narcotic medications is another area
that could be taught.
3. An outpatient hospice. This hospice could be organized by
first utilizing the current clinic nursing staff. A discussion
with the chief administrators may be helpful in creating
a cadre of palliative care nurses to visit patients in their
homes. Economic issues may be problematic, but motorbike
transportation is relatively inexpensive, and Huế is easy to
traverse for an experienced cyclist.
4. More efficient use of space in the clinic. Putting six chairs
in each of the rooms may prove more helpful than five cots.
Chairs would be more comfortable than cots and would allow
more patients to be treated in a shorter amount of time.
5. Mammography and breast conservation training. Again,
acquisition of a linear accelerator would make this a possibility and could potentially cut down on the number of
local recurrences seen in the cancer patients. Purchase of a
new machine, however, may be problematic in a developing
nation. Better surgical techniques would include the addition of more accurate sentinel node assessments.
6. Teaching medical students. In Huế, we had the privilege of
lecturing to the students, all of whom were respectful and
attentive. With many of them interested in oncology, there is
great opportunity for volunteers to help with improvement
in oncology education and screening. A series of basic lectures in medical oncology would likely be well received.
7. English as a second language. The students wanted to learn
better English. Evening practice sessions with team members
and students, accompanied by an excellent local beer, would
be a good way to facilitate this process.
PARTING THOUGHTS
Our trip to Vietnam really opened our eyes to what others
in the world must contend with in their medical practices. Even
though we were able to teach them a great deal, they taught us
about how to take good care of patients with limited resources.
We were able to experience, on a limited level, what people in
Vietnam experience on a daily basis. All was not work on our
trip, however, as we took some time to see some of the sites of
Vietnam. We stopped in Hố Chi Minh City (formerly Saigon)
April 2013
Figure 5. Cao Ðài Temple in Tây Ninh, about 90 km northwest of Hố Chi Minh
City (formerly Saigon). Cao Ðài is a faith indigenous to Vietnam, which includes
the teachings of the major world religions.
and saw the

tunnels of Cu
Chi, a vast
network used
by the Viet
Cong guerrillas during the
Vietnam War.
They were the
Viet Cong’s
base of operations for the
Tết Offensive
in 1968 and
now an important part of
their history.
We also took a
day trip to Tây Figure 6. A parting gift of flowers from our hosts in front
Ninh, about of a statue of Ho Chi Minh. Drs. James Ewing (left) and
90 km north- John Pippen (right).
west of Hố
Chi Minh City. There we saw the Cao Đài Temple (Figure 5).
The Cao Đài faith, indigenous to Vietnam, includes the teachings of the major world religions. It was quite interesting to see
how the Vietnamese integrated so many diverse faiths. When
our trip came to an end, we were thanked profusely by our hosts,
including a presentation of flowers (Figure 6). We all learned
much on our journey and hope to make it again soon.
1.
2.
Vietnam average monthly wage rises to $185. Thanh Niên Daily News
Online, January 25, 2012. Available at http://www.thanhniennews.
com/2010/pages/20120125-salaries-rise-in-vietnam-income-gap-stillwide.aspx; accessed January 15, 2013.
World Health Organization. Appendix VIII—Table 1: Surveys of adult
tobacco use in WHO member states. In WHO Report on the Global Tobacco
Epidemic, 2009. Geneva, Switzerland: WHO, 2009.
Our experience as a Health Volunteers Overseas–sponsored team in Huế, Vietnam
141
A forgotten landmark medical study from 1932
by the Committee on the Cost of Medical Care
Thomas B. Gore, MD
M
ost physicians are aware of the history of the Flexner
Report, published in 1910. It gave a detailed report
card of the nation’s medical schools, prepared by
Abraham Flexner with funding from the Carnegie
Foundation. This report revolutionized medical education in
America and will be the subject of a future review article. Why
do few physicians know about the work and findings of the
Committee on the Cost of Medical Care (CCMC)?
During the 1920s, the rising cost of physician and hospital
care became a concern to many. At a national economic conference in 1925 in Washington, DC, a committee was self-organized to address this issue and became known as the CCMC. This
effort received funding of $1 million from eight foundations,
and its activities were directed by a staff of employees. The
Carnegie Foundation and Milbank Memorial Fund were the
largest contributors. The committee included 15 physicians in
private practice and was chaired by Ray Lyman Wilbur, MD,
of Stanford University. He was a well-known figure with conservative Republican credentials, and he soon became secretary
of the interior under President Hoover. Dr. Stewart R. Roberts
of Atlanta was one of the doctors on the panel. He was on the
Emory faculty at the time and had been president of the Fulton
County Medical Society and was active in the Southern Medical Association. He was later president of the American Heart
Association. He was well published and well respected and was
considered to be Georgia’s first cardiologist.
The CCMC and its staff issued 15 separate reports over
5 years, which were published and available as pamphlets. The
final report with all its recommendations was printed in book
form (Figure). This was the first time that many economic aspects of medical care in the US were documented. Among its
many findings, the CCMC estimated that health care consumed
4% of the gross domestic product. Spending for physician services was the largest category, accounting for 29.8¢ of each dollar.
Hospital care consumed 23.4¢, medications 18.2¢, dental care
12.2¢, nursing care 5.5¢, “cultists” 3.4¢, public health 3.3¢, and
other 4.2¢. The average gross income of physicians in 1929 was
$9000 per year at a time when the average family income was
$1700 per year. An overhead of 40% was typical for a physician in practice, and 10% to 20% of fees were uncollected.
Despite much charity care by physicians, hospitals, and health
departments, in the lowest-income groups about half received
142
Figure 1. The committee’s final report, Medical Care for the American People,
published by the University of Chicago Press in 1932.
no medical care at all. It was estimated that if medical care was
organized economically, all the usual needed care for the entire
country could be provided for $20 to $40 per person per year
(excluding capital costs). The most quoted statement from the
report indicated the basic problem in medical care was “not the
system, but the lack of a system” to organize care.
The most common physician practice then was the solo
private general practitioner. The CCMC also documented other
styles of practice, such as industrial medicine, group practice with
or without hospital employment, capitated models, public health
system practice, and university-sponsored student health care.
These nontraditional types of practice needed to grow. The final
report supported expansion of group practice and formation of
the “community medical center” as the most effective means
of providing care. More national spending on overall medical
care was required to meet all the needs, especially to provide for
those who had no medical care. Preventive care was thought best
provided through public health facilities. The most controversial
recommendation of the CCMC was for national health insurance, either voluntary or compulsory through taxation.
From the Division of Cardiology, West Georgia Medical Center, LaGrange, Georgia.
Corresponding author: Thomas B. Gore, MD, 1602 Vernon Road, Suite 300,
LaGrange, GA 30240 (e-mail: [email protected]).
Notable was the fact that eight physicians dissented and
wrote a minority report. They supported continued experimentation with such models and new proposals but strongly felt that
the independent practicing physician should be in charge of any
programs or changes. They objected to competition based on
price as “unprofessional.” This group felt that even voluntary
health insurance would lead to a compulsory national health
insurance, as was in place in many European countries. Georgia’s
Dr. Roberts supported the work of the committee and signed
the final report.
Two of the nonphysician committee members felt that the
report did not go far enough or make strong enough recommendations for national health insurance. They stated that the
purpose of the committee had not been fulfilled. Edgar Sydenstricker and Walton Hamilton were these two.
Little time passed before the editor of the Journal of the
American Medical Association, Dr. Morris Fishbein, penned
a blistering denouncement of the work of the CCMC on
December 3, 1932, stating it was “incitement to revolution,”
“socialist,” and “communist.” The American Medical Association (AMA), in its 1933 House of Delegates, took a position
of opposition to any further government involvement with
medical care. Franklin Roosevelt had been elected president in
the depth of the Depression, and the winter of 1933 was the
nadir of despair. Any changes in the health care system took
a back seat to more pressing matters. The famous “First Hundred Days” dealt with banking reforms, help with mortgage
foreclosures, and many regulations for businesses in an effort
to stabilize a critically damaged economy and put people to
work, even if it was “make-work.” The Civilian Conservation
Corps, Works Progress Administration, and Public Works Administration were funded with unheralded deficit spending. In
many respects, the report of the CCMC was a tiny blip on any
graphic of the crisis.
Within 2 years, Roosevelt appointed an Economic Security Committee in June 1934, which included several of his
cabinet members, and called an Economic Security Conference in Washington in November 1934 under the leadership of
Frances Perkins, secretary of labor, and Harry Hopkins, director
of federal relief programs. Roosevelt asked for unemployment
insurance, old age pensions, and proposals on medical care insurance. He spoke in November and advocated medical efforts
“whether soon or at some point later,” indicating ambivalence
about the health care proposals. A technical staff had been drafting proposals on all these areas since Roosevelt’s first speech in
July 1934 on the subject, including national health insurance
models. During the November conference, an invited Medical
Advisory Committee attended and expressed their reservations
about the program.
This group then met separately in January 1935, ostensibly
to give their approval. The meeting was chaired by Edgar Sydenstricker, one of the main dissenters of the CCMC. Dr. Walter
Bierring, president of the AMA, was among the panel members.
The prior work of the CCMC was discussed and provided the
statistical basis for many recommendations. The charge of the
advisory group was to respond to the proposed changes for
April 2013
potential legislation. The minutes of these meetings, available
online through the Social Security historical archives, provide
interesting insight into medical issues of the time. The advisory
committee allowed the recommendation for national health
insurance to survive, but there was much internal opposition.
Harvey Cushing, the prominent Boston neurosurgeon, was on
the advisory committee and spoke outside the committee in
opposition. Other physicians on the committee were opposed.
Dr. Stewart Roberts appears to have been in support and stated
that the medical community was “on trial” and would “regret
its actions” if it did not move forward to include medical care
with other aspects of Social Security legislation. He apparently
felt that the committee members and their work was maligned
by the position of the AMA.
With leaks from the committee and the impression that
health insurance was coming soon, the AMA called an emergency House of Delegates meeting in February 1935 and vehemently opposed any efforts at national health care insurance or
government regulation of medicine. The AMA assumed from
the committee structure and technical work that a health care
proposal was sure to follow. This strong stance by the House of
Delegates generated many telegrams from local physicians and
state and county medical societies to the White House. It can
be safely assumed that the physicians of the day were mostly
held in high regard locally and nationally. What impact did
this vocal opposition really have on the final decisions? Harry
Hopkins continued to favor inclusion of medical assistance, but
Frances Perkins advised against it, fearing that the whole Social
Security bill would go down. Roosevelt showed caution and held
his cards. Whether the medical opposition led to its exclusion or
whether Roosevelt was reluctant from the beginning to include
national health care in his bold social initiative is the subject
of much debate among historians. Roosevelt was known for
skillfully making each side feel he agreed with them. The final
report of the Medical Advisory Committee did not materialize in 1935 and was not published until many years later. The
Senate finance committee gave the Economic Security Bill a
beating but ultimately let it through by a small margin, with
Senator Thomas Pryor Gore of Oklahoma famously explaining
his view that “the dole ruins the soul.” Although some public
health funding was given, comprehensive national health programs were excluded from the final bill approved by Congress
in June 1935.
Many of the proposals advocated in the 1930s still retain
their fire as public debate and divided opinions on the Affordable Care Act of 2010 loom large.
Flexner A. Medical Education in the United States and Canada: A Report
to the Carnegie Foundation for the Advancement of Teaching. Boston:
Merrymount, 1910.
The Committee on the Costs of Medical Care. Editorial and abstract summary.
JAMA 1932;99(23):1950–1952, 1954–1958.
The Committee on the Costs of Medical Care. Medical care for the American
people. Chicago, IL: University of Chicago Press, 1932.
Kooijman J. …And the Pursuit of National Health. The Incremental Strategy
Toward National Health Insurance in the United States of America. Amsterdam and Atlanta, GA: Rodopi, B.V., 1999.
A forgotten landmark medical study from 1932 by the Committee on the Cost of Medical Care
143
Invited commentary
Charles Stewart Roberts, MD
A
fter much debate, national health insurance was excluded
from the Economic Security Bill of 1935, which passed
during the first administration of President Roosevelt.
As Dr. Thomas B. Gore points out in an adjacent article,
my paternal grandfather, Stewart R. Roberts, MD (1) (Figure 1),
was involved in this debate and took a rather contrary position
as a physician.
Roberts was a member of two pertinent groups in this national debate, the Committee on the Cost of Medical Care
(CCMC), organized in 1925, and the Medical Advisory Board,
organized in 1934. He appears to have been strongly supportive
of national health insurance and found himself in direct opposition to the American Medical Association (AMA) under
the leadership of Dr. Morris Fishbein, who viewed such a plan
as socialist, if not communist.
The CCMC final report in 1932 highlighted the disconnect between lay reformers, who generally wanted national
health insurance, and physicians, who generally opposed
that level of governmental involvement. Some physicians,
however, including Roberts, went against the majority view
within the medical profession. In his 1999 book, …And the
Pursuit of National Health, Jaap Kooijman described the circumstance:
The polarization within the medical profession reappeared,
however, with a statement by Dr. Stewart Roberts, who bitterly
criticized the obstinate position of the AMA. When in 1932 he
had signed the CCMC majority report [written by lay members
and physicians, advocating national health insurance], Roberts
had been, as he claimed, condemned by the editorials in the
Journal of the American Medical Association. The medical profession’s obstruction had to stop, Roberts argued: “Now this
American Medical Association, we doctors of America, are on
trial in this room this afternoon. If we obstruct and reason and
dally, we are going to receive the contempt of the American
people, and will rightly deserve it” (2).
The Medical Advisory Board, organized in 1934 and composed of 11 physicians, appeared to favor the expansion of
existing public health services, as an alternative to a national
health insurance plan. The “round robin” letter generated by the
board (Figure 2) recommended that “experiments in voluntary
insurance” be done first, before establishing compulsory health
144
insurance. Roberts
was the only board
member who did
not evidently support this cautious
position.
My paternal
grandfather disliked Roosevelt,
but I thought it
was because the
USA was being
drawn into a Second World War in
Europe (through
the lend-lease program, etc.), an inevitability which
Figure 1. Stewart R. Roberts, MD, 1878–1941.
my grandfather,
an isolationist, like
Charles Lindbergh, opposed. The attack on Pearl Harbor,
which occurred after my grandfather’s death in 1941, would
certainly have changed this view.
What did not occur to me until Dr. Gore shared his research
was that my grandfather probably disliked Roosevelt more for
excluding a national health insurance plan in his Economic
Security Bill of 1935. I am grateful to Dr. Gore for reminding
us of these national deliberations, which occurred some 80 years
before the Affordable Care Act of 2010. It proves again that
there is nothing new under the sun (Ecclesiastes 1:9).
1.
2.
Roberts CS. Stewart R. Roberts, MD: Georgia’s First Heart Specialist. Spartanburg, SC: Reprint Company, 1992.
Kooijman J. …And the Pursuit of National Health. The Incremental Strategy
Toward National Health Insurance in the United States of America. Amsterdam and Atlanta, GA: Rodopi, 1999.
From Trident Health, HCA, Charleston, South Carolina.
Corresponding author: Charles Stewart Roberts, MD, Palmetto Cardiovascular
and Thoracic Associates, Trident Health, HCA, 9313 Medical Plaza Drive, Suite
304, Charleston, SC 29406 (e-mail: [email protected]).
Figure 2. Round robin letter from the Medical Advisory Board in 1935 with recommendations concerning national health.
April 2013
145
Radiology Report
Kelli Y. Ha, MD, Jean C. Wang, MD, and Javed I. Gill, MD
Lymphoma is a rare neoplasm in the breast. In this location, it may be primary or secondary, depending on whether there is lymphoma elsewhere
in the body. The most common presentation of breast lymphoma is a
painless palpable mass, indistinguishable from that of breast carcinoma,
although the treatment regimens for these two neoplasms differ vastly.
Knowledge of the varied mammographic and sonographic presentations
of breast lymphoma should prompt more frequent recognition of this
unusual malignant entity. Proper diagnosis of this neoplasm is of the
utmost importance to guide appropriate treatment planning and prevent
unnecessary and potentially harmful surgery. We describe secondary
breast lymphoma in a woman who had been diagnosed and treated for
non-Hodgkin’s lymphoma several years earlier.
A percutaneous, ultrasound-guided core needle biopsy of the
ovoid mass within the right breast was consistent with a grade I
(low-grade) follicular B-cell lymphoma (Figure 3). The B lymphoid cells stained positive for CD20 and CD79a, and follicular
structures demonstrated a 10% positive reaction for BCL-2. A
positron emission tomography (PET) scan 2 months later for
restaging purposes demonstrated a hypermetabolic ovoid mass
within the medial right breast, corresponding to the biopsied lesion at the patient’s palpable area of concern (red circles, Figures
4 and 5). Additional hypermetabolic foci identified at various
locations above and below the diaphragm were compatible with
recurrent or residual lymphoma (Figure 4). The enlarged right
axillary node previously identified on the right breast sonogram
showed intense hypermetabolic activity on PET scan.
The patient was treated with cyclophosphamide, vincristine,
prednisone, and rituximab, and a follow-up PET scan (not
shown) performed 1 month following the patient’s last round
of chemotherapy demonstrated interval resolution of all hypermetabolic foci previously identified, compatible with a complete
CASE REPORT
A 49-year-old white woman presented for a bilateral diagnostic mammogram in February 2009 with complaints of a painless,
palpable lump in the medial right breast. She had non-Hodgkin’s
lymphoma of unknown histologic subtype diagnosed and treated into remission at age 40
a
b
(2003). Approximately 1 month before presentation, a computed tomography (CT) scan demonstrated a mass within the right breast.
Routine craniocaudal and mediolateral
oblique views of both breasts demonstrated scattered fibroglandular densities within the breast
parenchyma (Figure 1). An additional spot tangential view of the right breast over the patient’s
palpable area of concern (Figure 2a) demonstrated a 5 cm gently lobulated, ovoid mass at
the 3 o’clock position, located approximately 7
cm from the nipple (yellow circles, Figure 1). A
right breast sonogram (Figure 2b) demonstrated Figure 1. Routine (a) craniocaudal and (b) mediolateral oblique views of both breasts demonstrate
scattered fibroglandular densities within the breast parenchyma. A dense, gently lobulated ovoid mass
a 4 × 2 × 1 cm well-circumscribed, hypoechoic measuring 5 cm is identified at the 3 o’clock position of the right breast, approximately 7 cm from
ovoid mass at the 3 o’clock position, 8 cm from the nipple (yellow circle). An intramammary lymph node is also noted at the 11 o’clock position of the
the nipple, corresponding to the patient’s pal- right breast (blue circle).
pable area of concern. An 0.8 cm ovoid mass at
the 11 o’clock position, 8 cm from the nipple, corresponded to
From the Department of Radiology, Baylor University Medical Center at Dallas.
an intramammary lymph node (blue circle, Figure 1). In addiCorresponding author: Kelli Y. Ha, MD, Department of Radiology, Baylor
tion, sonographic evaluation of the right axilla demonstrated a
2.7 cm lymph node with a thickened cortex.
146
a
therapeutic response
to chemotherapy.
DISCUSSION
Breast involvement by lymphoma
constitutes ≤0.5% of
all mammary malignancies (1–5). The
rarity of lymphoma
in the breast may
be attributed to its
relative paucity of
lymphoid tissue.
Lymphomas demonstrate a bimodal age
distribution, with
peaks in the fourth
b
and seventh decades
of life (4, 5). Most
breast lymphomas are
of the non-Hodgkin’s
B-cell type, with difFigure 2. (a) Spot tangential view of the right fuse large B-cell lymbreast at the patient’s palpable area of concern, phoma constituting
as designated by a metallic BB marker. This addi- the most prevalent
tional view confirms the presence of a dense ovoid
subtype (6).
mass at the 3 o’clock position. (b) Sonographic
Intramammary
image of the right breast at the 3 o’clock position,
masses,
most of
8 cm from the nipple, demonstrates a well-defined,
hypoechoic mass measuring up to 4 cm at the which are round or
patient’s palpable area of concern.
oval in shape with
circumscribed or
gently lobulated margins, are the most common mammographic
finding. Calcific deposits and spiculated margins are uniformly
absent, and architectural distortion is rare (1, 4). High-grade
lymphomas have been reported to manifest more frequently as
diffuse breast enlargement, whereas low- to intermediate-grade
neoplasms preferentially display a more nodular pattern (4, 7).
Sonographically, breast lymphoma appears as a hypoechoic to
almost anechoic round or oval-shaped mass with relatively welldefined margins with or without posterior acoustic enhancement
(4, 6). In addition, a pseudocystic serpentine mass appearance
has been documented on sonographic evaluation of two breast
lymphoma cases in a study by Gal-Gombos et al (8).
Although few studies have described the magnetic resonance
imaging (MRI) characteristics of breast lymphoma, certain features have been elucidated to date. Surov et al (4) and Yang
et al (5) characterized these lesions as hyperintense compared
with surrounding breast parenchyma on T2-weighted images
and isointense on T1-weighted images. Global intense heterogeneous or homogeneous contrast enhancement was identified
after the administration of intravenous gadolinium. Kinetic
analysis of contrast enhancement demonstrated rapid initial
signal increase, which plateaued or rapidly washed out (type 2
or type 3 kinetic curves), the findings of which are characteristic
for malignancy.
April 2013
Figure 3. BCL-2 stained tissue from the right breast demonstrates an extensive
lymphoid infiltrate, vaguely nodular, with the positive BCL-2 stain consistent with
a diagnosis of follicular B-cell lymphoma.
In an attempt to
differentiate between
primary and secondary breast lymphoma,
a few distinguishing characteristics
may be helpful,
though they are not
pathognomonic in
and of themselves.
In contrast to primary disease, masses
in secondary breast
lymphoma often
demonstrate smaller
diameters upon initial presentation.
Sabaté et al (7) indicated that the average
diameter of a mass
in secondary breast
lymphoma measured
2.8 cm compared
with an average of
4.6 cm for primary Figure 4. A PET scan performed for restaging
breast lymphoma. demonstrates a hypermetabolic ovoid mass within the right breast (red circle). Multiple additional
This finding may be hypermetabolic foci are identified both above and
partially explained by below the diaphragm.
the fact that the duration of symptoms
prior to clinical and radiologic examination may be shorter in
patients in whom lymphomatous disease is known. Likewise,
the number of intramammary masses has been reported to be
higher in secondary than in primary breast lymphoma (4), in
keeping with the overall extent of primary versus secondary
lymphomatous disease. Parenchymal breast involvement in association with bilateral axillary lymph node enlargement may
147
a
b
treatment regimen consisting of combination
chemotherapy with or without concurrent radiotherapy.
1. Fruchart C, Denoux Y, Chasle J, Peny AM, Boute V,
Ollivier JM, Genot JY, Michels JJ. High grade primary
breast lymphoma: is it a different clinical entity? Breast
Cancer Res Treat 2005;93(3):191–198.
2. Liberman L, Giess CS, Dershaw DD, Louie DC,
Deutch BM. Non-Hodgkin lymphoma of the breast:
imaging characteristics and correlation with histopathologic findings. Radiology 1994;192(1):157–160.
Figure 5. Axial images from (a) PET scan and (b) localization CT demonstrate an ovoid hypermeta3.
Meyer
JE, Kopans DB, Long JC. Mammographic apbolic mass within the medial right breast (red circles). This lesion corresponds to the ovoid soft tissue
pearance of malignant lymphoma of the breast. Radioldensity in this location and to the dense ovoid mass seen on prior mammography and sonography
ogy 1980;135(3):623–626.
(see Figures 1–4).
4. Surov A, Holzhausen HJ, Wienke A, Schmidt J,
Thomssen C, Arnold D, Ruschke K, Spielmann RP.
Primary and secondary breast lymphoma: prevalence,
be suggestive of lymphoma, particularly secondary breast lymclinical signs and radiological features. Br J Radiol
phoma, although widespread metastatic breast carcinoma could
2012;85(1014):e195–e205.
also have a similar presentation (7).
5. Yang WT, Lane DL, Le-Petross HT, Abruzzo LV, Macapinlac HA. Breast
Treatment of breast lymphoma remains somewhat controlymphoma: imaging findings of 32 tumors in 27 patients. Radiology
2007;245(3):692–702.
versial; however, certain guidelines have been elucidated. In a
6. Cox J, Lunt L, McLean L. Haematological cancers in the breast and axilla:
study by Fruchart et al (1), all patients undergoing mastectomy,
a drop in an ocean of breast malignancy. Breast 2005;14(1):51–56.
either alone or in association with chemotherapy, died of their
7. Sabaté JM, Gómez A, Torrubia S, Camins A, Roson N, De Las Heras P,
lymphoma. It has been postulated that this may have resulted
Villalba-Nuño V. Lymphoma of the breast: clinical and radiologic features
from delay of appropriate systemic treatment. Correct diagnosis
with pathologic correlation in 28 patients. Breast J 2002;8(5):294–304.
8. Gal-Gombos EC, Esserman LE, Poniecka AW, Poppiti RJ Jr. Is a pseudowith tissue sampling is therefore of the utmost importance to
cystic serpentine mass a sonographic indicator of breast lymphoma? Raprevent the morbidity and mortality associated with unnecessary
diologic-histologic correlation of an unusual finding. AJR Am J Roentgenol
surgery. Alternatively, multiple studies (1, 7) have suggested a
2001;176(3):734–736.
148
Volume 26, Number 2
Radiology Report
Inflammatory breast carcinoma
Kelli Y. Ha, MD, Shannon B. Glass, MD, and Louba Laurie, MD
Inflammatory breast carcinoma is a rare form of invasive breast cancer
often characterized by erythema, warmth, and a classic “peau de orange”
or “orange peel” appearance of the affected breast. The average age of
onset is within the fourth and fifth decades. Lesions are usually detected
and evaluated with mammography, sonography, and recently, breast
magnetic resonance imaging. We present the case of a 49-year-old
woman with inflammatory breast carcinoma in her left breast and describe the imaging appearance of this aggressive lesion on the modalities
listed above. Because this lesion may be misdiagnosed as infection (i.e.,
mastitis) or as the sequelae of a dermatologic disorder, proper characterization of inflammatory breast carcinoma is of the utmost clinical and
radiologic importance.
CASE REPORT
A 49-year-old woman presented with a history of a palpable
mass within her left breast, which had been present for 2 years.
Routine digital mammographic imaging of the right breast (not
shown) did not demonstrate any abnormality. Within the upper
outer aspect of the left breast at the palpable area of concern,
a region of asymmetry, partially obscured by coarse trabecular
thickening, was seen in addition to marked left axillary lymphadenopathy (Figure 1). Diffuse cutaneous thickening was also
demonstrated within the left breast. Sonography demonstrated a
large heterogeneous mass at the palpable area of concern, in the
2:00 position, 10 cm from the nipple, measuring approximately
4.6 × 4.5 × 4.4 cm (Figure 2). Left axillary lymphadenopathy,
measuring up to 4.4 cm in the long axis, was also observed. The
patient underwent surgical biopsy, and the histology proved
consistent with inflammatory breast carcinoma (IBC). She was
subsequently treated with a neoadjuvant chemotherapy regimen consisting of six cycles of 5-fluorouracil, doxorubicin, and
cyclophosphamide. Mastectomy was then performed.
DISCUSSION
IBC is an infrequent form of invasive breast cancer that
often presents with a rapid onset of diffuse erythema, warmth,
edema, and/or peau d’orange changes of the breast. In addition, these changes are accompanied by breast tenderness and/or
pain, palpable mass or masses, and diffuse rapid breast enlargement in conjunction with cutaneous thickening and dermal
ridging. In the absence of clinical symptoms and abnormal
laboratory values, i.e., fever, chills, and/or an elevated white
blood cell count, one should immediately consider a diagnosis
of IBC. This disease entity accounts for 1% to 6% of all breast
cancers in the United States, with the average age of onset between 45 and 54 years (1–3). Similar to other types of breast
carcinoma, IBC can occur in men, but usually at an older age
(median age at diagnosis 66.5 years) than in women. IBC cases
in men constitute between 0.6% and 1.4% of all newly diagnosed breast cancers (4).
Pathologic diagnosis of this clinical entity is generally based
upon the presence of tumor emboli within dilated lymphatic
vessels and a surrounding lymphocytic reaction in the dermis
(2, 5; Figure 3). Although infiltration of dermal lymphatics
confirms a diagnosis of IBC, the disease may only be evident
clinically, and punch biopsies may be negative. In such cases,
patients are treated for IBC based upon clinical data. While IBC
is relatively uncommon compared with other malignancies, it
remains aggressive, with a tendency to metastasize early (3).
Therefore, information about this malignancy is of interest and
importance to both radiologists and clinicians alike.
On mammography, IBC demonstrates a pattern of diffuse
“inflammatory change,” to include cutaneous and trabecular
thickening, increased parenchymal density, breast distortion,
and nipple retraction. Changes on mammography are secondary to dermal lymphatic infiltration and obstruction by tumor,
rather than a true inflammatory process. Because of the increased
parenchymal density, which is often seen throughout the affected
breast, a focal mass lesion or group of suspicious calcifications is
less often seen mammographically (2, 6). Additional associated
mammographic findings, albeit observed less consistently, include
axillary lymphadenopathy and nipple retraction. Of particular
note, the contralateral breast should be carefully inspected for
developing asymmetry and trabecular and/or cutaneous thickening, given the possibility of cancer spread or a simultaneous lesion
in the contralateral breast, which occurs in approximately 1% to
5% of patients with primary IBC (5).
From the Department of Radiology, Baylor University Medical Center at Dallas.
Corresponding author: Kelli Y. Ha, MD, Department of Radiology, Baylor
149
IBC may be divided into two clinical subgroups, first
described by Taylor
and Meltzer in 1938.
The primary form is
seen in patients with
IBC characteristics
that are evident from
the onset, while the
secondary form is
described in those
whose clinical features appear subsequent to appropriate
treatment of a primary noninflammatory
breast carcinoma (7).
Given that our current patient presented without a known
history of previously
treated breast carb
cinoma, her disease
was characterized as
a primary lesion.
Sonographic evaluation of IBC is helpful in demonstrating
lymphatic dilatation
in association with
tumor emboli, as
well as depiction of
hypoechoic shadowing masses, cutaneous thickening,
skin/pectoral muscle
invasion, and axillary lymphadenopathy. Sonography is
notably a better modality for depicting
these characteristics
and should be used
in conjunction with
mammography and
Figure 1. Routine digital mammographic imaging physical examinaof the left breast: (a) craniocaudal view, (b) medio- tion for diagnosis
lateral view. Both views demonstrate a region of whenever possible.
asymmetry (arrow), which corresponds to the pal- Sentinel node biopsy
pable area of concern in the upper outer quadrant. is ultimately used for
Diffuse cutaneous and trabecular thickening is also the diagnosis of axilidentified about the surface of the left breast, which
lary involvement, as
gives the appearance of increased breast density.
skin punch biopsy or
ultrasound-guided core needle biopsy of suspicious masses is
for IBC (3).
a
150
Figure 2. Sonographic image of the left breast demonstrates a large heterogeneous, predominantly hypoechoic mass at the 2:00 position of the left breast,
10 cm from the nipple, measuring approximately 4.6 × 4.5 × 4.4 cm.
Figure 3. An example of inflammatory breast carcinoma (taken from a different
patient) with a characteristic tumor embolus in a dermal lymphatic channel.
Reprinted from Kleer CG, van Golen KL, Braun T, Merajver SD. Persistent E-cadherin
expression in inflammatory breast cancer. Mod Pathol 2001;14(5):458–464, with
permission from Nature Publishing Group.
Recently, breast magnetic resonance imaging (MRI) has
become a primary modality for the depiction of IBC disease entities, either in conjunction with or in replacement of standard
mammography. MRI can be obtained in place of mammography if mammography would be too painful or uncomfortable
for the patient or if compression is inadequate secondary to
tumor bulk. Although patients are usually evaluated initially
with mammography, MRI is useful for determining the extent
of disease and may be helpful in monitoring treatment response
in some cases.
Global skin thickening, enhancing masses, breast enlargement, breast/chest wall edema, and/or tumor infiltration is often
obscured on mammography. However, these entities are well
characterized on MRI, leading to a higher detection rate of
primary breast parenchymal lesions/masses using this modality. Multiple enhancing breast masses are more often described
Volume 26, Number 2
on MRI than a single index breast lesion in IBC (1). Primary
tumors in IBC often demonstrate low signal intensity on T1WI
and heterogeneous iso- or high signal intensity on T2WI. Increased signal intensity and enhancement of the thickened skin
are also consistently reported attributes of IBC (2).
Inflammatory breast carcinoma is not the only disease
process that presents with mammographic or physical signs
of breast tissue inflammation. In fact, the differential for these
findings remains vast, and correlation with patient history in
conjunction with physical and radiologic examination findings
remains crucial in these situations. Inflammation of the breast
tissue may be seen after surgery and postradiation therapy, as
well as from trauma, infection (i.e., mastitis), and various dermatologic disorders. Breast edema may be secondary to other
systemic conditions such as superior vena cava syndrome, congestive heart failure, and lymphoma. In patients who present
with inflammatory signs that continue despite proper antibiotic
treatment, biopsy is indicated to definitively exclude a diagnosis
of IBC (3).
Goldfarb and Pippen recently reviewed treatment of IBC at
Baylor University Medical Center at Dallas (8). As they noted,
the recommended therapy is induction chemotherapy with an
anthracycline-based regimen with or without the addition of
taxanes, followed by mastectomy with axillary lymph node dissection in those who respond well. Preoperative trastuzumab
may be considered for patients with HER2-positive disease. Any
remaining cycles of planned chemotherapy can be completed after surgery, and patients with hormone receptor–positive disease
may begin endocrine therapy after surgery as well. Postsurgical
radiotherapy of the chest wall and regional axillary nodes should
follow completion of the chemotherapy regimens.
April 2013
The current case describes a patient who presented for
her first mammogram with an advanced inflammatory breast
carcinoma, undoubtedly neglected for some time given initial
palpation 2 years prior. This case highlights the importance of
mammography in screening for breast carcinoma and of seeking
proper and timely evaluation upon palpation of a new breast
mass. It is unique given the extensive inflammatory change
that was denied evaluation until a late and advanced stage.
Although IBC can easily be mistaken for an infection or other
disease process as discussed previously, failure to improve with
antibiotics/treatment should remain a “red flag” for the relatively
rare diagnosis of IBC.
1.
2.
3.
4.
5.
6.
7.
8.
Le-Petross HT, Cristofanilli M, Carkaci S, Krishnamurthy S, Jackson EF,
Harrell RK, Reed BJ, Yang WT. MRI features of inflammatory breast
cancer. AJR Am J Roentgenol 2011;197(4):W769–W776.
Lee KW, Chung SY, Yang I, Kim HD, Shin SJ, Kim JE, Chung BW,
Choi JA. Inflammatory breast cancer: imaging findings. Clin Imaging
2005;29(1):22–25.
Günhan-Bilgen I, Ustün EE, Memiş A. Inflammatory breast carcinoma:
mammographic, ultrasonographic, clinical, and pathologic findings in
142 cases. Radiology 2002;223(3):829–838.
Anderson WF, Schairer C, Chen BE, Hance KW, Levine PH. Epidemiology of inflammatory breast cancer (IBC). Breast Dis 2005–2006;22:9–
23.
Kushwaha AC, Whitman GJ, Stelling CB, Cristofanilli M, Buzdar AU.
Primary inflammatory carcinoma of the breast: retrospective review of
mammographic findings. AJR Am J Roentgenol 2000;174(2):535–538.
Yang WT. Advances in imaging of inflammatory breast cancer. Cancer
2010;116(11 Suppl):2755–2757.
Taylor GW, Meltzer A. “Inflammatory carcinoma” of the breast. Am J
Cancer 1938;33:33–49.
Goldfarb JM, Pippen JE. Inflammatory breast cancer: the experience of
Baylor University Medical Center at Dallas. Proc (Bayl Univ Med Cent)
2011;24(2):86–88.
Inflammatory breast carcinoma
151
Michael J. Van Vrancken, MD, MPH, Latoya Keglovits, MD, and John Krause, MD
Posttransplant lymphoproliferative disorder is a serious complication following solid organ as well as hematopoietic stem cell transplantation due to
prolonged immunosuppressive therapy. Plasmablastic lymphoma, although
classically associated with HIV infection, has since been described in transplant patients as a variant of posttransplant lymphoproliferative disorder
with varying clinical presentations. Here we add two additional cases to the
literature: one following lung transplantation and one following pancreatic
transplantation. In addition, the demographic, therapeutic, and immunophenotypic characteristics from prior reported cases are summarized.
P
lasmablastic lymphoma was first described
in 1997 as an oral mucosal lesion associated with HIV-positive individuals as a
subtype of diffuse large cell lymphoma (1,
2). Since its initial description, it has now become
well established as an entity seen in HIV-negative
individuals as well, albeit rarely (3). In 2003, the
first case of plasmablastic lymphoma in a posttransplant lymphoproliferative disorder (PTLD)
was reported as a cutaneous leg ulcer (4). Since
this original description, several additional cases
have been reported following various solid organ
and bone marrow transplantations. We present
two cases of plasmablastic lymphoma, one following lung transplantation with subsequent immunosuppressive therapy (previously reported in
the context of unusual clinical findings) (5) and
another following pancreatic transplantation.
a
respiratory status continued to decline, and he developed worsening pulmonary infiltrates. Repeat biopsy again showed acute lung
injury with organization. He was again treated with high-dose
corticosteroids as well as a 10-day trial of antithymocyte globulin (Atgam) for possible rejection. The patient began to recover
clinically, and at the time of his discharge 45 days later, he was
breathing room air and his tracheostomy site was healing. To
modulate his posttransplant immune function, the patient was
treated with tacrolimus, prednisone, and azathioprine.
In February 2012, the patient presented with facial swelling,
numbness, right lower lip swelling, and mild erythema within
b
Figure 1. Wright stain of bone marrow aspirate showing larger “blast”-like plasma cells with abundant
cytoplasm, nucleoli, and open chromatin pattern. The cells also have vague perinuclear hofs and eccentrically placed nuclei. ×1000.
a
b
CASE 1
A 67-year-old man with idiopathic pulmonary fibrosis diagnosed at age 63 (2008) underwent sequential bilateral lung transplantation in
October 2011. The patient had a complicated Figure 2. (a) Hematoxylin and eosin staining of the aspirate clot preparation showing sheet-like infiltrate
predominantly composed of larger “blast”-like cells with prominent nucleoli. ×400. (b) Epstein-Barr virus
clinical course thereafter with repeated episodes early RNA in situ hybridization showing strong nuclear positivity within the infiltrative cells. ×400.
of respiratory failure requiring reintubation and
eventual tracheostomy. He subsequently develFrom the Department of Pathology, Baylor University Medical Center at Dallas.
oped bilateral pulmonary infiltrates and was placed on antibiotics.
Corresponding author: Michael J. Van Vrancken, MD, MPH, Department of
Biopsy showed acute lung injury, and the patient was placed on
Pathology, Baylor University Medical Center at Dallas, 3500 Gaston Avenue,
Dallas, TX 75246 (e-mail: [email protected]).
high-dose steroids for presumed acute rejection. The patient’s
152
the inner lip with corresponding numbness. He had macrocytic anemia with normal folate and vitamin B12 levels. Brain
magnetic resonance imaging revealed multifocal patchy regions
of marrow signal abnormality involving the calvaria, skull base,
and visualized upper cervical spine. He had elevated copies of
Epstein-Barr virus (EBV).
Histologic analysis of a bone marrow biopsy specimen disclosed
scattered cellular sheets of a plasmacytoid infiltrate composed of
medium- to large-sized cells with an abundant amount of basophilic cytoplasm, eccentrically located nuclei with a clock-faced
chromatin, and a perinuclear hof. Many malignant cells displayed
a large central nucleolus with finely dispersed immature chromatin
consistent with a “plasmablast”-type morphology (Figures 1 and 2).
Occasional cells showed bi- and trinucleated forms, and mitotic
activity was increased with many atypical figures seen.
Immunophenotypically, these cells were characterized by
strong immunohistochemical staining to CD138 with patchy
membranous positivity seen with CD56. CD30 and CD20 were
negative in the plasmacytoid cells. Most malignant infiltrates
were negative for both kappa and lambda in situ hybridization
with rare scattered cells showing positivity. Additionally, most
cells stained positively for EBV early RNA (EBER) by in situ
hybridization (Figure 2).
Figure 3. Hematoxylin and eosin staining of the mesenteric mass showing large
cells with open chromatin and prominent nucleoli consistent with a “blast”-type
morphology. ×400.
After a diagnosis of posttransplant plasmablastic lymphoma was made, the patient was started on a cyclophosphamide,
hydroxydaunorubicin, vincristine (Oncovin), and prednisone/
Table 1. Reported cases of plasmablastic lymphoma in transplanted patients
Study
No.
Sex
Age (years)
Transplant
Location
Treatment
Status (months)
Nicol et al,
2003 (4)
1
F
68
Heart
Cutaneous
Local radiotherapy
Alive (9)
Teruya-Feldstein
et al, 2004 (19)
1
M
73
Kidney
Cutaneous
Chemotherapy
Alive (7)
Verma et al,
2005 (20)
1
F
38
Kidney
Cutaneous
Resection and radiotherapy
Alive (32)
Borenstein et al,
2007 (21)
4
M
27
Kidney
Prostate
Not reported
Not reported
M
46
Heart
Oral cavity
M
48
Bone marrow
Lymph node
M
57
Kidney
Cutaneous
F
14 mo
Small bowel, liver
Cutaneous
IR
Progression (<1)
Apichai and
Hernandez et al.,
2009 (22, 23)
1
Zimmermann
et al, 2012 (24)
8
Present study
(including
Shahriar et al,
2012 [5])
2
F
30
Heart, lung
Disseminated
IR + chemo
Progression (<1)
M
37
Heart
Nasal cavity
IR + chemo + radiation
Alive (48)
F
42
Kidney
Disseminated
None
Progression (<1)
M
44
Heart
Disseminated
IR + chemo
Progression (4)
M
49
Kidney
Subcutaneous
IR + chemo + radiation
Alive (14)
M
54
Heart
Disseminated
Chemo
Progression (6.5)
M
62
Heart
Disseminated
IR + chemo
Alive (29.5)
M
67
Kidney
Disseminated
IR + chemo
Progression (10)
M
67
Lung
Bone marrow
Limited chemo
Alive (<1)
F
42
Pancreas
Mesenteric
Resection
Progression (<1)
IR indicates immunosuppressant reduction.
April 2013
153
Table 2. Immunophenotypes in reported cases of plasmablastic lymphoma in transplanted patients
VS38c
CD79a
CD20
␬
␭
EBER
CD138
CD56
IgG
IgM
CD30
EMA
LCA
HHV-8
Ki-67
Nicol et al,
2003 (4)
1/1
0/1
0/1
0/1
–
–
0/1
0/1
1/1
–
–
0/1
–
–
–
TeruyaFeldstein
et al, 2004
(19)
–
0/1
0/1
–
–
1/1
1/1
–
–
–
–
–
Weak
1/1
–
>80%
Verma et al,
2005 (20)
–
1/1
0/1
0/1
1/1
1/1
–
1/1
–
–
0/1
–
–
1/1
–
Borenstein
et al, 2007
(21)
4/4
Weak
4/4
0/4
2/4
1/4
3/4
2/3
0/3
–
–
1/2
1/3
–
–
70%–
90%
Apichai and
Hernandez
et al, 2009
(22, 23)
–
Weak
1/1
0/1
0/1
1/1
–
1/1
1/1
–
–
0/1
–
–
–
>90%
Zimmermann
et al, 2012
(24)
–
–
0/7
4/7
2/7
5/8
6/8
1/6
–
–
–
–
–
–
80%–
100%
Present study
(including
Shahriar
et al,
2012 [5])
–
–
0/2
0/2
0/2
2/2
2/2
2/2
–
–
0/2
–
–
–
–
Study
␬ indicates kappa; ␭, lambda; EBER, Epstein-Barr virus early RNA; EMA, epithelial membrane antigen; LCA, leukocyte common antigen; HHV-8, human herpes virus-8.
prednisolone (CHOP) chemotherapy regimen. After 1 cycle of
treatment, the patient elected to receive palliative care only.
CASE 2
In 2008, a 45-year-old woman received a pancreas transplant for brittle diabetes mellitus type I. Over the next year, the
patient was hospitalized multiple times with abdominal pain,
which was attributed to pancreatitis. In May 2009, the patient
was hospitalized for abdominal pain, again with a failed pancreatic transplant. She underwent a planned pancreatectomy. During the procedure, a 16-cm loop of small bowel was identified
wrapping around a 6.0 × 5.0 × 4.0 cm soft tissue mass within
the abdomen, and it was resected.
Histomorphologically, the mass was composed of large
round to oval-shaped cells with finely dispersed immature
chromatin and prominent nucleoli consistent with a “blast”type morphology (Figure 3). Immunohistochemically, the cells
had a positive stain for CD138 and CD56 and were positive
for EBER by in situ hybridization, confirming the diagnosis
of plasmablastic lymphoma. Postoperatively, the patient had
a complicated course and died 7 days following the procedure
due to overwhelming gram-negative sepsis.
DISCUSSION
PTLD is a heterogenous disease seen in patients who have
undergone solid organ or hematopoietic stem-cell transplantation. It was first described in 1968 in association with renal
154
transplantation. In patients who have received a transplant, the
risk of lymphoma is increased 20% to 120% compared with the
general population (6). Additionally, several risk factors have
been shown to increase the risk of PTLD, including immunosuppression (6–8), EBV (9–12), genetic susceptibility (13), and
a host of other miscellaneous factors including Caucasian race
(14), hepatitis C, cytomegalovirus, and human herpes virus-8
infection (15–17). PTLD is classified into four categories based
on immunophenotype, morphology, and molecular criteria.
These include early lesions, polymorphic, monomorphic, and
classical Hodgkin lymphoma (18).
Traditionally, plasmablastic lymphomas have been described
in HIV-positive individuals, typically occurring in the mucosa
of the oral cavity. The lesion is characterized morphologically
by blastic cells with a plasma cell immunophenotype. In recent
years, this entity has also been described in individuals who have
previously undergone a transplantation procedure, including
kidney, heart, heart/lung, liver/small bowel, and bone marrow
(Table 1) (4, 19–24). To our knowledge, the present report is the
first describing plasmablastic lymphoma following pancreatic
transplantation.
Morphologically, PTLD plasmablastic lymphoma is characterized by larger immature cells with abundant cytoplasm,
nucleoli, and an open chromatin pattern. Immunophenotypically (Table 2), previously reported cases have been predominantly positive for CD138 and VS38 and usually display either
a kappa or lambda restriction. B-cell markers, such as CD20
Volume 26, Number 2
and CD79a, are typically negative, and the proliferative index
(Ki-67) is invariably high, usually above 80%. The preponderance of reports demonstrates positivity for EBER through in
situ hybridization, with one other case demonstrating an EBV
and human herpes virus-8 coinfection (20).
The role of EBV in the development of PTLDs (including
plasmablastic lymphoma) is well established. EBV preferentially
infects B cells, where its genome can lay dormant as an episome
(25). In healthy immunocompetent individuals, activated T cells
play an important role in controlling the proliferation and elimination of infected B cells. Due to immunosuppressive therapy
severely impairing T-cell activity, immunosuppressed patients are
at risk for uncontrolled proliferation of the infected B cells.
The treatment for PTLD has many modalities with varying
degrees of effectiveness. Antiviral therapies, particularly ganciclovir, have been used as prophylactic agents to prevent EBV-related
PTLD, although the data are not definitive. Donor-derived
EBV-specific cytotoxic T-cell lymphocyte infusions (adoptive
immunotherapy) have also been shown to play a role in PTLD
prophylaxis in both adult and pediatric populations (26, 27).
Treatment modalities of diagnosed PTLD have included reduced
immunosuppression as well as CHOP-based chemotherapy with
or without rituximab. A recent study looking at treatment options for PTLD plasmablastic lymphoma by Zimmermann et
al found that immunosuppression with systemic chemotherapy
(CHOP-21) achieved a more lasting and complete remission
than immunosuppression with local therapy (24).
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H. Plasmablastic lymphomas of the oral cavity: a new entity associated with the
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2. Flaitz CM, Nichols CM, Walling DM, Hicks MJ. Plasmablastic lymphoma:
an HIV-associated entity with primary oral manifestations. Oral Oncol
2002;38(1):96–102.
3. Lee OJ, Kim KW, Lee GK. Epstein-Barr virus and human immunodeficiency virus-negative oral plasmablastic lymphoma. J Oral Pathol Med
2006;35(6):382–384.
4. Nicol I, Boye T, Carsuzaa F, Feier L, Collet Villette AM, Xerri L, Grob JJ,
Richard MA. Post-transplant plasmablastic lymphoma of the skin. Br J
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chin syndrome as the initial presentation of posttransplant lymphoproliferative disorder. Proc (Bayl Univ Med Cent) 2012;25(3):243–245.
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155
Recurrent acute inflammatory demyelinating
polyradiculoneuropathy following R-CHOP treatment
for non-Hodgkin lymphoma
Jackson J. Liang, DO, Preet P. Singh, MD, and Thomas E. Witzig, MD
Acute flaccid paralysis following chemotherapy has a wide differential diagnosis, including drug toxicity, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), and malignant nerve infiltration. We present a
case of recurrent acute quadriparesis due to AIDP following chemotherapy
for non-Hodgkin lymphoma, which resolved each time following administration of intravenous immunoglobulin. Although many chemotherapeutic
agents can cause neurologic side effects, such as peripheral neuropathy,
drug toxicity as a cause is a diagnosis of exclusion.
A
cute flaccid paralysis following chemotherapy has a wide
differential diagnosis, including drug toxicity, acute
inflammatory demyelinating polyradiculoneuropathy
(AIDP), and malignant nerve infiltration. We present
a case of recurrent acute quadriparesis due to AIDP following
chemotherapy for non-Hodgkin lymphoma, which resolved
each time following administration of intravenous immunoglobulin (IVIG).
CASE PRESENTATION
A 62-year-old man with recently diagnosed stage IV diffuse large B-cell lymphoma presented for his first cycle of chemotherapy with rituximab, cyclophosphamide, doxorubicin,
vincristine, and prednisone (R-CHOP). The diagnosis had
been confirmed by pleural and testicular biopsies. Pretreatment positron emission tomography (PET) scan had revealed
diffuse nodal activity and extranodal involvement in the pleura,
testicles, and bones (Figure 1a). The patient had been otherwise
healthy.
He tolerated his first cycle of R-CHOP chemotherapy with
no issues. Two days after completing the R-CHOP cycle, he began to notice bilateral lower-extremity weakness, which began at
his feet and gradually moved upwards to his hip girdle muscles.
The weakness gradually worsened to the point where he needed
to use his hands to push off and stand from a seated position.
Shortly thereafter, he noted bilateral arm weakness and became
unable to stand due to the inability to push off with his arms.
He also developed numbness in all four extremities from his mid
forearms distally and the knees down. Throughout this time, he
retained bowel and bladder function. His severe weakness and
156
footdrop prompted a trip to the emergency department, and
he was admitted for workup.
Examination at this time revealed mild upper-extremity
weakness proximally with moderate to severe upper-extremity
distal weakness. He had profound lower-extremity weakness,
distal worse than proximal. While lying supine, he could move
his legs minimally from side to side but was unable to lift them
against gravity. He was unable to move his feet at all. Deep
tendon reflexes at the knees were markedly diminished bilaterally, and ankle reflexes were completely absent. The Babinski
sign was negative.
Due to concern for Guillain Barré syndrome, lumbar puncture and electromyography with nerve conduction studies were
ordered. Cerebrospinal fluid from the lumbar puncture exhibited albuminocytologic dissociation with an elevated protein (77
g/dL) and a cell count of 1 cell per microliter. Electromyogram
revealed diffusely abnormal motor nerve conduction with low
amplitude; slow, dispersed compound muscle action potentials; and conduction block in the median, ulnar, tibial, and
peroneal nerves. HIV and hepatitis studies were negative. He
was diagnosed with AIDP, and IVIG was initiated at 400 mg/
kg/day for 5 days.
Shortly after being given the first dose of IVIG, his strength
began to improve. Upon awakening the following morning, he
was able to raise both knees and his left arm against gravity. By
that afternoon, he was able to stand and walk a few steps with
a wheeled walker and assistance. Upon completion of the 5-day
course of IVIG, the numbness in his forearms and hands had
resolved completely. He was discharged to the inpatient rehabilitation unit, where he continued to recover. At discharge after
just 4 days of rehabilitation, he was able to ambulate without
the assistance of a cane.
During his second R-CHOP cycle, the vincristine dose was
halved. Afterwards he experienced a brief episode of tingling
and mild weakness in his hands and feet, which resolved completely after 48 hours. Follow-up PET scan prior to cycle 3
demonstrated complete radiologic remission (Figure 1b) with
From the Department of Medicine (Liang) and the Divison of Hematology and
Medical Oncology (Singh, Witzig), Mayo Clinic, Rochester, Minnesota.
Corresponding author: Jackson Liang, DO, 200 1st Street SW, Rochester, MN
peripheral nerves. The weakness
was not likely due to vincristine
or rituximab, as the symptoms
developed after the first dose. Furthermore, vincristine toxicity was
unlikely as he had a severe recurrence of weakness following his
fourth cycle when vincristine was
withheld. His malignancy responded extraordinarily to R-CHOP, as
his testicles decreased to normal
size a few days after his first cycle.
Ultimately, his recurrent neurologic
symptoms were attributed to AIDP
from the underlying lymphoma, as
his miraculous rapid improvement
with IVIG did not fit with drug
toxicity or direct lymphomatous
nerve infiltration.
Non-Hodgkin lymphoma is
the most common cause of lymphomatous neuropathy syndromes
(1). Although AIDP is most classically associated with Hodgkin
lymphoma (2, 3), non-Hodgkin
lymphoma can also cause a clinical
picture of AIDP with evidence of
demyelination on electromyelography and needle conduction studies.
R-CHOP, a frequently used regimen
in the treatment of non-Hodgkin
lymphoma, has been linked to the
Figure 1. (a) Pretreatment PET scan demonstrating diffuse nodal activity and extranodal involvement in the pleura, development of AIDP (4, 5), partictesticles, and bones. (b) Follow-up PET scan prior to R-CHOP cycle 3 demonstrating complete radiologic remission. ularly rituximab (6) and vincristine
(7–10). AIDP, the major variant of
no sign of lymphomatous involvement of the nerves. Full-dose
the group of neurologic disorders commonly referred to by the
vincristine was given with his third R-CHOP cycle. After 5 days,
eponym “Guillain Barré syndrome,” is believed to be due to
he noted complete loss of sensation in his fingers and feet. His
autoimmune attack on the myelin of peripheral nerves, leading
symptoms resolved over the next few days and were attributed to
to electrical conduction slowing and muscular weakness. It is
vincristine. As such, vincristine was withheld during his fourth
often preceded by an upper respiratory or gastrointestinal tract
cycle. Five days following this fourth cycle, he experienced severe
infection, most commonly due to Campylobacter jejuni, Epsteinweakness in his legs bilaterally in addition to numbness in his
Barr virus, or cytomegalovirus (11). Other systemic illnesses
hands and feet, similar to his initial episode of AIDP. A repeat
associated with AIDP include HIV, viral hepatitis, sarcoidosis,
electromyogram once again demonstrated findings consistent
and systemic lupus erythematosus (2).
with polyradiculoneuropathy. Lumbar puncture demonstrated
The diagnosis is multifaceted. Clinical findings include
protein of 98 g/dL with 1 total nucleated cell per microliter. A
progressive symmetric muscle weakness and diminished or
complete serum and cerebrospinal fluid paraneoplastic panel
absent deep tendon reflexes. Lumbar puncture with analysis
and cerebrospinal fluid cytology sent at that time were negative.
of cerebrospinal fluid typically reveals normal cell count with
He was treated again with a 5-day course of IVIG (400 mg/kg/
elevated protein, also known as albuminocytologic dissociaday) with complete resolution of symptoms.
tion. Electromyography with needle conduction study is helpful
in the diagnosis of AIDP, typically revealing slowing of nerve
DISCUSSION
conduction with conduction block or abnormal dispersion,
The differential diagnosis in our patient’s acute ascending
prolonged distal latencies, and delayed F waves (12).
weakness included autoimmune AIDP secondary to his underTreatment consists of supportive care and disease-modifying
lying lymphoproliferative malignancy, vincristine or rituximab
therapy. Up to 30% of patients require mechanical ventilation
neurotoxicity, and direct lymphomatous involvement of the
due to weakness of muscles of respiration or inability to swallow
a
April 2013
b
Recurrent AIDP following R-CHOP treatment for non-Hodgkin lymphoma
157
and protect the airway. Plasmapheresis and IVIG are the main
therapies for AIDP. Plasmapheresis removes circulating autoantibodies in the blood, while IVIG may neutralize autoantibodies
(13) and prevent complement-mediated nerve damage (14).
1.
2.
3.
4.
5.
6.
7.
Kelly JJ, Karcher DS. Lymphoma and peripheral neuropathy: a clinical
review. Muscle Nerve 2005;31(3):301–313.
Ropper AH. The Guillain-Barré syndrome. N Engl J Med
1992;326(17):1130–1136.
Hughes RA, Britton T, Richards M. Effects of lymphoma on the peripheral
nervous system. J R Soc Med 1994;87(9):526–530.
Magné N, Foa C, Castadot P, Otto J, Birtwisle-Peyrottes I, Thyss A.
Guillain-Barré syndrome and non-Hodgkin’s lymphoma. Report of one
case and review of literature. Rev Med Brux 2005;26(2):108–111.
Terenghi F, Ardolino G, Nobile-Orazio E. Guillain-Barré syndrome after
combined CHOP and rituximab therapy in non-Hodgkin lymphoma. J
Peripher Nerv Syst 2007;12(2):142–143.
Carmona A, Alonso JD, de las Heras M, Navarrete A. Guillain-Barre
syndrome in a patient with diffuse large B-cell lymphoma, and rituximab
maintenance therapy. An association beyond anecdotal evidence? Clin
Transl Oncol 2006;8(10):764–766.
Weiden PL, Wright SE. Vincristine neurotoxicity. N Engl J Med
1972;286(25):1369–1370.
8.
9.
10.
11.
12.
13.
14.
Wanschitz J, Dichtl W, Budka H, Löscher WN, Boesch S. Acute motor
and sensory axonal neuropathy in Burkitt-like lymphoma. Muscle Nerve
2006;34(4):494–498.
Bahl A, Chakrabarty B, Gulati S, Raju KN, Raja A, Bakhshi S. Acute
onset flaccid quadriparesis in pediatric non-Hodgkin lymphoma: vincristine induced or Guillain-Barré syndrome? Pediatr Blood Cancer
2010;55(6):1234–1235.
Moudgil SS, Riggs JE. Fulminant peripheral neuropathy with severe
quadriparesis associated with vincristine therapy. Ann Pharmacother
2000;34(10):1136–1138.
Jacobs BC, Rothbarth PH, van der Meché FG, Herbrink P, Schmitz PI,
de Klerk MA, van Doorn PA. The spectrum of antecedent infections in
Guillain-Barré syndrome: a case-control study. Neurology 1998;51(4):1110–
1115.
Cornblath DR. Electrophysiology in Guillain-Barré syndrome. Ann Neurol
1990;27(Suppl):S17–S20.
Buchwald B, Ahangari R, Weishaupt A, Toyka KV. Intravenous immunoglobulins neutralize blocking antibodies in Guillain-Barré syndrome.
Ann Neurol 2002;51(6):673–680.
Jacobs BC, O’Hanlon GM, Bullens RW, Veitch J, Plomp JJ, Willison
HJ. Immunoglobulins inhibit pathophysiological effects of anti-GQ1bpositive sera at motor nerve terminals through inhibition of antibody
binding. Brain 2003;126(10):2220–2234.
Avocations
A red fox from Alaska. Copyright © Jed Rosenthal, MD. Dr. Rosenthal is a cardiologist in Dallas, Texas (e-mail: [email protected]).
158
Volume 26, Number 2
Radiology Report
Mehrzad Zarghouni, MD, Michael L. Kershen, MD, Lauren Skaggs, MD, Amol Bhatki, MD, Steven C. Gilbert, MD,
Conan E. Gomez, MD, and Michael J. Opatowsky, MD
a
b
c
d
e
f
Otalgia is a common complaint seen by
general practitioners, but its etiology is
vast. Rarely, otalgia could be secondary to
a neoplasm. We describe a case of otalgia
and ear discharge in which the imaging revealed a rare neoplasm, an endolymphatic
sac tumor, which contributed to the patient’s
symptoms. The primary diagnosis was
made via characteristic imaging features
that were later confirmed by histology.
Endolymphatic sac tumor is an
uncommon neoplasm arising from
the endolymphatic sac or endolymphatic duct. This tumor is generally
classified as a papillary adenoma. We
report a case of endolymphatic sac
tumor in which the patient presented
with otalgia and ear discharge.
CASE DISCUSSION
A 49-year-old woman presented
with recent onset of left ear pain and Figure 1. (a, b) Head CT and (c–f) MRI images from this patient presenting with otalgia, showing characteristic
discharge. The patient had a remote features of endolymphatic sac tumor.
history of left ear tumor resection as a
DISCUSSION
child; however, the type of tumor was not known with certainty at
The most common clinical presentation of endolymphatic
the time of the current evaluation. A noncontrast head computed
sac tumor is sensorineural hearing loss (1). Tinnitus, vertigo,
tomography (CT) as part of the initial examination revealed an exand facial nerve palsy can also occur. While these tumors
pansile mass destroying much of the temporal bone (Figures 1a–1b,
are generally benign, they can be lethal. Late recurrence is
white arrows). Given the absence of parenchymal brain edema,
possible, although there is generally a very favorable prognoan indolent slow-growing tumor was suspected. Unenhanced and
sis following complete resection. This tumor may be associgadolinium-enhanced magnetic resonance imaging (MRI) showed
ated with the neurocutaneous syndrome von Hippel-Lindau
a large, heterogeneous, and avidly enhancing mass centered on the
left mastoid and petrous bones (Figures 1c–1f, white arrows). A
fluid-fluid level within the dependent portion of the mass on the T2
From the Departments of Radiology (Zarghouni, Kershen, Skaggs, Gilbert, Gomez,
axial image (Figure 1c, yellow arrow) was present. Areas of T1 bright
Opatowsky) and Otolaryngology (Bhatki), Baylor University Medical Center at
hyperintensity were suggestive of hemorrhage (Figure 1d, yellow
Dallas.
arrow). An endolymphatic sac tumor was ultimately confirmed by
Corresponding author: Mehrzad Zarghouni, MD, Department of Radiology, Baylor
histologic correlation following operative resection. The patient was
discharged postoperatively without adverse neurological deficits.
159
disease (2, 3). In contrast to its sporadic form in which hearing loss is inevitable, in von Hippel-Lindau disease these
tumors are generally small, which allows for hearing preservation (2, 3).
The best diagnostic clues on imaging for an endolymphatic sac tumor include its characteristic location in addition
to central calcified deposits and bone spicules on CT along
with intratumoral high signal intensity on noncontrast T1
MRI evaluation (1–3). This is seen in conjunction with avid
160
enhancement on gadolinium-enhanced T1-weighted MRI
sequences.
1.
2.
3.
Lo WW, Applegate LJ, Carberry JN, Solti-Bohman LG, House JW,
Brackmann DE, Waluch V, Li JC. Endolymphatic sac tumors: radiologic
appearance. Radiology 1993;189(1):199–204.
Leung RS, Biswas SV, Duncan M, Rankin S. Imaging features of von
Hippel-Lindau disease. Radiographics 2008;28(1):65–79.
Ayadi K, Mahfoudh KB, Khannous M, Mnif J. Endolymphatic sac tumor
and von Hippel-Lindau disease: imaging features. AJR Am J Roentgenol
2000;175(3):925–926.
Volume 26, Number 2
Inguinal lymphadenopathy as the initial presentation of
sarcoidosis
Jim George, MD, Reese Graves, MD, and Robert Meador Jr., MD
Sarcoidosis is a multisystem disease of unknown etiology characterized
by granuloma formation. Despite pulmonary involvement in most patients,
sarcoidosis can have a varied presentation. Lymph node involvement is
rarely found in isolation. Even rarer are cases of sarcoidosis presenting
with peripheral edema. We describe a case of sarcoidosis presenting
with isolated unilateral peripheral edema.
CASE PRESENTATION
A 50-year-old African American woman with iron deficiency
anemia secondary to menorrhagia and uterine fibroids was admitted for symptomatic anemia, requiring blood transfusions.
The patient reported worsening right groin swelling and right
leg swelling over the last 10 years with progressive pain with
activity. A brother had lymphoma.
On admission, she was afebrile and normotensive. Her right
leg was 1.5 times larger in circumference than her left leg with
nonpitting edema and a negative Homan’s sign. A 7 × 4 cm
nodular mass was palpable in her right groin. There was no associated erythema or tenderness to palpation. Her white blood
cell count was 4.6 K/uL, hemoglobin 6.5 g/dL, and platelets
331 K/uL. She had a positive antineutrophil antibody result
with a 1:320 titer, an angiotensin-converting enzyme level of 25
mg/L, a vitamin D level of 52.9 ng/mL, an erythrocyte sedimentation rate of 47 mm/hr, a C-reactive protein level of 4.8 mg/
dL, a complement 3 (C3) level of 147 g/L, and a complement
4 (C4) level of 48.4 g/L. A computed tomography (CT) scan
of the chest, abdomen, and pelvis revealed right deep pelvic
and inguinal bulky adenopathy, with an 8.1 × 5.3 cm right
pelvic sidewall mass, multiple enlarged right inguinal lymph
nodes measuring 6 cm, and a large left uterine mass, measuring
8 cm (Figure 1). No abnormalities were noted in the chest or
abdomen. A dilatation and curettage with endometrial biopsy
was completed. An ultrasound-guided core needle biopsy was
performed to further evaluate her inguinal mass. Her endometrial biopsy showed numerous myometrial tissue fragments and
acute and chronic inflammation with squamous metaplasia, all
suggestive of underlying submucosal leiomyoma and atrophy.
The tissue sample was negative for granulomas, atypia, or malignancy. The ultrasound-guided core needle biopsy of the large
right inguinal lymph node showed noncaseating granulomatous
Figure 1. Admission CT scan with right inguinal lymphadenopathy.
Figure 2. Low power field microscopy of lymph node biopsy showing a granuloma without central necrosis, suggestive of sarcoidosis; 100× magnification,
hematoxylin and eosin stain.
inflammation with special stains negative for acid-fast bacilli and
fungi (Figure 2). Flow cytometric analysis showed no evidence
of a malignant hematolymphoid process.
From the Department of Family Medicine (George, Graves), and the Division of
Rheumatology, Department of Internal Medicine (Meador), Baylor Medical Center
at Garland, Garland, Texas.
Corresponding author: Jim George, MD, 1009 East Grubb Drive, Mesquite, TX
161
The patient was started on prednisone 40 mg daily and
discharged home. She experienced an initial yet short-lived
improvement in her right groin and lower extremity swelling. Attempts to taper the prednisone dose below 20 mg daily
resulted in worsening right lower leg lymphedema. Multiple
ultrasounds of her right lower extremity were done to rule out
deep venous thrombosis, all of which were negative.
A repeat CT scan of her chest, abdomen, and pelvis 5
months after her initial diagnosis suggested progressive sarcoidosis with increasing pelvic and inguinal lymphadenopathy, new
low-density areas within the spleen, and multiple subcentimeter
scattered pulmonary nodules. One month later, she died. The
cause of death was not known.
DISCUSSION
Three main mechanisms of sarcoidosis causing asymmetric
peripheral edema have been described. The first is lymphatic
obstruction due to peripheral lymphadenopathy. Our patient’s
edema illustrated this mechanism and, to our knowledge, is
only the sixth case reported to date. Of these cases, four (including ours) were described in black patients, one in an Indian
patient, and one in an Asian patient (1–5). This distribution
is consistent with findings from a US study that demonstrated
that extrathoracic lymph node involvement is more common
in black patients than in white patients (6). The location of
the obstructing lymph nodes was inguinal in three cases and
retroperitoneal in two (1–5). In these cases, systemic steroid
treatment resulted in prompt resolution of the lymphadenopathy and associated edema within 2 months.
A second mechanism by which sarcoidosis can cause peripheral edema is by direct infiltration into surrounding tissues.
Two cases displaying this mechanism have been reported. One
involved a 39-year-old black man (7). He had known sarcoidosis with pulmonary and skin involvement and presented with
asymmetric lower-extremity edema. A CT scan revealed “diffuse,
infiltrative masses involving the subcutaneous tissues of the
right leg” (7). His symptoms abated within 1 month following
162
systemic steroids. A second case involved a 59-year-old woman
with cutaneous nodules, bilateral lower-extremity edema, and
ulceration (8). Her symptoms improved with prednisolone but
recurred when doses were decreased below 15 mg.
A third mechanism is tenosynovitis, producing distal peripheral edema. In one case series, five patients presented with
lower-extremity pitting edema localized to the dorsal foot and
ankle associated with acute sarcoidosis (9). Magnetic resonance
imaging showed extensive tenosynovitis. As with previous cases,
all responded quickly to systemic steroid treatment.
Acknowledgments
The authors thank Paul Bannister, MD, from the Department of Pathology at Baylor Medical Center at Garland, for
providing histology images.
1.
2.
3.
4.
5.
6.
7.
8.
9.
Tomoda F, Oda Y, Takata M, Futamura A, Fujii N, Inoue H, Kitagawa
M. A rare case of sarcoidosis with bilateral leg lymphedema as an initial
symptom. Am J Med Sci 1999;318(6):413–414.
Nathan MP, Pinsker R, Chase PH, Elguezabel A. Sarcoidosis presenting
as lymphedema. Arch Dermatol 1974;109(4):543–544.
Silver HM, Tsangaris NT, Eaton OM. Lymphedema and lymphography
in sarcoidosis. Arch Intern Med 1966;117(5):712–714.
Sweeney T, Ramsby G, Keohane M. Edema of the lower extremities secondary to obstructive sarcoidosis. Angiology 1980;31(1):69–71.
Mahajan VK, Sharma NL, Sharma RC, Sharma VC. Cutaneous sarcoidosis: clinical profile of 23 Indian patients. Indian J Dermatol Venereol Leprol
2007;73(1):16–21.
Baughman RP, Teirstein AS, Judson MA, Rossman MD, Yeager H, Brsnitz
EA. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001;164(10):1885–1889.
Hoover RD Jr, Stricklin G, Curry TW, Carmichael LC. Unilateral lower
extremity edema caused by infiltrative sarcoidosis. J Am Acad Dermatol
1994;30(3):498–500.
Muhlemann MF, Walker NP, Tan LB, Champion RH. Elephantine sarcoidosis presenting as ulcerating lymphoedema. J R Soc Med
1985;78(3):260–261.
Cantini F, Niccoli L, Olivieri I, Barozzi L, Pavlica P, Bozza A, Macchioni
PL, Padula AA, Salvarani C. Remitting distal lower extremity swelling
with pitting oedema in acute sarcoidosis. Ann Rheum Dis 1997;56(9):565–
566.
Volume 26, Number 2
Raghad Abdul-Karim, MD, Caitriona Ryan, MD, Christina Rangel, and Michael Emmett, MD
Levamisole-contaminated cocaine is an increasingly
reported cause of a syndrome characterized by vasculitic skin lesions and immunologic abnormalities. With
approximately 70% of cocaine in the United States now
contaminated with levamisole, the incidence of this syndrome is likely to increase. We report two cases of this
syndrome and review its clinical presentation, course,
and prognosis.
a
b
c
Figure 1. Case 1: (a) leg ulcer, (b) nasal skin necrosis, and (c) ear skin necrosis.
DESCRIPTION
a
b
c
The first patient, an African American
woman, presented with recurrent necrotizing vasculitis of her ears (Figure 1) and was
found to have positive serology for cytoplasmic antineutrophil cytoplasmic antibody,
human neutrophil elastase antibody, and anticardiolipin antibody. The second patient
was an African American woman with widespread necrotizing vasculitis of her ears, nose,
cheeks, and about 30% of her body surface area
(Figure 2). She also had necrotizing pneumonia. Figure 2. Case 2: (a) ear necrosis, (b) facial scar, and (c) leg scars and bullae formation.
Serologic findings were similar to those of the
first case. She did not improve despite maximum
human market in 1999 because of serious side effects including
supportive management and died. The Table shows the major
leukopenia, agranulocytosis, and skin vasculitis (2). It is still
laboratory and clinical features of the cases.
available as a veterinarian deworming drug.
Relevant to this manuscript, levamisole has also been recogDISCUSSION
nized as an adulterant in illicit cocaine since 2003 (3). A 2009
Levamisole-induced vasculitis was first described in the
national survey found that approximately 70% of cocaine in the
1970s. This syndrome produces a characteristic clinical presUSA is contaminated with levamisole (2, 3). Levamisole is added
entation of vasculitis in association with a variable pattern of
to cocaine because it potentiates its stimulant effects by inhibitimmunologic disturbances. In a case series of five children treating both monoamine oxidase and catechol-O-methyltransferase
ed with levamisole for nephrotic syndrome, all five developed
activity, thereby prolonging the action of catecholamines in
necrosis of their ears, with variable involvement of their cheeks
the neuronal synapse and increasing the reuptake-inhibition
and extremities (1). Levamisole was originally marketed as an
anthelmintic agent but was also found to have major immunomodulatory properties. It induced interferon synthesis and
From the Department of Internal Medicine, Baylor University Medical Center at
synergized the effect of steroids and other immunosuppressants.
Dallas (Abdul-Karim, Ryan, Emmett); and the University of Texas Southwestern
It was used in cancer therapy, to treat various immunological
Medical School, Dallas (Rangel).
renal diseases, and to treat a number of skin diseases, including
Corresponding author: Raghad Abdul-Karim, MD (e-mail: raghadkareem@
Behçet’s disease. However, the drug was withdrawn from the
yahoo.com).
163
involves the ears, but purpura can also be observed on the nose, cheeks, extremities, and
diffusely. Cutaneous lesions tend to be stellate
Variable
Case 1
Case 2
with a bright erythematous border and necrotic
Age (years)
40
50
center. This lesion usually resolves spontaneously
Race
African American
African American
within a few weeks of drug discontinuation and
Urine cocaine screen
Positive
Positive
recurs with subsequent contaminated cocaine
abuse.
ESR (mm/hr)
52
40
The half-life of levamisole is 5.6 hours, and
CRP (mg/dL)
4.5
13.8
only
3% to 5% of the drug is found in urine
Serum levamisole
Negative
Not checked
within 48 hours of last use. Leukopenia can
Antinuclear antibody titer
1:12,560
1:640
occur in 50% to 60% of cases (3) and can first
Antineutrophil cytoplasmic
p-ANCA, 1:2,560
p-ANCA, 1:10,240
develop after as long as 12 months of continuous
antibody (indirect immunoc-ANCA, negative
c-ANCA, 1:320
use (5). Agranulocytosis has also been reported
fluorescence)
in patients with cocaine/levamisole abuse (6).
Anti-HNE, positive
Antibodies against neutrophil Anti-HNE, positive
The syndrome has a very interesting spectrum
cytoplasmic antigens (ELISA
Anti-PR3, positive
Anti-PR3, positive
of autoantibody findings. High-titer perinuclear
capture)
Anti-MPO, positive
Anti-MPO, negative
antineutrophil antibodies (p-ANCA) are almost
IgM anticardiolipin antibody
21.4
14.4
always found (86%–100%), and about 50% of
(normal 0.0–12.4 U/mL)
the cases also have cytoplasmic antineutrophil
Extensive black discolorSkin findings
Markedly tender, black
antibodies (c-ANCA) (4–10). However, the speation and necrosis of the
discoloration and necrosis
cific antigens responsible for generating these
ears, eyelashes, forehead,
of the helices and antihepositive ANCA fluorescent patterns are not yet
and bilateral cheeks; digital
lices of both ears; a large,
clearly defined. Antibodies against proteinase-3
necrosis of both hands and
necrotic, indurated, inflam(anti-PR3), the autoantibody most commonly
feet; rapidly progressive areas
matory plaque on her nose;
associated with a c-ANCA pattern, are present
a 5.0-cm-diameter punched- of epidermal detachment,
in about 50% of these patients, while antibodnecrosis, and bulla formation
out ulcer on her left lateral
of the trunk and upper and
shin; an indurated livedoid
ies against myeloperoxidase (anti-MPO), the
plaque on her left upper arm; lower limbs
antibody most often responsible for a p-ANCA
nailfold infarcts
pattern, are found in almost every case (3, 10).
Skin biopsy
Gangrenous necrosis with
Leukocytoclastic vasculitis
In addition, antiphospholipid antibodies and
acute inflammation and
with fibrinoid necrosis of the
antinuclear antibodies are also often present. The
fibrosis
blood vessel walls and subMayo group has reported another antibody in
epidermal bullae formation
these patients that is directed against human neuTreatment
Short course of high-dose
Mechanical ventilation; steroid
trophil elastase. Anti–human neutrophil elastase
prednisone
tapering induced worsening
(anti-HNE) is also present in most patients with
of her respiratory status and
cocaine-induced midline destructive lesions, but
skin lesions
not in patients with classic ANCA vasculitis (4,
Outcome
Spontaneous resolution of
Deep eschars of the face with
9). Both PR3 and HNE belong to the same family
skin lesions
extensive destruction of nasal
of serine proteases, and cross-reactivity between
and ear cartilages; death after
these antibodies/antigens may occur. These two
60 days in the hospital
cocaine abuse–associated syndromes are distinctly
ESR indicates erythrocyte sedimentation rate; CRP, C-reactive protein; c-ANCA, cytoplasmic antineutrophil
cytoplasmic antibody; p-ANCA, perinuclear antineutrophil cytoplasmic antibody; anti-PR3, anti-proteinase
different. Cocaine-induced midline destructive
3 antibody; anti-MPO, anti-myeloperoxidase antibody; ELISA, enzyme-linked immunosorbent assay.
lesions may be caused by the cocaine itself and
do not generate the distinctive skin involvement
that occurs with the levamisole-related condition
effect of cocaine. Levamisole metabolites also have a stimulatory
(11). Conversely, the levamisole-related vasculitis does not usually
effect. Very importantly, levamisole reacts as cocaine in the
cause destructive damage to the nose, sinuses, and palate.
“bleach test,” a quick, widely utilized street test for cocaine
The histology of cutaneous lesions typically shows thrompurity. Therefore, it adds bulk to illicit cocaine without reducing
botic vasculitis or leukocytoclastic vasculitis with or without
the native drug’s apparent purity, as occurs with other bulking
vascular occlusion (2–4). The natural history of levamisoleagents such as sugar or lidocaine (2). Both snorting and smoking
induced vasculitis is spontaneous resolution without treatment
levamisole-contaminated cocaine have been associated with the
when the levamisole is withdrawn. Immunologic abnormalities
vasculitic syndrome (4).
generally resolve within 2 to 14 months of withdrawal of the
Levamisole-induced syndrome has a characteristic presenlevamisole (2). However, some severe cases may not improve, as
tation (2, 4). The distinctive vasculopathic purpura typically
in our second patient, who had a fulminant form of vasculitis
Table. Characteristics of the two cases of levamisole-induced vasculitis
164
Volume 26, Number 2
and a fatal outcome. Although steroids have been used for treatment of this syndrome, it is unclear if they provide any benefit.
The side effects may be harmful, especially since most reported
cases had no internal organ involvement (3, 4).
1.
2.
3.
4.
5.
Rongioletti F, Ghio L, Ginevri F, Bleidl D, Rinaldi S, Edefonti A, Gambini
C, Rizzoni G, Rebora A. Purpura of the ears: a distinctive vasculopathy
with circulating autoantibodies complicating long-term treatment with
levamisole in children. Br J Dermatol 1999;140(5):948–951.
Chang A, Osterloh J, Thomas J. Levamisole: a dangerous new cocaine
adulterant. Clin Pharmacol Ther 2010;88(3):408–411.
Gross RL, Brucker J, Bahce-Altuntas A, Abadi MA, Lipoff J, Kotlyar D,
Barland P, Putterman C. A novel cutaneous vasculitis syndrome induced by levamisole-contaminated cocaine. Clin Rheumatol 2011;30(10):1385–1392.
Trimarchi M, Gregorini G, Facchetti F, Morassi ML, Manfredini C,
Maroldi R, Nicolai P, Russell KA, McDonald TJ, Specks U. Cocaine-induced midline destructive lesions: clinical, radiographic, histopathologic,
and serologic features and their differentiation from Wegener granulomatosis. Medicine (Baltimore) 2001;80(6):391–404.
Chung C, Tumeh PC, Birnbaum R, Tan BH, Sharp L, McCoy E,
Mercurio MG, Craft N. Characteristic purpura of the ears, vasculitis, and
neutropenia—a potential public health epidemic associated with levamisole-adulterated cocaine. J Am Acad Dermatol 2011;65(4):722–725.
6. Buchanan JA, Oyer RJ, Patel NR, Jacquet GA, Bornikova L, Thienelt
C, Shriver DA, Shockley LW, Wilson ML, Hurlbut KM, Lavonas EJ. A
confirmed case of agranulocytosis after use of cocaine contaminated with
levamisole. J Med Toxicol 2010;6(2):160–164.
7. Gross RL, Brucker J, Bahce-Altuntas A, Abadi MA, Lipoff J, Kotlyar D,
Barland P, Putterman C. A novel cutaneous vasculitis syndrome induced
by levamisole-contaminated cocaine. Clin Rheumatol 2011;30(10):1385–
1392.
8. Bhinder SK, Majithia V. Cocaine use and its rheumatic manifestations:
a case report and discussion. Clin Rheumatol 2007;26(7):1192–1194.
9. Wiesner O, Russell KA, Lee AS, Jenne DE, Trimarchi M, Gregorini G,
Specks U. Antineutrophil cytoplasmic antibodies reacting with human
neutrophil elastase as a diagnostic marker for cocaine-induced midline
destructive lesions but not autoimmune vasculitis. Arthritis Rheum
2004;50(9):2954–2965.
10. McGrath MM, Isakova T, Rennke HG, Mottola AM, Laliberte KA, Niles
JL. Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease. Clin J Am Soc Nephrol 2011;6(12):2799–2805.
11. Specks U. The growing complexity of the pathology associated with cocaine use. J Clin Rheumatol 2011;7(4):167–168.
Avocations
“Medusa of the Sea” by Jay Hoppenstein, MD. Dr. Hoppenstein (e-mail: [email protected]) is a surgeon who was on the medical staff at Baylor University Medical
Center at Dallas from 1971 until his retirement in 2005. He also served as chairman of the Department of Surgery at Presbyterian Hospital of Dallas.
April 2013
165
Alexander Michael Mantas, MD, Jennifer Wells, MD, and James Trotter, MD
Here we describe a case of a 22-year-old woman who presented with
acute liver failure and Kayser-Fleischer rings suggesting the diagnosis
of Wilson’s disease.
A
22-year-old woman with no known past medical history
presented to an emergency department with a 3-week
history of fatigue, decreased appetite, and jaundice. Her
initial laboratory workup indicated acute liver injury
with a total bilirubin level of 12.1 mg/dL (reference range, 0.2–
1.0); alkaline phosphatase of 45 U/L (reference range, 50–136);
aspartate aminotransferase of 111 U/L (reference range, 15–37);
alanine aminotransferase of 27 U/L (reference range, 12–78);
ceruloplasmin of 19 mg/dL (reference range, 20–60); and prothrombin time of 29.11 seconds (reference range, 9.0–12.0).
Additionally, she was found to have concurrent acute kidney
injury and a Coombs-negative hemolytic anemia.
The patient underwent a laparoscopic cholecystectomy at
an outside hospital that revealed the presence of ascites and a
nodular liver with an otherwise normal gallbladder. The patient
quickly decompensated into acute liver failure during her postoperative course, and physical examination revealed the presence
of Kayser-Fleischer (KF) rings (Figure).
The presence of KF rings and jaundice with abnormal liver
function tests, including low ceruloplasmin and alkaline phosphatase, suggested the diagnosis of Wilson’s disease. The patient
was transferred to Baylor University Medical Center at Dallas,
where she underwent evaluation for orthotopic liver transplantation, which was successfully performed on hospital day 4.
Elevated hepatic copper (2145 mcg/g; reference range, 10–35)
on dry weight liver biopsy was consistent with the diagnosis of
Wilson’s disease. Mutation analysis indicated that the patient
was homozygous for the pathogenic mutation 3201 C>A in
exon 14, resulting in the amino acid change His1069Gln.
DISCUSSION
Wilson’s disease is an autosomal recessive mutation of
the ATP7B gene, whose protein both traffics excess copper
into the bile canaliculus for excretion and binds copper to
apoceruloplasmin, forming holoceruloplasmin. Oxidative
damage ensues when uncomplexed copper begins to accumulate in hepatocytes. Liver injury can present in various
forms ranging from asymptomatic abnormal liver function
tests to acute and chronic liver failure. With ongoing hepatic
damage, uncomplexed copper is released from the liver and
deposited in other organs, including the lenticular nucleus of
the basal ganglia, resulting in Parkinson-like symptoms; the
proximal renal tubule, resulting in Fanconi’s syndrome; and
the red blood cells, resulting in a Coombs-negative hemolytic
anemia. Other organs affected include the heart, pancreas,
Figure. Kayser-Fleischer ring in a patient with acute liver failure from Wilson’s
disease.
166
From the Division of Gastroenterology, Department of Internal Medicine (Mantas),
and the Department of Transplant Hepatology (Wells, Trotter), Baylor University
Medical Center at Dallas.
Corresponding author: Alexander Michael Mantas, MD, Baylor University
Medical Center at Dallas, 3600 Gaston Avenue, Wadley Tower, Suite 260, Dallas,
TX 75246 (e-mail: [email protected]).
parathyroid gland, and bone. The eye is uniquely affected, as
copper accumulates in Descemet’s membrane of the corneal
limbus, resulting in KF rings (Figure), and in the lens, resulting
in sunflower cataracts. The observation of the characteristic
brown-gold-yellow KF ring at the margin of the cornea and
sclera generally requires a slit-lamp examination, but some
rings can be seen under normal light. Each of these ocular
findings resolves over time following transplant (1, 2).
1.
2.
Cox DW, Roberts EA. Wilson disease. In Feldman M, Friedman LS,
Brandt LJ, eds. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease,
9th ed. Philadelphia: Elsevier Saunders, 2010:1249–1258.
Schilsky ML, Tavill AS. Wilson disease. In Schiff ER, Maddrey WC,
Sorrell MF, eds. Schiff’s Diseases of the Liver, 11th ed. Hoboken, NJ: WileyBlackwell, 2011:805–824.
Avocations
A Chihuly exhibit, Dallas Arboretum, © Amanullah Khan, MD, PhD. Dr. Khan (e-mail: [email protected]) is an oncologist on the medical staff of Baylor Medical
Center at McKinney.
April 2013
167
Ascites with elevated protein content as the presenting sign
of constrictive pericardial disease
Betsy Ann George, MD, Gregory dePrisco, MD, James Ford Trotter, MD, Albert Carl Henry III, MD,
and Robert Craig Stoler, MD
Two men, one 63 and one 52 years old, presented with ascites. Analysis
of the ascitic fluid in both patients revealed a high protein content and
an elevated serum-ascites gradient. Various studies showed the cause
of the ascites to be constrictive pericardial disease. Total excision of their
parietal pericardia relieved their symptoms, decreased their cardiac filling
pressures, and increased their cardiac indices. These cases highlight
the importance of suspecting pericardial constriction as an etiology for
high-protein-count ascites.
W
e describe two patients who presented with highprotein-count ascites as the initial sign of constrictive pericardial disease. These cases highlight the
importance of early recognition of a cardiac etiology
for ascites, as prompt treatment with a total pericardiectomy
significantly improved the patients’ quality of life.
DESCRIPTION OF CASES
Pertinent clinical features in each of the two patients prior
to surgery are summarized in Table 1. The two patients had
evidence of ascites for 6 and 60 months, respectively. Both
received multiple therapeutic paracenteses and escalating doses
of diuretics for refractory ascites. The first patient had no attributable hepatic cause for his ascites, but the second had a history
of heavy alcohol use prior to its cessation at age 47. Despite
receiving a Denver shunt, the second patient continued to
have intractable ascites so was referred for possible transjugular
intrahepatic portosystemic shunt and liver transplantation. Both
patients had no previous cardiothoracic surgery, pericarditis,
radiation treatment, or collagen vascular diseases. Neither
patient had cardiopulmonary symptoms. Physical examination
in these patients revealed normal blood pressure and heart rate,
distended jugular veins, clear lungs, and no precordial murmurs
or abnormal heart sounds. Their abdomens had clear evidence
of ascites. Laboratory tests in the first patient were normal.
The second patient had renal insufficiency and mildly elevated
bilirubin. Analysis of their ascitic fluid revealed an elevated total
protein content and a high serum-ascites albumin gradient.
The patients were then referred to cardiology for evaluation
of a cardiac cause of the ascites. Transthoracic echocardiograms
in both patients revealed a bright, thickened parietal pericar168
Table 1. Pertinent features of the two men prior to pericardiectomy
Variable
Case 1
Case 2
Age (years)
63
52
Age of onset of ascites (years)
Previous hepatitis or alcohol use
62
0
47
+
Serum creatinine (mg/dL)
1.3
1.8
International normalized ratio
1.0
1.1
Total bilirubin (mg/dL)
0.4
1.8
Aspartate aminotransferase (U/L)
17
19
Alanine aminotransferase (U/L)
15
8
Alkaline phosphatase (U/L)
100
169
Ascitic fluid total protein (g/dL)
4.2
4.6
Serum-ascites albumin gradient (g/dL)
1.6
1.7
dium, “septal bounce,” exaggerated respiratory variation across
the tricuspid and mitral valves, a dilated inferior vena cava,
expiratory hepatic vein diastolic flow reversal, normal tissue
Doppler velocities, and no pericardial effusion (Figure 1).
Cardiac catheterization pressure waveforms in each showed
equalization of the elevated diastolic pressures and discordance
of right and left ventricular systolic pressures (Figure 2). Cardiac
magnetic resonance imaging scans disclosed marked thickening
of the parietal pericardium (Figure 3).
Both patients underwent total excision of their parietal pericardia with resolution of their ascites and elevated cardiac filling
pressures. Hemodynamics before and after pericardiectomy are
shown in Table 2. The parietal pericardium in each was severely
thickened by dense fibrous tissue (Figure 4).
From the Department of Internal Medicine, Division of Cardiology (George, Stoler)
and Division of Hepatology (Trotter), the Department of Radiology (dePrisco), and
the Department of Cardiothoracic Surgery (Henry), Baylor University Medical
Center at Dallas.
Corresponding author: Betsy Ann George, MD, Baylor Heart and Vascular
Institute, 621 N. Hall Street, #H030, Dallas, TX 75226-1312 (e-mail: Betsy.
[email protected]).
a
b
c
d
Figure 1. Case 1. Transthoracic echocardiogram. (a) Apical view of bright, thickened parietal pericardium (arrows). (b) Doppler analysis showing exaggerated variation of tricuspid valve blood flow
with respiration. (c) Hepatic vein diastolic flow reversal during expiration (arrows). (d) Normal Doppler
tissue velocities at the lateral mitral annulus.
Figure 2. Case 1. Simultaneous right ventricular (RV) and left ventricular (LV) cardiac catheterization
pressure waveform tracings demonstrating equalization of diastolic pressures (arrow) and discordance
of systolic pressures. The arrow also depicts the square root sign or dip and plateau sign—a finding
due to diastolic pressures rising abruptly to a level that is sustained until systole because of the
restricted filling from the pericardium.
DISCUSSION
Constrictive pericardial disease is a rare cause of recurrent ascites. Both of our patients had high-protein-count ascites with an
elevated serum-ascites albumin gradient, a finding well described
in previous reports of constrictive pericarditis (1–3). A serumascites albumin gradient ≥1.1 g/dL and an ascites fluid total
protein >2.5 g/dL is typical of constrictive pericardial disease and
other postsinusoidal causes of ascites. Sinusoidal diseases, such
April 2013
as liver cirrhosis, exhibit a serum-ascites albumin
gradient >1.1 g/dL but an ascites fluid total protein
<2.5 g/dL (1).
A common finding in our cases was jugular
venous distention, a sign not usually seen in patients with hepatic cirrhosis. Previous case series
indicate that about 80% of patients with constrictive pericardial disease present with elevated
jugular venous pressures. Neither of our patients
had dyspnea or orthopnea. As many as half of
the patients who undergo a pericardiectomy
lack cardiopulmonary symptoms (4). Therefore,
a high index of suspicion is required to diagnose
this entity, especially in patients with elevatedprotein-count ascites, jugular venous distention,
and no cardiopulmonary symptoms.
The echocardiograms in our two patients were
quite specific for constrictive pericardial disease.
However, a transthoracic echocardiogram typically has low sensitivity in detection of this entity, and a constrictive pericardium may easily be
overlooked. Thus, a physician should not be reassured with a negative echocardiogram if there is a
high concern for this disease. Constrictive disease
differs from restrictive disease by having normal
tissue Doppler velocities on echocardiogram and
discordance of right and left ventricular systolic
pressures on cardiac catheterization.
Constrictive pericardial disease can lead to
significant morbidity. Both patients suffered from
the sequelae of ascites with repeated therapeutic
paracenteses and escalating doses of diuretics before the proper diagnosis was made.
Pericardiectomy is the treatment of choice for
patients with symptomatic chronic constrictive
pericardial disease. The early hospital mortality
is about 7% (5). The most common cause of
death in the perioperative period is low-output
heart failure (6). The long-term survival curves
after pericardiectomy differ according to the
etiology of the constrictive pericarditis and the
type of surgery. Idiopathic/viral and postsurgical
constrictive pericardial disease have the best 10year survival rates after pericardiectomy of about
67% and 56%, respectively, while postradiation
pericarditis has the worst at 11% (5). Also, total
pericardiectomy has a better survival rate than
partial pericardiectomy (7).
Acknowledgments
We gratefully acknowledge William Clifford Roberts, MD,
for editorial assistance with the report and Jong Mi Ko, BA, for
the photography of the surgical specimens.
1.
Howard JP, Jones D, Mills P, Marley R, Wragg A. Recurrent ascites due
to constrictive pericarditis. Frontline Gastroenterol 2012;3(4):233–237.
Ascites with elevated protein content as the presenting sign of constrictive pericardial disease
169
a
b
Figure 4. Necropsy specimens contrasting (a) abnormal thickened parietal
pericardium in Case 2 constrictive disease with (b) normal, thin parietal pericardium.
Figure 3. Case 2. A magnetic resonance imaging scan showing marked asymmetric pericardial thickening preferentially over the right ventricle (arrows) and
gynecomastia in this patient with cirrhosis (ovals).
Van der Merwe S, Dens J, Daenen W, Desmet V, Fevery J. Pericardial
disease is often not recognised as a cause of chronic severe ascites. J Hepatol
2000;32(1):164–169.
3. Runyon BA, Montano AA, Akriviadis EA, Antillon
MR, Irving MA, McHutchison JG. The serum-ascites
albumin gradient is superior to the exudate-transudate
Table 2. Hemodynamics before and after pericardiectomy
concept in the differential diagnosis of ascites. Ann Intern Med 1992;117(3):215–220.
Case 1
Case 2
4. Wood P. Chronic constrictive pericarditis. Am J Cardiol
1961;7(1):48–61.
Measurement
Preop
Postop
Preop
Postop
5. George TJ, Arnaoutakis GJ, Beaty CA, Kilic A,
Baumgartner WA, Conte JV. Contemporary etiologies,
19
–
19
–
Mean right atrial pressure (mm Hg)
risk factors, and outcomes after pericardiectomy. Ann
Thorac Surg 2012;94(2):445–451.
Right ventricular pressure (mm Hg)
35/19
–
28/15
–
6. Bertog SC, Thambidorai SK, Parakh K, Schoenhagen P,
Pulmonary artery pressure (mm Hg)
38/18
–
41/19
–
Ozduran V, Houghtaling PL, Lytle BW, Blackstone EH,
Lauer MS, Klein AL. Constrictive pericarditis: etiology
Pulmonary capillary wedge pressure (mm Hg)
19
–
20
–
and cause-specific survival after pericardiectomy. J Am
Coll Cardiol 2004;43(8):1445–1452.
Left ventricular pressure (mm Hg)
111/22
–
95/16
–
7. Chowdhury UK, Subramaniam GK, Kumar AS, Airan
B, Singh R, Talwar S, Seth S, Mishra PK, Pradeep KK,
Central venous pressure (mm Hg)
19
3*
27
13*
Sathia S, Venugopal P. Pericardiectomy for constrictive
2.1
3.9*
1.2
2.8*
Cardiac index (L/min/m2)
pericarditis: a clinical, echocardiographic, and hemodynamic evaluation of two surgical techniques. Ann Thorac
*Intraoperatively.
Surg 2006;81(2):522–529.
170
2.
Volume 26, Number 2
Congenitally bicuspid aortic valve in brothers: coarctation of
the aorta with a normally functioning aortic valve in one and
no coarctation but severe aortic stenosis in the other
Saleha Zafar, MD, and William C. Roberts, MD
Described herein are two brothers, both with a congenitally bicuspid
aortic valve—one of which was stenotic and one of which functioned
normally—and one with associated aortic isthmic coarctation.
Summarized also are previously reported families with more than one
member with a congenitally bicuspid aortic valve.
T
he occurrence of a congenitally bicuspid aortic valve
(BAV) in more than one family member has been described in several published reports (1–7). Of the 47
family members in whom the BAV was confirmed at
the time of aortic valve replacement or at necropsy, the valve
was stenotic in at least 27 of them, and none had associated aortic isthmic coarctation. In this report we describe
two brothers with a congenitally BAV—stenotic in one and
functionally normal in the other—and aortic coarctation in
one of them (Figure).
PATIENT DESCRIPTIONS
Case 1
A 16-year-old white boy had been well until about a month
before hospitalization when he had an episode of severe dizziness followed by progressive breathlessness. He was hospitalized for “pneumonia” but never had any microorganisms
cultured from sputum. When the chest radiograph cleared,
cardiac catheterization disclosed the following pressures in mm
Hg: pulmonary artery wedge a wave 34, v 32, and mean 32;
pulmonary trunk 55/38; right ventricle 57/29; left ventricle
133/36 and aorta 77/66, yielding a peak systolic pressure gradient of 56 mm Hg; and mean systolic gradient 39 mm Hg.
The calculated aortic valve area was 0.6 cm2, and the cardiac
output was 4.6 L/min/m2. A cardiac operation was performed,
and he died 2 weeks later.
Case 2
This 21-year-old white man had been well until he was
found dead in the bathroom at home, shortly after taking an
amphetamine. He apparently never had evidence of cardiac
dysfunction. Necropsy disclosed the pericardial sac to be filled
with blood (550 mL). The ascending aorta had a 5-cm long tear
without dissection with a through-and-through perforation.
Figure 1. Diagram showing the cardiovascular features of each of the two patients. Both had congenitally bicuspid aortic valves. In case 1, the valve was
severely stenotic, and there was no coarctation of the aorta. In case 2, the valve
functioned normally, and there was a severe coarctation of the aorta. A indicates
anterior aortic valve cusp; I, innominate artery; L, left; LCC, left common carotid;
LMCA, left main coronary artery; LS, left subclavian; P, posterior aortic valve cusp;
R, right aortic valve cusp; RCA, right coronary artery.
The ascending aorta was quite dilated. At the aortic isthmus
(that portion of aorta just distal to the origin of the left subclavian artery), a severe coarctation was found. The aortic valve
was congenitally bicuspid but the cusps were very pliable and
noncalcified. Thus, the aortic valve function was considered to
have been normal. A fibrous, nonstenotic ring was located in
the left ventricular outflow tract about 1 cm below the base of
the aortic valve cusps. The mitral valve was normal. The left
main coronary artery ostium was located about 1 cm cephalad
to the sinotubular junction.
From the Baylor Heart and Vascular Institute (Zafar, Roberts) and the Departments
of Internal Medicine (Division of Cardiology) and Pathology (Roberts), Baylor
Institute, 621 North Hall Street, Dallas, TX 75226 (e-mail: wc.roberts@
BaylorHealth.edu).
171
Table. Previously published reports of patients with a familial congenitally bicuspid aortic valve
with aortic valve replacement or necropsy
Family
Case
number
McKusick
I
1
44
46
2
–
19
Son
+
–
–
Gale
I
3
38
–
Brother
–
+
–
4
44
–
Brother
+
+
–
6
–
62
Uncle
–
+
–
7
–
–
Mother
–
–
–
8
20
–
Son
–
–
–
9
–
–
Mother
–
–
–
10
41
–
Son
–
+
–
11
–
–
Mother
–
–
–
12
–
–
Son
–
+
–
13
–
–
Niece
+
+
–
14
–
–
Nephew
–
+
–
15
–
68
Grandfather
–
+
–
16
–
–
Mother
–
–
–
17
16
–
Son
–
+
–
18
93
–
Mother
–
+
–
19
–
–
Son
–
–
–
20
–
97
Mother
–
+
–
21
–
–
Son
–
–
–
Year of
publication
First
author
1972
1977
1978
Emanuel*
I
II
III
IV
V
VI
1987
1989
1994
Bicuspid aortic valve
Patient
age (yrs)
at AVR
Godden
McDonald
Glick
I
I
I
II
III
IV
V
VI
Patient
age (yrs)
at death
Patient
relation
AR
AS
Functionally
normal
Father
+
–
–
22
57
–
Brother
–
+
–
23
57
61
Brother
+
+
–
24
–
19
Brother
–
+
–
25
23
–
Brother
–
+
–
26
26
–
Brother
+
+
–
27
58
58
Father
0
+
–
28
–
–
Daughter
+
0
–
29
44
58
Father
+
+
–
30
26
26
Son
+
0
–
31
53
60
Sister
–
+
–
32
72
–
Brother
+
+
–
33
–
70
Sister
–
+
–
34
21
–
Brother
+
0
–
35
26
26
Brother
+
0
–
36
–
–
Sister
–
–
–
37
–
–
Sister
–
–
–
38
–
–
Brother
–
–
–
39
70
80
Brother
–
+
–
40
69
73
Brother
–
+
–
41
78
–
Mother
–
+
–
continues
172
Volume 26, Number 2
Table. Continued.
Year of
publication
1996
First
author
Clementi
Family
I
II
Patient
age (yrs)
at death
Bicuspid aortic valve
Case
number
Patient
age (yrs)
at AVR
42
65
–
Daughter
–
+
–
43
–
–
Daughter
–
+
–
44
–
47
Brother
–
+
–
45
42
–
Brother
+
–
–
46
–
–
Sister
+
–
–
46
–
–
Mother
+
–
–
47
–
–
Son
+
0
+
Patient
relation
AR
AS
Functionally
normal
*The bicuspid nature of the aortic valve was “surgically proven” in all patients listed here.
AR indicates aortic regurgitation; AS, aortic stenosis; AVR, aortic valve replacement; –, no information or not applicable.
DISCUSSION
The Table lists previously published reports (1–7) describing a BAV in more than one family member with study of the
valve at either aortic valve replacement or at necropsy. In the
18 families, 47 members had a congenitally BAV: 11 families
had 2 members, 5 families had 3 members, and 2 families had 5
members with a BAV. Of the involved family members, 3 were
fathers, 8 were mothers, 20 were sons, 8 were daughters, and
the remaining were siblings or other relatives. Of the 47 family members, 30 (64%) were male and 17 (36%) were female.
Twenty-three family members had aortic valve replacement;
their ages ranged from 16 to 93 years (mean 47). Sixteen family
members had died, 9 after aortic valve replacement. In the 18
families, all with BAVs were male in 3 families, all were female
in 1 family, and both males and females were represented in
14 families.
In addition to the studies where the bicuspid structure of
the aortic valve was confirmed morphologically, an echocardiographic study (8) described 11 families in whom 28 members
April 2013
had a BAV, 3 (11%) of whom had associated coarctation of
the aorta.
1.
2.
3.
4.
5.
6.
7.
8.
McKusick VA. Association of congenital bicuspid aortic valve and Erdheim’s cystic medial necrosis. Lancet 1972;1(7758):1026–1027.
Gale AN, McKusick VA, Hutchins GM, Gott VL. Familial congenital
bicuspid aortic valve: secondary calcific aortic stenosis and aortic aneurysm. Chest 1977;72(5):668–670.
Emanuel R, Withers R, O’Brien K, Ross P, Feizi O. Congenitally bicuspid aortic valves. Clinicogenetic study of 41 families. Br Heart J
1978;40(12):1402–1407.
Godden DJ, Sandhu PS, Kerr F. Stenosed bicuspid aortic valves in twins.
Eur Heart J 1987;8(3):316–318.
McDonald K, Maurer BJ. Familial aortic valve disease: evidence for a
genetic influence? Eur Heart J 1989;10(7):676–677.
Glick BN, Roberts WC. Congenitally bicuspid aortic valve in multiple
family members. Am J Cardiol 1994;73(5):400–404.
Clementi M, Notari L, Borghi A, Tenconi R. Familial congenital bicuspid aortic valve: a disorder of uncertain inheritance. Am J Med Genet
1996;62(4):336–338.
Huntington K, Hunter AG, Chan KL. A prospective study to assess the
frequency of familial clustering of congenital bicuspid aortic valve. J Am
Coll Cardiol 1997;30(7):1809–1812.
Congenitally bicuspid aortic valve in brothers
173
Electrocardiographic Report
A 21-year-old pregnant woman with congenital heart
disease
D. Luke Glancy, MD
Figure 1. Admission electrocardiogram. See text for explication.
A
21-year-old woman was transferred from another hospital in her 23rd week of pregnancy. She had had an
audible precordial murmur the day of her birth and
had had pneumonia three times in the first few years
of life. Otherwise, she was asymptomatic during childhood
and adolescence. Aside from being small (4′11″ tall and 85
lbs before becoming pregnant), she had developed normally.
When she was transferred, she was asymptomatic and on no
medication.
Pertinent physical findings were a regular pulse at 96 beats/
min; a blood pressure of 116/60 mm Hg; normal neck veins;
brisk, full, symmetrical arterial pulses in the arms and legs with
no radial-femoral delay; a loud and palpable second heart sound
along the upper and mid left sternal border; and a small apical
impulse just outside the left mid-clavicular line. A harsh, grade
4/6, systolic ejection murmur, heard over the entire chest and
back and in the neck, was loudest at the cardiac base and of
174
equal intensity on the right and left sides. A decrescendo diastolic murmur was maximal in the third left intercostal space.
There was no gallop, ejection click, cyanosis, or clubbing.
The admission electrocardiogram showed normal sinus
rhythm, left axis deviation of the QRS complex, and no septal Q waves in leads I, aVL, V5, or V6, but Q waves were
present in leads II, III, aVF, and V1 (Figure 1). The history,
physical examination, chest radiograph (Figure 2), and electrocardiogram provided some, albeit incomplete, insight into
the patient’s congenital cardiac malformations and the consequent pathophysiology. A systolic murmur heard the day
From the Sections of Cardiology, Departments of Medicine, Louisiana State
University Health Sciences Center and the Interim Louisiana State University
Public Hospital, New Orleans.
Corresponding author: D. Luke Glancy, MD, 7300 Lakeshore Drive, #30, New
Orleans, LA 70124 (e-mail: [email protected]).
Figure 2. Admission posterior-anterior chest radiograph. The proximal right and
left pulmonary arteries are at the same level. A hump is seen on the left cardiac
border, and the ascending aorta is seen on the left side of the cardiac base rather
than the right. The right border of the descending aorta can be seen to cross the
spine obliquely from right to left and arrive in its usual location at the level of the
diaphragm. These are features suggesting congenitally corrected transposition of
the great arteries. In addition, the dilated pulmonary arteries suggest poststenotic
dilation and/or increased pulmonary arterial pressure/flow.
of birth suggested right or left ventricular outflow obstruction; it would have taken several days for pulmonary vascular
resistance to fall sufficiently for the murmur of a ventricular
septal defect to be heard. The patient’s brisk pulses excluded
aortic stenosis, so the outflow tract obstruction had to be right
ventricular. Frequent bouts of pneumonia in infancy suggested
a sizable left-to-right shunt, a supposition supported by the
large pulmonary arteries and pulmonary plethora noted on
chest radiograph (Figure 2). The absence of septal Q waves in
leads I, aVL, V5, and V6 and their presence in leads V1, II, III,
and aVF suggested ventricular inversion, an integral feature
of congenitally corrected transposition of the great arteries,
a diagnosis also brought to mind by the chest radiograph
(Figure 2) (1). The anterior position of the aortic valve in
that condition would have produced the loud and palpable
second heart sound.
In congenitally corrected transposition of the great arteries, there are discordant atrioventricular and ventriculo-arterial
connections. The right atrium receives blood from the two vena
cavas and sends it across a mitral valve into a morphologic left
ventricle that pumps it across a pulmonic valve, which is in
fibrous continuity with the mitral valve, and into the pulmonary
artery. Pulmonary venous blood travels through the left atrium
and across a tricuspid valve into a morphologic right ventricle
that pumps the blood across the infundibulum and the aortic
valve into the aorta. Thus, ventriculoarterial discordance “corrects” the atrioventricular discordance, and the path of the blood
through the heart is normal if there are no other malformations
(2). Such patients have lived into their 70s (3). Whether the
morphologic right ventricle, i.e., the systemic ventricle, in a
patient with isolated congenitally corrected transposition of the
great arteries functions as long and as well as a morphologic left
April 2013
ventricle does in a normal person has been affirmed by some
experts (4) and denied by others (5).
The vast majority of patients with congenitally corrected
transposition of the great arteries, however, have associated cardiac malformations. Three of these occur frequently enough to
be considered part of the anomaly: ventricular septal defect in
approximately two thirds of patients (2); left ventricular (pulmonary ventricular) outflow tract obstruction, which can be
valvular and/or subvalvular, in one half (1); and anatomic abnormalities of the tricuspid (systemic atrioventricular) valve in
90%, many of which are not clinically significant and the most
common of which is Ebstein’s anomaly (2). Other malformations seen in patients with congenitally corrected transposition of the great arteries include atrial septal defect; subaortic
obstruction, which is often associated with coarctation of the
aorta; aortic valve atresia with hypoplasia of the morphologic
right ventricle; and pulmonary atresia with hypoplasia of the
morphologic left ventricle.
Because of malalignment of the atrial septum with the inlet
ventricular septum, the atrioventricular conduction system is
abnormal (2), and up to 75% of patients with congenitally
corrected transposition of the great arteries eventually have
atrioventricular block ranging from first degree to third degree
(1). Wolff-Parkinson-White type ventricular preexcitation may
occur, as it does in other persons with Ebstein’s anomaly of the
tricuspid valve, and some, but not all, supraventricular arrhythmias in congenitally corrected transposition of the great arteries
are associated with a left-sided accessory pathway (1). Because
the morphologic left ventricle and the left bundle branch lie
to the right of the morphologic right ventricle in congenitally
corrected transposition of the great arteries, initial septal depolarization is from right to left and often inferosuperiorly as
well, as seen in Figure 1.
As is often the case, especially with congenital heart disease,
the echocardiogram and Doppler examination added important diagnostic information to that obtained by history, physical, chest radiograph, and electrocardiogram. In this patient,
echo-Doppler confirmed congenitally corrected transposition
of the great arteries, a nonrestrictive ventricular septal defect,
and pulmonic valvular and subvalvular stenosis with a 75 mm
Hg peak systolic pressure gradient between the pulmonary ventricle (morphologic left ventricle) and the pulmonary artery.
Because her systemic arterial systolic pressure at the time was
105 mm Hg and the ventricular septal defect was nonrestrictive,
her pulmonary arterial systolic pressure was approximately 30
mm Hg. The echo-Doppler also revealed a restrictive patent
ductus arteriosus, which explained the full, brisk pulses and
the decrescendo diastolic murmur. The systolic component of
the continuous murmur of the patent ductus was obscured by
the louder murmur of pulmonic stenosis. Both ventricles had
normal systolic function, and both atrioventricular valves were
completely competent.
The patient stayed on the obstetrical service throughout the
remainder of her pregnancy. She entered active labor at 34 weeks
of gestation and under epidural anesthesia delivered a 2425 g
daughter with Apgar scores of 8 and 9. Bilateral tubal ligation
175
was then performed. Mother and daughter were doing well at
discharge on postoperative day 4.
Two questions remain. First, why, with such a complex congenital cardiac malformation, was this woman asymptomatic
after the first years of life and able to have a successful pregnancy? It was because the severe malformations were balanced
in such a way that the circulatory system was quite adequate.
Pulmonic stenosis prevented early severe heart failure or subsequent Eisenmenger reaction from the nonrestrictive ventricular
septal defect. At the same time, there was sufficient blood flow
through the pulmonic valve and the restrictive ductus to prevent
cyanosis and allow normal activity and a successful pregnancy.
Thus far she has avoided two common accompaniments of
congenitally corrected transposition of the great arteries, i.e.,
tricuspid (systemic atrioventricular) valvular regurgitation and
atrioventricular block.
Second, should the patient undergo operative repair? An
article from the Mayo Clinic points out that most persons with
congenitally corrected transposition of the great arteries eventually undergo cardiac surgery and that for many, the operation
comes too late for optimal results (6). Those statements are
difficult to refute. On the other hand, in this patient, so-called
complete repair would require extensive complicated surgery,
176
which is difficult to recommend to an asymptomatic patient.
In addition, few institutions have a Gordon Danielson, one of
the paper’s authors and one of the foremost congenital cardiac
surgeons of his or any other day. Most importantly, the patient
prefers not to undergo an operation as long as she feels well.
1.
2.
3.
4.
5.
6.
Perloff JK. The Clinical Recognition of Congenital Heart Disease, 4th ed.
Philadelphia: WB Saunders, 1994:67–90.
Ho SY, Baker EJ, Rigby ML, Anderson RH. Color Atlas of Congenital Heart
Disease: Morphologic and Clinical Correlations. London: Mosby-Wolfe,
1995:145–156.
Lieberson AD, Schumacher RR, Childress RH, Genovese PD. Corrected transposition of the great vessels in a 73-year-old man. Circulation
1969;39(1):96–100.
Benson LN, Burns R, Schwaiger M, Schelbert HR, Lewis AB, Freedom
RM, Olley PM, McLaughlin P, Rowe RD. Radionuclide angiographic
evaluation of ventricular function in isolated congenitally corrected transposition of the great arteries. Am J Cardiol 1986;58(3):319–324.
Graham TPJ Jr, Parrish MD, Boucek RJ Jr, Boerth RC, Breitweser JA,
Thompson S, Robertson RM, Morgan JR, Friesinger GC. Assessment of
ventricular size and function in congenitally corrected transposition of
the great arteries. Am J Cardiol 1983;51(2):244–251.
Beauchesne LM, Warnes CA, Connolly HM, Ammash NM, Tajik AJ,
Danielson GK. Outcome of the unoperated adult who presents with
congenitally corrected transposition of the great arteries. J Am Coll Cardiol
2002;40(2):285–295.
Volume 26, Number 2
Matthew N. Peters, MD, Morgan J. Katz, MD, Lucius A. Howell, MD, John C. Moscona, MD, Thomas A. Turnage, MD, and
Patrice Delafontaine, MD
Figure. Electrocardiogram revealing deeply inverted U waves, most notable in the lateral precordial leads, V3–V5.
Various electrocardiographic changes have been reported in the setting
of acute neurological events, among them large, upright U waves. In
contrast, the occurrence of inverted U waves is strongly suggestive of
cardiovascular disease, most commonly hypertension, coronary artery
disease, or valvular abnormalities. Presented herein is the case of a
29-year-old man with previous anoxic brain injury (but without apparent
cardiovascular disease) whose electrocardiogram demonstrated persistent giant inverted U waves.
CASE PRESENTATION
A 29-year-old Caucasian man with previous anoxic brain
injury presented to our facility with a 3-day history of nausea
and vomiting. According to his mother, he had overdosed on
alprazolam in an apparent suicide at the age of 17 and was in a
coma for several days. During the subsequent year, he had daily
seizures and was started on levetiracetam, eventually becoming
seizure free. Current medications (all of which were administered via percutaneous endoscopic gastrostomy tube) included
twice-daily levetiracetam, daily 20 mg citalopram, and daily
40 mg esomeprazole. Initial vital signs were all within normal
limits. His blood pressure was 100/70 mm Hg. He was nonverbal. Complete blood count, complete metabolic profile, and
thyroid studies were within normal limits. A chest radiograph
revealed no evidence of acute cardiopulmonary processes, and
an abdominal radiograph revealed a nonobstructive bowel gas
pattern. An initial electrocardiogram (ECG) demonstrated deep,
symmetric T wave inversions in the inferior and lateral leads
followed by large negative deflections, of varying amplitude,
most prominent in the lateral precordial leads (Figure). Three
sets of cardiac troponins separated by 6 hours each were <0.05
g/dL. A transthoracic echocardiogram showed a normal left
ventricular ejection fraction, normal intracardiac chamber sizes,
From the Department of Internal Medicine, Tulane University Health Sciences
Center, New Orleans, LA (Peters, Katz, Howell, Moscona, Turnage); and Tulane
University Heart and Vascular Institute, New Orleans, LA (Delafontaine).
Corresponding author: Matthew N. Peters, MD, 1430 Tulane Avenue SL-50,
New Orleans, LA 70112 (e-mail: [email protected]).
177
and no regional wall motion abnormalities. Repeat ECGs over
the subsequent 36 hours revealed a similar pattern. An ECG
when he was 26 years old (9 years following the anoxic brain
injury) appeared almost identical. After 24 hours of intravenous
fluid administration and cessation of tube feedings, the patient
demonstrated marked clinical improvement and 12 hours later
was discharged.
DISCUSSION
The T wave and U wave are thought to represent the terminal component of ventricular repolarization. While the
mechanism of U wave genesis remains uncertain, the clinical
specificity of a negative U wave (defined as any discrete negative deflection >0.05 mV within the T-P segment) for heart
disease is high (1). Occurring in only 1% of all hospital ECGs,
the presence of an inverted U wave suggests the presence of
coronary artery disease, valvular heart disease, or hypertension
(2). Historically, the correlation of negative U waves with acute
myocardial infarction has been felt to be important, given the
ability of negative U waves to precede typical ECG changes of
acute myocardial infarction by several hours (1). When combined with the presence of T wave inversion, a negative U wave
has specificity for coronary artery disease as high as 88% (1). In
the presence of myocardial ischemia, U wave vectors are typically directed away from the akinetic or dyskinetic myocardial
segment (1). It is difficult to assess whether or not U wave vectors would have similar orientation in the presence of ischemia
without wall motion abnormalities because these two entities
usually occur in tandem and subsequent revascularization typically leads to the complete disappearance of inverted U waves
(1). While association with ischemic heart disease has been
regarded as the most clinically important cause of negative U
waves, the most common cause (according to a 1982 study of
488 patients with negative U waves) has been found to be hypertension (39.5%), followed by coronary artery disease (33.2%)
and valvular heart disease (15.4%). Other less common causes
of negative U waves include congenital heart disease (2.5%),
hyperthyroidism (1.4%), primary cardiomyopathy (0.8%), and
in 7.2%, no manifestations of heart disease (2).
178
Association between ECG changes and acute neurological
events is well known, with causes including subarachnoid hemorrhage, subdural hematoma, neoplasm, infection, epilepsy, and
cerebrovascular accident (3). Associated ECG changes include
prolonged QT interval, deep, symmetrical T wave inversions,
pathologic Q waves, and tall, upright U waves. Cardiac insult
related to an acute neurological event is thought to be related
to alterations in the autonomic nervous system. Specifically,
release of norepinephrine from sympathetic nerve terminals
causes widespread opening of calcium channels within the myocardium and subsequent calcium ion influx (4). Consequently,
ECG changes do not typically persist past the acute setting.
We believe that the occurrence of persistent giant negative
U waves in the absence of apparent cardiac disease is a unique
clinical finding and likely somehow related to our patient’s previous anoxic brain injury. The possibility of artifact was also
considered but deemed unlikely given the fact that multiple
ECGs obtained during the patient’s hospitalization as well as
an ECG obtained from 3 years prior appeared nearly identical.
The actual mechanism of these findings is uncertain. His current medications have not been reported to produce any such
abnormalities. Coronary artery disease cannot be completely
excluded as an etiology (since coronary arteriography was not
performed), but we think it very unlikely in a 29-year-old person without other evidence of heart disease. It is possible that the
changes may be related to ongoing autonomic nervous system
dysfunction, especially in light of his hypotension, although this
explanation is purely speculative at the present time.
1.
2.
3.
4.
Pérez Riera AR, Ferreira C, Filho CF, Ferreira M, Meneghini A, Uchida
AH, Schapachnik E, Dubner S, Zhang L. The enigmatic sixth wave of
the electrocardiogram: the U wave. Cardiol J 2008;15(5):408–421.
Kishida H, Cole JS, Surawicz B. Negative U wave: a highly specific but
poorly understood sign of heart disease. Am J Cardiol 1982;49(8):2030–
2036.
Reinig MG, Harizi R, Spodick DH. Electrocardiographic T- and U-wave
discordance. Ann Noninvasive Electrocardiol 2005;10(1):41–46.
Strauss WE, Samuels MA. Electrocardiographic changes associated with
neurologic events. Chest 1994;106(5):1316–1317.
Volume 26, Number 2
Mariangeli Arroyo, MD, Andrew Z. Fenves, MD, and Michael Emmett, MD
The milk-alkali syndrome was a common cause of hypercalcemia, metabolic alkalosis, and renal failure in the early 20th century. It was caused
by the ingestion of large quantities of milk and absorbable alkali to treat
peptic ulcer disease. The syndrome virtually vanished after introduction
of histamine-2 blockers and proton pump inhibitors. More recently, a
similar condition called the calcium-alkali syndrome has emerged as a
common cause of hypercalcemia and alkalosis. It is usually caused by
the ingestion of large amounts of calcium carbonate salts to prevent or
treat osteoporosis and dyspepsia. We describe a 78-year-old woman who
presented with weakness, malaise, and confusion. She was found to have
hypercalcemia, acute renal failure, and metabolic alkalosis. Upon further
questioning, she reported use of large amounts of calcium carbonate
tablets to treat recent heartburn symptoms. Calcium supplements were
discontinued, and she was treated with intravenous normal saline. After
5 days, the calcium and bicarbonate levels normalized and renal function
returned to baseline. In this article, we review the pathogenesis of the
calcium-alkali syndrome as well as the differences between the traditional
and modern syndromes.
T
he milk-alkali syndrome was originally described in the
early 20th century when patients developed hypercalcemia, metabolic alkalosis, and renal failure after ingesting
large quantities of milk, cream, and absorbable alkali to
treat peptic ulcer disease (1, 2). For a period of time after the
introduction of histamine-2 blockers and proton pump inhibitors, this syndrome was virtually eliminated. However, a new
form of milk-alkali syndrome, that some have proposed should
be called calcium-alkali syndrome, has more recently emerged
as a relatively common cause for hypercalcemia and metabolic
alkalosis (3). The calcium-alkali syndrome is caused in part by
the ingestion of large quantities of calcium carbonate, which
is available over the counter. The use of calcium carbonate has
steadily increased as an antacid and as a calcium supplement to
treat or prevent osteoporosis (3). We report a case of calciumalkali syndrome.
CASE REPORT
A 78-year-old Caucasian woman presented to the emergency department after falling and injuring her right arm. She
complained of general malaise, weakness, and dizziness for sevProc (Bayl Univ Med Cent) 2013;26(2):179–181
eral days. She denied fevers, chills, weight changes, bone pains,
dyspnea, chest pains, palpitations, or urinary symptoms. Her
past medical history was significant for chronic obstructive pulmonary disease, hypertension, atrial fibrillation, and chronic
kidney disease with a baseline creatinine of 1.3 mg/dL. Her
regular medications included verapamil 180 mg twice daily,
ramipril 5 mg daily, warfarin 5 mg daily, ibandronate 2.5 mg
daily, and calcium with vitamin D over-the-counter supplements. The patient lived in an independent living facility. She
had a previous 15 pack-year history of tobacco use but quit 17
years ago. She denied any alcohol or recreational drug use.
On initial examination, her blood pressure was 215/90 mm
Hg, pulse 100 beats/minute, respiratory rate 20 breaths/minute,
and temperature 97°F. She was alert and oriented to person,
place, and time; however, she was irritable, drowsy, and slow
to answer questions. She had dry mucous membranes and poor
skin turgor. Her chest was clear to auscultation bilaterally. On
precordial examination, no murmurs were heard. Her abdomen
was soft, nontender, and nondistended. Her extremities had full
range of motion and normal strength.
Initial laboratory results included hemoglobin, 16.2 g/
dL; hematocrit, 48.2%; sodium, 138 mEq/L; potassium,
4.2 mEq/L; chloride, 96 mEq/L; bicarbonate, 32 mEq/L;
blood urea nitrogen, 35 mg/dL; creatinine, 2.9 mg/dL;
calcium, 14.4 mg/dL; albumin, 4.0 g/dL; ionized calcium,
1.52 mmol/L; phosphorus, 5.2 mg/dL; intact parathyroid hormone, 21.0 pg/dL; thyroid-stimulating hormone, 2.66 microIU/L;
free thyroxine, 1.26 ng/dL; and 25-hydroxy-vitamin D, 11.0 pg/dL.
Serum and urine protein electrophoreses did not reveal any
monoclonal proteins.
Her chest radiograph was normal. Renal sonography showed
bilateral increased echogenicity and cortical thinning, consistent
with chronic renal disease.
Upon further questioning, the patient reported that she had
ingested about one bottle (>50 tablets) of calcium carbonate
tablets (500 mg) over the previous 3 days to treat heartburn
From the Department of Internal Medicine, Baylor University Medical Center at
Dallas.
Corresponding author: Mariangeli Arroyo, MD, Department of Internal Medicine,
Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, Texas
179
symptoms. During this time she also continued taking her
regular calcium and vitamin D supplements. The diagnosis of
calcium-alkali syndrome was made.
Intravenous normal saline was administered, and all calcium
and vitamin D supplements were discontinued. On day 2, the
patient was more lucid, awake, and able to readily communicate. Calcium and creatinine levels dropped to 12.8 mg/dL and
2.7 mg/dL, respectively. On day 5, the calcium and bicarbonate
levels were normal at 9.6 mg/dL and 27 mEq/L. The creatinine
and blood urea nitrogen were at her baseline values of 1.3 mg/
dL and 16 mg/dL, respectively.
The patient was educated on the proper use and dosing of
all over-the-counter medications, including calcium and vitamin
D supplements. She was discharged home on the fifth day of
hospitalization.
DISCUSSION
The calcium-alkali syndrome is the third leading cause of
hypercalcemia in hospitalized patients after primary hyperparathyroidism and malignant neoplasms (4). The current version
of this syndrome has several biochemical and epidemiological
differences from the traditional milk-alkali syndromes described
in the early to mid 1900s. The historic conditions were more
common in middle-aged men with peptic ulcer disease and
were due to the hourly ingestion of sodium bicarbonate, magnesium carbonate, and bismuth subcarbonate (“Sippy Powder”)
together with cream and milk. In 1949, Burnett et al described
a chronic, more persistent variant of this disorder (5). The introduction of histamine-2 receptor blockers (in 1976) and proton
pump inhibitors (in 1989) to block acid secretion, as well as
treatments directed at eradicating Helicobacter pylori, virtually
eliminated the classic acute and chronic forms of the milk-alkali
syndrome. Over the last several decades, the “modern” version
was recognized. This form more commonly affects postmenopausal women who ingest large amounts of calcium supplements, sometimes together with vitamin D and occasionally
with thiazide diuretics to prevent or treat osteoporosis (6–8).
It has also occurred in transplant patients taking high doses of
calcium carbonate to prevent osteoporosis related to chronic
steroid use (6). The use of calcium-containing antacids to treat
dyspepsia also may occur, as was the case in the current report.
It has been suggested that the modern syndrome be called the
calcium-alkali syndrome because it is due to ingestion of soluble
calcium salts instead of milk, cream, and the other alkali sources
listed above (3).
The calcium-alkali syndrome, similar to the traditional version, is characterized by hypercalcemia, metabolic alkalosis, and
renal injury. However, serum phosphorus levels were usually
high in the historic forms due to the high phosphorus load
from cream and milk and the development of acute and chronic
renal injury. The current calcium-alkali syndrome more typically presents with a normal or even low serum phosphorus
concentration resulting from the dietary phosphate-binding
properties of calcium carbonate (6–8).
Although serum vitamin D is usually suppressed in patients with calcium-alkali syndrome, it may be normal or even
180
increased if vitamin D supplements have contributed to the
disorder (8). Serum parathyroid hormone levels, which would
be expected to be low, are sometimes normal. This may be
due to renal insufficiency or related to a rapid fall in serum
calcium soon after initiation of aggressive intravenous saline
infusion (7).
The pathogenesis of calcium-alkali syndrome involves the
interplay of multiple organ systems, including bone, intestines,
and the kidney. The ingestion of large amounts of calcium-containing compounds increases intestinal absorption of calcium
and causes hypercalcemia. Hypercalcemia will constrict the renal
arterioles, reduce the glomerular filtration rate, and decrease
renal calcium excretion (9). Calcium-sensing receptors (CaSRs)
are located in many tissues throughout the body, including the
renal tubules, the intestines, and the parathyroid and thyroid
glands. When high calcium levels activate the CaSRs in the
thick ascending loop of Henle, sodium chloride reabsorption
at this site is inhibited, causing diuresis and increasing renal
calcium excretion (i.e., a loop diuretic-like effect). This effect
also contributes to volume depletion and metabolic alkalosis
(10). CaSRs are also present on the luminal membrane of the
distal convoluted tubules, and activation of these receptors (by
high renal tubule calcium concentrations) increases calcium
reabsorption via TRVP5 channels (10). In addition, CaSRs
are found on the luminal membranes of the collecting duct
cells, and their activation reduces expression of aquaporin 2
water channels. This reduces renal tubule water reabsorption
and causes the excretion of dilute urine (10). The net effect is
a salt and water diuresis with variable impact on renal calcium
excretion. Metabolic alkalosis helps to perpetuate this cycle by
increasing the affinity of the CaSRs to calcium, which enhances
the natriuresis. An alkaline pH also stimulates the activity of
an important calcium selective receptor called the transient receptor potential vanilloid member 5 (TRPV5); this enhances
calcium reabsorption and leads to worsening hypercalcemia
(10, 11). To the extent hypercalcemia suppresses serum parathyroid hormone, renal bicarbonate reabsorption is promoted.
Additionally, hypercalcemia may generate nausea and vomiting,
which worsens the volume depletion and alkalosis (9).
The diagnosis of calcium-alkali syndrome should be considered when a patient presents with acute renal injury, metabolic
alkalosis, hypercalcemia, and a history of excessive calcium (±
vitamin D) intake. Generally, the first and most important
treatment for calcium-alkali syndrome is extracellular volume
expansion with intravenous saline. This will hopefully improve
renal function and increase renal calcium and bicarbonate excretion. It is also essential to identify all calcium salt and vitamin
D–containing medications that the patient is taking and to
provide education about appropriate dosing. It may be difficult to determine the appropriate dose of calcium salts for a
given patient. The syndrome has been reported after ingestion
of doses as low as 1 g of elemental calcium daily (11). However,
most reported cases of the syndrome document ingestion of at
least 4 g of elemental calcium per day. Although a daily intake
of 2 g of calcium is considered safe for the general population,
smaller doses of 1.2 to 1.5 g daily should be used when patients
Volume 26, Number 2
have risk factors that increase their likelihood of developing
the calcium-alkali syndrome (3, 8, 9). For example, the elderly
and patients with chronic kidney disease are more susceptible
because they will have a lower glomerular filtration rate and
decreased calcium clearance (9, 11). Additionally, the skeleton
of elderly subjects does not buffer calcium loads as well as that
of younger subjects (9).
Thiazide diuretic use may also predispose to the development of this condition by enhancing renal tubule calcium absorption and by promoting volume depletion and alkalosis.
Furthermore, any medications that reduce glomerular filtration rate, such as nonsteroidal antiinflammatory drugs and
angiotensin-converting enzyme inhibitors, can contribute to
the development of the syndrome (9).
1.
2.
3.
Hardt LL, Rivers AB. Toxic manifestations following the alkaline treatment of peptic ulcer. Arch Intern Med 1923;31(2):171–180.
Cope CL. Base changes in the alkalosis produced by the treatment of
gastric ulcer with alkalies. Clin Sci 1936;2:287–300.
Patel AM, Goldfarb S. Got calcium? Welcome to the calcium-alkali syndrome. J Am Soc Nephrol 2010;21(9):1440–1443.
April 2013
4.
Beall DP, Scofield RH. Milk-alkali syndrome associated with calcium
carbonate consumption. Report of 7 patients with parathyroid hormone
levels and an estimate of prevalence among patients hospitalized with
hypercalcemia. Medicine (Baltimore) 1995;74(2):89–96.
5. Burnett CH, Commons RR, Albright F, Howard JE. Hypercalcemia
without hypercalciuria or hypophosphatemia, calcinosis and renal insufficiency: a syndrome following prolonged intake of milk and alkali. N
Engl J Med 1949;240(20):787–794.
6. Kapsner P, Langsdorf L, Marcus R, Kraemer FB, Hoffman AR. Milkalkali syndrome in patients treated with calcium carbonate after cardiac
transplantation. Arch Intern Med 1986;146(10):1965–1968.
7. Beall DP, Henslee HB, Webb HR, Scofield RH. Milk-alkali syndrome: a
historical review and description of the modern version of the syndrome.
Am J Med Sci 2006;331(5):233–242.
8. Medarov BI. Milk alkali syndrome. Mayo Clin Proc 2009;84(3):261–
267.
9. Felsenfeld AJ, Levine BS. Milk alkali syndrome and the dynamics of
calcium homeostasis. Clin J Am Soc Nephrol 2006;1(4):641–654.
10. Riccardi D, Brown EM. Physiology and pathophysiology of the
calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol
2010;298(3):F485–F499.
11. Picolos MK, Lavis VR, Orlander PR. Milk-alkali syndrome is a major
cause of hypercalcaemia among non-end-stage renal disease (non-ESRD)
inpatients. Clin Endocrinol (Oxf ) 2005;63(5):566–576.
181
Hepatitis C and recurrent treatment-resistant acute ischemic
stroke
Aneeta Saxsena, MD, Joseph Tarsia, MD, Casey Dunn, MD, Aimee Aysenne, MD, Basil Shah, MD,
and David F. Moore, MD, PhD
Since the introduction of recombinant tissue plasminogen activator and
thrombolysis, acute ischemic stroke has become a treatable disorder if
the patient presents within the 4.5-hour time window. Typically, sporadic
stroke is caused by atherosclerotic disease involving large or small cerebral arteries or secondary to a cardioembolic source often associated
with atrial fibrillation. In the over-65-year age group, more rare causes
of stroke, such as antiphospholipid syndromes, are unusual; such stroke
etiologies are mostly seen in a younger age group (<55 years). Here we
describe acute ischemic stroke in three patients >65 years with hepatitis
C–associated antiphospholipid antibodies. We suggest that screening
for antiphospholipid disorders in the older patient might be warranted,
with potential implications for therapeutic management and secondary
stroke prevention.
T
he risk factors for ischemic stroke have been well categorized by major epidemiological studies, such as the
Framingham population-based study established in
the 1950s. Such epidemiological studies particularly
highlight modifiable risk factors of ischemic stroke such as
hypertension, diabetes mellitus, smoking, alcohol usage, and
dyslipidemia. The contribution of other risk factors for ischemic
stroke, such as hypercoagulable states, is typically found in persons <55 years old (1). The typical antiphospholipid patient
with acute ischemic stroke is a young woman of childbearing
age with recurrent miscarriages (2). The etiology of stroke is customarily defined according to the TOAST (Trial of Org 10172
in Acute Stroke Treatment) classification, with the presumption
that the main attributable stroke risk factors are derived in the
general stroke population from the presence of atherosclerotic
vascular disease (3). The occurrence of other modifiable risk
factors in the multifactorial etiology of acute ischemic stroke is
an area of active study. In this report, we present three patients
>65 years where we found an association between hepatitis C
and the occurrence of antiphospholipid antibodies more typically found in younger patients.
CASE REPORTS
In all patients, coagulation screens were performed, including factor 8, homocysteine, antiphospholipid, factor V Leiden,
antithrombin III, Russell viper venom assay, and protein C and
182
S. Only the antiphospholipid screen was found to be abnormal
in our patients. The Table summarizes patient demographic data
and results of the antiphospholipid screens.
Case 1
Six months prior to his third hospital admission, a 72-yearold right-handed African American man presented with a past
medical history of hyperlipidemia and a 2-day history of left
leg weakness, dizziness, and left-sided facial numbness with a
National Institutes of Health Stroke Scale (NIHSS) score of 3.
Evaluation for acute stroke with diffusion-weighted magnetic
resonance imaging (MRI) demonstrated a subacute lesion in
the right posterior internal capsule. The extended symptom
time course precluded use of recombinant tissue plasminogen
activator (rt-PA) or another neurovascular intervention. The
patient was admitted to address secondary stroke prevention
and was found to have a cholesterol of 142 mg/dL; high-density
lipoprotein cholesterol of 9 mg/dL; low-density lipoprotein
cholesterol of 71 mg/dL; triglycerides of 639 mg/dL; cardiac
ejection fraction of ~60%; regular cardiac rhythm; and no persistent foramen ovale or pulmonary hypertension. In addition,
blood cultures showed no growth, and cerebral computed tomographic angiography showed minimal atherosclerotic disease
in the carotid bulbs with a hypoplastic left vertebral artery. A
diagnosis of small vessel stroke was made and the patient was
encouraged to be more compliant with his hypertension regime
and adopt a heart and stroke–healthy diet together with smoking cessation. Secondary prevention therapy included lisinopril,
aspirin, and atorvastatin. An albumin-immunoglobulin protein
gap was noted, and the patient was subsequently screened and
diagnosed with hepatitis C; he was referred to gastroenterology
for further evaluation.
Approximately 5 months later, the patient presented with
sudden onset of right facial numbness, slurred speech, and right
From the Department of Neurology (Saxsena, Tarsia, Dunn, Aysenne) and
Department of Radiology (Shah), Tulane University Medical Center, New Orleans,
Louisiana; and the Baylor Neuroscience Center, Baylor University Medical Center
at Dallas (Moore).
Corresponding author: David F. Moore, MD, PhD, FAAN, Baylor Neuroscience
Center, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas,
TX 75246 (e-mail: [email protected]).
he received rt-PA with a doorto-needle time of approximately
2.5 hours. Since his NIHSS score
Variable
Case 1
Case 2
Case 3
was estimated to be 19 and he was
Age (years)
72
67
65
noted to be in atrial fibrillation,
his stroke was presumed to have a
Blood pressure (mm Hg)
treated 147/74
treated 140/90
189/100
cardioembolic etiology. A diffusionNIHSS score
3
19
5
weighted MRI after administration
Total cholesterol (mg/dL)
142
141
146
of rt-PA showed a small ischemic
LDL cholesterol (mg/dL)
71
92
85
area in the right posterior parietal
HDL cholesterol (mg/dL)
9
47
25
cortical area. The patient was discharged on warfarin with a theraTriglycerides (mg/dL)
639
57
219
peutic INR goal of 2 to 3.
Smoker
1–3 packs/day
1–2 packs/day
N/A
Over the next 6 months, the
Hemoglobin A1C (%)
<4.5
<3.5
10.7
patient’s warfarin regime was difIgM anticardiolipin antibody (0–12 MPL U/mL)*
13
<9
13
ficult to maintain within goal deIgG anticardiolipin antibody (0–14 GPL U/mL)*
spite patient adherence. The patient
21
12
20
then presented with a further acute
IgA anticardiolipin antibody (0–11 APL U/mL)*
31
10
<9
ischemic stroke episode with inIgM β-2 glycoprotein (GPI IgM units)
<9
<9
9
creased left-sided weakness and
IgG β-2 glycoprotein (GPI IgG units)
<9
<9
<9
problems with gait and balance over
IgA β-2 glycoprotein (GPI IgA units)
18
<9
10
a 3- to 4-day period. MRI demonIgM phosphatidylcholine (0–25 MPS IgM)*
29
6
23
strated a new lesion in the left cerIgG phosphatidylcholine (0–11 GPS IgG)*
7
48
24
ebellar hemisphere, together with a
IgA phosphatidylcholine (0–20 APS IgA)*
21
10
1
lesion in the right parieto-occipital
region and a further lesion on the
*Units indicate the value showing absence (versus low, moderate, or high positivity).
left frontal area. The patient’s INR
HDL indicates high-density lipoprotein; LDL, low-density lipoprotein; NIHSS, National Institutes of Health
at the time of presentation was 1.7,
Stroke Scale.
and a diagnosis of cardioembolic
stroke secondary to chronic atrial
arm and leg weakness. These symptoms were confirmed on
fibrillation was again made. The patient’s warfarin regime was
physical examination. Presentation to the emergency room was
discontinued, and he was started on dabigatran.
outside the 4.5-hour window, and thrombolysis with rt-PA was
Approximately 2 months after this admission, the patient
not administered. Diffusion-weighted MRI was positive for a
presented with a generalized tonic-clonic seizure, and epilepsy
left thalamic lacunar stroke, again consistent with small vessel
secondary to ischemic stroke structural damage was diagnosed.
disease. The patient’s final admission was due to statin-induced
The patient was started on antiepileptic drugs and at that time
rhabdomyolysis and an associated pancreatitis. During this adwas also noted to have an albumin-immunoglobulin protein
mission, the patient’s creatinine kinase was >8000 mcg/L with
gap. Screens for hepatitis and HIV were performed with the
an elevated aspartate transaminase of 1735 IU/L and an alanine
patient’s consent. The hepatitis C screen returned positive, and
transaminase of 395 IU/L. Diffusion-weighted MRI was cona full gastroenterology workup was performed. As part of an
sistent with no new acute ischemic stroke and represented T2
extended workup for etiological factors associated with the
“shine through.” During the final admission, the patient was
patient’s stroke, antiphospholipid screening was performed.
examined for a hypercoagulable state and was found to have
Antiphosphatidylcholine IgG returned elevated at 48. The paelevated values for several antiphospholipid antibodies: IgM
tient was continued on dabigatran, with the introduction of
anticardiolipin, 13; IgA anticardiolipin, 31; IgA phosphatidylaspirin 81 mg daily as part of his secondary stroke prevention
choline, 21; and IgM phosphatidylcholine, 29. The patient was
regime.
started on warfarin for antiplatelet failure and has not had any
further acute ischemic strokes on extended warfarin therapy
Case 3
for 12 months with an international normalized ratio (INR)
A 65-year-old right-handed Caucasian man with a history
goal of 2 to 3.
of hypertension, dyslipidemia, posttraumatic stress disorder, and
hepatitis C contracted during service in Vietnam was admitted
Case 2
with significant left-sided weakness affecting the face, arm, and
A 67-year-old right-handed African American man with
leg. The patient initially presented at an out-of-state hospital and
a past medical history of hypertension presented to the emerwas not treated with rt-PA. Computed tomography and MRI
gency department with sudden onset of weakness on the left
showed ischemic lesions in the right parietal area. The patient
side of his body. Since he was within the 4.5-hour window,
underwent angiographic evaluation and a stent placement in
Table 1. Patient demographics and antiphospholipid screen in the three described male patients
April 2013
183
the right M1 branch of the middle cerebral artery for a critical
large vessel stenosis. The stroke was believed to be caused by
large vessel disease, and the patient was continued on aspirin
325 mg and clopidogrel 75 mg once daily for secondary stroke
prevention. The patient was found to have elevated anticardiolipin antibody at IgG 20, anticardiolipin antibody at IgM 13,
and antiphosphatidylcholine at IgG 24.
DISCUSSION
We present a single-center observational case series of hepatitis C and antiphospholipid antibody positivity in the older
stroke patient population (>65 years) that altered therapeutic
management from antiplatelet therapy to warfarin in two cases
and from warfarin to dabigatran in one case. Screening for
antiphospholipid antibodies is not part of the usual clinical
workup for modifiable stroke risk factors in those >65 years, although it is well described as an independent risk factor for acute
ischemic stroke in those <55 years. We suggest that in patients
with hepatitis C and acute ischemic stroke, such screening may
have a higher yield than in the <55-year demographic.
There are limited references reporting hepatitis C–associated antiphospholipid antibodies and stroke, and most consist
of incidental case reports (4–6). One case report described a
43-year-old woman with ischemic stroke, while a further case
report described a 54-year-old man with chronic hepatitis C
and antiphospholipid-positive serology and ischemic stroke. Of
interest, the treatment of hepatitis C with interferon appeared
to contribute to the patient’s remission from further ischemic
stroke events (6). The only case-control patient series came from
a Romanian publication, where 58 patients (age range 46–77
years, mean 62 years; 39 women and 19 men) were found to
have a higher prevalence (P < 0.001) of antiphospholipid antibodies in the hepatitis C–positive group with stroke compared
to age- and sex-matched controls (5).
The presence of antiphospholipid antibodies is known to
contribute to the development of acute ischemic stroke. Our small
184
observational case series suggests that no particular type of stroke
is favored, since we had patients with both small- and large-vessel
disease together with cardioembolic stroke. The additional risk
of antiphospholipid-positive serology should suggest optimization of antiplatelet therapy and possibly extension of therapy to
anticoagulation with warfarin or direct thrombin inhibitors such
as dabigatran. The control of hepatitis C virus expression through
interferon therapy is a further therapeutic consideration in these
patients and may reduce the risk of stroke (5). Our patients were
all noted to have an elevated albumin-immunoglobulin protein
gap, suggesting that there is an abnormal immune response to
hepatitis C. The infection of vascular endothelial cells by hepatitis
C may result in the exposure of previously nonimmunogenic
antigens to immunocompetent cells, promoting endothelial dysfunction and potential stroke. However, dysregulation of hepatic
synthetic function following hepatitis C infection may also be an
important etiologic consideration.
1.
2.
3.
4.
5.
6.
Wolf PA, Kannel WB. Epidemiology of stroke. In Mohr JP, Wolf PA,
Grotta JC, Moskowitz MA, Mayberg MR, von Kummer R, eds. Stroke:
Pathophysiology, Diagnosis and Management. Philadelphia: Saunders Elsevier, 2011:198–218.
Coull BM, Drake K. Coagulation abnormalities in stroke. In Mohr JP,
Wolf PA, Grotta JC, Moskowitz MA, Mayberg MR, von Kummer R, eds.
Stroke: Pathophysiology, Diagnosis and Management. Philadelphia: Saunders
Elsevier, 2011:772–789.
Gordon DL, Bendixen BH, Adams HP Jr, Clarke W, Kappelle LJ,
Woolson RF; TOAST Investigators. Interphysician agreement in the
diagnosis of subtypes of acute ischemic stroke: implications for clinical
trials. Neurology 1993;43(5):1021–1027.
Rafai MA, Fadel H, Gam I, Hakim K, El Moutawakkil B, Kissani N, Slassi
I. Recurrent stroke revealing catastrophic antiphospholipid syndrome
with hepatitis C viral infection [article in French]. Rev Neurol (Paris)
2006;162(11):1131–1134.
Cojocaru IM, Cojocaru M, Iacob SA. High prevalence of anticardiolipin
antibodies in patients with asymptomatic hepatitis C virus infection associated acute ischemic stroke. Rom J Intern Med 2005;43(1–2):89–95.
Malnick SD, Abend Y, Evron E, Sthoeger ZM. HCV hepatitis associated
with anticardiolipin antibody and a cerebrovascular accident. Response
to interferon therapy. J Clin Gastroenterol 1997;24(1):40–42.
Volume 26, Number 2
Diagnosis and management of delayed hemoperitoneum
following therapeutic paracentesis
Morgan J. Katz, MD, Matthew N. Peters, MD, John D. Wysocki, MD, and Chayan Chakraborti, MD
Abdominal paracentesis is a frequently employed diagnostic and therapeutic procedure for patients with refractory ascites, typically in patients with
cirrhosis. It is generally regarded as a safe procedure with significant complications occurring in <1% of cases. Most hemorrhagic complications are
due to abdominal wall trauma, during which clear evidence of active bleeding is usually visualized during the procedure. Delayed hemoperitoneum is
a rare complication of large-volume paracentesis in which clinical evidence
of active bleeding is typically absent until substantial blood loss has taken
place (often several days to a week later), leading to an exceedingly high
mortality rate. Herein we describe a case of delayed hemoperitoneum in a
55-year-old man with heart failure. This case emphasizes the importance
of identifying patients who are at high risk for delayed hemoperitoneum
as well as the need to closely monitor complete blood counts in the days
following a large-volume paracentesis.
CASE DESCRIPTION
A 55-year-old man presented with a 2-week history of worsening dyspnea and abdominal distention. He had atrial fibrillation, chronic heart failure (last known ejection fraction 25%),
and chronic kidney disease. He reported nonadherence to his
furosemide for 3 weeks. He had a massively tense and protruding abdominal wall and 3/4+ pitting lower extremity edema to
his knees bilaterally. His international normalized ratio was 2.3
(on warfarin), serum creatinine 2.33 mg/dL (baseline: 2.0–3.0
mg/dL), and albumin 2.3 g/dL. Abdominal ultrasound revealed
hepatomegaly without cirrhosis. Two doses of 80 mg intravenous
furosemide led to minimal reduction of his abdominal ascites. A
paracentesis under ultrasound guidance was performed in the left
lower quadrant and yielded 5 L of clear, transudative fluid. No
evidence of hematoma was noted, and the procedure provided
immediate symptomatic relief.
Three days later the patient began complaining of mild, diffuse
abdominal discomfort. Over the previous 3 days his hemoglobin
level had dropped from 8.4 to 6.9 g/dL. No evidence of gastrointestinal or genitourinary blood loss was noted. The patient,
a Jehovah’s Witness, refused transfusion of any blood products
and in the next 2 days his hemoglobin declined to 2.9 g/dL. A
repeat diagnostic paracentesis was performed and showed 10 mL
of blood-tinged fluid. The following day a tagged red blood cell
scan indicated evidence of increased activity near the duodenum
and gastric antrum (Figure 1). An urgent upper endoscopy demonstrated no evidence of active upper gastrointestinal bleeding
but did demonstrate a bluish hue on the posterior stomach wall,
suggestive of a possible intraperitoneal or retroperitoneal bleed.
Subsequent noncontrast computed tomography (CT) of the abdomen and pelvis showed likely hemoperitoneum localized to
the mid-lower abdominal wall (Figure 2). An urgent epigastric
and gastroduodenal angiogram did not reveal any evidence of
active bleeding.
The patient continued to refuse blood transfusion and
was treated supportively with intravenous fluid and albumin infusions. Slight improvements in serum creatinine
(3.6 mg/dL) and hemoglobin (4.1 g/dL) were noted. The patient refused any further intervention and was discharged to
home hospice; he died 3 days later, 11 days after the initial
paracentesis.
DISCUSSION
Large-volume paracentesis (>4 L) is a common bedside procedure utilized in patients with refractory abdominal ascites with
Figure 1. Red blood cell scan tagged with Technetium-99m to evaluate for active
gastrointestinal bleed shows increased activity in the region of the duodenum
and the gastric antrum.
From the Department of Internal Medicine, Tulane University Health Sciences
Center, New Orleans, Louisiana.
Corresponding author: Morgan J. Katz, MD, 1430 Tulane Avenue, SL-50, New
Orleans, LA 70112 (e-mail: [email protected]).
185
poor response to diuretic therapy. The procedure is typically
regarded as safe and carries a hemorrhagic complication rate of
<1% (1, 2) (further reduced with ultrasound guidance and a
left lower quadrant approach [3, 4]). When hemorrhagic complications occur, they are typically due to abdominal wall vessel
puncture, with visible bleeding during the procedure (2). Consequently, many patients are discharged soon after the procedure
and without close follow-up.
Delayed hemoperitoneum is a rare hemorrhagic complication of large-volume paracentesis. The proposed mechanism is
the large volume fluid removal, which results in a rapid drop
in intraperitoneal pressure. This promotes a transient pressure
gradient in the splanchnic circulation, promoting dilation and
rupture of friable mesenteric varices (1, 5, 6). Due to slow venous bleeding rates, patients are often initially asymptomatic.
The most commonly reported symptom is vague abdominal
pain (1), which may be overlooked in patients with chronic
ascites. Peritoneal signs typically do not occur until late stages
(if at all), and any clinical signs of bleed may be absent until
substantial blood loss has taken place as long as several days to
a week later (1, 5). Consequently, patients have been known to
present in hemorrhagic shock, and mortality rates are reported
to exceed 70% (5).
Given the rare occurrence of delayed hemoperitoneum, clinicians must be made aware of high-risk patient groups. Previously established risk factors include advanced cirrhosis with
refractory ascites, history of previous large-volume paracentesis,
and the appearance of retrograde mesenteric venous flow on
ultrasound (due to the occurrence of large mesenteric collaterals, which are predisposed to rupture) (5). Additionally, an association between postparacentesis hemorrhagic complications
and chronic kidney disease has also been noted (likely due to
platelet dysfunction) (6). Surprisingly, no associations between
coagulopathy and hemorrhagic complications of paracentesis
have been shown, so there are currently no guidelines for either preprocedural coagulation parameters that contraindicate
paracentesis or the prophylactic administration of fresh frozen
plasma or platelets (3, 5).
Previously described cases of delayed hemoperitoneum have
not demonstrated evidence of intraprocedural abdominal wall
trauma or other complications; thus, it is critical to recognize
potential warning signs (1, 6). Complete blood counts should
be closely monitored for a minimum of several days in high-risk
groups, and once a notable drop in hemoglobin is detected, a
diagnostic paracentesis should be performed to assess the presence of visible blood (5). If blood is detected on diagnostic
paracentesis, an abdominal CT scan or ultrasound should be
performed to evaluate for abdominal wall hematoma. In the
absence of apparent hematoma formation, angiography should
be strongly considered (5, 6).
Initial management should focus on identification of a
bleeding source with interim supportive management. Coagulopathies should be corrected, and patients should be fluid
resuscitated with normal saline and packed red blood cells as
needed (6). In the event of patient blood transfusion refusal
(as in our case), albumin or artificial colloid solution should
be given. Previously described successful interventions include
portocaval shunting and embolization or surgical ligation of
bleeding vessels (2, 5). Unfortunately, angiographic visualization
of bleeding vessels is often difficult, and in the setting of hemodynamic instability, laparotomy may be needed for adequate
visualization of the bleeding site (5).
The most important preventative measure in delayed hemoperitoneum is daily monitoring of complete blood counts
for a minimum of several days to ensure rapid detection and
minimize blood loss (1, 5). Patients with underlying renal dysfunction may benefit from prophylactic transfusion of fresh
frozen plasma or desmopressin acetate—a target of future studies (6). Finally, patients with risk factors for hemoperitoneum
may benefit from either a lower-volume paracentesis, slower
drainage of ascites, or concurrent administration of albumin
to guard against rapid changes in the intraperitoneal pressure
gradient (1).
1.
2.
3.
4.
5.
6.
Figure 2. CT of the abdomen and pelvis without contrast reveals hemoperitoneum
(arrows) localized to the lower left and middle quadrant.
186
Webster ST, Brown KL, Lucey MR, Nostrant TT. Hemorrhagic complications of large volume abdominal paracentesis. Am J Gastroenterol
1996;91(2):366–368.
Martinet O, Reis ED, Mosimann F. Delayed hemoperitoneum following
large-volume paracentesis in a patient with cirrhosis and ascites. Dig Dis
Sci 2000;45(2):357–358.
Runyon BA; AASLD Practice Guidelines Committee. Management
of adult patients with ascites due to cirrhosis: an update. Hepatology
2009;49(6):2087–2107.
Grabau CM, Crago SF, Hoff LK, Simon JA, Melton CA, Ott BJ, Kamath
PS. Performance standards for therapeutic abdominal paracentesis. Hepatology 2004;40(2):484–488.
Arnold C, Haag K, Blum HE, Rössle M. Acute hemoperitoneum after
large-volume paracentesis. Gastroenterology 1997;113(3):978–982.
Pache I, Bilodeau M. Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease. Aliment Pharmacol Ther
2005;21(5):525–529.
Volume 26, Number 2
Baylor news
■ Baylor, Scott & White sign agreement
of intent to join forces, create new
health system
The boards of Baylor Health Care System
(BHCS) and Scott & White Healthcare signed an
agreement of intent to combine the strengths of
their two health systems to create a $7.7 billion
organization with the vision and resources to offer
its patients continued exceptional care while creating a model system for an industry undergoing
fundamental transformation. The alliance reflects
a vision to create a new health system engineered to meet the demands of health care reform, the changing needs of patients and payers,
and the extraordinary advances in clinical care.
With approval of the agreement of intent, the
organizations have entered a period of exclusive
negotiations and due diligence. The next stage
in the transaction—a definitive agreement—is
anticipated to be complete in 2013.
The new system, named Baylor Scott &
White Health, would include the organizations’
combined 42 hospitals, more than 350 patient
care sites, more than 4000 active physicians,
34,000 employees, and the Scott & White Health
Plan. It would be the largest not-for-profit health
system in Texas and one of the largest in the
United States. It would be governed by a single board with equal representation from both
founding members.
“Baylor has a century-long tradition of quality, innovation, and service. And in this time of
great change in the health care industry, Baylor
is looking forward and preparing to once again
lead by joining forces with Scott & White to
ACCOLADES
Paul Grayburn, MD, of the Baylor Heart
and Vascular Institute received the Simon
Dack Award for Outstanding Scholarship
from the Journal of the American College of
Cardiology.
Becker’s Hospital Review included
the Jack and Jane Hamilton Heart and
Vascular Hospital in its “100 Hospitals with
Great Heart Programs” list. Hospitals included
on the list offer outstanding heart care, and
the Becker’s editorial team selected them
based on clinical accolades, recognition for
quality care, and contributions to the field of
cardiology and cardiovascular surgery.
create this new model of care,” said Joel Allison,
president and CEO, BHCS. “Scott & White is a
perfect partner for us as it is nationally known
for its high-quality, efficient care. Our proposed
new organization reflects many months of discussion between our two like-minded systems
on how we could work together to continue to
meet the needs of the communities we serve
in this dramatically changing environment. The
new organization will continue to honor and
carry forward Baylor’s 100-plus-year legacy as
a Christian ministry of healing.”
“Our new organization will not only prepare
us for health care reform but will help drive and
shape what health care delivery in this country
will become,” said Robert Pryor, MD, president
and CEO, Scott & White Healthcare. “Scott &
White has been recognized as a national leader
for our strong physician-led population health
model. Our shared vision with Baylor is to build
upon our unique approach and create an innovative health care delivery model enhanced by
medical education and research.”
Both organizations are affiliated with Texas
A&M Health Sciences Center and have extensive
investments in medical education and research.
Baylor Scott & White Health will have the ability to
expand training opportunities for the next generation of health care professionals by integrating
education programs at both organizations.
Some details of the agreement of intent:
• Unified board: A unified board of trustees
will comprise 14 individuals, with an equal
number of representatives from each institution. Drayton McLane Jr., the chair of the
Scott & White board of trustees, will serve
as chair of the new organization’s board.
Jim Turner, the chair of the BHCS board of
trustees, will serve as chair-elect of the new
organization’s board.
• Leadership: The new organization will be led
by a single executive leadership team. Joel
Allison will serve as chief executive officer of
the new company. Dr. Robert Pryor will serve
as president and chief operating officer of
the new organization.
• Operations: The new system will have two
operating divisions, which will consolidate
over time. The Scott & White division will
be headquartered in Temple, and the Baylor
division will be headquartered in Dallas.
• Brands: The new organization will be called
Baylor Scott & White Health. Both Baylor and
Scott & White will retain their individual
brand names.
• Foundations: The foundations will remain
separate.
• Medical staffs: The medical staffs will remain independent.
“This partnership is the right thing for Baylor.
It’s the right thing for Scott & White. And, it’s the
right thing for our communities,” said Drayton
McLane Jr., chair of the Scott & White board
of trustees. “Both health systems are wellorganized, well-run, best-in-class organizations.
We can learn from each other, and I think this
only benefits the patients we serve by allowing
us to deliver better quality care and increased
access to care.”
For patients, the new organization will ultimately mean
• Greater, more convenient access to highquality care through an extensive network of
physicians, advanced practice professionals, medical centers and hospitals throughout North and Central Texas
• Increased coordination of patient care
• Improved patient outcomes, by combining
the expertise of primary care physicians and
medical specialists and adopting the best
practices of both organizations
• The ability to attract, retain, and train
the very best national and international
talent
• Greater access to world-class primary and
pediatric care and centers of excellence in
cardiology, oncology, transplant, rehabilitative medicine, and other specialties
“Together, our two health systems will cover two geographically diverse areas that are
nearly contiguous and highly complementary,”
said Jim Turner, chair of the BHCS board of
trustees. “We strongly believe our neighboring
geographies will allow us to be well positioned
to lead the transformation of health care in
Texas and beyond.”
■ Introducing the Baylor Charles A.
Sammons Cancer Center Network
For the past 2 years, Baylor medical
centers throughout North Texas have been
working to achieve the distinction of using the Baylor Sammons Cancer Center
name for their oncology programs by
meeting or exceeding the stringent criteria established by BHCS. In addition to the
187
RECENT GRANTS
• JC virus and human colorectal
neoplasia
Principal investigator: C. Richard
Boland, MD
Sponsor: National Cancer Institute
Funding: $267,374
Award period: 2/1/2013–8/1/2013
• Glycemia reduction approaches in
diabetes: a comparative effectiveness study
Principal investigator: Priscilla Hollander,
MD
Sponsor: George Washington University/
National Institute of Diabetes and
Digestive and Kidney Diseases
Funding: $186,241
Award period: 1/1/2013–7/31/2013
• Molecular mechanisms of pDC
interactions
Principal investigator: Yong-Jun Liu,
MD
Sponsor: MD Anderson Cancer Center/
National Cancer Institute
Funding: $313,600
Award period: 9/1/2012–8/31/2013
• Expanding the impact of the Baylor
Health Care system delirium research program
Principal investigator: Andrew Masica,
MD
Sponsor: The Discovery Foundation
Funding: $36,080
Award period: 12/4/2012–6/15/2015
• The high value healthcare collaborative: engaging patients to meet the
triple aim
Principal investigator: Andrew Masica, MD
Sponsor: Dartmouth College/Centers for
Medicare and Medicaid Services
Funding: $176,952
Award period: 7/1/2012–6/30/2013
• Enhancing clinical effectiveness research with natural language processing EMR
Principal investigator: Andrew Masica, MD
Sponsor: Kaiser Foundation Research
Institute
Funding: $209,336
Award period: 9/30/2012–9/29/2013
• Vaccination with IL-15 dendritic cells to
generate melanoma-specific protective
memory T cells
Principal investigator: A. Karolina Palucka, MD
Sponsor: National Cancer Institute
Funding: $230,897
Award period: 2/1/2013–1/31/2014
• Role of mucosal DC subsets in the
control of influenza A virus immunity
Principal investigator: A. Karolina
Palucka, MD
Sponsor: Mt. Sinai School of Medicine/
National Institute of Allergy and Infectious
Diseases
Funding: $74,000
Award period: 7/15/2012–6/30/2013
• MIRA—Cellular therapy for cancer (C1)
Principal investigator: A. Karolina Palucka, MD
original Baylor Charles A. Sammons Cancer
Center at Dallas, six other BHCS facilities are
now Sammons Cancer Centers:
• Baylor Charles A. Sammons Cancer Center
at Fort Worth
at Irving
at Garland
at Grapevine
at Plano
at Waxahachie
The cancer programs at the two newest hospitals in the health care system—Baylor Medical
Center at Carrollton and Baylor Medical Center
at McKinney—are well on their way to achieving
accreditation and designation.
Each BHCS institution that wanted to join the
network had to submit a request to BHCS oncology leadership showing its readiness. To qualify,
they had to be accredited by the Commission on
Cancer of the American College of Surgeons as
an approved cancer program. They also had to
demonstrate active participation in a number of
areas, including BHCS oncology strategic initiatives; oncology safety and health care improvement projects; oncology educational efforts in
nursing, medicine, or other ancillary education
related to oncology; and research initiatives,
either within the facility or by supporting other
Baylor facilities and their oncology research
by making clinical trials available to patients,
regardless of the location of the trials. After a
188
•
•
•
•
Sponsor: Baylor College of Medicine/Cancer
Prevention and Research Institute of Texas
Funding: $46,303
Award period: 7/1/2012–6/30/2013
MIRA—Cellular therapy for cancer (C2)
Principal investigator: A. Karolina Palucka,
MD
Sponsor: Baylor College of Medicine/Cancer
Prevention and Research Institute of Texas
Funding: $102,612
Award period: 7/1/2012–6/30/2013
North Texas Hepatitis B Consortium:
clinical site for the Hepatitis B network
Principal investigator: Robert Perrillo, MD
Sponsor: UT Southwestern Medical Center
Funding: $114,527
Award period: 6/1/2012–5/31/2013
Role and function of prohibitin in intestinal inflammation
Principal investigator: Arianne L. Theiss, MD
Sponsor: National Institute of Diabetes and
Digestive and Kidney Diseases
Funding: $146,459
Award period: 2/1/2013–1/31/2014
A novel replication competent flavivirus-based HIV vaccine platform, i.e.
RepliVax, as a priming component for
improving antibody response
Principal investigator: Gerard Zurawski, MD
Sponsor: Centre Hospitalier UV/Gates
Foundation
Funding: $92,222
Award period: 9/6/2012–8/31/2015
determination that all criteria have been met,
the Baylor facility has the distinction of using
the Baylor Charles A. Sammons Cancer Center
name.
Patients will be the major beneficiaries of
the Baylor Sammons Cancer Center network.
When initially deciding upon a treatment center,
they will have the assurance that any institution
carrying the Baylor Sammons brand will offer
quality cancer care. By receiving care at a Baylor
Charles A. Sammons Cancer Center, patients
can be treated close to home for most of their
cancer care needs.
Vikas Aurora, MD, hematologist and medical oncologist on the medical staff as well as
the chairman of the Cancer Committee at Baylor
Grapevine, is excited about the growth of the
program. “We are working to be at the forefront
Volume 26, Number 2
of community cancer care by integrating physician and nurse enthusiasm with administrative
support,” he said. “It takes time and resources to
fuel growth but we have it here, with the strong
support of Baylor Health Care System.”
Rather than having to “reinvent the wheel”
at each site to develop new treatment options or patient outreach programs, physician
leaders from each institution can come to the
quarterly BHCS Oncology Council to share
ideas and best practices with colleagues at
their sister facilities. A program that has been
developed and perfected at one center can be
used as a model at other sites. Cooperation
among cancer centers can bring the strength
of numbers to bear on conducting new clinical
trials that make innovative treatment options
available to patients.
■ Ultragenyx announces in-licensing
of clinical-stage product from Baylor
Research Institute
Ultragenyx Pharmaceutical Inc., a biotechnology company focused on the development of
treatments for rare and ultrarare genetic disorders, announced on January 10, 2013, that it
has in-licensed rights for triheptanoin, a promising treatment for long-chain fatty acid oxidation
disorders, from Baylor Research Institute (BRI),
the research arm of BHCS.
“It is gratifying to see the fruits of everyone’s
labor as this agreement moves forward,” said Dr.
Raphael Schiffmann, director of BRI’s Institute
of Metabolic Disease. “Staff have put a lot of
time and effort into the study of triheptanoin
UPCOMING CME PROGRAMS
The A. Webb Roberts Center for Continuing Education of Baylor Health Care System is
offering the following programs:
Urology Update 2013 with Clinical Cases in Oncology, April 5–6, 2013, at BUMC
Wound Care: The Next Generation, April 27, 2013, at BUMC
Fourth Annual Latest Advances in Ischemic and Hemorrhagic Stroke Therapy
Conference, May 18, 2013, at Westin Galleria Dallas
40th Annual Williamsburg Conference on Heart Disease, December 8–10, 2013, at
the Williamsburg Conference Center, Williamsburg, Virginia
For more information, call 214-820-2317 or visit www.cmebaylor.org.
and its use for fat oxidation and glycogen storage diseases, among others. Triheptanoin has a
potential benefit for these disorders and others
with an underlying energy deficit, many of which
do not have adequate therapy. We are confident
that Ultragenyx will advance triheptanoin therapy
for the benefit of these patients in the US and
abroad.”
donates mobile clinic to local charity
Less than a month after opening its doors
in October 2012, the Avenue F Family Health
Center, one of the first charity care clinics in
Collin County, was quickly running out of space.
That’s when leaders at Baylor Medical Center
at Garland stepped in with a solution, donating
a fully functioning mobile clinic on wheels. The
vehicle had been unused for a number of years.
“We are thrilled to be able to help Avenue F
Family Health Center with this donation. It truly
is a win-win situation for everyone involved. The
mobile clinic van will allow the organization to
reach more patients in need within the community and continue to honor Baylor’s mission to
serve all people through exemplary healthcare,”
said Tom Trenary, president, Baylor Medical
Center at Garland.
The Avenue F Family Health Center serves
patients who are uninsured and live in the
75074 and 75075 zip codes of Plano, with a
particular focus on the Douglass and East Plano
communities. The clinic is open 5 days a week
but visits with the physician are currently available only on Mondays and Wednesdays. Avenue
F Church of Christ serves as the current location
of the clinic and founding institution of AFFECT,
Inc. The mobile clinic van will be parked on the
church campus and used as the interim home
of the clinic until a permanent physical space is
transform lives and the communities we serve.
To date, more than $160 million has been
raised toward the $250 million goal, including
transformational gifts from the men and women
of Sammons Enterprises, Inc., Annette C. and
Harold C. Simmons, and T. Boone Pickens.
“We are grateful for the support our community has already shown and encouraged
by the momentum we have,” said Rowland K.
Robinson, Foundation president. “We are proud
that we have made it two thirds to our goal, but
we have not yet met our challenge.”
Completely donor-driven, this comprehensive
campaign focuses on four priorities—capital,
education, research, and programmatic initiatives
at Baylor—and offers significant opportunity to
redefine health care, both locally and nationally.
Donors can determine where they wish to make an
impact and give to the area for which they have
the greatest passion. With increased community support, we can develop innovative models
of care, utilize advanced medical technology,
engage in game-changing research, and train
more physicians to care for future generations.
While Baylor has already earned national
recognition for safety, quality, leadership, and
bedside care, sustaining this level of excellence requires more than stewardship; it requires investment and innovation.
“With your partnership and support, we can
maintain Baylor’s steadfast commitment to excellence and secure the future of health care
for our community,” said Joel Allison, president
and chief executive officer of BHCS.
For more information, visit Give.
BaylorHealth.com.
■ Baylor Medical Center at Garland
PHILANTHROPY NOTES
■ Baylor Foundation launches $250
million campaign
BHCS Foundation formally launched the
first comprehensive campaign in Baylor’s history with an event at the AT&T Performing Arts
Center’s Wyly Theatre on February 27. The
$250 million fundraising effort—Campaign
2015: Baylor Makes Us All Better—marks
Baylor’s most ambitious fundraising effort
to date and is designed to strengthen every
aspect of Baylor, from patient-centered
programs and capital needs to innovative
research and medical education.
The simple phrase, “Baylor Makes Us
All Better,” was the impetus for a bold vision: take BHCS to national preeminence in
areas of health care that have the power to
April 2013
Baylor news
189
located and built. Once that goal is achieved, the
mobile unit will travel around Plano and Dallas to
help meet the needs of uninsured and underinsured individuals in those communities.
■ Five Baylor hospitals chosen to
pioneer state project to improve
breastfeeding rates
Despite the benefits of breastfeeding, Texas
has one of the lowest breastfeeding rates in the
US, with only 13.7% of Texas mothers exclusively
breastfeeding for 6 months. Five BHCS hospitals—Baylor All Saints Medical Center, Baylor
Medical Center at Carrollton, Baylor Medical
Center at McKinney, Baylor Regional Medical
Center at Grapevine, and Baylor University Medical
Center at Dallas—were recently chosen to join a
190
pioneering group of hospitals hoping to reverse
this trend. They are among 20 hospitals/facilities
in North Texas selected to be part of the “Texas
Ten Step Star Achiever Breastfeeding Learning
Collaborative,” a 5-year quality improvement
project designed to improve facility environments
to better support a mother’s choice to breastfeed.
What distinguishes this new project is collaboration. What these hospitals learn will be shared
among other participants, helping more mothers across the state become more successful in
exclusively breastfeeding their babies.
■ Baylor Irving awarded advanced cer-
tification for primary stroke centers
The Joint Commission, in conjunction with
the American Heart Association/American
Stroke Association, has awarded Baylor
Medical Center at Irving Advanced Certification
for Primary Stroke Centers. This certification
demonstrates that the program meets critical elements of performance to achieve longterm success in improving outcomes for stroke
patients.
“This designation has given us the opportunity to highlight the quality stroke care we
provide for our patients,” said Cindy Schamp,
president, Baylor Irving. “In collaboration with
the emergency department physicians on our
medical staff and our staff, we remain poised
and ready to serve the residents who present
in our hospital with signs and symptoms of
stroke.”
Volume 26, Number 2
Allen B. Weisse, MD
W
hen it comes to the depiction of the medical world
on the motion picture screen or on television, you
can count me out. The errors and inconsistencies
that pop up there are more than this observer can
tolerate. A story set in the 1930s or 1940s meticulously observes the clothing, furniture, and even automobile models of
the period. Then, when a senior physician appears, he is not
wearing a long white laboratory coat appropriate to his position
but, rather, a short white jacket, more properly worn by medical students and junior houseofficers. We are shown a scene in
an examining room or operating suite, and there on the x-ray
view box is the chest film of the patient—inserted backwards.
(And no, Virginia, the story is not about an outbreak of situs
inversus.)
On the popular series ER, we witnessed junior residents in
the emergency room performing all kinds of sophisticated diagnostic and therapeutic procedures short of open heart surgery.
Then there was Dr. House, showing up week after week badly
in need of a shave, a haircut, and, possibly, delousing judging
from his appearance. The only thing more distasteful than that
was his personality. When he strode with impunity into an isolation unit, alarms should have gone off rather than the welling
up of stirring background music. How this character became
an icon simply baffles me.
Complaining about such misrepresentations as these might
be called nitpicking. They are clearly in the realm of fiction.
There is another example of malpractice in the world of make
believe that, unlike the other transgressions, extends into the real
world. What I refer to is the practice of attempting to auscult
the chest through one or more layers of clothing. Aside from
seeing this on TV and in films, I had noticed it occurring every
once in a while in real life, most often in the setting of a busy
outpatient clinic with doctors pressed to rush patients through
that particular gantlet.
The presence of any layers of clothing lying between the
stethoscope head and the patient’s skin is bound to muffle any
findings—normal or otherwise—that might be present. Faint
heart murmurs and gallops as well as fine rales in the lungs
might well be lost to detection. Appreciation of the splitting of
the heart sounds, present in most patients, even those without
heart disease, might be reduced as well. Such failures in auditory
perception might lead to serious failures in diagnosing heart or
lung pathology and following up with appropriate diagnostic
technologies. Conversely, a patient with dramatic symptoms
unsupported by history or physical findings may prompt a
physician, uncertain of his bedside skills, to order a number
of expensive tests that might only increase the patient’s fears as
well as his medical bill.
Such considerations got me to wondering how widespread
this deviation from good clinical practice had become. To get
some idea of this, I began tabulating all representations of chest
auscultation in the public media, almost exclusively television,
and noting whether proper technique was being demonstrated
(SKINS) or the improper technique of listening to the chest
through one or more layers of apparel (CLOTHES). All these
examples were placed in the category of either professional
representations (doctors and nurses on newscasts and in documentaries) or commercials (actors in dramas, pharmaceutical
advertisements, or health care facility promotions). I also made
note of the sex of the subject being examined. (Would the
reluctance about representing free frontal nudity of women on
television work against their being included among the SKINS?)
Instances in which the clothing remained in place but with the
stethoscope inserted under it to make contact with the skin
were registered as SKINS. It took about 2 years to collect the
100 cases I wished to accumulate for analysis.
It turned out that of the 100 individuals portrayed, 71 appeared in the professional category and 29 in the commercial
category. Among the latter, only 16% were SKINS, not terribly
surprising considering the source. I turned my attention to
the professional group. Here 37% were SKINS. Surprisingly,
gender did not have a hand in this distribution: among men the
proportion of SKINS was 36% and among women the finding
was 42%. In both groups, however, the number of correctly
performed examinations was depressingly low.
Recent studies evaluating skills in performing physical examinations by medical students, housestaff, and even medical
school faculty have uniformly shown a 20% to 80% error rate in
recognizing actual or simulated findings (1–5). Such deficiencies
From the Department of Medicine (retired), University of Medicine and Dentistry
of New Jersey, Newark.
Corresponding author: Allen B. Weisse, MD, 164 Hillside Avenue, Springfield,
NJ 07081 (e-mail: [email protected]).
191
can only be exacerbated by improper auscultatory technique
such as that described here. For those of us too easily prone
to become overwrought or even incensed at certain troubling
realities, our friends and colleagues may properly caution, “Keep
your shirt on.” But when our patients’ bodies are trying to tell
us through an examination of the heart and lungs, for example,
what may or may not be troubling them and when such findings
are so clearly obfuscated by faulty technique, perhaps we should
be swayed by a different kind of advice. Recall the sultry Swedish
blonde in that classic Noxzema shaving cream commercial who
urged us to “Take it off. Take it all off.”
1.
2.
3.
4.
5.
St Clair EW, Oddone EZ, Waugh RA, Corey GR, Feussner JR. Assessing
housestaff diagnostic skills using a cardiology patient simulator. Ann Intern
Med 1992;117(9):751–756.
Mangione S, Nieman LZ. Cardiac auscultatory skills of internal medicine and family practice trainees. A comparison of diagnostic proficiency.
JAMA 1997;278(9):717–722.
Roldan CA, Shively BK, Crawford MH. Value of the cardiovascular physical examination for detecting valvular heart disease in asymptomatic subjects. Am J Cardiol 1996;77(15):1327–1331.
March SK, Bedynek JL Jr, Chizner MA. Teaching cardiac auscultation: effectiveness of a patient-centered teaching conference on improving cardiac
auscultatory skills. Mayo Clin Proc 2005;80(11):1443–1448.
Vukanovic-Criley JM, Criley S, Warde CM, Boker JR, Guevara-Matheus
L, Churchill WH, Nelson WP, Criley JM. Competency in cardiac examination skills in medical students, trainees, physicians, and faculty: a
multicenter study. Arch Intern Med 2006;166(6):610–616.
Reader comments
Dear Dr. Roberts:
Thank you for including the image of mine, Vespers, in
the January edition of the BUMC Proceedings in the Avocations “department.” It is an honor to have an image of mine
presented.
This issue is another wonderful publication. Dr. O’Brien’s
article, “My Surgical Heroes,” included many surgeons that I
know and hold in the same high esteem: Dr. Sparkman and
Dr. Bookatz, both of whom were examples to me of excellent
physicians. I met Dr. Bookatz as a medical student during my
rotation through surgery at Parkland as a junior and senior
medical student at Southwestern Medical School in 1963 and
1964. I later met Dr. Sparkman when I joined the surgical staff
at Baylor in 1971 as a member of his surgical department. Dr.
Sparkman influenced not only the residents that he trained but
also the staff members of his department. He set an example
for perfection and extracted the utmost from those who strove
to practice medicine up to the standards he set. My own surgical heroes include Dr. Owen Wangansteen and Dr. Walton
Lillehei, under whom I trained at the University of Minnesota
in 1954–1955.
Your article, “Facts and ideas from anywhere,” is an exciting compendium of revelations concerning so many aspects
of medicine and helps one focus on the timeline of medical
192
thought and practice. It is a marvel the way you can accumulate
and present such a wide spectrum of ideas.
—Jay Hoppenstein, MD
Dallas, Texas
Dear Dr. Roberts:
I keep a stack of “to-read” magazines and journals on my
coffee table for times of leisure reading, and any unread Baylor
Proceedings is always at the top.
Last Saturday, with a fire going in the den fireplace and our
cat beside me in our chair (the cat thinks it is her chair), I opened
up the new January issue of the Proceedings and, as I always do,
read it cover to cover. Your “Facts and ideas from anywhere” is
the first thing I always read, and the section on hydrophobia was
really fascinating—so much so I gave it to my wife, who also
read it and enjoyed it as well. You have an easy-to-read writing
style for this section that is unmatched.
The other articles were excellent as well—important and right
to the point. The ECG in hypothermia even prompted me to add
this to our Internet-based disease surveillance program. The ECG
stood out particularly well on that great paper you use.
Please keep up the good work and keep those Proceedings
coming for their place at the top of the stack!
— Vincent E. Friedewald, MD, FACC
Spicewood, Texas
Volume 26, Number 2
In memoriam
GEORGE E. HURT JR., MD
Department of Urology, Baylor University Medical Center
at Dallas
George Ellison Hurt Jr., MD, died on November 11, 2012,
after a long illness. He was born on December 21, 1932, in Dallas
and spent most of his life there, graduating from Highland Park
High School, Southern Methodist University, and the University of Texas Southwestern Medical School. Graduating first in
his medical school class, he received the Ho Din award for the
graduating student deemed most outstanding by his peers and
the faculty. Dr. Hurt completed his internship at Denver General Hospital and his general surgery and urology residencies at
Parkland Memorial Hospital in Dallas. He then enjoyed a thriving
private urology practice at Baylor University Medical Center for
41 years, with partners Drs. Alexander, King, Fuqua, and Ware.
He was a member of the Combined Examination Committee
of the American Board of Urology and the American Urological
Association and served as president of both the National Society for Pediatric Urology and the South Central Section of the
American Urological Association, in addition to holding many
other leadership and service positions. Beyond his practice at
Baylor, he founded the urology clinic for spina bifida patients
at Texas Scottish Rite Hospital and directed it for 40 years. He
was also associate clinical professor of urology at UT Southwestern, a member of medical advisory committees at Parkland
Memorial Hospital, and director of the pediatric urology service
at Children’s Medical Center. He was internationally regarded as a
surgeon, educator, and innovator in urology and was the recipient
of numerous community and humanitarian awards. Tributes to
Dr. Hurt appear on p. 194 of this issue.
HAROLD C. URSCHEL JR., MD
Department of Thoracic Surgery, Baylor University Medical
Center at Dallas
Harold Clifton Urschel Jr. died on November 12, 2012, at the
age of 82. He was interviewed in Proceedings (2003;16(3):315–
333), and the introduction to his interview by Dr. Roberts appears
below. Tributes to Dr. Urschel appear on p. 196 of this issue.
Hal Urschel was born in Toledo, Ohio, in 1930 and grew up
primarily in Bowling Green, 20 miles away. After public schools,
he went to Princeton University on a football scholarship and
graduated cum laude in 1951. The Princeton team was undefeated during his freshman and senior years. He also had a scholarship to Harvard University School of Medicine, where he again
graduated cum laude in 1955. His internship, residency, and chief
residency in general, vascular, cardiac, and thoracic surgery were
at the Massachusetts General Hospital in Boston. After serving
in the US Navy as chief of experimental surgery at the National
Naval Medical Research Center in Bethesda, Maryland, he and
his young family moved to Dallas. In addition to his practice at
Baylor University Medical Center at Dallas, Dr. Urschel taught
extensively and was clinical professor of cardiovascular and thoracic surgery at the University of Texas Southwestern Medical
School. He published over 300 articles in medical journals or
chapters in books and was an editor of and major contributor to
seven books. He was visiting professor at a number of medical
centers in the USA and abroad and was an honorary member of
the thoracic surgery faculty of the University of Toronto and the
Harvard Medical School. He served as president of five major
surgical societies: the Society of Thoracic Surgeons, American
College of Chest Physicians, International Academy of Chest
Physicians, Southern Thoracic Surgical Association, and Texas
Surgical Society. He received a number of honors for his achievements, including two honorary doctorates. He and his lovely and
brilliant wife, Betsey, were the proud parents of five children, all
of whom are graduates of Princeton University.
ELGIN WILLIS WARE JR., MD
Department of Urology, Baylor University Medical Center
at Dallas
Dr. Elgin Willis Ware Jr. died on November 20, 2012, at the
age of 88. He recently established a lectureship in medical history
at Baylor, and the introduction to the lecture provided by Dr.
Michael Emmett appears below. A tribute to Dr. Ware appears
on p. 199 of this issue.
Dr. Elgin Ware, a long-time urologist at Baylor University
Medical Center at Dallas and chief of urology from 1986 to 1987,
spent his entire life in Dallas: he graduated from Highland Park
High School, Southern Methodist University, and the University
of Texas Southwestern Medical School before completing an internship at Baylor Hospital and a urology residency at Parkland
Hospital. After completing his training, Elgin entered the practice
of urology and quickly became a leader at the local, state, and
national level. He was the president of the Dallas County Medical
Society in 1976, was a delegate of the Texas Medical Association
(TMA) for many years, and served as a trustee of the TMA from
1980 to 1990. He was elected president of the American Association of Clinical Urologists in 1978. Beyond the hospital, he
served as a member of the Highland Park School Board for 14
years, worked as a volunteer and then director of the Stewpot, a
downtown Dallas soup kitchen, and initiated a medical clinic to
provide care to the indigent. Finally, Elgin had a profound interest
in medical history. He chaired the History of Medicine Committee of the TMA from 1989 to 2001. In 1995, he established
the Elgin W. Ware Jr. TMA collection of prints and drawings at
the Blanton Museum of Art on the University of Texas campus
to educate the public about the profound connections between
medicine, art, and print making from the renaissance to the present. He also coestablished, with Robert Mickey, the History of
Medicine Photography Gallery at the TMA. The Elgin W. Ware
Jr., MD, Lectureship in Medical History at Baylor is one of three
lecture series he endowed.
193
BOB ALLISON, MD
Happy, with apologies to Rodgers and Hammerstein’s Sound
of Music, “How do you hold a ‘sunbeam’ in your hand?”
I met George Hurt poolside at a Phi Chi rush party, September
1953, just prior to entry into the freshman class at Southwestern
Medical School. We pledged Phi Beta Pi. He organized our
anatomy table—six students to a cadaver in the shacks on Oak
Lawn Avenue. It was a macabre scene: 18 bodies and 100+ students in a relatively small space with no air-conditioning! This
was Dr. Hal Weathersby’s first year at Southwestern.
George was one of the smartest people I’ve ever known, if
not the smartest. He was academically number one in our medical school class. He was five average points ahead of the next
classmate. The next 20 guys were within two average points of
each other. He was the obvious choice for the Ho Din award of
the class. We had a great time in medical school, playing widow
whist or ping-pong at lunch the first 2 years. Ann and George
married after our freshman year. Happy drove a yellow cab that
summer. Catherine was born our senior year. We topped off the
fourth year by wearing our tuxes with short pants with long
white socks to the spring formal at the Dallas Country Club.
George completed his urology training at Parkland Memorial Hospital with Dr. Harry Spence. He joined the firm of
Alexander, King, Fuqua, and Ware in Dallas. Happy did a lot
of things for a lot of people, most of which he took little or no
credit for. George founded the urology clinic for spina bifida
patients at Texas Scottish Rite Hospital and served as director
of the clinic for 40 years.
He really helped a lot of friends and acquaintances down
on their luck as well as visiting national and international professors and others. I once sent one of the principals of Texas
Instruments to see Happy as a work-in without calling ahead;
George questioned my judgment. I told him it did not make
any difference. He treated all patients the same, rich or poor,
famous or infamous.
George was honored as a Distinguished Alumnus at both
Highland Park High School and Southern Methodist University.
His senior year in high school, he was recognized as the best allaround athlete, lettering in football, basketball, and baseball.
Happy always had time for his children: coaching Y teams,
going horseback riding, skiing, going on hunting and fishing
trips and multiple trips in and out of the USA.
I can never adequately express my admiration for the care
Ann provided Happy during the years of his very protracted
illness.
194
I may not be able to hold a sunbeam in my fingers, but I
can in my heart.
CATHERINE HURT SCHEIHING
You can read about my father’s many honors and accolades,
but the true essence of this amazing man was much more than a
title. Daddy was a brilliant man with the heart of a child. That
translated into incredible adventures for us, his kids. He was
always laughing and thinking of crazy fun stuff. The list of our
activities—like helicopter rides, horses in our front yard, river
rafting, and so much more—reads like an adventure series.
Family road trips in the station wagon were a vacation staple.
The Hurts traveled to both coasts, more than once, plus a couple
of times to Canada, south into Mexico, and everywhere in between. Daddy was happiest behind the wheel, in control, going
80 miles an hour, faster if Mother wasn’t looking.
Every winter there were road trips to Colorado. He was
the most beautiful skier I have ever seen. You could spot him
from far away gliding like an angel down the black slopes. He
proudly skied until his late 60s, finally qualifying for a free
senior lift pass. Most of the time you could find Daddy on
the bunny slopes, always helping whomever was the youngest
at that time—since you never knew when another Hurt kid
would enter this world.
One summer Daddy called one of his famous family meetings. With great joy, we felt certain that all the begging for a
swimming pool had come to fruition. Instead we were stunned
to find out that instead of a pool, we were getting a new baby
brother. Hello Gregory, good-bye swimming pool.
All of these multiple car trips made for terrific memories,
tremendous family times, outrageous laughter, singing, story
telling, and catching Daddy’s contagious thirst for learning and
seeing all there was to our wonderful nation. On one trip after
many battlefield visits and historical sites, Daddy instilled such a
powerful reverence for our country that Doug and I are saluting
in every photo from that trip.
Daddy also traveled around the globe. For many of the years,
Mama stayed home with “the baby,” whoever that was at the
time. Daddy almost always took one or two or even three of
us with him on his travels. Eventually even Mama joined in on
the adventures. Once Daddy crossed the border leaving Texas,
his cowboy hat was on his head and his boots on his feet. He
was so proud to be a Texan.
Carolyn went with him to Red China as it first began to
open its borders to Americans. He took the boys to Africa; all of
us went to Europe, many times. We went to Israel, too. Other
travels included India, Saudi Arabia, South America, Australia,
and countless other places.
The language barrier was never a problem for Daddy. He
had his own universal language. Daddy would smile from ear
to ear and give a Tootsie Pop. In Kazakhstan, on the far eastern
side of what was then the Soviet Union, Daddy was the first
American most of the people there had ever seen. They were
terribly afraid of him at first, but Daddy’s sincerity, smile, and
Tootsie Pop language won their hearts.
Once I witnessed this myself. We were driving through Yugoslavia just when Eastern Europe had begun to allow a few
people in. We were on a one-lane road barely passing ox-pulled
carts. We saw a group of children and their mothers in the field
harvesting their wheat with scythes. Daddy stopped the car,
hopped out, gave a loud whistle, and the curious folks walked
over. When the mothers saw his smile and the Tootsie Pops
Daddy was holding high in the air, they gave a nod and the
children rushed forward laughing and smiling. Tootsie Pops
for everyone!
Daddy was magical with children. He was the kind of person that sat on a bench at a park and before you knew it, little
children had gathered around him. He took our entire neighborhood on bike rides; I’m talking 20 to 25 kids on bikes and one
adult, Daddy. The youngest would be sitting in the front basket
of his bike. Our doorbell would ring, and when we answered we
were likely to hear, “Can Dr. Hurt come out and play?”
Daddy coached every sport offered at the YMCA to every
age group imaginable. He loved every second of it. I remember
when he first started coaching Ellison’s soccer team. None of the
parents even knew the rules of soccer at the time, so volunteers
were few. Daddy went into coaching soccer full steam ahead,
just like all the other sports. He just loved being with his kids
and their friends.
At my wedding, the overwhelming memory most people
have is that we had an ice cream Sundae bar. Why? Because
my dad said, “I don’t like to eat cake without ice cream.” Dad
proved that a human could live on coffee, Diet Dr. Pepper, and
Bluebell ice cream.
Daddy really lived. He burned the candle at both ends.
Daddy worked long, hard hours, but when he got home, he
would go to the front porch and whistle. The Hurt kids would
come running, along with a few other neighbors. Once Daddy
was home, he was all ours. The fun had arrived!
One year in high school, the school phone book came out.
There was an ad in it that read simply, “No phone calls after 9:00
pm. Dad.” I was mortified and went straight home and demanded to know if he had put that ad in the phone book. Daddy
looked at me puzzled. His answer? “How did you know?”
Daddy liked to go to bed by 9:00 pm. That rarely happened,
but that was always his plan. He was up and gone by 4:30, 5:00
at the latest. His rounds were done by 6:00 am and then surgery
started. By mid morning he was in the office seeing patients.
Every Tuesday afternoon was Daddy’s time off. Instead of
taking the time off, this was his day to work at the Texas Scottish Rite Hospital and later the hospital’s Spina Bifida Clinic
April 2013
that he founded. It was a labor of love. He loved on all those
special kids, and they loved him back. Those donated afternoons
gave him countless wealth in his heart. He showed us how to
be generous with our time in helping others.
So many people I know and have met have wonderful stories
about how Daddy saved their life or changed their life for the
better. He was a true physician. He cared tremendously about his
patients. The time and concern he gave each one was genuine.
Daddy loved people—all people, every kind of person imaginable. He had the uncanny gift to make each person feel as if
he or she mattered. Indeed, each person did matter to Daddy.
Daddy loved his children and grandchildren. Most of all he
loved Mama. It was a joy to see Daddy come home and grab
Mama in a bear hug and tell her he loved her. Then Mama would
shake her head and say, “Oh Happy!” It made us all laugh.
Daddy was passionate about many things. He showed us
by the way he lived that love of family mattered. He showed us
to love the Lord with all your heart. He showed us that love of
country and the great state of Texas should be ingrained. Do
your best. Never stop trying. Do what is right. Forgive. Find
the best in all people. Friends are a blessing and a joy.
Daddy told us often that family is enormously important.
You stick together. Family is whom you can count on. Never let
anything come between us brothers and sisters. I guess somehow
that got through to us. My younger brothers and sister and I
have muddled through all these years, sticking together and
loving each other as Daddy taught us. I can’t say it was always
easy; we are so different. But to this day we remain very close.
I am proud to have passed that belief on to my own children,
who are each other’s best friends.
The stories about Daddy are countless, incredible, crazy,
hilarious, and all true. I imagine all those who knew him have
their own encyclopedia of hair-raising tales about or including
Happy Hurt. I know I do. If I told even a small amount, we’d be
laughing, we’d be crying. And we would still be here when the sun
came up. I know that Daddy would say to each of you here: You
matter so much to me. I love you. Now go out and love others.
Laugh and take a handful of Tootsie Pops with you to share.
WILLIAM C. ROBERTS, MD
I was fortunate at Southern Methodist University to be a
classmate and fraternity brother of George Hurt. I knew no one
when arriving in Dallas, but George and his friends rapidly took
me in. A trip to Mexico with George and several others and then
a visit to his family’s ranch remain vivid in my mind all the years
since. The more I learned about George, the more I was awed
by him. I heard that he had never made less than an A through
junior high and high school, and he never made less than an A
in college either, going to medical school after 3 years. George,
I believe, could walk out of a class and quote the lecture he had
just heard, and read a page and recite it. He certainly had one of
the most brilliant minds that I have encountered. Additionally,
George was a wonderful athlete. You name the sport and he was
good at it. And all the time he was friendly, fun, humble, and
modest. His nickname “Happy” was most appropriate. George,
you were special and you will be missed.
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AMANDA URSCHEL GOLDSTEIN
I am Hal’s fourth child and first girl (in the whole generation on both sides, as he would always say). Dad was one of
my very favorite people in this world, my biggest inspiration.
He was a man of excellence, a man of great faith, and a man
who made it his mission to serve others. His devotion to his
family and friends proved paramount. Dad loved to learn and
even more to teach. Humor was his modus operandi. We are
so lucky to have had him so long and so great until the end!
When he died, he was 82 and still working full-time, still on
the cutting edge. In fact, he had just finished a weekend in
Los Angeles, coordinating research on the use of stem cells
to treat heart failure.
While it is so sad and shocking for those of us left behind,
we take great comfort in knowing that he went the way he told
us he had hoped to go—instantly and traveling while working
on what he loved most. What a blessing for him. The Lord was
especially nice to take him the day before the election.
As many of you know from his fabulous stories, Dad grew
up in Bowling Green, Ohio, as Tubby. Having witnessed his
dad dying from a heart attack when he was just 13 years old,
Dad was determined to find a way to prevent that for others by
committing himself to study heart surgery. At home, he quickly
took over as the head of the household to help his mom raise
his younger brother, Bill, and his sister, Ann, who had Down’s
syndrome. They counted completely on their friends for food
and the basics of life. I believe this is why he cherished every
friend, more than most do. His faith carried him through those
days and proved to be the foundation of his life.
We always joke that nobody had more best friends than
Dad—but it was true! He constantly called to check in, remembered something significant, or thanked us for a simple
deed. Every little gesture was noticed and appreciated. He was
a man who managed dozens of tasks simultaneously, yet when
you called, it seemed as if he had nothing else on his mind but
you. He was so proud of his family. He would send out e-mails
to hundreds of people describing his grandkids’ accomplishments—with excessive exaggeration.
He always fought for and supported those in need. In fact,
he had a special gift with those in need and took care of so
many for years.
Dad approached life with humor. He was perpetually telling jokes, many of which can’t be repeated. One of his favorites
was: When I die, I want to go peacefully in my sleep like my
grandfather did, not screaming like the other passengers in the
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back of his car. Then he’d laugh and laugh—usually with tears
streaming down his face.
Dad loved sports and loved to win. He loved football, particularly the St. Mark’s Lions, the Princeton Tigers, and the
Dallas Cowboys. He believed sports taught one more about
life than anything else. And he believed that coaches are the
most influential people in one’s life, next to one’s parents. As
we watched the Cowboys this past Sunday, as he did faithfully,
we could hear him cheering along with us. In high school, we
had to be the captain of every sport we played. If a coach didn’t
put his kid or grandkid in the game, you could hear Dad yelling
across the field to put his kid in, with a few choice expletives
added.
Many of you know that Dad could out-cuss anyone—
whether at home, in the OR, or at Grandparents’ Day. Nurses
would tally his f-bombs in the OR, and he clearly set records.
And then, after each operation, he would grade them on how
they performed in the surgery. He left owing Liam (his youngest grandson) 9 minutes for bad language. On Liam’s timeout
chart the penalty was 1 minute for each bad word. Grandpa
would cuss and laugh, and Liam would say, “Grandpa, you are
up to 9 minutes already!”
Dad always amazed us with the latest technology and
medical advances. He always had the latest camera and took
so many pictures that it was painful. He’d bark to us, “Smile,
and like it!” Then we were lucky enough to be forced to sit and
watch the unedited versions of countless family movies over the
holidays.
Growing up in the Urschel family was always entertaining.
We always had breakfast/dinner together. Often Dad would
come home to eat, then go back to work. He would serenade
us on his ukulele with his two favorite songs: Take Me Out to
the Ballgame and Mr. Moon.
Dad also often embarrassed us. We were known as the family that showed up to church on Christmas morning in our
pajamas and thought that was normal. Dad and Mom, out
of sheer enthusiasm, belted out hymns during the service, as
if they were competing to see who could sing the loudest. My
friend would come pick me up early on Sunday mornings and
hope she didn’t arrive as Dad was out getting the paper—naked.
Other times, he would lecture and then force my friends to eat
their vegetables at our dinner table.
Dad could roar louder than most. It didn’t take me long
to realize, though, that if you just gave it right back to him,
he would respect you. My kids would just smile as Dad yelled,
and he would soon break and start laughing himself. While he
seemed like a big, burly grizzly bear, he was really a big, snuggly
teddy bear. He would pull out the yellow legal pad every few
months and call me in to go over everything I had done wrong.
I would just smile and say, “Yes, Sir.” Nobody was ever good
enough for his daughters. In fact, no boy was allowed on our
property when we lived at home.
Dad loved St. Mark’s, Harvard Medical School, and especially Princeton. Our Christmas presents were always Princeton
glasses, blankets, doormats, and trash cans. He bled orange
and black. And he played the Tigertones in his car until the
very end.
PawPaw also loved to hunt and fish. He cherished sharing
the outdoors with us and enjoying things as simple as watching
a cardinal in a tree. He would give us guns for Christmas or
birthday presents and we’d go to the shooting range for family
outings over the holidays—again a little different than most.
Dad traveled the world and wanted everyone else to. He and
Mom would pack all seven of us in the station wagon and drive
to Colorado in the summer. We would laugh too much in the
back seat and get screamed at, only to make us laugh harder and
get in more trouble. We always had to stop at the Big Tex Steak
House in Amarillo so all four boys in the family could eat the
72-oz steak, appetizer, baked potato, roll, and a dessert in less
than an hour, so we could get it free. They succeeded every time,
of course. Once Brad and Hal could drive, we started taking
two cars. Mom would quiz us on vocabulary words over the
CB radio, only to get bashed by the truckers using that same
channel. We were known for our eating contests at the hotel
buffets and our tanning contests on the beach.
Dad always wanted the best and nothing less. Dad often
preached to us that “learning is fun!” His excitement about
learning was clearly contagious. He lived every single minute of
his life. He worked at night and then would fall asleep sitting
up, mid meal, or mid conversation the next day. He would come
in our rooms at 7:00 am on weekends, raise the curtains, and
say, “Wake up. You are wasting your day!” Dad never settled
for the status quo or mediocrity. Do everything to perfection,
regardless of what you were doing. Marry the best, as he did,
and marry for good breeding genes. Fight for what is right and
refuse to lose.
Our stories with Dad are endless, just as our love for him
is. The love he doled out will last forever more. Dad was our
biggest fan and our biggest inspiration. What an example. What
a gift to this world! I challenge you: Be the friend he was, laugh
as he did, love to learn, take care of others, and live life to the
very fullest—just as Hal Urschel would have. What a beautiful
life! How lucky we are to have had him as our Dad in full form
for as long as we did. We are truly blessed! Dad, I love you!
Save us all a big hug!
MICHAEL RAMSAY, MD
Hal was described to me recently as an icon of cardiothoracic surgery by Dr. Mike Mack—what a fitting description
of a great physician and man. We celebrate the life of a truly
amazing individual who has contributed so much to medicine,
April 2013
research, and mankind. I knew Hal as a great family person; in
the operating room as a world-class surgeon; and in research as
a cutting-edge physician-scientist.
I first met Hal and Betsey when Zoe and I arrived in
Dallas at Baylor 36 years ago at a cardiac surgery meeting at the
Petroleum Club that he and his good friend Denton Cooley
were hosting. Hal gave many talks—an invited speaker around
the world—scientific as well as “after dinner.” He was never at
a loss for words and could ad lib on any topic. He would also
give great introductions to renowned individuals like Denton
Cooley, but somewhere he would often include the sentence, “I
taught him everything he knows—but not everything I know!”
Hal published extensively, and this included the authoritative
tome on thoracic surgery that he edited with Joel Cooper.
Family first—always—Betsey, Hal, Brad, Locke, Amanda,
and Susanna. He was always supporting the young. He would
call my children and tell them in no uncertain terms which
schools to go to—no discussion! Tara, my daughter, came to me
one day and said, “Dad, Hal Urschel just called. I am going to
Williams College!”
In the operating room, it was not for the weak, faint-hearted.
or incompetent. Hal was intolerant of incompetence, complacency, and particularly less than 110% commitment. He was
very fast to unleash expletives but always had patients’ best
interest at heart. At the peak, he, Drs. Donovan Campbell,
Maruf Razzuk, and Guy Prater were a world-leading team in
cardiovascular and thoracic surgery and in bringing new innovations to the patient. Hal had the personality to make things
happen. He did not pull punches and was very direct in his
commentary. He awarded grades to everyone after a surgery, and
F minus was frequently given; he set the bar high. Later Hal kept
his prominence with his unique transaxillary approach to cure
thoracic outlet syndrome, which he continued to this day.
Hal was the epitome of the clinical scientist, bringing research from the bench to the bedside. As he slowed down his
surgery practice, he increased his drive to make major advances
in cardiovascular research. He was the Baylor Chair in Cardiovascular and Thoracic Research and Clinical Excellence. With
Cara East, Baron Hamman, Greg Pearl, Jeff Schussler, and the
team, he led a stem cell program where bone marrow cells were
taken, prepared, and injected back into damaged heart muscle
to grow back into healthy heart cells. Hal was the “behindthe-scenes” mantra, always striving to make the field and the
patients better. He was preparing his presentation on this work
for the American Heart Association when he sustained his cardiac arrest.
I was asked by Hal and Betsey to join them on a trip to
Israel a couple of months ago, where Hal was going to teach
the lead surgeons how to do his thoracic outlet procedure. I
almost did not go because of commitments back at Baylor but
I am so glad I did. It was truly a trip to remember. Zoe and I
arrived in Tel Aviv and were picked up at the airport. We had
just brought carry-on bags—we travel light—but we had to wait
for the Urschels’ checked bags. The physician greeting us announced, “OK, we need 6 camels for the Urschels and one mule
for the Ramsays.” Hal operated at the Rabin Medical Center,
197
teaching the whole cardiothoracic surgical team. Then we went
to Jerusalem—escorted by Dr. Dan Meyer’s sister, Devorah,
who runs the YMCA there, and her husband, Robert Buerger,
the CBS reporter who you will hear every morning on KRLD
reporting on latest events in the Middle East. In Jerusalem we
visited Calvary and the site of Christ’s crucifixion. Hal confided
to me there that it would not be too much longer before he
would join him. I wondered if God realized what he was taking
on. I am sure he did! At least he surely does now!
Hal will be remembered for his strong personality, his drive,
and his impatience with anyone who was preventing progress,
but also for his compassion, family first, and inspiration for
the young. He was committed to making Baylor Health Care
System great. He was at Baylor for 50 years and loved it and did
198
everything he could to make it thrive in the forefront of medicine. In his pursuit of excellence, Hal would say: “Excellence is
a result of caring more than others think is wise, dreaming more
than others think is practical, risking more than others think is
safe, and expecting more than others think is possible.”
It does not seem that long ago that Hal joined a team climbing Mt. Everest. He would often say:
Life is short
And the art long
The occasion instant
The experiment perilous
The decision difficult.
Hal, your life was too short, but you lived it to the full. We
love you and Betsey—you will never be forgotten.
Volume 26, Number 2
STEVE FROST, MD
The city of Dallas, and for that matter, the state of Texas,
has lost a legend. Elgin W. Ware Jr., MD, passed away recently.
And with his passing, we’ve lost a truly great physician. His
contributions to medicine were multiple. I first met him as a
resident here at Baylor, where he would patiently teach surgical
technique but also “the art” of medicine. I was fortunate to later
join him in private practice where his partners all called him
“the Squire “ because he was such a gentleman to all we came
in contact with and always had a story to share.
He was born, educated, and trained in Dallas and joined
the urology group at Baylor in 1953, where he practiced until
2003. He held many leadership positions, including chief of
urology at Baylor, president of the American Association of
Clinical Urologists, president of the Texas Medical Association
50 Year Club, president of the Texas Urological Society, and
president of the Dallas County Medical Society, among others.
When he retired from the practice of medicine, he became the
medical director of the Stewpot Medical Clinic, caring for the
homeless of Dallas. He was also very interested in the history
of medicine.
In an article in Texas Medicine in 2008, he reflected on a
comment from a colleague that his generation was the greatest generation in medicine. He first noted, “Beginning after
World War II, this ‘greatest generation’ witnessed and indeed
was involved in a veritable explosion of knowledge in all areas
of medicine, discoveries and advances far too many to enumerate.” Yet, what had set the generation apart probably had more
to do with the art of medicine, “nothing more or less than a
sincere and compassionate care and caring for the patient.” He
hoped that for the younger generations, “their claim to greatness
might be marked not only by those scientific advances, but more
importantly, by an awareness and a continuation of their long
heritage of those qualities that are a vital component of the Art
of Medicine”—an art he practiced so well.
Good job, Squire! You will be missed!
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Book Review
Making Rounds with Oscar: The
Extraordinary Gift of an Ordinary
Cat by David Dosa
New York, NY: Hyperion, 2010.
Paperback, 256 pp., $13.99.
Reviewed by James Marroquin, MD
n a 2007 issue of the New
England Journal of Medicine,
amid the usual fare of the latest and greatest in biomedical
research, there appeared a short
piece about a cat named Oscar
(1). Living as a pet in a nursing home dementia unit, Oscar
demonstrated an uncanny ability to predict which of its residents
were about to die. The furry creature’s presence at a person’s
bedside invariably signaled that life’s end was near. The story
generated a good deal of interest, earning the feline 15 minutes of
fame. Now, years later, a book entitled Making Rounds with Oscar
chronicles a doctor’s discovery of the animal’s special gift.
The author, David Dosa, is a geriatrician at the Steere House
Nursing Center in Rhode Island where Oscar lives. He begins
the book by explaining why he made the unusual choice to
specialize in care for the elderly. I call his career decision unusual
because gerontology remains among the least popular fields
of practice for medical students to enter. Geriatric fellowship
training programs at even the most prestigious institutions are
sometimes unable to find willing candidates. Why is this the case
at a time when our aging population needs more practitioners
equipped to care for its elderly members? In a fee-for-service
system that pays physicians for performing procedures and seeing a high volume of patients, the time-intensive nature of
geriatric medicine makes it a specialty with some of the lowest
reimbursement for the greatest amount of work. And while
many young people enter medicine hoping to someday be the
celebrated bearers of miracle cures, geriatric care focuses on
helping individuals adapt to the inevitable frailties and limitations that come with age.
But Dosa does not lament or even mention what he has
foregone in money, power, and prestige. The fulfillment he derives from his vocation among the elderly does not seem to leave
much room for feelings of martyrdom or envy. It is a fulfillment,
he says, that comes from bearing witness to the stories of his
patients as they live the last of their days. These stories form
the heart of the book, and Oscar’s tale serves as an ideal vehicle
for sharing them.
When a trustworthy nurse at the Steere House tells Dosa
about the cat’s extraordinary talent, he is at first skeptical and
I
200
sets about investigating the matter. One by one, he interviews
the families of the patients Oscar accompanied in their final
hours. Since all of them suffered from dementia, a revealing
portrait of this devastating illness emerges. Dementia is characterized by deterioration in cognition, resulting in behavioral
problems and difficulty performing the basic activities of daily
life. Alzheimer’s, defined by the accumulation of certain proteins
in the brain, is the most common form of dementia, accounting for 60% to 70% of cases. Dr. Dosa’s clinical expertise and
the poignant narratives of patients and families dealing with
this disease combine to make the book a valuable educational
resource. In fact, the afterword contains some explicit guidance
for those doing the admirable and arduous work of caring for
people with intellectual disabilities.
But beyond being useful, Making Rounds with Oscar’s depiction of dementia speaks profoundly to the nature of personhood and the practice of modern medicine. Since at least the
time of John Locke, philosophers have reflected upon the idea
of personal identity. As an individual changes, what remains
constant and defining, allowing him or her to be considered
to be the same person over time? For the loved one of somebody with dementia, this can be much more than a matter
for idle speculation. When the essential qualities and traits of
your parent, spouse, or sibling are no longer present in their
diminished state, who is it exactly that you are caring for and
relating to? The son of one Steere House patient implicitly
responds to this question by remarking, “I said good-bye to
my mother a long time ago. Now I’ve just fallen in love with
this little lady!” Other characters in the book do not share
such a sanguine approach to what has been lost. When one
day, after 63 years together, the wife of a man named Frank
Rubenstein no longer recognizes him, he never again returns
to the nursing home to see her. Though Rubenstein continues
to call daily to check on his wife’s status, he cannot bear to see
the fear and suspicion on her face when she encounters him as
a stranger entering her room. But even as dementia surrounds
a self in isolating darkness, creative acts of engagement can
sometimes reconnect us, if only briefly, to the person we once
knew. For example, Jean Ferretti, the wife of the pioneering
musical composer and Steere House patient Ercolino Ferretti,
reports to Dosa that “one of the things I found most interesting about my husband’s disease was that even toward the end
of his life he responded to music. Here was this man who
could no longer do much of anything. Sometimes he would
get agitated. If you put on a jazz record, though, he would
just sit there contentedly for hours.” As dementia transforms
these individuals’ relationships with their affected loved ones,
what does not and cannot change are the covenantal bonds
they share with them. No matter how faintly these victims of
dementia resemble who they once were, to their family they
are still father, mother, husband, wife, sister, and brother.
Closely related to the issue of personal identity is the question of what makes human beings valuable and worthy of care.
The residents of the Steere House dementia unit have lost capacities that many people see as essential for a meaningful life. In
their impaired state, they can no longer contribute anything to
society. Given these realities, is the tremendous work required to
care for them warranted? Based on a certain utilitarian calculus,
the answer to this question is no. But if all people are considered
to have intrinsic dignity and worth, then a radically different
response is demanded. For instance, in the Christian tradition,
the Gospel is most manifest when people embody Jesus’ special
love for those who can offer nothing in return.
But we must not confuse our sacred call to care for people
with dementia with the automatic, reflexive use of all available
technologies in efforts to extend their lives. When a medical
intervention is more likely to be burdensome than beneficial,
the more loving course of action may be to aim for comfort
rather than the prolongation of life at all costs. This is illustrated
in a heartrending story about a frail, debilitated Steere House
resident named Saul Strahan. When Strahan develops a severe
infection, Dosa discusses his grave condition with Strahan’s
daughter and recommends against sending her father to the
hospital’s intensive care unit (ICU) for aggressive and likely
futile treatment. He suggests instead that Strahan remain in the
familiar surroundings of the nursing home with a focus on providing him a peaceful death as the infection worsens. Viewing
this approach as giving up on her dad, she insists that “everything be done,” even if there is very little chance of his recovery.
Dosa later finds Saul Strahan in the ICU on life support—a
breathing tube down his throat, a central line in his neck, and a
dialysis machine at his bedside about to be used as a substitute
for his failing kidneys. Dosa is saddened, but not surprised to
soon thereafter learn of his patient’s death.
April 2013
All available medical technology had been utilized on this
man’s behalf. But amid the heroic efforts to save his life, nobody was really present with him during his lonely transition
into the unknown. This tragic irony reflects many patients’ and
practitioners’ conflicted experience of contemporary medicine.
The past century witnessed the emergence of biomedical innovations our ancestors could have scarcely imagined. We can
administer vaccines and antibiotics to prevent and eliminate
previously fatal infections. We can replace insulin and other
vital hormones when our bodies’ production of them is insufficient. We can open obstructed arteries during heart attacks and
strokes, halting lethal damage to our hearts and brains. We can
cure certain cancers with surgery, radiation, and chemotherapy.
This growing, seemingly limitless capacity to triumph over afflictions before which humans had hitherto been helpless has
radically altered our expectations of health care. For the first 23
centuries of Western medical practice (dating from the time of
Hippocrates), clinicians’ primary role was to accompany and
guide their patients through the experience of illness. In contrast, now that efficacious interventions are available, achieving
desirable results is what matters. Yet positive outcomes are not
always possible. Indeed, despite modern medicine’s numerous
successes, death is still the ultimate outcome for us all. And as
the focus has turned to most efficiently fixing patients’ problems, the healing, pastoral aspect of care that once constituted
the heart of medicine has been neglected, to the frustration of
patients and physicians alike. The simple example of a cat lying
lovingly at a dying person’s side calls health care practitioners
back to the sacred role of being a compassionate presence.
1.
Dosa DM. A day in the life of Oscar the cat. N Engl J Med 2007;357(4):328–
329.
The reviewer, James Marroquin, MD, completed his residency at Baylor
University Medical Center at Dallas and now is an internist in Austin, Texas. He
can be reached at [email protected].
Book Review
201
From the Editor
US HEALTH
An expert panel appointed
by the US Institute of Medicine
reported their findings in January 2013 (1, 2). We in the US
live shorter lives than any of 16
peer nations, including Australia,
Canada, Japan, and 13 European
countries (Figure 1). Swiss men
live nearly 4 years longer than
William C. Roberts, MD.
American men, and Japanese
women live >5 years longer than
American women. Americans get their health care in a less
coordinated system than in any of the 16 other nations, and
we in the US pay more for it. The cost of care in the US in
2011 was $2.7 trillion, or $8680 for each American. The
closest among the other 16 nations was Switzerland, which
spent $5489 per person. Americans are more reckless than
those in the other 16 countries. Only Italians wear seatbelts
less often. Nowhere else do motorcyclists go without helmets
as often. Americans die more often in traffic accidents linked
to alcohol consumption, and they own far more guns (89 per
100 people compared with 46 per 100 people in Switzerland,
the peer group country with the next highest rate of gun
ownership).
Far fewer Americans than in the past use tobacco, and only
the Swedes now smoke fewer cigarettes than Americans. This is
a reversal of the situation in the 1950s, when Americans smoked
the most. Nevertheless, in 2003, smoking accounted for 1 in 5
deaths among Americans >50 years of age. But, smoking-related
deaths are expected to decline further in the USA with the drop
in the number of smokers and the rise in countries like France,
where 46% of adults smoke.
The panel pointed out, of course, that what we eat is
a major factor in the lower US lifespan. Americans eat,
on average, 3770 calories a day. That’s 1100 more calories
than the average adult male needs, and 1700 more calories
than an average woman should consume. Between 1999
and 2001, Austrians, Belgians, and Italians ate more but,
by 2007, Americans were well ahead of anyone else. Th e
average Swede consumes 17% fewer calories daily than the
average American.
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Figure 1. Mortality from noncommunicable diseases in 17 peer countries, 2008.
Reprinted with permission from National Academies Press.
GLOBAL OBESITY
Overweight and obese people now outnumber the malnourished by nearly 2 to 1. According to the World Health Organization (WHO), in 2010, 80% of American adult men and
77% of women were overweight (3). Obesity costs at least $150
billion a year in American health care spending. But obesity is
spreading rapidly in other parts of the world. Saudi Arabia and
other Arab states and many Pacific Island nations are fatter than
in the USA. Most of the adult population of Samoa is obese; in
2008, 46% of Egyptian women were obese. Mexican women
are heavier than US women, and Mexican men will soon eclipse
US men in poundage. These changes in part reflect advances in
public health. In 1900, pneumonia, tuberculosis, and childhood
diarrhea were the leading killers of Americans. Now, the top
causes of death are noninfectious diseases, mainly atherosclerosis, hypertension, and cancer. In 2008, 63% of deaths around
the world were caused by noncommunicable diseases and 80%
of them occurred in low- and middle-income countries.
Many countries are trying to come to grips with this major
shift in public health. Japanese companies require employees to
undergo annual physicals that include waistline measurements.
Measurements of over 33.5 inches in men and over 35.4 inches in
women count against the company. If too many fail the test, the
firm has to increase its contribution to public health care for the
elderly. Several countries tax soft drinks and other sugared beverages. Mexican legislators introduced a bill in December 2012
that would add a 20% tax to the cost of such drinks. In 2011,
the average Mexican adult consumed 728 servings of Coca-Cola;
the average American, 403 servings. The China Health Ministry
has asked Dr. Kenneth Cooper of Dallas, founder and chairman
of Cooper Aerobics, to explore the introduction of Fitness Gram
Testing among its schoolchildren. Cooper indicated that Ross
Perot contributed $2 million to help pay for a computer system
to aggregate the results. Ten years ago there was hardly any obesity in China, according to Cooper. WHO estimates that 45% of
Chinese men and 32% of Chinese women are now overweight or
obese. The fast-food chains are rapidly expanding in China. Yum
Brands, which owns Pizza Hut, KFC, and Taco Bell restaurants,
has 38,000 restaurants globally, including 740 Pizza Huts and
4,043 KFC establishments in China.
Business groups complain that taxes, regulations, and unfair
trade practices hurt their international competitiveness. Now, we
can add body weight to that list. The Organization for Economic
Cooperation and Development (OECD) in 2012 updated an
obesity epidemic watch among its 34 country members (usually
described as the wealthier developed countries) and found that the
average rate of obesity across the OECD was 17% (4); in the USA,
34%; in Korea, 4%; in Germany, nearly 15%; in the UK, 23%;
and in Mexico, 30%. In 19 of the 34 OECD countries, most
of the population is now either obese or overweight. In the US
and in Texas, more than two thirds of the population is either obese or overweight (Figure 2).
Texas comptroller Susan Combs has estimated
that obesity costs Texas employers nearly $10
billion in 2009.
drinks in 2005 was over 50 gallons, and by 2012, 42 gallons.
Soda companies raised prices in 2011 and again in 2012 and
volumes kept falling. The sugary bubbles are simply unhealthy.
Sodas’ traditional target market, namely youth, is often now
turning to water, energy drinks, and coffee instead. This of
course is good news unless you happen to be an investor in
Coca-Cola, PepsiCo, or Dr. Pepper/Snapple, which I avoid.
US MILK CONSUMPTION
In 1975, the US milk consumption per capita was 28.6 gallons and by 2011 it had fallen to 20.2 gallons (7). This decline
is good news. Cows are the biggest source of our cholesterol,
including their muscle, milk, butter, and cheese, and also our
biggest source of saturated fat.
RELATION OF PHYSICAL ACTIVITY AND SEDENTARY BEHAVIOR
TO SERUM PROSTATE-SPECIFIC ANTIGEN
A recent piece in the Mayo Clinic Proceedings (8) involving
1672 men found that for every 1-hour increase in sedentary
behavior, the participants were 16% more likely to have an
elevated prostate-specific antigen (PSA) concentration, and
for every 1-hour increase in light physical activity, participants were 18% less likely to have an elevated PSA concentration. We men sit on our prostate gland. Get up and keep
moving.
FASTING VS NONFASTING MEASUREMENTS OF BLOOD LIPIDS
Current guidelines recommend that total lipids and lipid
subclass levels be measured with a patient in a fasting state
BODY WEIGHT AND LEADERSHIP ABILITY
New research suggests that extra pounds
or enlarged waistlines affect an executive’s perceived leadership ability as well as stamina on
the job (5). Leadership experts and executive
recruiters say that staying trim is now virtually
required for anyone on track for the CEO corner office. Executives with larger waistlines and
higher body mass indexes tend to be perceived
as less effective both in performance and interpersonal relationships. While weight remains
a taboo conversation topic in the workplace,
heavy executives are judged to be less capable
because of assumptions about how weight affects health and stamina. A business school professor recently stated that he could not name a
single overweight Fortune 500 CEO.
SODA CONSUMPTION
Figure 2. Prevalence of obesity among adults, 2009 (or nearest year). Reprinted with permission from
In the USA, soda consumption is declining OECD (2011), “Overweight and obesity among adults,” in Health at a Glance 2011: OECD Indicators,
(6). Per capita consumption of carbonated soft OECD Publishing. http://dx.doi.org/10.1787/health_glance-2011-18-en
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203
(>8 hours after the last meal). Fasting recommendations were
originally introduced to decrease variability and achieve consistency in the metabolic states of patients at the time of sample
collection. Several studies, however, suggest that measurement
of lipid subclasses in a nonfasting state is an acceptable alternative, with some nonfasting markers being better at predicting the
risk of cardiac events. Sidhu and Naugler (9) measured various
lipid levels with fasting intervals varying from 1 to >16 hours
in 209,180 individuals. The mean levels of total cholesterol
and high-density lipoprotein cholesterol differed little among
individuals with various fasting times. The mean calculated
low-density lipoprotein cholesterol levels showed up to 10%
variation among groups of patients with differing fasting intervals. The mean triglyceride levels showed variations of up
to 20%.
MORE ON TATTOOS
Tattoos have become increasingly popular in recent years. In
the USA, in 2012, an estimated 21% of adults had tattoos, up
from 14% in 2008. The process of tattooing exposes the recipient
to risks of infections, some of which are serious and difficult to
treat. Historically, as LeBlanc and colleagues (10) emphasize, the
control of tattoo-associated dermatologic infections has focused
on ensuring safe tattooing practices and preventing contamination of ink used in the tattoo parlors—a regulatory task overseen
by state and local authorities. In 2012, several outbreaks of nontuberculous microbacterial infections associated with contaminated
tattoo ink raised questions about the adequacy of prevention efforts implemented at the tattoo-parlor level. The Food and Drug
Administration (FDA) began reaching out to health care providers, public health officials, consumers, and the tattoo industry
to develop more effective measures for tattoo ink-related public
health problems. Some reports of tattoo-related nontuberculous
microbacterial infections suggested that tap water or distilled
water used to dilute inks at tattoo parlors was a likely source of
contamination. Findings from more recent outbreaks suggested
that the inks were contaminated before distribution.
Under the Federal Food, Drug, and Cosmetic Act, tattoo
inks are considered to be cosmetics, whereas the pigments used
in the inks are color additives that require premarketing approval. This law requires that cosmetics and their ingredients
not be adulterated or misbranded, which means, among other
things, that they cannot contain poisonous or deleterious substances or unproved color additives, be manufactured or held
in unsanitary conditions, or be falsely labeled. Furthermore,
cosmetic manufacturers are supposed to ensure the safety of a
product before marketing it. But, the FDA does not have the
authority to require premarketing submission of safety data from
manufacturers, distributors, or marketers of cosmetic products,
with the exception of most color additives (dyes, pigments, or
other substances used to impart color). The FDA, however, can
conduct investigations, request that a manufacturer recall volatile
products, issue advisory letters, and request that the Department
of Justice conduct seizures, enjoin a firm or person from manufacturing or distributing products, or file criminal charges against
a firm or responsible persons on behalf of the FDA.
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It is particularly important to increase awareness about certain types of tattoo ink–related infections because of several
features of nontuberculous microbacteria. They may be difficult
to diagnose and treat. It can take up to 6 weeks to identify the
organism. A special culture medium and a skin biopsy may
be required. Antibiotic choices are limited by the susceptibility profile of the organism, and prolonged treatment may be
necessary to clear the infection. Moreover, complications such
as co-infections with pathogens such as methicillin-resistant
Staphylococcus aureus may pose additional challenges. Beware
of tattoos.
RENAL SYMPATHETIC DENERVATION FOR DRUG-RESISTANT
HYPERTENSION
Esler and colleagues (11) for the Symplicity HTN-2 investigators indicate that among the 7 billion people residing on
Planet Earth, nearly 1 billion adults have high blood pressure.
Despite the availability of numerous effective antihypertensive
medicines, hypertension remains uncontrolled for various reasons, including inadequate treatment. Among hypertensive patients receiving treatment, the estimated proportion of patients
with blood pressure uncontrolled (>140/90 mm Hg) ranges
from 45% to 85% in Europe and North America. Furthermore,
a subset of patients who adhere to a prescribed pharmaceutical
regimen of ≥3 drugs, including a diuretic, continue to have
uncontrolled or resistant hypertension. In the US, estimates of
resistant hypertension prevalence range from 10% to 30% of
adults receiving drug treatment for hypertension. These numbers reflect a serious health challenge because every 20/10 mm
Hg increase in blood pressure leads to a doubling of cardiovascular mortality.
The sympathetic nervous system plays an important role
in hypertension. Catheterization-based renal denervation is
a minimally invasive procedure involving the application of
radiofrequency energy in short bursts along the length of the
main renal arteries to ablate the renal nerves that lie within and
just beyond the artery’s adventitia.
The Symplicity HTN-2 trial randomized patients with resistant hypertension to either renal denervation or to no renal
denervation, with both groups maintained for 6 months on
antihypertensive medications. The primary endpoint, change
in office-based systolic blood pressure at 6-month follow-up,
demonstrated a significant difference in systolic blood pressure
between the treatment and control groups. Patients in the control group then had the option to receive the renal denervation
procedure. The 1-year results of this second trial, which included
6-month outcomes for the control group who were treated with
renal denervation, resulted in a significant drop in blood pressure similar to that observed in patients receiving immediate
denervation. Thus, renal denervation appears to provide a safe
and sustained reduction of blood pressure to 1 year in patients
with previous resistant hypertension.
WHY PATIENTS VISIT DOCTORS
St. Sauver and colleagues (12) from the Mayo Clinic
analyzed medical records of 142,377 patients in the county
Volume 26, Number 2
in which the Mayo Clinic is located to learn of the various
conditions that prompted patients to visit their physicians
during a 5-year period (2005–2009). Fifty-three percent of
the patients were female. The 20 most common conditions
among these individuals were as follows: skin disorders, 43%;
osteoarthritis and joint disorders, 34%; back problems, 24%;
disorders of lipid metabolism, 22%; upper respiratory disease
(excluding asthma), 22%; anxiety, depression, and bipolar
disorders, 20%; chronic neurologic disorders, 20%; hypertension, 18%; headaches, including migraine, 14%; diabetes
mellitus, 14%; arrhythmias, 13%; esophageal disorders, 10%;
asthma, 9%; thyroid disorders, 9%; iron deficiency and other
anemia, 9%; bowel disorders, 9%; cancer, 8%; biliary and
liver disorders, 8%; obstructive pulmonary disorders, 8%;
and coronary heart disease, 8%. Ten of the 15 most prevalent
disease groups were more common in women in almost all age
groups, whereas disorders of lipid metabolism, hypertension,
and diabetes were more common in men. The prevalence of
7 of the 10 most common groups increased with advancing age. Prevalence also varied across ethnic groups (whites,
blacks, and Asians).
steak, sausage, biscuit and gravy, fried okra and squash, strawberries, black-eyed peas, grits, corn, cornbread, and pecan pie.
A survey by the Centers for Disease Control and Prevention
(CDC), published in 2012, indicates that only 1% of adults in
Oklahoma are free from risk factors for or behaviors increasing
the risk for heart disease—the highest rate for any state in the
nation (15). Oklahomans also are less likely to report eating 5
or more servings of fruits and vegetables a day, and they are the
most likely to be overweight.
BEDBUGS AND SNIFFING DOGS
Canines trained to detect bedbugs did big business in Dallas during the summer of 2012 (13), and that infestation may
be back this summer. Bedbugs are resilient and can travel on
everything. As someone said, “It’s basically a hitchhiker. It goes
on suitcases and people spread it to other people. And once they
make their way into a home, getting rid of them can cost several
thousand dollars.” Apparently there is a pheromone in the bedbugs that dogs can smell. Dogs are about 97% accurate in finding
the bugs, while humans are only about 30% accurate.
DROWSY DRIVING
According to a study by the CDC, one in 24 motorists admitted to falling asleep behind the wheel in the past month (16,
17). The problem is more common in men than women and
in drivers aged 25 to 34 compared to older drivers. According
to Angie Wheaton, the lead author of the CDC study, approximately 2.5% of all fatal motor vehicle crashes (around 730 in
2009) involved drowsy drivers, as did 2% of crashes that resulted
in nonfatal injuries (around 30,000 in 2009). They also found
that around 4% of respondents fell asleep while driving in the
previous year. The government estimated that approximately 3%
of fatal traffic crashes involve drowsy drivers, but some studies
have put that estimate as high as 33%. Brief moments of nodding
off can be extremely dangerous, particularly when traveling 60
miles per hour. A single second translates to moving 90 feet, the
length of 2 school buses. According to Dr. Kingman Strohl, a
pulmonologist in Cleveland, a typical driver makes about 1000
decisions a minute. If a person has not slept for 18 consecutive
hours, his or her impairment on those decision-making tasks is
similar to that of someone above the legal alcohol limit. Everyone
knows about driving and alcohol drinking, but there is much less
emphasis on the importance of sleep before driving.
GRAPHOLOGY
I have kept a visitor’s book in my office for years and request
a signature and address from all those willing to provide it. A
number of years ago, while visiting The Greenbrier in West
Virginia, I took a class on graphology. The teacher talked about
letters leaning to the left or right, whether or not the long letters
touched the top line or the lower letters went below the lower
line, and whether or not there were lively movements in the
top one and flamboyant swirls in the lower ones and what they
meant. She recommended that potential spouses before marriage have a couple of paragraphs of their handwriting analyzed
by a graphologist.
Sherlock Holmes asked Dr. Watson in The Sign of Four,
“What do you make of this fellow’s scribble?” (14). “Look at
his long letters,” he said. “They hardly arise above the common
herd. That d might be an a, and that l an e. Men of character
always differentiate their long letters, however illegibly they
may write. There is vacillation in his k’s and self-esteem in his
capitals.”
FALLING TELEVISIONS
According to Kim Painter, falling TV sets have killed >200
children since 2000 (18). The Consumer Products Safety Commission showed that 29 people in the US, most of them children, were killed by falling TVs in 2011 alone, and 18,000
people a year in the US, most of them children, are treated
for injuries from falling TVs. That is happening despite the
widespread switch to lighter flat-screens. Safety experts say the
switch may actually be making the problem worse, because
consumers often take old, heavy sets out of their family rooms
and put them atop unstable bedroom dressers and playroom
shelves. Children climb up on furniture to turn the TV on and
there goes the heavy television as well as the piece of furniture.
The 50- to 100-pound TVs can crush a child. The TVs often
are on shelves never designed to hold the heavy weight. Flatscreen TVs also fall on kids because parents do not install them
in the safest way. Let’s secure these TVs, and if anchoring is not
an option, place the TV on a low sturdy base and remove any
items from the top that might attract children.
THE LEAST HEART-HEALTHY STATE IN THE USA
The official state meal of Oklahoma—designated by the
legislature in 1988—includes barbecue pork, chicken-fried
GUNS
The US has about 315 million people and about 290 million
guns. Germany has about 80 million people and 5.5 million
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guns (19). Germany has recently initiated a large registry that
details every legal gun owner in the country, along with information about all of their firearms. The new gun database,
which went into service January 1, 2013, allows law enforcement officials to scroll through lists of owners and their guns
in seconds on their computers. And the gun owners did not
resist the establishment of this registry. Many gun advocates
in Germany say that if cars can be registered and regulated,
so can weapons. It’s not quite that way in the USA, but
the US has about 50 times as many guns as are present in
Germany.
In the US it is easy to acquire any number of weapons and
unlimited amounts of ammunition. Those who pass laws make
it possible. The National Rifle Association traditionally muzzles
any congressional attempts at gun control laws. Surely there is
a relation between the number of people killed with guns and
the number of guns available.
VIRGINIA TECH, FORT HOOD, AURORA, SANDY HOOK . . .
Using news accounts and records from the Federal Bureau of
Investigation (FBI) from 2006 through 2010, the most recent
years for which complete records were available, USA Today
identified 156 murders that met the FBI definition of mass killings, in which 4 or more people are killed by the attacker (20).
The attacks killed 774 people, including at least 161 children
aged 12 or younger. Mass killers, in other words, target Americans once every 2 weeks on average, in attacks that range from
robberies to horrific public shooting sprees like the massacre in
Newtown, Connecticut. The USA Today review did not include
murders in 2011 or 2012, both of which were marked by a series
of high-profile public shootings. The 2006 to 2010 killings offer
a portrait of mass murder that in many ways belies the stereotype
of a lone gunman targeting strangers: lone gunmen, such as the
one who terrorized Sandy Hook Elementary School, account for
fewer than half of the nation’s mass killers. About one quarter
of mass murderers involved 2 or more killers. A third of mass
killings did not involve guns. Mass murderers tend to be older
than other killers, an average of nearly 32 years of age. Like all
killers, they are overwhelmingly men. The mass killings during
those 5 years accounted for about 1% of all murders during
that time in the USA.
DALLAS CRIME
Despite increases in some major areas—rape, robbery, and
murder—overall reported crime in Dallas dropped nearly 11%
in 2012 compared to 2011, a record ninth consecutive year
crime has fallen in the city (21, 22). The drop is in line with
what is happening nationally and was driven by significant
decreases in every area of property crime, which had about
7600 fewer offenses in 2012 than the previous year. Twenty
percent more thieves were arrested in 2012 than in 2011
through the help of a task force that targets rings that buy
and sell stolen property. Police Chief David Brown indicated
that the longer a thief is in jail, the better the stats are going
to be. Murders in Dallas in 2012 numbered 151, an increase
from 133 the previous year. In comparison, Chicago had 506
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murders in 2012, nearly twice as many killed than US troops
in Afghanistan.
MILITARY SUICIDES
Suicides in the US military surged to a record 349 in 2012,
far exceeding American combat deaths in Afghanistan (n = 295
Americans), and up from 301 in 2001 (23). Defense Secretary
Leon Panetta and others have called the problem an epidemic.
The problem appears to reflect severe strains on military personnel burdened with more than a decade of combat in Afghanistan
and Iraq, complicated by anxiety over being forced out of a
shrinking workforce. The 349 total in 2012 was the highest since
the Pentagon began tracking suicides in 2001. The army, by far
the largest of the military services, had the highest number of
suicides among active-duty troops in 2012 at 182. The Marine
Corps had the highest percentage increase—a 50% jump to 48.
The Air Force had 59, and the Navy, 60 suicides, an increase in
each of about 15% over the previous year.
GENDERCIDE
There are too many examples of global violence against
women. Beverly Hill, who is founder and president of the Gendercide Awareness Project, calls it gendercide—the elimination
of females, both young and old, through sex-selective abortion,
infanticide, gross neglect, and in the case of older women (particularly widows), lack of access to food and shelter (24). The
United Nations Population Fund, which tracks this problem,
has estimated that 117 million women are missing in the world
because of these practices. “Missing,” as Ms. Hill indicates,
equals death. That’s more deaths than World War I and World
War II combined. She indicates that it is no exaggeration to
say that gendercide is an atrocity as colossal as any the world
has seen. East Asia, South Asia, West Asia, the Middle East,
Africa, and Southeastern Europe are all ravaged by gendercide.
Every year, according to Ms. Hill, we lose 2 million baby girls
to sex-selective abortion and infanticide alone. That equates to
4 girls every minute.
The United Nations reports that China has the greatest sex
imbalance in the world, with 10% of its female population
eliminated; India and Afghanistan follow with 7%. These sex
imbalances lead to a host of social problems. Contrary to popular belief, the status of women does not improve when females
are in short supply. In fact, just the opposite occurs. Sex trafficking increases, as does the buying and selling of brides. Aging
bachelors, unable to find women of appropriate age, marry ever
younger girls. These child brides leave school and begin bearing
children. Maternal death rates are high. Ms. Hill goes on to
indicate that there is a strong correlation between sex imbalance and crime. Sex ratios apparently are the best predictors of
murder rates in India—better predictors than poverty, illiteracy,
or urbanization. Crime spiked in the Chinese regions where
sex-selective technology first became available. And finally, Ms.
Hill writes: “Gendercide proceeds from the belief that female
life is disposable. Gendercide devastates the hopes of women
everywhere. It is unworthy of us as human beings. It is time to
end this slaughter.”
Volume 26, Number 2
WOMEN IN CONGRESS
Of the 100 US Senators, 20 (20%) are women and of the
435 House Representatives, 78 (18%) are women; both of these
are records (25).
FIBRONACCI NUMBERS
By definition, the first 2 numbers of the Fibronacci sequence
are 0 and 1. Each subsequent number is the sum of the previous
two (26). The Fibronacci sequence is:
0, 1, 1, 2, 3, 5, 8, 13, 21, 34, 55, 89, 144, etc.
The ratio of any two consecutive numbers eventually approaches the “golden ratio” of 0.618.
1/11/22/33/55/88/1313/2121/3434/5555/8989/144
1.00.500.6670.600.6250.6150.6190.6180.6180.6180.618
The sequence made its first appearance in the West in the
book Liber Abaci (1202) by Leonardo of Pisa, also known as
Fibronacci. (The sequence first appeared in Indian literature
centuries before.) The Fibronacci sequence is important in nature: it describes the branching in trees, the arrangement of
leaves on a stem, the fruitlets of a pineapple, the flowering of
an artichoke, the uncurling of a fern, and the arrangement of a
pine cone. Fibronacci numbers are truly fascinating. They have
many implications for mathematicians.
PUBLIC HIGH SCHOOL GRADUATION RATES
The percentage of students at public high schools who
graduate on time has reached its highest level in nearly 40
years (27). The public high school graduation rate, i.e., students earning a diploma within 4 years of starting high school,
reached 78% for the class of 2010, the highest rate since 1974.
Graduation rates improved for every race and ethnicity in
2010. The student graduation rates were as follows: Asians,
93%; Whites, 83%; Hispanics, 74%; American Indians and
Alaskan natives, 69%; African Americans, 66%. In 2010, 38
states had higher graduation rates, while rates for the other
12 states were flat.
SMART DEVICES WINNING
Using a cellphone during class used to mean possible confiscation and perhaps detention for students (28). Now, a growing
number of schools are turning to the smart phones students
bring to school as an instructional device that can augment classroom learning. Teachers ask students to use their smart phones
to look up vocabulary words, take photos of an assignment
written on the board, or text themselves homework reminders.
Teachers use countless apps to better connect students with
coursework on a platform they are familiar with. The Verizon
Foundation chose 12 schools in 2012 and 24 in 2013 to receive
up to $50,000 in grant funding to bring laptops, tablets, and
mobile phones to class. The focus is on science, math, and
technology studies. The apps offer an easy way to do research,
solve problems quickly, and motivate students.
IQ
The average American in 1900 had an IQ that by today’s
standards would measure about 67 (29). Since the traditional
April 2013
definition of mental retardation was an IQ < 70, that leads to
the remarkable conclusion that most Americans at the beginning
of the 20th century would today be considered “intellectually disabled.” The trend of rising intelligence is known as the
Flynn effect, named for James R. Flynn, the New Zealander who
pioneered this area of research. The average American IQ has
been rising steadily by 3 points a decade. Spaniards gained 19
points over 28 years, and the Dutch, 20 points over 30 years.
Kenyan children gained nearly 1 point a year. These figures
are from Flynn’s new book entitled Are We Getting Smarter?
It’s an uplifting tale, a reminder that human capacity is on the
upswing. The country that tops the IQ charts is Singapore, at
108. Singaporeans have great respect for learning and an outstanding school system. Flynn argues that IQ is rising because
in industrialized societies we give our brains a constant mental
workout, much greater than when we were mostly living on isolated farms. Modern TV shows and other entertainment can be
cognitively demanding, and video games require more thought
that Solitaire. It appears that talent is universal but opportunity
is not. Our public school budgets are being slashed. According
to Nicholas Kristof, some 61 million children in the world still
don’t attend primary school. The cost of a single F-35 fighter
could pay for more than 4 years of the Reading Is Fundamental
program in the entire USA.
DEGREES AND INCOMES OF US ETHNIC GROUPS
As reported by Siegel (30), in 2010, the percentages of
Americans aged 25 and older with at least a bachelor’s degree
were as follows: all US, 28%; Asians, 49%; Whites, 31%; Blacks,
18%; and Hispanics, 13%. The median household income in
the US in 2010 was as follows: all US, $49,800; Asians, $66,000;
Whites, $54,000; Hispanics, $40,000; and Blacks, $33,300.
TWO INTERESTING HERBIVORES
My friend, Dr. Vince Friedewald in Austin, sent me the
following information on camels and kangaroos (31). Camels
can live where food and water are scarce. They have an amazing
ability to conserve water. When dehydrated, a camel can drink as
much as 120 liters (32 gallons) in 15 minutes. To conserve water,
camels can regulate their body temperature so that they hardly
sweat, their kidneys can concentrate the urine, and they store a
lot of water in their erythrocytes, which have the ability to swell
to over twice their normal size without bursting. The camel’s
hump functions as a reservoir of adipose tissue that they can
metabolize to provide emergency energy. As the fat is depleted,
the hump wilts and flops to one side. The fatty humps also help
keep the animal cool, as fat conducts the sun’s heat relatively
slowly and their woolly covering provides extra insulation. Thus,
camels can go for weeks with little or no water or food.
Kangaroos in Australia have the ability to cross vast distances
in search of food and water, keys to their survival. Capable of
an 8-meter (25-foot) single bound across level ground, the red
kangaroo is one of the world’s greatest long jumpers. Thanks
to large feet and strong legs, it can travel at over 50 kilometers
(30 miles) per hour for hours. While a kangaroo’s hind legs are
big and powerful, they can’t work independently of each other,
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and so kangaroos have to hop on two feet. The hind leg tendons
are strong and elastic. With every hop, elastic energy is recaptured in the tendons ready for the next jump. The kangaroos use
their long tail for balance and counterbalance. It swings up as
the animal leaves the ground and down as the legs swing back
with every bounce to help propel the kangaroo. A kangaroo’s
big toes are in the center of the other toes, not to one side like
in humans, and are thus in line with their leg bones, enabling
them to push off with great force. The kangaroo has a pouch
to carry the newborn for about 10 months after birth. To win
the Olympics a human has to jump further than a kangaroo
(to nearly 9 meters). The best jumper of all is the snow leopard,
who can leap 15 meters.
THE AVALANCHE OF UNFUNDED DEBT
Mortimer B. Zuckerman, the editor of U.S. News & World
Report and the publisher of The New York Daily News, in a
December 2012 column paints the picture well (32, 33): “A
sound in the mountain range. . . . It’s the sound made by an
avalanche, the trillions of dollars of debt that’s heading our way,
gathering speed and mass. For most people, it’s out of earshot.”
Liabilities are not set out by our government in accordance with
well-established norms of the private sector, where our overhang
of liabilities would set off alarm bells in the markets, with boards
of directors in emergency sessions. We have gone from being the
world’s largest creditor nation, with no foreign debt at the end
of World War II, to the world’s largest debtor, with half of our
public debt held by foreign countries. During the last 4 years
alone, our national debt has grown by more than $5 trillion to
over $16 trillion. Although the Federal Reserve is keeping borrowing rates historically low, the cost of paying interest on the
debt for fiscal year 2012 was just under $360,000,000,000!
Despite our huge annual deficit, the greatest fiscal challenge
to the US government, opines Zuckerman, is its total liabilities. Our federal balance sheet, he indicates, does not include
the unfunded obligations of Medicare, Social Security, and the
future retirement benefits of federal employees. The estimated
unfunded total of these commitments is more than $87 trillion,
or 550% of our gross domestic product. And the debt per household is more than 10 times the median family income! The real
annual accrued expense of Medicare and Social Security is $7
trillion. The government’s balance sheet does not include any of
these obligations but focuses on the current year deficits and the
accumulated national debt. The annual budget deficit, however,
is only about one fifth of the more accurate figure! Zuckerman
argues that if Americans saw our financial statements in the same
way that public companies report their pension liabilities, these
liabilities would require borrowing on a scale that would not
only bankrupt the programs themselves but would bankrupt
the entire government. Zuckerman adds that the Social Security
programs and other mandatory programs are not subject to an
annual spending limit. Today, <40% of our budget is actually
decided by Congress and the president, down from 62% 40
years ago. Our liabilities are so huge and are multiplying so fast
that eventually they cannot be honored. Today, all payroll taxes
for Social Security and Medicare are spent in the year that they
208
are collected, leaving no leftovers for the unfunded obligations!
And this does not take into account other risks such as the fact
that the Federal Housing Authority confronts a $16.3 billion
net deficit after its latest audit that may force a taxpayer bailout
for the first time in its 78-year history. And, by 2016, the Disability Insurance Trust Fund will be fully depleted.
US TAX RATES
Taking into account all taxes on earnings and consumer
spending—including federal, state, and local income taxes, Social Security and Medicare payroll taxes, excise taxes, and state
and local sales taxes—the US average effective tax rate is around
40%. High tax rates—on labor, income, and consumption, as
indicated by Prescott and Ohanian (34)—reduce the incentive
to work by making consumption more expensive relative to
leisure. The incentive to produce goods for the market is particularly depressed when the tax revenue is returned to households
either as government transfers or transfers in kind—such as
public schooling, police and fire protection, food stamps, and
health care—that substitute for private consumption. In the
1950s, when European tax rates were low, many Western Europeans, including the French and Germans, worked more hours
per capita than did Americans. Over time, tax rates that affect
earnings and consumption rose substantially in Western Europe
and have accounted for much of the nearly 30% decline in work
hours in several European countries—to 1000 per adult per year
today from around 1400 in the 1950s. The average American
today works just over 1300 hours per year, the same as Japan,
which has the same tax rate essentially as does America.
OBAMACARE’S INDEPENDENT PAYMENT ADVISORY BOARD
The Independent Payment Advisory Board (IPAB) is a government-appointed panel to help slow the growth of Medicare
spending (35). The 15-person IPAB will propose Medicare cuts
if the growth in the program’s spending exceeds inflationary
targets. Some fear that their decisions will lead to rationing. The
law, however, gives the panel no authority to ration care or cut
benefits for Medicare recipients. It can’t touch reimbursement
to hospitals until 2020. Instead, it is expected to find savings by
eliminating fraud and reducing payments to private insurance
companies that work with Medicare and prescription drug providers. And, it can only do that if the government is projected
to spend more than it’s supposed to. Each spring, the Office of
the Actuary of the Centers for Medicare and Medicaid Services
forecasts how much the programs will cost 2 years in the future.
On April 30, 2013, the panel will issue its per capita estimates
for 2015. The actuary also will release a spending target, based
on predictions about the pace of health care inflation. If the
increase in expected Medicare costs exceeds the spending target,
the IPAB steps in to propose cuts. It will take a 60% Senate
vote to reject its recommendations, and then legislators must
find alternate cuts that achieve the same savings. The law allows
them to debate the IPAB’s proposal for 30 hours maximum,
making it filibuster proof.
How will the White House recruit the board members? So
far no IPAB members have been appointed, even though the
Volume 26, Number 2
board is supposed to get to work by April 2013. The law requires
the panel to be made up of prominent physicians, economists,
hospital executives, and insurance industry representatives.
Candidates are subject to Senate approval, which means that
they must endure potentially hostile public hearings. Board
members willing to go through all that must also agree to serve
for 6 years, full time; they have to quit their current jobs because of conflict of interest concerns. The annual salary for each
board member is $165,300. And, the life of an IPAB member
may be rather dull since its powers kick in only if spending is
surging. It’s no wonder that Obama has yet to announce his
candidates. If there is no IPAB in place by the time its services
are needed, the law allows the secretary of the US Department
of Health and Human Services to do its job until the panel is
up and running. I can’t imagine who would want to be one of
the 15 on that panel!
US OIL BOOM
It’s really unbelievable, at least to me. The US oil output is
surging so fast that the USA could soon overtake Saudi Arabia
as the world’s biggest producer (37). Driven by high prices and
new drilling methods, US production of crude and other liquid
hydrocarbons rose approximately 7% in 2012 to an average of just
under 11 million barrels per day. This is the fourth straight year of
crude increases and the biggest single year since 1951. The Energy
Department forecast that US production of crude and other liquid
hydrocarbons, which include biofuels, will average 11.4 million
barrels per day in 2013. That would be a record for the US and just
below Saudi Arabia’s output of 11.6 million barrels per day. The
production is forecast to reach 13 to 15 million barrels per day in
the US by 2020, helping to make North America “the new Middle
East.” I used to think that making the US “energy independent”
was a joke, but it is great to see that it isn’t.
WATER
When the headline of the Dallas Morning News reads “The
word on water: Conserve,” we have a problem (36). The state
is running out of water, as shown in Figure 3. The projected
Texas population in the next 50 years is expected to grow from
25 million to about 46 million (54%↑) and the projected
need for additional water from 3.62 to 8.33 million acre-feet
per year (43%↑). Get ready. Life with limited water will not
be the same. Quick showers, low-flush toilets, and irrigation
restrictions will be the norm. San Antonio, Texas, apparently
is already in the swing of water conservation, and we must
follow in Dallas.
BALLPOINT PEN
We all use them. Peter Pesic summarized the book Ballpoint
written by Hungarian author György Muldova (38, 39). The
Hungarians are astonishingly creative. Eleven won the Nobel
Prize during the 20th century, far more per capita than from
other nations. There were other Hungarian geniuses, including
mathematician John Von Neumann and physicists Leo Szilard and
Edward Teller. Talented students flourished in some Budapest
schools until the 1920s when the government began limiting
university admissions to those “who are completely reputable in
respect of their national allegiance,” effectively excluding Jews,
who thereafter emigrated when they could.
One of the Jewish beneficiaries of those Budapest schools
was László Biró (1899–1985), a journalist and artist in the 1930s
who noted that the ink used for newspapers dried relatively
quickly compared with the ink for fountain pens. Handwritten papers had to be carefully blotted or set aside until the ink
dried. Biró tried using quick-drying ink in a fountain pen, but
the fluid was too thick to flow down to the nib and simply
clogged the reservoir. He solved the problem of how to deliver
thick, quick-drying ink to a paper surface without requiring the
ink to flow by closing the end of the pen instead of using a nib,
leaving an opening with just enough room for a tiny metal ball
that would spin against the ink in the reservoir, distributing it
to the paper. Through much trial and error and with the help of
an early backer and business partner, Endor Goy (1896–1991),
Biró developed a working ballpoint pen. The two men signed
a contract to produce and market the pen in 1938. Biró kept
refining the pen and experimenting with recipes for the ink paste
essential for his concept while fleeing dangers in Europe and
finally settling in Argentina. Though Biró faced the hardships of
wartime immigration, he soon started up a pen-manufacturing
operation in Argentina. Biró’s story is relatively well known in
much of the English-speaking world. “Biró” is synonymous with
ballpoint pen. In Argentina, the pen is known as a “Birome,” and
Biró’s birthday, September 29, is celebrated as “Inventor’s Day”
in Argentina. Thus, the ballpoint took its place alongside the
zipper, the pencil, and the paperclip devised by inventors who
long struggled to produce objects we now take for granted.
Figure 3. The supply and demand for water in Texas. Reprinted with permission
from The Dallas Morning News.
April 2013
209
EPPIE AND POPO
These were their nicknames. They were identical twins, Esther Pauline Friedman Lederer and Pauline Esther Friedman
Phillips, aka Abigail Van Buren, born in Sioux City, Iowa, on
July 4, 1918. They shared a joint wedding and honeymoon
trip. Esther was the first to become a columnist, taking over the
Chicago Sun-Times’ “Ann Landers” column in 1955. Pauline,
living in California, started a replacement advice column for the
San Francisco Chronicle, “Dear Abby,” in 1956. She created her
own byline, combining a biblical wise woman with the eighth
president of the US. Within 2 years, both columns were in a
combined 400 newspapers. Pauline’s Dear Abby column at its
peak appeared in 1400 papers. Life magazine in 1958 said the
sisters were “the most widely read and most quoted women in
the world.” For a long time they did not speak to each other,
but their differences were eventually patched up. Mother and
daughter started sharing the byline in 2000, and Jeanne Phillips
took over in 2002. Amazing (40).
SPORTS
Stan Musial: Years ago I was invited to give a talk in St. Louis
by the son-in-law of Stan Musial, a physician, who brought me
a baseball signed by Stan-the-Man. It is one of my favorite sport
collectibles. When I was growing up, Musial was one of my
baseball heroes. He played 22 years in the Major Leagues, all
with St. Louis, in 3026 games. He had 10,972 at-bats and only
struck out just over 600 times (41). He had 3630 hits, scored
1942 runs, had 6134 total bases, and hit 475 home runs. He
won the National League batting title 7 times and participated
in 24 all-star games. And all the time he was a great guy. He
contributed to his community generously. He was 6 feet tall
and weighed 175 pounds. Those also are my dimensions, but
Musial had a much better eye for the ball.
Stacy Lewis: She is the first American to be named Player of
the Year on the Ladies Professional Golf Association tour since
1994 (42). She had severe scoliosis and wore a back brace 18
hours a day for 7 years as a child. She had a steel rod with 5
screws installed in her spine just after getting her high school
diploma. She didn’t know at that time whether she could play
golf again, but she certainly did.
Johnny Manzial: As a red-shirt freshman, “Johnny Football”
won the Heisman Trophy Award for 2012 and shortly after
doing so set the Cotton Bowl record for total offense with 516
yards (43, 44). Seven other college football players have played
in the Cotton Bowl after receiving the Heisman Award, but
none came close to doing what Johnny Manzial did in the
January 2013 classic.
Golf: The average professional golfer takes 15,000 steps during an 18-hole round, walks 7 miles, and burns 2000 calories.
The numbers when using a cart are unclear.
BODY WEIGHT IN THE NATIONAL FOOTBALL LEAGUE
Fran Tarkenton, a National Football League quarterback
from 1961 to 1978 and member of the Pro Football Hall of
Fame, in a recent piece in The Wall Street Journal discussed
body weight of professional football players when he played
210
and subsequently (45). When Tarkenton entered pro football
in 1961, every member of his offensive line weighed <250
pounds. During his last year, 1978, the biggest lineman on
his team weighed 260 pounds. No Super Bowl–winning team
had a 300 pounder on its roster until the 1982 Washington
Redskins. Now, it is unusual for a team to have fewer than ten
300 pounders. This year’s Super Bowl teams, the San Francisco 49ers and the Baltimore Ravens, had twenty-four 300
pounders between them.
Have players gotten bigger thanks to genetics, diet, and
nutrition? Or is there something else going on? Shortly after
retiring from football, Tarkenton learned from an owner of one
of the biggest gym chains in the country that muscles can only
get so big by weightlifting regimes alone. Huge muscles come
from performance-enhancing drugs, which Tarkenton indicated
were just starting to enter professional football during his time.
The National Football League does not talk about steroids or
human growth hormone, but these drugs make players bigger, faster, and stronger, and they are used widely in football.
Why do so many former players look like miniature versions
of themselves after they retire?
In their most recent collective-bargaining agreement, signed
in 2011, the National Football League and the Player’s Union
agreed to start testing players for human growth hormone. Yet,
two seasons later there still isn’t any testing! (In contrast, Major
League Baseball in recent years worked out a testing regime that
includes human growth hormone.) At the college football level,
meanwhile, testing looks almost exclusively for recreational drugs,
with practically no attention to performance-enhancing ones.
Although everyone claims to care about player safety at all
levels of the game, the use of performance-enhancing drugs,
which have made current players bigger and stronger than ever,
causes collisions to be more violent and players therefore to
suffer worse injuries. These violent encounters on the field not
only affect the safety of the players during games but they clearly
affect long-term health—dementia, Alzheimer’s disease, depression, suicide, and early death.
William Clifford Roberts, MD
1 February 2013
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by P. Hensher, Faber, 270 pages]. U.S. News & World Report, December
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Birnbaum M. Germany begins gun registry. Washington Post, January 20,
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names only hint at mass killings crisis: one every two weeks. USA Today,
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but rape, murder rise slightly. Dallas Morning News, January 15, 2013.
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35. Leonard D. The boring, awful life of a death panelist. Bloomberg Businessweek, January 21–27, 2013.
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211
AMERICAN JOURNAL OF CARDIOLOGY
Necropsy findings early after transcatheter aortic valve
implantation for aortic stenosis
Roberts WC, Stoler RC, Grayburn PA, Hebeler RF Jr, Ko JM, Brown DL,
Brinkman WT, Mack MJ, Guileyardo JM
Am J Cardiol 2013;111(3):448–452. Reprinted with permission from
Elsevier.
Although transcatheter aortic valve implantation has been available
for 10 years, reports of cardiovascular morphologic studies after the
procedure are virtually nonexistent. The investigators describe such
findings in 2 patients, both 86 years of age, who died early (hours or
several days) after transcatheter aortic valve implantation. Although
the prosthesis in each was seated well, and each of the 3 calcified
cusps of the native aortic valves was well compressed to the wall of
the aorta, thus providing a good bioprosthetic orifice, the ostium
of the dominant right coronary artery in each was obliterated by
the native right aortic valve cusp. Atherosclerotic plaques in the
common iliac artery led to a major complication in 1 patient, who
later died of hemorrhagic stroke. The other patient developed fatal
cardiac tamponade secondary to perforation of the right ventricular
wall by a pacemaker catheter.
AMERICAN JOURNAL OF NEURORADIOLOGY
Interobserver variability in retreatment decisions of recurrent
and residual aneurysms
McDonald JS, Carter RE, Layton KF, Mocco J, Madigan JB, Tawk RG, Hanel
RA, Roy SS, Cloft HJ, Klunder AM, Suh SH, Kallmes DF
AJNR Am J Neuroradiol 2012 Oct 25 [Epub ahead of print]. Reprinted
with permission from the American Society of Neuroradiology.
Background and purpose: The degree of variation in retreatment
decisions for residual or recurrent aneurysms among endovascular
therapists remains poorly defined. We performed a multireader study
to determine what reader and patient variables contribute to this
variation.
Materials and methods: Seven endovascular therapists (4 neuroradiologists, 3 neurosurgeons) independently reviewed 66 cases of patients
treated with endovascular coil embolization for ruptured or unruptured aneurysm. Cases were rated on a 5-point scale recommending
for whether to retreat and a recommended retreatment type. Reader
agreement was assessed by intraclass correlation coefficient and by
identifying cases with a “clinically meaningful difference” (a difference in score that would result in a difference in treatment). Variables
that affect reader agreement and retreatment decisions were examined
by using the Wilcoxon signed-rank test, Pearson χ2 test, and linear
regression.
Results: Overall interobserver variability for decision to retreat was
moderate (ICC = 0.50; 95% CI, 0.40–0.61). Clinically meaningful differences between at least 2 readers were present in 61% of
cases and were significantly more common among neuroradiolo212
gists than neurosurgeons (P = .0007). Neurosurgeons were more
likely to recommend “definitely retreat” than neuroradiologists
(P < .0001). Previously ruptured aneurysms, larger remnant size, and
younger patients were associated with more retreat recommendations. Interobserver variability regarding retreatment type was fair
overall 0.25 (95% CI, 0.14–0.41), but poor for experienced readers
0.14 (95% CI, 0–0.34).
Conclusions: There is a large amount of interobserver variability regarding the decision to retreat an aneurysm and the type of retreatment.
This variability must be reduced to increase consistency in these subjective outcome measurements.
BREAST CANCER RESEARCH AND TREATMENT
Pooled analysis of individual patient data from capecitabine
monotherapy clinical trials in locally advanced or metastatic
breast cancer
Blum JL, Barrios CH, Feldman N, Verma S, McKenna EF, Lee LF, Scotto N,
Gralow J
Breast Cancer Res Treat 2012;136(3):777–788. Reprinted with permission from Springer.
We assessed the efficacy and safety of capecitabine across treatment
lines, and the impact of patient and disease characteristics on outcomes using data from phase II/III trials. Individual patient data were
pooled from seven Roche/Genentech-led trials conducted from 1996
to 2008 where single-agent capecitabine was the test or control regimen for metastatic breast cancer (MBC). Data were analyzed from
805 patients: 268 in the first-line metastatic setting and 537 in the
second-line or later setting. Baseline characteristics were balanced
across treatment lines. Patients receiving second-line or later versus first-line capecitabine had lower objective response rates (ORR:
19.0 vs. 25.0%, respectively, odds ratio 0.70; 95% CI: 0.5–1.0)
and significantly shorter progression-free survival (PFS: median
112.0 days [3.7 months] vs. 150.0 days [4.9 months]; P < 0.0001)
and overall survival (OS: median 396.0 days [13.0 months] vs.
666.0 days [21.9 months]; P < 0.0001). In multivariate analysis by
backward elimination, significantly improved ORR (P = 0.0036),
PFS (P < 0.0001) and OS (P < 0.0001) with capecitabine were
demonstrated in patients with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive versus both ER and PgR-negative
tumors. Hand-foot syndrome (HFS) was the most common adverse
event (AE) in 63% of patients. Overall, 7% of patients discontinued
and two patients (<1%) died from treatment-related AEs. Significantly improved survival was observed in patients developing capecitabine-related HFS (P < 0.0001 PFS/OS) or diarrhea (P = 0.004
OS; P = 0.0045 PFS) versus patients without these events. In this
pooled analysis of individual patient data, first-line capecitabine was
associated with improved ORR, PFS, and OS versus second or later
lines. Multivariate analyses identified greater ORR, PFS, and OS
with capecitabine in patients with ER and/or PgR-positive versus
ER/PgR-negative tumors. Safety was in line with previous phase
III trials in MBC.
CLINICAL TRANSPLANTATION
Safety and tolerability of the T-cell depletion protocol coupled
with anakinra and etanercept for clinical islet cell transplantation
Takita M, Matsumoto S, Shimoda M, Chujo D, Itoh T, Sorelle JA,
Purcell K, Onaca N, Naziruddin B, Levy MF
Clin Transplant 2012;26(5):E471–E484. Reprinted with permission
from John Wiley and Sons.
Background: Islet cell transplantation (ICT) is a promising approach
to cure patients with type 1 diabetes. We have implemented a new
immunosuppression protocol with antithymoglobulin plus anti-inflammatory agents of anakinra and eternacept for induction and tacrolimus plus mycophenolate mofetil for maintenance [T-cell depletion
with anti-inflammatory (TCD-AI) protocol], resulting in successful
single-donor ICT.
Methods: Eight islet recipients with type 1 diabetes reported adverse
events (AEs) monthly. AEs were compared between three groups:
first infusion with the TCD-AI protocol (TCD-AI-1st) and first and
second infusion with the Edmonton-type protocol (Edmonton-1st
and Edmonton-2nd).
Results: The incidence of symptomatic AEs within the initial three
months in the TCD-AI-1st group was less than in the Edmonton-1st
and Edmonton-2nd groups, with a marginally significant difference
(mean ± SE: 5.5 ± 0.3, 7.5 ± 0.5, and 8.3 ± 1.3, respectively; P =
0.07). A significant reduction in liver enzyme elevation after ICT was
found in the TCD-AI-1st group compared with the Edmonton-1st
and Edmonton-2nd groups (P < 0.05). Because of AEs, all patients in
the Edmonton protocol eventually converted to the TCD-AI protocol,
whereas all patients tolerated the TCD-AI protocol.
Conclusions: TCD-AI protocol can be tolerated for successful ICT,
although this study includes small cohort, and large population trial
should be taken.
GENE THERAPY
Stimulation of adult resident cardiac progenitor cells by durable
myocardial expression of thymosin beta 4 with ultrasoundtargeted microbubble delivery
Chen S, Shimoda M, Chen J, Grayburn PA
Gene Ther 2012 Nov 15 [Epub ahead of print]. Reprinted with permission from Nature Publishing Group.
It has been proposed that thymosin beta 4 (TB4)-protein delivery stimulates differentiation of resident adult WT1-positive cardiac progenitor
cells, but with very low efficiency. We determined whether gene therapy with human TB4 stimulates proliferation of resident adult cardiac
progenitor cells in normal rat heart. Ultrasound-targeted microbubble
destruction (UTMD) was used to deliver the human TB4 gene under
a piggybac transposon plasmid to normal rat heart. The rat hearts were
assayed by quantitative reverse transcription-PCR and immunohistology
with a confocal microscope at 1, 2, 3, 4 and 12 weeks after UTMD.
Exogenous TB4 stimulation resulted in the presence of WT1-positive
cardiac progenitor cells from epicardium to endocardium. TB4 stimulated angiogenesis and arteriogenesis. One month after TB4 gene therapy
by UTMD, the percentage of NKX2.5-positive cardiomyocytes was 5.5
± 1.0% and NKX2.5 mRNA was 24-fold higher than in the control
groups (P < 0.001). Similar results were found for ISL-1, BrDu, Ki-67,
April 2013
PHH3 and aurora B (P < 0.001). Cardiac-specific delivery of exogenous
human TB4 gene efficiently stimulates proliferation and differentiation
of resident WT1-positive adult cardiac progenitor cells into three intact
cardiac cell lineages—vascular endothelial cells, coronary artery smooth
muscle cells and cardiac muscle cells in normal adult rat heart.
JOURNAL OF INTERVENTIONAL CARDIOLOGY
A pilot study of prasugrel followed by post-procedural
maintenance with clopidogrel in patients receiving percutaneous
coronary intervention
Benjamin MM, Filardo G, Donsky MS, Schussler JM
J Interv Cardiol 2012 Dec 30 [Epub ahead of print]. Reprinted with
permission from John Wiley and Sons.
Background: Dual anti-platelet therapy including clopidogrel or prasugrel is standard of care for patients receiving stents. Prasugrel has
quicker onset so it can be loaded later than clopidogrel with greater efficacy. However, prasugrel is much more expensive than clopidogrel.
Objectives: To describe the incidence of 30-day death from cardiovascular causes, myocardial infarction, unstable angina requiring intervention, and minor and major bleeding in patients loaded with 60 mg of
prasugrel prior to percutaneous coronary intervention (PCI) and then
continued on 75 mg of clopidogrel daily after the procedure.
Methods: We reviewed sequential medical records of 102 patients (mean
age: 67.8, male 68.6%, smokers: 22.6%, BMI: 29.5%, hypertension:
90.2%, DM: 33.3%, average ejection fraction: 49.7%) who underwent
PCI (3.9% STEMI, 12.7% NSTEMI, 35.3% unstable angina and
48.1% electively) at Baylor University Medical Center between October
2009 and December 2011 who were loaded with prasugrel 60 mg prior
to procedure, and then continued on 75 mg clopidogrel daily.
Results: None of the patients died or experienced a myocardial infarction (MI) within 30 days of the procedure. Three patients experienced unstable angina requiring intervention but none had in-stent
thrombosis or restenosis on repeat angiography. None of the patients
experienced a major bleeding event. One patient developed a gastrointestinal bleed which did not require blood transfusion and the bleeding
resolved on discontinuation of the clopidogrel.
Conclusion: In this retrospective pilot study, a strategy of loading patients needing PCI with prasugrel 60 mg immediately prior to coronary
intervention, then continuation of anti-platelet therapy with 75 mg
clopidogrel daily was safe and effective.
JOURNAL OF NURSING ADMINISTRATION
Decisional involvement in Magnet®, magnet-aspiring, and nonmagnet hospitals
Houston S, Leveille M, Luquire R, Fike A, Ogola GO, Chando S
J Nurs Adm 2012;42(12):586–591. Reprinted with permission from
Wolters Kluwer Health.
Background: Empowered decision making can help establish innovative work cultures.
Objective: This study used the Decisional Involvement Scale to determine differences in actual and preferred decisional involvement
among staff RNs and administrators in Magnet®, Magnet-aspiring,
and non-Magnet hospitals.
213
Methods: Two facilities were Magnet designated, 3 were Magnet aspiring, and 9 were non-Magnet. A total of 5000 staff RNs and administrators were asked to participate in the nonexperimental descriptive
survey.
Results: The difference observed in actual global scale score by Magnet
status was statistically significant (P = .01). Respondents in Magnet
hospitals had the highest actual global scale score on average, followed
by Magnet-aspiring, then non-Magnet.
Conclusions: Decisional involvement is higher among Magnet-designated than non-Magnet facilities.
MICROBIAL PATHOGENESIS
Dendritic cells and vaccine design for sexually-transmitted
diseases
Duluc D, Gannevat J, Joo H, Ni L, Upchurch K, Boreham M, Carley M,
Stecher J, Zurawski G, Oh S
Microb Pathog 2012 Nov 29 [Epub ahead of print]. Reprinted with
permission from Elsevier.
Dendritic cells (DCs) are major antigen presenting cells (APCs)
that can initiate and control host immune responses toward either
immunity or tolerance. These features of DCs, as immune orchestrators, are well characterized by their tissue localizations as well as by
their subset-dependent functional specialties and plasticity. Thus, the
level of protective immunity to invading microbial pathogens can be
dependent on the subsets of DCs taking up microbial antigens and
their functional plasticity in response to microbial products, host
cellular components and the cytokine milieu in the microenvironment. Vaccines are the most efficient and cost-effective preventive
medicine against infectious diseases. However, major challenges still
remain for the diseases caused by sexually-transmitted pathogens,
including HIV, HPV, HSV and Chlamydia. We surmise that the
establishment of protective immunity in the female genital mucosa,
the major entry and transfer site of these pathogens, will bring significant benefit for the protection against sexually-transmitted diseases.
Recent progresses made in DC biology suggest that vaccines designed
to target proper DC subsets may permit us to establish protective
immunity in the female genital mucosa against sexually-transmitted
pathogens.
TRANSPLANTATION
Sirolimus and cardiovascular disease risk in liver transplantation
McKenna GJ, Trotter JF, Klintmalm E, Ruiz R, Onaca N, Testa G,
Saracino G, Levy MF, Goldstein RM, Klintmalm GB
Transplantation 2013;95(1):215–221. Reprinted with permission from
Wolters Kluwer Health.
Background: Two adverse effects of sirolimus are hypertriglyceridemia
and hypercholesterolemia. These elevated levels often lead clinicians to
discontinue the sirolimus from concerns of an increased cardiovascular
disease (CVD) risk; however, evidence suggests that sirolimus might
be cardioprotective. There are no published reports of sirolimus CVD
in liver transplantation.
Methods: We reviewed all 1812 liver recipients who underwent transplantation from 1998 to 2010, identifying a cohort using sirolimus
as part of the initial immunosuppression (SRL Cohort) and a control
group of the remaining patients from this period where SRL was
never given (Non-SRL Control). A prospectively maintained database
identified all episodes of myocardial infarction (MI), congestive heart
failure (CHF), abdominal aortic aneurysm (AAA), and cerebrovascular accident and tracked triglyceride, high-density and low-density
lipoproteins, and total cholesterol levels. A Framingham Risk Model
calculated the predicted 10-year risk of CVD for both groups.
Results: The SRL Cohort (n = 406) is older, more predominantly male,
with more pretransplantation hypertension and diabetes and posttransplantation hypertension compared to Non-SRL Controls (n =
1005). The SRL Cohort has significantly higher triglyceride, lowdensity lipoprotein, and cholesterol levels at 6 months and 1 year.
There is no difference in MI incidence in the SRL Cohort (1.0% vs.
1.2%) and no difference in AAA, cerebrovascular accident, and CHF.
The Framingham Risk Model predicts that the SRL Cohort should
have almost double the 10-year risk of CVD compared to the NonSRL Control (11% vs. 6%).
Conclusions: Sirolimus causes hypertriglyceridemia and hypercholesterolemia, but it does not increase the incidence of MI or other CVDs.
Considering the SRL Cohort has more cardiac risk factors and nearly
double 10-year predicted CVD risk, the fact that the CVD incidence
is similar suggests that sirolimus is in fact cardioprotective.
If you are a Baylor researcher and would like your published abstract to
be included in this section, please e-mail the PubMed citation to Cynthia.
[email protected].
214
Volume 26, Number 2
2012
publications of the
Baylor Health Care System
medical and scientific staff
ANESTHESIOLOGY AND PAIN MANAGEMENT
1.
Mason KP, Green SM, Piacevoli Q; International Sedation Task Force.
Adverse event reporting tool to standardize the reporting and tracking of
adverse events during procedural sedation: a consensus document from
the World SIVA International Sedation Task Force. Br J Anaesth 2012;
108(1):13–20.
CARDIOLOGY/CARDIAC, VASCULAR, AND THORACIC SURGERY
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Adams J, Jordan S, Spencer K, Belanger J, Cheng D, Shock T, Karcher
J. Energy expenditure in US automotive technicians and occupationspecific cardiac rehabilitation. Occup Med (Lond) 2012 Nov 8 [Epub
ahead of print].
Askar M, Hsich E, Reville P, Nowacki AS, Zhang AW, Klingman L,
Bakdash S, Baldwin W, Smedira N, Taylor D, Starling R, Gonzalez-Stawinski G. Ventricular assist devices (VAD) are highly significantly associated
with class I HLA allosensitization. Hum Immunol 2012;73(Suppl):53.
Benjamin MM, Filardo G, Donsky MS, Schussler JM. A pilot study of
prasugrel followed by post-procedural maintenance with clopidogrel in
patients receiving percutaneous coronary intervention. J Interv Cardiol
2012 Dec 30 [Epub ahead of print].
Benjamin MM, Khetan RA, Kowal RC, Schussler JM. Diagnosis of left
ventricular noncompaction by computed tomography. Proc (Bayl Univ
Med Cent) 2012;25(4):354–356.
Benjamin MM, Roberts WC. Fatal aortic rupture from nonpenetrating
chest trauma. Proc (Bayl Univ Med Cent) 2012;25(2):121–123.
Brown CR, Brozzi NA, Vakil N, Shafii AE, Murthy SC, Pettersson GB,
Mason DP. Donor lungs with pulmonary embolism evaluated with ex
vivo lung perfusion. ASAIO J 2012;58(4):432–434.
Chamogeorgakis T, Koval CE, Smedira NG, Starling RC, Gonzalez-Stawinski GV. Outcomes associated with surgical management of infections
related to the HeartMate II left ventricular assist device: Implications
for destination therapy patients. J Heart Lung Transplant 2012;31(8):
904–906.
Chamogeorgakis T, Lima B, Shafii AE, Nagpal D, Pokersnik JA, Navia
JL, Mason D, Gonzalez-Stawinski GV. Outcomes of axillary artery side
graft cannulation for extracorporeal membrane oxygenation. J Thorac
Cardiovasc Surg 2012 Sep 20 [Epub ahead of print].
Chen S, Shimoda M, Chen J, Grayburn PA. Stimulation of adult resident
cardiac progenitor cells by durable myocardial expression of thymosin beta
4 with ultrasound-targeted microbubble delivery. Gene Ther 2012 Dec 6
[Epub ahead of print].
Deja MA, Grayburn PA, Sun B, Rao V, She L, Krejca M, Jain AR, Leng
Chua Y, Daly R, Senni M, Mokrzycki K, Menicanti L, Oh JK, Michler R,
Wróbel K, Lamy A, Velazquez EJ, Lee KL, Jones RH. Influence of mitral
regurgitation repair on survival in the surgical treatment for ischemic heart
failure trial. Circulation 2012;125(21):2639–2648.
Dolmatch BL, Duch JM, Winder R, Butler GM, Kershen M, Patel R, Trimmer CK, Lopera JE, Davidson IJ. Salvage of angioplasty failures and complications in hemodialysis arteriovenous access using the FLUENCY Plus Stent
Graft: technical and 180-day patency results. J Vasc Interv Radiol 2012;23(4):
479–487.
Edgerton JR. Surgical therapy for atrial fibrillation. J Cardiovasc Med
(Hagerstown) 2012;13(2):125–130.
14. Edgerton ZJ, Edgerton JR. A review of current surgical treatment of patients
with atrial fibrillation. Proc (Bayl Univ Med Cent) 2012;25(3):218–223.
15. Falcone AM, Matter GJ, Schussler JM. Right atrial appendage thrombus
found in a patient in normal sinus rhythm with normal right ventricular
systolic function. Echocardiography 2012 Nov 27 [Epub ahead of print].
16. Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP,
Douglas PS, Foody JM, Gerber TC, Hinderliter AL, King SB 3rd, Kligfield
PD, Krumholz HM, Kwong RY, Lim MJ, Linderbaum JA, Mack MJ,
Munger MA, Prager RL, Sabik JF, Shaw LJ, Sikkema JD, Smith CR Jr,
Smith SC Jr, Spertus JA, Williams SV. 2012 ACCF/AHA/ACP/AATS/
PCNA/SCAI/STS guideline for the diagnosis and management of patients
with stable ischemic heart disease. J Am Coll Cardiol 2012;60(24):e44–
e164. Also published in Circulation 2012;126(25):e354–e471, with executive summary published in Circulation 2012;126(25):3097–3137.
17. Filardo G, Hamilton C, Grayburn PA, Xu H, Hebeler RF Jr, Hamman
B. Established preoperative risk factors do not predict long-term survival in isolated coronary artery bypass grafting patients. Ann Thorac Surg
2012;93(6):1943–1948.
18. Friedewald VE, Hare JM, Miller LW, Walpole HT Jr, Willerson JT, Roberts WC. The editor’s roundtable: advances in stem cell therapy for treatment of cardiovascular disease. Am J Cardiol 2012;110(6):807–816.
19. Friedewald VE, Kowal RC, Olshansky B, Yancy CW, Roberts WC. The
editor’s roundtable: medical management of atrial fibrillation. Am J Cardiol 2012;109(4):563–569.
20. George BA, Roberts BJ, Grayburn PA. Diastolic left main coronary
flow reversal as a marker of severe aortic regurgitation. Tex Heart Inst J
2012;39(5):764–765.
21. Glower D, Ailawadi G, Argenziano M, Mack M, Trento A, Wang A, Lim
DS, Gray W, Grayburn P, Dent J, Gillam L, Sethuraman B, Feldman
T, Foster E, Mauri L, Kron I; EVEREST II Investigators. EVEREST
II randomized clinical trial: predictors of mitral valve replacement in de
novo surgery or after the MitraClip procedure. J Thorac Cardiovasc Surg
2012;143(4 Suppl):S60–S63.
22. Gonzalez-Stawinski GV, Mountis MM, Cohn WE, Frazier OH. Inflow
graft interruption as a simple method for left ventricular assist device
removal after successful bridge to recovery. J Card Surg 2012;27(3):
397–399.
23. Grayburn PA. Interpreting the coronary-artery calcium score. N Engl J
Med 2012;366(4):294–296; 366(16):1551.
24. Grayburn P, Sangli C, Massaro J, Mauri L, Weissman N, Glower D,
Feldman T, Foster E. The relationship between the magnitude of reduction in mitral regurgitation severity and left ventricular and left atrial
volumes post-treatment with the MitraClip device. J Am Coll Cardiol
2012;59(13, Suppl 1):59.
25. Grayburn PA, Weissman NJ, Zamorano JL. Quantitation of mitral regurgitation. Circulation 2012;126(16):2005–2017.
26. Hall S, Gonzalez-Stawinski G, Meyer D, Bethea B, Kuiper J, Hardaway
B. Unplanned hospital readmissions and continuous flow pump therapy.
J Cardiac Fail 2012;18(Suppl 1):S37.
27. Hall S, Hardaway B, Meyer D, Bethea B, Kuiper J. Reducing length of stay
in the Heartmate II era. J Cardiac Fail 2012;18(Suppl 1):S46–S47.
28. Hall S, Kuiper J, Grimsley B, Pearl G, Matter G, Hamman B, Hardaway
B. The use of Impellas 5.0/LD in the management of heart failure patients
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35.
36.
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39.
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with cardiogenic shock: a multidisciplinary team approach. J Cardiac Fail
2012;18(Suppl 1):S47-S47.
Head SJ, Holmes DR Jr, Mack MJ, Serruys PW, Mohr FW, Morice MC,
Colombo A, Kappetein AP; SYNTAX Investigators. Risk profile and
3-year outcomes from the SYNTAX percutaneous coronary intervention
and coronary artery bypass grafting nested registries. JACC Cardiovasc
Interv 2012;5(6):618–625.
Holmes DR Jr, Mack MJ, Kaul S, Agnihotri A, Alexander KP, Bailey
SR, Calhoon JH, Carabello BA, Desai MY, Edwards FH, Francis GS,
Gardner TJ, Kappetein AP, Linderbaum JA, Mukherjee C, Mukherjee
D, Otto CM, Ruiz CE, Sacco RL, Smith D, Thomas JD, Harrington
RA, Bhatt DL, Ferrari VA, Fisher JD, Garcia MJ, Gardner TJ, Gentile
F, Gilson MF, Hernandez AF, Jacobs AK, Kaul S, Linderbaum JA, Moliterno DJ, Weitz HH. 2012 ACCF/AATS/SCAI/STS expert consensus
document on transcatheter aortic valve replacement. J Thorac Cardiovasc
Surg 2012;144(3):e29–e84.
Jett GK. Thoracic robotics at the Heart Hospital Baylor Plano: the first
20 cases. Proc (Bayl Univ Med Cent) 2012;25(4):324–326.
Kappetein AP, Head SJ, Généreux P, Piazza N, van Mieghem NM, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane
AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodés-Cabau J, Vranckx
P, Webb JG, Windecker S, Serruys PW, Leon MB. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the
Valve Academic Research Consortium-2 consensus document. J Am Coll
Cardiol 2012;60(15):1438–1454. Also published in Eur J Cardiothorac
Surg 2012;42(5):S45–S60; Eur Heart J 2012;33(19):2403–2418; and
EuroIntervention 2012;8(7):782–795.
Kennedy K, Adams J, Cheng D, Berbarie RF. High-intensity track and
field training in a cardiac rehabilitation program. Proc (Bayl Univ Med
Cent) 2012;25(1):34–36.
Keshava HB, Farver CF, Brown CR, Shafii AE, Murthy SC, Yun JJ, Vakil
N, Pettersson GB, Mason DP. Timing of heparin and thrombus formation
in donor lungs after cardiac death. Thorac Cardiovasc Surg 2012 Dec 3
Khvilivitzky K, Mountis MM, Gonzalez-Stawinski GV. Heartmate II
outflow graft ligation and driveline excision without pump removal for left
ventricular recovery. Proc (Bayl Univ Med Cent) 2012;25(4):344–345.
Kowal RC. PVI’s inconvenient truths: lights out for dormant reconnection? J Cardiovasc Electrophysiol 2012;23(3):261–263.
Kowal RC. The allure of the F-files. J Cardiovasc Electrophysiol
2012;23(12):1286–1268.
Krucoff MW, Brindis RG, Hodgson PK, Mack MJ, Holmes DR Jr.
Medical device innovation: prospective solutions for an ecosystem in
crisis. Adding a professional society perspective. JACC Cardiovasc Interv
2012;5(7):790–796.
Loor G, Gonzalez-Stawinski G. Pulsatile vs. continuous flow in ventricular assist device therapy. Best Pract Res Clin Anaesthesiol 2012;26(2):
105–115.
Loor G, Khani-Hanjani A, Gonzalez-Stawinski GV. Use of RotaFlow
(MAQUET) for temporary right ventricular support during implantation
of HeartMate II left ventricular assist device. ASAIO J 2012;58(3):275–
277.
Lopes RD, Williams JB, Mehta RH, Reyes EM, Hafley GE, Allen KB,
Mack MJ, Peterson ED, Harrington RA, Gibson CM, Califf RM, Kouchoukos NT, Ferguson TB, Lorenz TJ, Alexander JH. Edifoligide and
long-term outcomes after coronary artery bypass grafting: PRoject of Exvivo Vein graft ENgineering via Transfection IV (PREVENT IV) 5-year
results. Am Heart J 2012;164(3):379–386.e1.
Mack M. Frailty and aortic valve disease. J Thorac Cardiovasc Surg 2012
Dec 20 [Epub ahead of print].
Mack MJ. Access for transcatheter aortic valve replacement: which is the
preferred route? JACC Cardiovasc Interv 2012;5(5):487–488.
Mack MJ. Transcatheter aortic valve implantation: changing patient populations and novel indications. Heart 2012;98(Suppl 4):iv73–79.
McMaster KS, Tandon A, Schussler JM. Renal infarction secondary to cor
triatriatum sinister. Am J Cardiovasc Dis 2012;2(4):331–333.
46. Mihaljevic T, Jarrett CM, Gonzalez-Stawinski G, Smedira NG, Nowicki
ER, Thuita L, Mountis M, Blackstone EH. Mechanical circulatory
support after heart transplantation. Eur J Cardiothorac Surg 2012;
41(1):200–206.
47. Murray SS, Smith EN, Villarasa N, Nahey T, Lande J, Goldberg H, Shaw
M, Rosenthal L, Ramza B, Alaeddini J, Han X, Damani S, Soykan O,
Kowal RC, Topol EJ; GAME Investigators. Genome-wide association
of implantable cardioverter-defibrillator activation with life-threatening
arrhythmias. PLoS One 2012;7(1):e25387.
48. Nachimuthu S, Assar MD, Schussler JM. Drug-induced QT interval
prolongation: mechanisms and clinical management. Ther Adv Drug Safety
2012;3:241–253.
49. Patankar GR, Donsky MS, Schussler JM. Delayed takotsubo cardiomyopathy caused by excessive exogenous epinephrine administration after
the treatment of angioedema. Proc (Bayl Univ Med Cent) 2012;25(3):
229–230.
50. Pearl GJ. Arterial thoracic outlet syndrome in the competitive athlete.
In Illig KA, Thompson RW, Freischlag JA, Donahue DM, Jordan SE,
Edgelow PI, eds. Thoracic Outlet Syndrome. New York: Springer Verlag,
2012.
51. Pearl GJ. Neurogenic thoracic outlet syndrome in the competitive athlete.
In Illig KA, Thompson RW, Freischlag JA, Donahue DM, Jordan SE,
Edgelow PI, eds. Thoracic Outlet Syndrome. New York: Springer Verlag,
2012.
52. Pearl GJ. Treatment of arterial thoracic outlet syndrome: results and longterm outcomes. In Illig KA, Thompson RW, Freischlag JA, Donahue
DM, Jordan SE, Edgelow PI, eds. Thoracic Outlet Syndrome. New York:
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53. Pinard EA, Fazal S, Schussler JM. Catastrophic paradoxical embolus after
hemodialysis access thrombectomy in a patient with a patent foramen
ovale. Int Urol Nephrol 2012 Feb 25 [Epub ahead of print].
54. Pokersnik JA, Buda T, Bashour CA, Gonzalez-Stawinski GV. Have changes
in ECMO technology impacted outcomes in adult patients developing
postcardiotomy cardiogenic shock? J Card Surg 2012;27(2):246–252.
55. Reading DW, Oza U. Unilateral absence of a pulmonary artery: a
rare disorder with variable presentation. Proc (Bayl Univ Med Cent)
2012;25(2):115–118.
56. Reynolds MR, Magnuson EA, Lei Y, Wang K, Vilain K, Li H, Walczak
J, Pinto DS, Thourani VH, Svensson LG, Mack MJ, Miller DC, Satler
LE, Bavaria J, Smith CR, Leon MB, Cohen DJ; PARTNER Investigators.
Cost-effectiveness of transcatheter aortic valve replacement compared with
surgical aortic valve replacement in high-risk patients with severe aortic
stenosis: results of the PARTNER (Placement of Aortic Transcatheter
Valves) trial (Cohort A). J Am Coll Cardiol 2012;60(25):2683–2692.
57. Roberts WC. Determining the quantity of alcohol consumed. Am J Cardiol 2012;110:761.
58. Roberts WC. Pathology of coronary artery disease. In Franco KL, Thourani VH, eds. Cardiothoracic Surgery Review. Philadelphia: Wolters Kluwer,
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59. Roberts WC. Pathology of heart failure. In Franco KL, Thourani VH, eds.
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60. Roberts WC. Pathology of valvular heart disease. In Franco KL, Thourani
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61. Roberts WC. Pathology of diseases of the aorta. In Franco KL, Thourani
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62. Roberts WC. Two observations suggesting that we die in ventricular systole. Am J Cardiol 2012;110(6):915–917.
63. Roberts WC, Alpert J, Hillis WD. Ten things all physicians should know about
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64. Roberts WC, Janning KG, Ko JM, Filardo G, Matter GJ. Frequency of
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regurgitation) and implications for transcatheter aortic valve implantation.
Am J Cardiol 2012;109(11):1632–1636.
Volume 26, Number 2
65. Roberts WC, Janning KG, Vowels TJ, Ko JM, Hamman BL, Hebeler
RF Jr. Presence of a congenitally bicuspid aortic valve among patients
having combined mitral and aortic valve replacement. Am J Cardiol
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66. Roberts WC, Roberts CC, Ko JM, Hall SA, Capehart JE. Cardiac transplantation in adults with aortic valve disease with focus on the bicuspid
aortic valve. Am J Cardiol 2012;109(8):1212–1214.
67. Roberts WC, Roberts CC, Vowels TJ, Ko JM, Filardo G, Hamman BL,
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valve structure on outcome in isolated valve replacement for aortic stenosis.
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68. Roberts WC, Taylor MA, Shirani J. Cardiac findings at necropsy in patients with chronic kidney disease maintained on chronic hemodialysis.
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69. Roberts WC, Vowels TJ, Ko JM. Natural history of adults with congenitally malformed aortic valves (unicuspid or bicuspid). Medicine (Baltimore)
2012;91(6):287–308.
70. Roberts WC, Vowels TJ, Ko JM, Guileyardo JM. Acute aortic dissection
with tear in ascending aorta not diagnosed until necropsy or operation
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operative therapy. Am J Cardiol 2012;110(5):728–735.
71. Rosenthal RL, Carrothers IA, Schussler JM. Benign or malignant anomaly?
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72. Satiani B, Matthews MA, Gable D. Work effort, productivity, and compensation trends in members of the Society for Vascular Surgery. Vasc
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73. Satiani BB, Motew SJ, Darling RC 3rd, Jain KM, Wixon CL, Johnson
BA, Weiss VJ, Gable DR. Changing practice paradigms: negotiating your
future. J Vasc Surg 2012;55(4):1206–1212.
74. Serruys PW, Farooq V, Vranckx P, Girasis C, Brugaletta S, Garcia-Garcia
HM, Holmes DR Jr, Kappetein AP, Mack MJ, Feldman T, Morice MC,
Ståhle E, James S, Colombo A, Pereda P, Huang J, Morel MA, Van Es
GA, Dawkins KD, Mohr FW, Steyerberg EW. A global risk approach
to identify patients with left main or 3-vessel disease who could safely
and efficaciously be treated with percutaneous coronary intervention: the
SYNTAX Trial at 3 years. JACC Cardiovasc Interv 2012;5(6):606–617.
75. Shafii AE, Brown CR, Murthy SC, Mason DP. High incidence of
upper-extremity deep vein thrombosis with dual-lumen venovenous
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2012;144(4):988–999.
76. Shafii AE, Chamogeorgakis T, Mountis M, Gonzalez-Stawinski G. Fate of
retained right ventricular assist device outflow grafts after right ventricular
recovery. J Heart Lung Transplant 2012;31(6):672–673.
77. Shafii AE, Gillinov AM, Mihaljevic T, Stewart W, Batizy LH, Blackstone
EH. Changes in left ventricular morphology and function after mitral
valve surgery. Am J Cardiol 2012;110(3):403–408.e3.
78. Shahian DM, He X, Jacobs JP, Rankin JS, Welke KF, Filardo G, Shewan
CM, O’Brien SM. The Society of Thoracic Surgeons isolated aortic valve
replacement (AVR) composite score: a report of the STS Quality Measurement Task Force. Ann Thorac Surg 2012;94(6):2166–2171.
79. Shafii AE, Mason DP, Brown CR, Vakil N, Johnston DR, McCurry KR,
Pettersson GB, Murthy SC. Growing experience with extracorporeal
membrane oxygenation as a bridge to lung transplantation. ASAIO J
2012;58(5):526–529.
80. Shafii AE, McCurry KR. Subclavian insertion of the bicaval dual lumen
cannula for venovenous extracorporeal membrane oxygenation. Ann Thorac Surg 2012;94(2):663–665.
81. Shafii AE, Vivacqua A, Albacker TB, Sheih C, Svensson LG. Total arch
replacement after a failed repair for Takayasu’s ascending aortitis. Ann
Thorac Surg 2012;93(1):300–302.
82. Van de Werf F, Brueckmann M, Connolly SJ, Friedman J, Granger CB,
Härtter S, Harper R, Kappetein AP, Lehr T, Mack MJ, Noack H, Eikelboom JW. A comparison of dabigatran etexilate with warfarin in patients
with mechanical heart valves: the randomized, phase II study to evaluate
the safety and pharmacokinetics of oral dabigatran etexilate in patients
April 2013
after heart valve replacement (RE-ALIGN). Am Heart J 2012;163(6):
931–937.e1.
83. Van de Werf F, Connolly SJ, Kappetein AP, Brueckmann M, Mack MJ,
Granger CB, Eikelboom J. Letter by Van de Werf et al regarding article,
“Using dabigatran in patients with stroke: a practical guide for clinicians.”
Stroke 2012;43(5):e46–e47.
DERMATOLOGY
84. Abramovits W, Oquendo M, Granowski P, Gupta A, Cather J. Pralatrexate
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85. Abramovits W, Oquendo M, Scheinfeld N, Gupta AK. Sorilux (calcipotriene) foam 0.005%. Skinmed 2012;10(5):301–304.
86. Abramson A, Menter A. An unusual facial ulcer. Proc (Bayl Univ Med
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87. Abramson A, Menter A, Perrillo R. Psoriasis, hepatitis B, and the tumor
necrosis factor-alpha inhibitory agents: a review and recommendations
for management. J Am Acad Dermatol 2012;67(6):1349–1361.
88. Corey K, Mattei P, Houston N, Tebbey PW, Menter A, van de Kerkhof
PCM, Kimball AB. Psoriasis, a proof-of-principle condition for immunemediated inflammatory disorders: perspectives toward optimal clinical
trial design. Clin Invest 2012;2(7):671–678.
89. Dhaliwal S, Patel M, Menter A. Secondary syphilis and HIV. Proc (Bayl
Univ Med Cent) 2012;25(1):87–89.
90. Feldman SR, Matheson R, Bruce S, Grande K, Markowitz O, Kempers S, Brundage T, Wyres M; U0267-301 & 302 Study Investigators.
Efficacy and safety of calcipotriene 0.005% foam for the treatment of
plaque-type psoriasis: results of two multicenter, randomized, doubleblind, vehicle-controlled, phase III clinical trials. Am J Clin Dermatol
2012;13(4):261–271.
91. Heller MM, Wong JW, Nguyen TV, Lee ES, Bhutani T, Menter A, Koo
JY. Quality-of-life instruments: evaluation of the impact of psoriasis on
patients. Dermatol Clin 2012;30(2):281–291, ix.
92. Jordan CT, Cao L, Roberson ED, Duan S, Helms CA, Nair RP, Duffin
KC, Stuart PE, Goldgar D, Hayashi G, Olfson EH, Feng BJ, Pullinger
CR, Kane JP, Wise CA, Goldbach-Mansky R, Lowes MA, Peddle L,
Chandran V, Liao W, Rahman P, Krueger GG, Gladman D, Elder JT,
Menter A, Bowcock AM. Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. Am J Hum Genet
2012;90(5):796–808.
93. Jordan CT, Cao L, Roberson ED, Pierson KC, Yang CF, Joyce CE,
Ryan C, Duan S, Helms CA, Liu Y, Chen Y, McBride AA, Hwu
WL, Wu JY, Chen YT, Menter A, Goldbach-Mansky R, Lowes MA,
Bowcock AM. PSORS2 is due to mutations in CARD14. Am J Hum
Genet 2012;90(5):784–795.
94. Kircik L, Jones TM, Jarratt M, Flack MR, Ijzerman M, Ciotti S, Sutcliffe
J, Boivin G, Stanberry LR, Baker JR; NB-001 Study Group. Treatment
with a novel topical nanoemulsion (NB-001) speeds time to healing of
recurrent cold sores. J Drugs Dermatol 2012;11(8):970–977.
95. Kragballe K, Menter A, Lebwohl M, Tebbey PW, van de Kerkhof PC;
International Psoriasis Council. Long-term management of scalp psoriasis:
perspectives from the International Psoriasis Council. J Dermatolog Treat
2012 Jun 5 [Epub ahead of print].
96. Lloyd P, Ryan C, Menter A. Psoriatic arthritis: an update. Arthritis
2012;2012:176298.
97. Menter A. Clobetasol propionate spray 0.05% for the treatment of moderate to severe plaque psoriasis. Cutis 2012;89(2):89–94.
98. Menter A. Psoriasis and psoriatic arthritis: similarities and differences.
Value-Based Care in Rheumatology, September 2012.
99. Menter A. Response to the letter to editor re: “Methotrexate and psoriasis:
consensus conference.” J Am Acad Dermatol 2012;66(4):689.
100. Menter MA, Caveney SW, Gottschalk RW. Impact of clobetasol propionate 0.05% spray on health-related quality of life in patients with plaque
psoriasis. J Drugs Dermatol 2012;11(11):1348–1354.
101. Menter A, Thrash B, Cherian C, Matherly LH, Wang L, Gangjee A,
Morgan JR, Maeda DY, Schuler AD, Kahn SJ, Zebala JA. Intestinal
transport of aminopterin enantiomers in dogs and humans with psoriasis
2012 publications of the Baylor Health Care System medical and scientific staff
217
102.
103.
104.
105.
106.
107.
108.
109.
110.
111.
112.
113.
114.
115.
116.
218
is stereoselective: evidence for a mechanism involving the proton-coupled
folate transporter. J Pharmacol Exp Ther 2012;342(3):696–708.
Olsen EA, Whiting DA, Savin R, Rodgers A, Johnson-Levonas AO,
Round E, Rotonda J, Kaufman KD; Male Pattern Hair Loss Study
Group. Global photographic assessment of men aged 18 to 60 years
with male pattern hair loss receiving finasteride 1 mg or placebo. J Am
Acad Dermatol 2012;67(3):379–386.
Oquendo M, Abramovits W, Morrell P. Topical vitamin D analogs available to treat psoriasis. Skinmed 2012;10(6):356–360.
Paller AS, Mercy K, Kwasny MJ, Choon SE, Cordoro KM, Girolomoni
G, Menter A, Tom WL, Mahoney AM, Oostveen AM, Seyger MM. Association of pediatric psoriasis severity with excess and central adiposity:
an international cross-sectional study. Arch Dermatol 2012:1–11.
Papp K, Cather JC, Rosoph L, Sofen H, Langley RG, Matheson RT, Hu C,
Day RM. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet 2012;380(9843):738–746.
Papp K, Menter A, Poulin Y, Gu Y, Sasso EH. Long-term outcomes of
interruption and retreatment vs. continuous therapy with adalimumab
for psoriasis: subanalysis of REVEAL and the open-label extension study.
J Eur Acad Dermatol Venereol 2012 Mar 16 [Epub ahead of print].
Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G,
Aras G, Li J, Russell CB, Thompson EH, Baumgartner S. Brodalumab,
an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med
2012;366(13):1181–1189.
Papp KA, Menter A, Strober B, Langley RG, Buonanno M, Wolk R,
Gupta P, Krishnaswami S, Tan H, Harness JA. Efficacy and safety of
tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis:
a phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol 2012;167(3):668–677.
Papp KA, Strober B, Augustin M, Calabro S, Londhe A, Chevrier M;
PSOLAR investigators and Steering Committee. PSOLAR: design, utility, and preliminary results of a prospective, international, disease-based
registry of patients with psoriasis who are receiving, or are candidates for,
conventional systemic treatments or biologic agents. J Drugs Dermatol
2012;11(10):1210–1217.
Patel M, Day A, Warren RB, Menter A. Emerging therapies for the treatment of psoriasis. Dermatol Ther (Heidelb) 2012;2(1):16.
Ryan C, Abramson A, Patel M, Menter A. Current investigational drugs
in psoriasis. Expert Opin Investig Drugs 2012;21(4):473–487.
Ryan C, Menter A. Psoriasis and cardiovascular disorders. G Ital Dermatol
Venereol 2012;147(2):179–187.
Ryan C, Patel M, Menter A. Are drug treatments for psoriasis a cardiovascular risk? Clin Pract 2012;9:5–9.
Strober BE, Armour K, Romiti R, Smith C, Tebbey PW, Menter A, Leonardi C. Biopharmaceuticals and biosimilars in psoriasis: what the dermatologist needs to know. J Am Acad Dermatol 2012;66(2):317–322.
Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE, Capon F, Ding
J, Li Y, Tejasvi T, Gudjonsson JE, Kang HM, Allen MH, McManus R,
Novelli G, Samuelsson L, Schalkwijk J, Ståhle M, Burden AD, Smith
CH, Cork MJ, Estivill X, Bowcock AM, Krueger GG, Weger W, Worthington J, Tazi-Ahnini R, Nestle FO, Hayday A, Hoffmann P, Winkelmann J, Wijmenga C, Langford C, Edkins S, Andrews R, Blackburn H,
Strange A, Band G, Pearson RD, Vukcevic D, Spencer CC, Deloukas
P, Mrowietz U, Schreiber S, Weidinger S, Koks S, Kingo K, Esko T,
Metspalu A, Lim HW, Voorhees JJ, Weichenthal M, Wichmann HE,
Chandran V, Rosen CF, Rahman P, Gladman DD, Griffiths CE, Reis
A, Kere J; Collaborative Association Study of Psoriasis (CASP); Genetic
Analysis of Psoriasis Consortium; Psoriasis Association Genetics Extension; Wellcome Trust Case Control Consortium 2, Nair RP, Franke A,
Barker JN, Abecasis GR, Elder JT, Trembath RC. Identification of 15
new psoriasis susceptibility loci highlights the role of innate immunity.
Nat Genet 2012;44(12):1341–1348.
Tyring SK, Plunkett S, Scribner AR, Broker RE, Herrod JN, Handke LT,
Wise JM, Martin PA; Valomaciclovir Zoster Study Group. Valomaciclovir
versus valacyclovir for the treatment of acute herpes zoster in immunocompetent adults: a randomized, double-blind, active-controlled trial. J
Med Virol 2012;84(8):1224–1232.
117. Wofford J, Patel M, Readinger A, Menter A. Widespread dermal ulcerations and bullae. Proc (Bayl Univ Med Cent) 2012;25(2):155–158.
EMERGENCY MEDICINE/TRAUMA
118. Abdalla A, Gunst M, Ghaemmaghami V, Gruszecki AC, Urban J, Barber
RC, Gentilello LM, Shafi S. Spatial analysis of injury-related deaths in
Dallas County using a geographic information system. Proc (Bayl Univ
Med Cent) 2012;25(3):208–213.
119. Cook A, Cade A, King B, Berne J, Fernandez L, Norwood S. Groundlevel falls: 9-year cumulative experience in a regionalized trauma system.
120. Michetti CP, Fakhry SM, Ferguson PL, Cook A, Moore FO, Gross R;
AAST Ventilator-Associated Pneumonia Investigators. Ventilator-associated pneumonia rates at major trauma centers compared with a national
benchmark: a multi-institutional study of the AAST. J Trauma Acute Care
Surg 2012;72(5):1165–1173.
121. Newgard CD, Fildes JJ, Wu L, Hemmila MR, Burd RS, Neal M,
Mann NC, Shafi S, Clark DE, Goble S, Nathens AB. Methodology
and analytic rationale for the American College of Surgeons Trauma
Quality Improvement Program. J Am Coll Surg 2012 Oct 10 [Epub
ahead of print].
122. Rayan N, Barnes S, Fleming N, Kudyakov R, Ballard D, Gentilello LM,
Shafi S. Barriers to compliance with evidence-based care in trauma. J
Trauma Acute Care Surg 2012;72(3):585–592.
123. Shafi S, Ogola G, Fleming N, Rayan N, Kudyakov R, Barnes SA, Ballard
DJ. Insuring the uninsured: potential impact of Health Care Reform
Act of 2010 on trauma centers. J Trauma Acute Care Surg 2012;73(5):
1303–1307.
124. Shafi S, Rayan N, Barnes S, Fleming N, Gentilello LM, Ballard D.
Moving from “optimal resources” to “optimal care” at trauma centers. J
Trauma Acute Care Surg 2012;72(4):870–877.
125. Shafi S, Renfro LA, Barnes S, Rayan N, Gentilello LM, Fleming N,
Ballard D. Chronic consequences of acute injuries: worse survival after
discharge. J Trauma Acute Care Surg 2012;73(3):699–703.
ENDOCRINOLOGY
See also Transplantation for articles on islet cell transplantation and Health Care
Research and Improvement for articles on improving diabetes care.
126. Chaudhuri A, Rosenstock J, DiGenio A, Meneghini L, Hollander
P, McGill JB, Dandona P, Ilgenfritz J, Riddle M. Comparing the effects of insulin glargine and thiazolidinediones on plasma lipids in
type 2 diabetes: a patient-level pooled analysis. Diabetes Metab Res Rev
2012;28(3):258–267.
127. DeVries JH, Bain SC, Rodbard HW, Seufert J, D’Alessio D, Thomsen
AB, Zychma M, Rosenstock J; Liraglutide-Detemir Study Group. Sequential intensification of metformin treatment in type 2 diabetes with
liraglutide followed by randomized addition of basal insulin prompted
by A1C targets. Diabetes Care 2012;35(7):1446–1454.
128. Farkouh ME, Domanski M, Sleeper LA, Siami FS, Dangas G, Mack M,
Yang M, Cohen DJ, Rosenberg Y, Solomon SD, Desai AS, Gersh BJ,
Magnuson EA, Lansky A, Boineau R, Weinberger J, Ramanathan K,
Sousa JE, Rankin J, Bhargava B, Buse J, Hueb W, Smith CR, Muratov
V, Bansilal S, King S 3rd, Bertrand M, Fuster V; FREEDOM Trial Investigators. Strategies for multivessel revascularization in patients with
diabetes. N Engl J Med 2012;367(25):2375–2384.
129. Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-Torres
M, Rosenstock J, Endahl LA, Francisco AM, Hollander P; NN12503582 (BEGIN BB T2D) Trial Investigators. Insulin degludec, an ultralongacting basal insulin, versus insulin glargine in basal-bolus treatment
with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type
2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial.
Lancet 2012;379(9825):1498–1507.
130. Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, Renard E,
Russell-Jones D, Philotheou A, Francisco AM, Pei H, Bode B; BEGIN
Basal-Bolus Type 1 Trial Investigators. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with
mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1):
Volume 26, Number 2
131.
132.
133.
134.
135.
136.
137.
138.
a phase 3, randomised, open-label, treat-to-target non-inferiority trial.
Lancet 2012;379(9825):1489–1497.
Hollander P, Spellman C. Controversies in prediabetes: do we have a
diagnosis? Postgrad Med 2012;124(4):109–118.
Hollander PA. Insulin detemir for the treatment of obese patients with
type 2 diabetes. Diabetes Metab Syndr Obes 2012;5:11–19.
Lingvay I, Roe ED, Duong J, Leonard D, Szczepaniak LS. Effect of
insulin versus triple oral therapy on the progression of hepatic steatosis
in type 2 diabetes. J Investig Med 2012;60(7):1059–1063.
Punthakee Z, Bosch J, Dagenais G, Diaz R, Holman R, Probstfield J,
Ramachandran A, Riddle M, Rydén LE, Zinman B, Afzal R, Yusuf S,
Gerstein H; TIDE Trial Investigators. Design, history and results of
the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE)
randomised controlled trial. Diabetologia 2012;55(1):36–45.
Roe ED, Raskin P. Managing inpatient hyperglycemia in a resource-constrained county hospital. Hosp Pract (Minneap) 2012;40(3):116–125.
Roe ED, Yoo JS, Raskin P. Doctor, stop needling me: an update on
alternative routes of insulin administration. Diabetes Management
2012;2(5):395–404.
Roe ED, Yoo JS, Raskin P. In search of improved glucose control: helping
the patient decide between insulin injections and infusion pump therapy.
Diabetes Management 2012;2(5):405–417.
Vora J, Bain SC, Damci T, Dzida G, Hollander P, Meneghini LF, Ross SA.
Incretin-based therapy in combination with basal insulin: A promising
tactic for the treatment of type 2 diabetes. Diabetes Metab 2012 Sep 26
GASTROENTEROLOGY
Note: See also Oncology for research on colon cancer.
139. American Association for Study of Liver Diseases; American College of
Gastroenterology; American Gastroenterological Association Institute;
American Society for Gastrointestinal Endoscopy; Society for Gastroenterology Nurses and Associates, Vargo JJ, DeLegge MH, Feld AD,
Gerstenberger PD, Kwo PY, Lightdale JR, Nuccio S, Rex DK, Schiller
LR. Multisociety sedation curriculum for gastrointestinal endoscopy.
Gastrointest Endosc 2012;76(1):e1–e25. Also published in Gastroenterology 2012;143(1):e18–e41.
140. Chandran B, Goel A. A randomized, pilot study to assess the efficacy and
safety of curcumin in patients with active rheumatoid arthritis. Phytother
Res 2012;26(11):1719–1725.
141. Evans TH, Schiller LR. Chronic vestibular dysfunction as an unappreciated cause of chronic nausea and vomiting. Proc (Bayl Univ Med Cent)
2012;25(3):214–217.
142. Hogan RB 3rd, Brill JV, Littenberg G, Demarco DC. Predict, resect, and
discard . . . really? Gastrointest Endosc 2012;75(3):503–505.
143. Quigley EM, Abdel-Hamid H, Barbara G, Bhatia SJ, Boeckxstaens G,
De Giorgio R, Delvaux M, Drossman DA, Foxx-Orenstein AE, Guarner
F, Gwee KA, Harris LA, Hungin AP, Hunt RH, Kellow JE, Khalif IL,
Kruis W, Lindberg G, Olano C, Moraes-Filho JP, Schiller LR, Schmulson
M, Simrén M, Tzeuton C. A global perspective on irritable bowel syndrome: a consensus statement of the World Gastroenterology Organisation Summit Task Force on irritable bowel syndrome. J Clin Gastroenterol
2012;46(5):356–366.
144. Sayuk GS, Hirano I, Fitzgerald JT, Stansfield RB, Armbruster BA, Jones
TN, Akinyi J, Willis CE; AGA Institute’s GTE Subcommittee. AGA
Gastroenterology Training Exam (GTE): a progress report. Gastroenterology 2012;142(2):201–204.e1-2.
145. Siersema PD, Rastogi A, Leufkens AM, Akerman PA, Azzouzi K, Rothstein RI, Vleggaar FP, Repici A, Rando G, Okolo PI, Dewit O, Ignjatovic
A, Odstrcil E, East J, Deprez PH, Saunders BP, Kalloo AN, Creel B, Singh
V, Lennon AM, DeMarco DC. Retrograde-viewing device improves
adenoma detection rate in colonoscopies for surveillance and diagnostic
workup. World J Gastroenterol 2012;18(26):3400–3408.
146. Steffer KJ, Santa Ana CA, Cole JA, Fordtran JS. The practical value of
comprehensive stool analysis in detecting the cause of idiopathic chronic
diarrhea. Gastroenterol Clin North Am 2012;41(3):539–560.
April 2013
147. Vargo JJ, Delegge MH, Feld AD, Gerstenberger PD, Kwo PY, Lightdale
JR, Nuccio S, Rex DK, Schiller LR. Multisociety Sedation Curriculum
for Gastrointestinal Endoscopy. Am J Gastroenterol 2012 May 22 [Epub
ahead of print].
GYNECOLOGY/CLINICAL GENETICS
148. Shavell VI, Diamond MP, Senter JP, Kruger ML, Johns DA. Hysterectomy subsequent to endometrial ablation. J Minim Invasive Gynecol
2012;19(4):459–464.
149. Schaaf CP, Boone PM, Sampath S, Williams C, Bader PI, Mueller JM,
Shchelochkov OA, Brown CW, Crawford HP, Phalen JA, Tartaglia NR,
Evans P, Campbell WM, Tsai AC, Parsley L, Grayson SW, Scheuerle A,
Luzzi CD, Thomas SK, Eng PA, Kang SH, Patel A, Stankiewicz P, Cheung SW. Phenotypic spectrum and genotype-phenotype correlations of
NRXN1 exon deletions. Eur J Hum Genet 2012;20(12):1240–1247.
HEALTH CARE RESEARCH AND IMPROVEMENT
Note: This section represents primarily the publications of the IHCRI staff, although
some of those publications are included under Trauma and other areas.
150. Ballard DJ. The potential of Medicare accountable care organizations
to transform the American health care marketplace: rhetoric and reality.
Mayo Clin Proc 2012;87(8):707–709.
151. Ballard DJ, Filardo G, da Graca B, Powell JT. Clinical practice change
requires more than comparative effectiveness evidence: abdominal aortic
management in the USA. J Comparative Effect Res 2012;1(1):31–44.
152. Brouwer ES, West SL, Kluckman M, Wallace D, Masica AL, Ewen E,
Kudyakov R, Cheng D, Bowen J, Fleming NS. Initial and subsequent
therapy for newly diagnosed type 2 diabetes patients treated in primary
care using data from a vendor-based electronic health record. Pharmacoepidemiol Drug Saf 2012;21(9):920–928.
153. Cheng D, Branscum AJ, Johnson WO. Sample size calculations for ROC
studies: parametric robustness and Bayesian nonparametrics. Stat Med
2012;31(2):131–142.
154. Compton J, Copeland K, Flanders S, Cassity C, Spetman M, Xiao Y,
Kennerly D. Implementing SBAR across a large multihospital health
system. Jt Comm J Qual Patient Saf 2012;38(6):261–268.
155. Convery P, Couch C, Luquire R. Training physician and nursing leaders for performance improvement. In From Front Office to Front Line:
Essential Issues for Health Care Leaders. Oakbrook Terrace, IL: The Joint
Commission, 2012.
156. Couch CE. Why Baylor Health Care System would like to file for Medicare shared savings accountable care organization designation but cannot.
Mayo Clin Proc 2012;87(8):723–726.
157. Dolor RJ, Masica AL, Touchette DR, Smith SR, Schumock GT. Patient
safety-focused medication therapy management: challenges affecting
future implementation. Am J Manag Care 2012;18(7):e238–244.
158. Filardo G, Powell JT, Martinez MA, Ballard DJ. Surgery for small
asymptomatic abdominal aortic aneurysms. Cochrane Database Syst Rev
2012;3:CD001835.
159. Herrin J, da Graca B, Nicewander D, Fullerton C, Aponte P, Stanek G,
Cowling T, Collinsworth A, Fleming NS, Ballard DJ. The effectiveness of
implementing an electronic health record on diabetes care and outcomes.
Health Serv Res 2012;47(4):1522–1540.
160. Johnson ES, Bartman B, Briesacher B, Fleming N, Gerhard T, Kornegay
C, Nourjah P, Sauer B, Schumock G, Sedrakyan A, Stürmer T, West S,
Schneeweiss S. The incident user design in comparative effectiveness
research. Pharmacoepidemiol Drug Saf Epub 2012 Oct 1.
161. Johnson ES, Bartman BA, Briesacher BA, Fleming NS, Gerhard T,
Kornegay CJ, Nourjah P, Sauer B, Schumock GT, Sedrakyan A, Stürmer
T, West SL, Schneeweiss S. The Incident User Design in Comparative Effectiveness Research. Effective Health Care Program Research Report No. 32
(AHRQ Publication No. 11(12)-EHC054-EF). Rockville, MD: Agency
for Healthcare Research and Quality, May 2012.
162. Kudyakov R, Bowen J, Ewen E, West SL, Daoud Y, Fleming N, Masica A.
Electronic health record use to classify patients with newly diagnosed versus preexisting type 2 diabetes: infrastructure for comparative effectiveness
219
163.
164.
165.
166.
167.
research and population health management. Popul Health Manag
2012;15(1):3–11.
Readhead AC, Gordon DE, Wang Z, Anderson BJ, Brousseau KS,
Kouznetsova MA, Forgione LA, Smith LC, Torian LV. Transmitted antiretroviral drug resistance in New York State, 2006–2008: results from
a new surveillance system. PLoS One 2012;7(8):e40533.
Rice D, Bain TM, Collinsworth A, Boyer K, Fleming NS, Miller E.
Effective strategies to improve the management of diabetes: case illustration from the Diabetes Health and Wellness Institute. Prim Care
2012;39(2):363–379.
Touchette DR, Masica AL, Dolor RJ, Schumock GT, Choi YK, Kim Y,
Smith SR. Safety-focused medication therapy management: a randomized
controlled trial. J Am Pharm Assoc 2012;52(5):603–612.
Walton JW, Snead CA, Collinsworth AW, Schmidt KL. Reducing diabetes disparities through the implementation of a community health
worker-led diabetes self-management education program. Fam Community Health 2012;35(2):161–171.
Zhang B, Youngblood L, Murphy GD, Ramsay M, Xiao Y. System
engineering approach to documentation: an evaluation of the documentation process in a gastroenterology laboratory. J Biomed Inform
2012;45(3):591–597.
HEPATOLOGY
Note: See also Transplantation.
168. Asrani SK, Asrani NS, Freese DK, Phillips SD, Warnes CA, Heimbach J, Kamath PS. Congenital heart disease and the liver. Hepatology
2012;56(3):1160–1169.
169. Asrani SK, LaRusso NF. Fibrolamellar hepatocellular carcinoma presenting with Budd-Chiari syndrome, right atrial thrombus, and pulmonary
emboli. Hepatology 2012;55(3):977–978.
170. Bajaj JS, O’Leary JG, Reddy KR, Wong F, Olson JC, Subramanian RM,
Brown G, Noble NA, Thacker LR, Kamath PS; NACSELD. Second
infections independently increase mortality in hospitalized patients with
cirrhosis: the North American consortium for the study of end-stage liver
disease (NACSELD) experience. Hepatology 2012;56(6):2328–2335.
171. Bajaj JS, O’Leary JG, Wong F, Reddy KR, Kamath PS. Bacterial infections in end-stage liver disease: current challenges and future directions.
Gut 2012;61(8):1219–1225.
172. Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A; OLT
for HCC Consensus Group. Recommendations for liver transplantation
for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 2012;13(1):e11–e22.
173. Corey KE, Zheng H, Mendez-Navarro J, Delgado-Borrego A, Dienstag
JL, Chung RT; HALT-C Trial Group. Serum vitamin D levels are not
predictive of the progression of chronic liver disease in hepatitis C patients
with advanced fibrosis. PLoS One 2012;7(2):e27144.
174. Dasher K, Trotter JF. Intensive care unit management of liver-related
coagulation disorders. Crit Care Clin 2012;28(3):389–398, vi.
175. Davis GL, O’Leary JG. Use of protease inhibitors in liver transplant
recipients. Gastroenterol Hepatol (N Y) 2012;8(3):183–184.
176. Everson GT, Shiffman ML, Hoefs JC, Morgan TR, Sterling RK, Wagner DA, Lauriski S, Curto TM, Stoddard A, Wright EC; HALT-C
Trial Group. Quantitative liver function tests improve the prediction
of clinical outcomes in chronic hepatitis C: results from the Hepatitis
C Antiviral Long-term Treatment Against Cirrhosis Trial. Hepatology
2012;55(4):1019–1029.
177. Gonzalez SA. Acute liver failure: diagnosis and management. In British
Medical Journal Point of Care, 3rd ed. June 15, 2012. Available at https://
online.epocrates.com/home.
178. Gonzalez SA. Hepatitis B virus. In Yu VL, ed. Antimicrobial Therapy and
Vaccines, vol. 1, 3rd ed. Pittsburgh, PA: ESun Technologies, 2012.
179. Gonzalez SA. Rare indications for liver transplantation. In Clavien P,
Trotter J, Mullhaupt B, eds. Medical Care of the Liver Transplant Patient,
4th ed. Oxford: Wiley-Blackwell, 2012:145–154.
180. Gonzalez SA, Davis GL. The demographics of hepatitis C virus today.
Clin Liver Dis 2012;1(1):2–5.
220
181. Gonzalez SA, Keeffe EB. Risk assessment for hepatocellular carcinoma in
chronic hepatitis B: scores and surveillance. Int J Clin Pract 2012;66(1):
7–10.
182. Kim JY, Asrani SK, Shah ND, Kim WR, Schneekloth TD. Hospitalization for underage drinkers in the United States. J Adolesc Health
2012;50(6):648–650.
183. Lai JC, O’Leary JG, Trotter JF, Verna EC, Brown RS Jr, Stravitz RT,
Duman JD, Forman LM, Terrault NA; Consortium to Study Health
Outcomes in HCV Liver Transplant Recipients (CRUSH-C). Risk of
advanced fibrosis with grafts from hepatitis C antibody-positive donors:
a multicenter cohort study. Liver Transpl 2012;18(5):532–538.
184. Lok AS, Ward JW, Perrillo RP, McMahon BJ, Liang TJ. Reactivation
of hepatitis B during immunosuppressive therapy: potentially fatal yet
preventable. Ann Intern Med 2012;156(10):743–745.
185. McGarry LJ, Pawar VS, Panchmatia HR, Rubin JL, Davis GL, Younossi ZM, Capretta JC, O’Grady MJ, Weinstein MC. Economic model
of a birth cohort screening program for hepatitis C virus. Hepatology
2012;55(5):1344–1355.
186. McMahon BJ, Block J, Haber B, London T, McHugh JA, Perrillo R,
Neubauer R. Internist diagnosis and management of chronic hepatitis
B virus infection. Am J Med 2012;125(11):1063–1067.
187. Moreland A, Trotter JF. Acute liver failure due to disseminated herpes simplex
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188. O’Connor JK, Trotter J, Davis GL, Dempster J, Klintmalm GB, Goldstein RM. Long-term outcomes of stereotactic body radiation therapy
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189. O’Leary JG, Neri MA, Trotter JF, Davis GL, Klintmalm GB. Utilization
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190. Trotter JF. Living donor liver transplantation for hepatocellular carcinoma:
through the looking glass. Am J Transplant 2012;12(11):2873–2874.
191. Trotter J, Kahn B. Renal dysfunction and the liver transplant recipient:
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therapies pretransplant and posttransplant. Curr Opin Organ Transplant
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192. Trotter JF, Everhart JE. Outcomes among living liver donors. Gastroenterology 2012;142(2):207–210.
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193. Banchereau J, Pascual V, O’Garra A. From IL-2 to IL-37: the expanding
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194. Banchereau J, Thompson-Snipes L, Zurawski S, Blanck JP, Cao Y, Clayton S, Gorvel JP, Zurawski G, Klechevsky E. The differential production
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195. Banchereau J, Zurawski S, Thompson-Snipes L, Blanck JP, Clayton S,
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196. Banchereau R, Jordan-Villegas A, Ardura M, Mejias A, Baldwin N, Xu H,
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197. Bao M, Hanabuchi S, Facchinetti V, Du Q, Bover L, Plumas J, Chaperot
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198. Bloom CI, Graham CM, Berry MP, Wilkinson KA, Oni T, Rozakeas F,
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Chau BN, Xin C, Hartner J, Ren S, Castano AP, Linn G, Li J, Tran
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Conrad C, Gregorio J, Wang YH, Ito T, Meller S, Hanabuchi S, Anderson S, Atkinson N, Ramirez PT, Liu YJ, Freedman R, Gilliet M.
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Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A,
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Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Bar NS, Batut P,
Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T,
Drenkow J, Dumais E, Dumais J, Duttagupta R, Falconnet E, Fastuca
M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez
D, Gordon A, Gunawardena H, Howald C, Jha S, Johnson R, Kapranov
P, King B, Kingswood C, Luo OJ, Park E, Persaud K, Preall JB, Ribeca P,
Risk B, Robyr D, Sammeth M, Schaffer L, See LH, Shahab A, Skancke
J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H,
Wrobel J, Yu Y, Ruan X, Hayashizaki Y, Harrow J, Gerstein M, Hubbard
T, Reymond A, Antonarakis SE, Hannon G, Giddings MC, Ruan Y,
Wold B, Carninci P, Guigó R, Gingeras TR. Landscape of transcription
in human cells. Nature 2012;489(7414):101–108.
Duluc D, Gannevat J, Anguiano E, Zurawski S, Carley M, Boreham M,
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vaginal APC subsets in directing T-cell responses. Mucosal Immunol 2012
Nov 7 [Epub ahead of print].
Duluc D, Gannevat J, Joo H, Ni L, Upchurch K, Boreham M, Carley
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for sexually-transmitted diseases. Microb Pathog 2012 Nov 29 [Epub
ahead of print].
Esashi E, Bao M, Wang YH, Cao W, Liu YJ. PACSIN1 regulates the
TLR7/9-mediated type I interferon response in plasmacytoid dendritic
cells. Eur J Immunol 2012;42(3):573–579.
Flamar AL, Zurawski S, Scholz F, Gayet I, Ni L, Li XH, Klechevsky E,
Quinn J, Oh S, Kaplan DH, Banchereau J, Zurawski G. Noncovalent assembly of anti-dendritic cell antibodies and antigens for evoking immune
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Hanabuchi S, Watanabe N, Liu YJ. TSLP and immune homeostasis.
Allergol Int 2012;61(1):19–25.
Jahan-Tigh RR, Ryan C, Obermoser G, Schwarzenberger K. Flow cytometry. J Invest Dermatol 2012;132(10):e1.
Joo H, Coquery C, Xue Y, Gayet I, Dillon SR, Punaro M, Zurawski G,
Banchereau J, Pascual V, Oh S. Serum from patients with SLE instructs
monocytes to promote IgG and IgA plasmablast differentiation. J Exp
Med 2012;209(7):1335–1348.
Kim TW, Yu M, Zhou H, Cui W, Wang J, DiCorleto P, Fox P, Xiao
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Li D, Romain G, Flamar AL, Duluc D, Dullaers M, Li XH, Zurawski S,
Bosquet N, Palucka AK, Le Grand R, O’Garra A, Zurawski G, Banchereau
J, Oh S. Targeting self- and foreign antigens to dendritic cells via DCASGPR generates IL-10-producing suppressive CD4+ T cells. J Exp Med
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Lin W, Piskol R, Tan MH, Li JB. Comment on “Widespread RNA
and DNA sequence differences in the human transcriptome.” Science
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Martirosyan A, Pérez-Gutierrez C, Banchereau R, Dutartre H, Lecine P,
Dullaers M, Mello M, Pinto Salcedo S, Muller A, Leserman L, Levy Y,
Zurawski G, Zurawski S, Moreno E, Moriyón I, Klechevsky E, Banchereau
J, Oh S, Gorvel JP. Brucella ␤ 1,2 cyclic glucan is an activator of human
and mouse dendritic cells. PLoS Pathog 2012;8(11):e1002983.
Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat
Rev Cancer 2012;12(4):265–277.
Parvatiyar K, Zhang Z, Teles RM, Ouyang S, Jiang Y, Iyer SS, Zaver
SA, Schenk M, Zeng S, Zhong W, Liu ZJ, Modlin RL, Liu YJ, Cheng
G. The helicase DDX41 recognizes the bacterial secondary messengers
cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune
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Pascual V, Banchereau J. Tracking interferon in autoimmunity. Immunity
2012;36(1):7–9.
Ramaswami G, Lin W, Piskol R, Tan MH, Davis C, Li JB. Accurate
identification of human Alu and non-Alu RNA editing sites. Nat Methods
2012;9(6):579–581.
Romain G, van Gulck E, Epaulard O, Oh S, Li D, Zurawski G, Zurawski
S, Cosma A, Adam L, Chapon C, Todorova B, Banchereau J, DereuddreBosquet N, Vanham G, Le Grand R, Martinon F. CD34-derived dendritic cells transfected ex vivo with HIV-Gag mRNA induce polyfunctional
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Schwingshackl P, Obermoser G, Nguyen VA, Fritsch P, Sepp N, Romani
N. Distribution and maturation of skin dendritic cell subsets in two forms
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Acta Derm Venereol 2012;92(3):269–275.
Simonini G, Xu Z, Caputo R, De Libero C, Pagnini I, Pascual V, Cimaz
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2013;65(2):513–518.
Tattermusch S, Skinner JA, Chaussabel D, Banchereau J, Berry MP,
McNab FW, O’Garra A, Taylor GP, Bangham CR. Systems biology
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Toyoshima M, Howie HL, Imakura M, Walsh RM, Annis JE, Chang AN,
Frazier J, Chau BN, Loboda A, Linsley PS, Cleary MA, Park JR, Grandori
C. Functional genomics identifies therapeutic targets for MYC-driven
cancer. Proc Natl Acad Sci U S A 2012;109(24):9545–9550.
Xu W, Joo H, Clayton S, Dullaers M, Herve MC, Blankenship D,
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Zhang Z, Bao M, Lu N, Weng L, Yuan B, Liu YJ. The E3 ubiquitin ligase
TRIM21 negatively regulates the innate immune response to intracellular
double-stranded DNA. Nat Immunol 2012;14(2):172–178.
INTERNAL MEDICINE AND FAMILY MEDICINE
Note: Most family medicine and internal medicine articles are subclassified by
specialty, even if generalists were first authors or coauthors.
227. Graves RC, Oehler K, Tingle LE. Febrile seizures: risks, evaluation, and
prognosis. Am Fam Physician 2012;85(2):149–153.
228. Kuo VC. Hepatitis E infection. Proc (Bayl Univ Med Cent) 2012;25(2):
119–120.
229. Vrček I, Gummelt KL. Diagnosis and treatment of a red, swollen eye.
221
METABOLIC DISEASES
230. Anderson BH, Kasher PR, Mayer J, Szynkiewicz M, Jenkinson EM,
Bhaskar SS, Urquhart JE, Daly SB, Dickerson JE, O’Sullivan J, Leibundgut EO, Muter J, Abdel-Salem GM, Babul-Hirji R, Baxter P, Berger
A, Bonafé L, Brunstom-Hernandez JE, Buckard JA, Chitayat D, Chong
WK, Cordelli DM, Ferreira P, Fluss J, Forrest EH, Franzoni E, Garone
C, Hammans SR, Houge G, Hughes I, Jacquemont S, Jeannet PY, Jefferson RJ, Kumar R, Kutschke G, Lundberg S, Lourenço CM, Mehta
R, Naidu S, Nischal KK, Nunes L, Ounap K, Philippart M, Prabhakar
P, Risen SR, Schiffmann R, Soh C, Stephenson JB, Stewart H, Stone
J, Tolmie JL, van der Knaap MS, Vieira JP, Vilain CN, Wakeling EL,
Wermenbol V, Whitney A, Lovell SC, Meyer S, Livingston JH, Baerlocher GM, Black GC, Rice GI, Crow YJ. Mutations in CTC1, encoding
conserved telomere maintenance component 1, cause Coats plus. Nat
Genet 2012;44(3):338–342.
231. Bottiglieri T, Arning E, Wasek B, Nunbhakdi-Craig V, Sontag JM, Sontag E. Acute administration of L-DOPA induces changes in methylation metabolites, reduced protein phosphatase 2A methylation,
and hyperphosphorylation of Tau protein in mouse brain. J Neurosci
2012;32(27):9173–9181.
232. Brown KJ, Vanderver A, Hoffman EP, Schiffmann R, Hathout Y. Characterization of transferrin glycopeptide structures in human cerebrospinal
fluid. Int J Mass Spectrom 2012;312:97–106.
233. Fogli A, Merle C, Roussel V, Schiffmann R, Ughetto S, Theisen M,
Boespflug-Tanguy O. CSF N-glycan profiles to investigate biomarkers
in brain developmental disorders: application to leukodystrophies related
to eIF2B mutations. PLoS One 2012;7(8):e42688.
234. Huyghe A, Horzinski L, Hénaut A, Gaillard M, Bertini E, Schiffmann
R, Rodriguez D, Dantal Y, Boespflug-Tanguy O, Fogli A. Developmental
splicing deregulation in leukodystrophies related to EIF2B mutations.
PLoS One 2012;7(6):e38264.
235. Inoue-Choi M, Nelson HH, Robien K, Arning E, Bottiglieri T, Koh
WP, Yuan JM. One-carbon metabolism nutrient status and plasma Sadenosylmethionine concentrations in middle-aged and older Chinese
in Singapore. Int J Mol Epidemiol Genet 2012;3(2):160–173.
236. Marin-Valencia I, Good LB, Ma Q, Duarte J, Bottiglieri T, Sinton CM,
Heilig CW, Pascual JM. Glut1 deficiency (G1D): epilepsy and metabolic
dysfunction in a mouse model of the most common human phenotype.
Neurobiol Dis 2012;48(1):92–101.
237. Mercimek-Mahmutoglu S, Sinclair G, van Dooren SJ, Kanhai W, Ashcraft P, Michel OJ, Nelson J, Betsalel OT, Sweetman L, Jakobs C, Salomons GS. Guanidinoacetate methyltransferase deficiency: first steps
to newborn screening for a treatable neurometabolic disease. Mol Genet
Metab 2012;107(3):433–437.
238. Mischoulon D, Alpert JE, Arning E, Bottiglieri T, Fava M, Papakostas
GI. Bioavailability of S-adenosyl methionine and impact on response in
a randomized, double-blind, placebo-controlled trial in major depressive
disorder. J Clin Psychiatry 2012;73(6):843–848.
239. Mochel F, Durant B, Meng X, O’Callaghan J, Yu H, Brouillet E, Wheeler
VC, Humbert S, Schiffmann R, Durr A. Early alterations of brain cellular energy homeostasis in Huntington disease models. J Biol Chem
2012;287(2):1361–1370.
240. Mochel F, Schiffmann R, Steenweg ME, Akman HO, Wallace M, Sedel
F, Laforêt P, Levy R, Powers JM, Demeret S, Maisonobe T, Froissart R,
Da Nobrega BB, Fogel BL, Natowicz MR, Lubetzki C, Durr A, Brice A,
Rosenmann H, Barash V, Kakhlon O, Gomori JM, van der Knaap MS,
Lossos A. Adult polyglucosan body disease: natural history and key magnetic resonance imaging findings. Ann Neurol 2012;72(3):433–441.
241. Novarino G, El-Fishawy P, Kayserili H, Meguid NA, Scott EM, Schroth
J, Silhavy JL, Kara M, Khalil RO, Ben-Omran T, Ercan-Sencicek AG,
Hashish AF, Sanders SJ, Gupta AR, Hashem HS, Matern D, Gabriel S,
Sweetman L, Rahimi Y, Harris RA, State MW, Gleeson JG. Mutations in
BCKD-kinase lead to a potentially treatable form of autism with epilepsy.
Science 2012;338(6105):394–397.
242. Papakostas GI, Shelton RC, Zajecka JM, Etemad B, Rickels K, Clain A,
Baer L, Dalton ED, Sacco GR, Schoenfeld D, Pencina M, Meisner A,
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245.
246.
247.
248.
Fava M. L-methylfolate as adjunctive therapy for SSRI-resistant major
depression: results of two randomized, double-blind, parallel-sequential
trials. Am J Psychiatry 2012;169(12):1267–1274.
Potic A, Brais B, Choquet K, Schiffmann R, Bernard G. 4H syndrome
with late-onset growth hormone deficiency caused by POLR3A mutations. Arch Neurol 2012;69(7):920–923.
Ramos-Roman MA, Sweetman L, Valdez MJ, Parks EJ. Postprandial
changes in plasma acylcarnitine concentrations as markers of fatty acid
flux in overweight and obesity. Metabolism 2012;61(2):202–212.
Segal MM, Schiffmann R. Decision support for diagnosis: co-evolution
of tools and resources. Neurology 2012;78(20):1546–1547.
Tétreault M, Putorti ML, Thiffault I, Sylvain M, Venderver A, Schiffmann R, Brais B, Bernard G. TACH leukodystrophy: locus refinement
to chromosome 10q22.3-23.1. Can J Neurol Sci 2012;39(1):122–123.
Thomas NK, Willis S, Sweetman L, Borges K. Triheptanoin in acute
mouse seizure models. Epilepsy Res 2012;99(3):312–317.
Vogel KR, Arning E, Wasek BL, Bottiglieri T, Gibson KM. Non-physiological amino acid (NPAA) therapy targeting brain phenylalanine reduction: pilot studies in PAH (ENU2) mice. J Inherit Metab Dis 2012 Sep
14 [Epub ahead of print].
NEPHROLOGY
Note: See also Transplantation.
249. Aggarwal N, Porter AC, Tang IY, Becker BN, Akkina SK. Creatininebased estimations of kidney function are unreliable in obese kidney donors. J Transplant 2012;2012:872894.
250. Akkina SK, Ricardo AC, Patel A, Das A, Bazzano LA, Brecklin C, Fischer
MJ, Lash JP. Illicit drug use, hypertension, and chronic kidney disease in
the US adult population. Transl Res 2012;160(6):391–398.
251. Colbert G, Richey D, Schwartz JC. Widespread tuberculosis including
renal involvement. Proc (Bayl Univ Med Cent) 2012;25(3):236–239.
252. Patel T, Fenves A, Colbert G. The de novo diagnosis of systemic lupus
erythematosus and lupus nephritis during pregnancy. Proc (Bayl Univ
Med Cent) 2012;25(2):129–131.
253. Sanchez C, Fenves A, Schwartz J. Focal segmental glomerulosclerosis and
parvovirus B19. Proc (Bayl Univ Med Cent) 2012;25(1):20–22.
254. Saxena R, Fenves A, Yu XQ, Vaziri ND, Silva FG, Zhou XJ. Renal function and disease in the aging kidney. In Schrier RW, ed. Schrier’s Diseases
of the Kidney and Urinary Tract, 9th ed. Baltimore: Lippincott Williams
& Wilkins, 2012.
255. Shroff GR, Akkina SK, Miedema MD, Madlon-Kay R, Herzog CA,
Kasiske BL. Troponin I levels and postoperative myocardial infarction
following renal transplantation. Am J Nephrol 2012;35(2):175–180.
NEUROLOGY/NEUROSURGERY
256. Black SB, Evans RW. Economic credentialing of physicians by insurance
companies and headache medicine. Headache 2012;52(6):1037–1040.
257. Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita
M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V,
Dawson KT; CONFIRM Study Investigators. Placebo-controlled
phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl
J Med 2012;367(12):1087–1097.
258. Freitag FG. Headache: advances in understanding and treatment. Lancet
Neurol 2012;11(1):10–12.
259. Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E.
Evidence-based guideline update: NSAIDs and other complementary
treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and
the American Headache Society. Neurology 2012;78(17):1346–1353.
260. Hostin R, McCarthy I, O’Brien M, Bess S, Line B, Boachi-Adjei O, Burton
D, Gupta M, Ames C, Deviren V, Kebaish K, Shaffrey C, Wood K, Hart R;
International Spine Study Group. Incidence, mode, and location of acute
proximal junctional failure following surgical treatment for adult spinal
deformity. Spine (Phila Pa 1976) 2012 Sept 13 [Epub ahead of print].
261. Khan O, Miller A, Tornatore C, Phillips J, Barnes C. Practice patterns
of US neurologists in secondary progressive and primary progressive
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263.
264.
265.
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multiple sclerosis: a modified Delphi consensus study. Neurol Clin Pract
2012;2(1):58–66.
Phillips JT. Consensus statements from a panel of U.S. managed care
pharmacists and physicians for management of multiple sclerosis agents.
J Manag Care Pharm 2012;18(3):277.
Phillips J, Stone L. Use of MRI in the clinical management of multiple
sclerosis. In Cohen J, Rudick R, eds. Multiple Sclerosis Therapeutics, 4th
ed. Cambridge: Cambridge University Press, 2012:645–653.
Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E.
Evidence-based guideline update: pharmacologic treatment for episodic
migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American
Headache Society. Neurology 2012;78(17):1337–1345.
Tornatore C, Phillips J, Khan O, Miller AE, Barnes CJ. Practice patterns
of US neurologists in patients with CIS, RRMS, or RIS: a consensus
study. Neurol Clin Pract 2012;2(1):48–57.
Weinstock-Guttman B, Galetta SL, Giovannoni G, Havrdova E, Hutchinson M, Kappos L, O’Connor PW, Phillips JT, Polman C, Stuart WH, Lynn
F, Hotermans C. Additional efficacy endpoints from pivotal natalizumab
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NURSING/ALLIED HEALTH
267. Ashmore JA, Frierson G, Blair SN. The role of physical activity in weight
loss and weight loss maintenance. In Akabas SR, Lederman SA, Moore
BJ, eds. Textbook of Obesity: Biological, Psychological and Cultural Implications. New York: John Wiley & Sons, 2012:344–353.
268. Cochran VY, Blair B, Wissinger L, Nuss TD. Lessons learned from implementation of postdischarge telephone calls at Baylor Health Care System.
J Nurs Adm 2012;42(1):40–46.
269. Custer JW, White E, Fackler JC, Xiao Y, Tien A, Lehmann H, Nichols DG. A qualitative study of expert and team cognition on complex
patients in the pediatric intensive care unit. Pediatr Crit Care Med
2012;13(3):278–284.
270. Hasse JM. Diet linked to cancer. Nutr Clin Pract 2012;27(5):581.
271. Hasse JM. Nutrition support safe practices. Nutr Clin Pract 2012;27(6):
713–714.
272. Hasse JM. Pre- and probiotics. Nutr Clin Pract 2012;27(2):149.
273. Houston S, Leveille M, Luquire R, Fike A, Ogola GO, Chando S. Decisional involvement in Magnet®, Magnet-aspiring, and non-Magnet
hospitals. J Nurs Adm 2012;42(12):586–591.
274. Leeper B, Centeno M. Disparities in cardiac care for patients with complex cardiovascular care needs. J Cardiovasc Nurs 2012;27(2):114–119.
275. Pilcher J. Growing dendrites and brain-based learning. Neonatal Net
2012;31(3):191–194.
276. Pilcher J. Owning your professional development. Neonatal Netw 2012;31(6):
401–406.
277. Pilcher J. Toolkit for NICU nurse preceptors. Neonatal Netw 2012;31(1):
39–44.
278. Pilcher J, Goodall H, Jensen C, Huwe V, Jewell C, Reynolds R,
Karlsen KA. Special focus on simulation: educational strategies in the
NICU: simulation-based learning: it’s not just for NRP. Neonatal Netw
2012;31(5):281–287.
279. Poskey GA, Hersch G. Listening to their voices: parents’ perspective on
infant crying. J Occup Ther Schools Early Intervent 2012;5(2):114–125.
280. Smith NZ. Treating metastatic breast cancer with systemic chemotherapies: current trends and future perspectives. Clin J Oncol Nurs
2012;16(2):E33–E43.
281. Tjiong L, Cyr A, Fox J. Comparison of manual compression alone versus
with hemostatic patch in achieving hemostasis after femoral catheter
removal. J Perianesth Nurs 2012;27(2):88–93.
282. Wyatt C, Jumper J. The human touch: learning that the job is about more
than machines. Biomed Instrum Technol 2012;46(3):181–183.
ONCOLOGY/HEMATOLOGY/SURGICAL ONCOLOGY
283. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR,
Cutler CS, Westervelt P, Woolfrey A, Couban S, Ehninger G, Johnston
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Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA,
Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell
carcinomas in patients treated with BRAF inhibitors. N Engl J Med
2012;366(3):207–215.
358. Takahashi M, Cuatrecasas M, Balaguer F, Hur K, Toiyama Y, Castells A,
Boland CR, Goel A. The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer. PLoS One
2012;7(10):e46684.
359. Takahashi M, Sung B, Shen Y, Hur K, Link A, Boland CR, Aggarwal BB,
Goel A. Boswellic acid exerts antitumor effects in colorectal cancer cells
by modulating expression of the let-7 and miR-200 microRNA family.
Carcinogenesis 2012;33(12):2441–2449.
360. Thomas VT, Hinson S, Konduri K. Epithelial-mesenchymal transition
in pulmonary carcinosarcoma: case report and literature review. Ther Adv
Med Oncol 2012;4(1):31–37.
361. Thompson P, Roe DJ, Fales L, Buckmeier J, Wang F, Hamilton SR,
Bhattacharyya A, Green S, Hsu CH, Chow HH, Ahnen DJ, Boland CR,
Heigh RI, Fay DE, Martinez ME, Jacobs E, Ashbeck EL, Alberts DS,
Lance P. Design and baseline characteristics of participants in a phase
III randomized trial of celecoxib and selenium for colorectal adenoma
prevention. Cancer Prev Res (Phila) 2012;5(12):1381–1393.
362. Toiyama Y, Goel A. The diagnostic, prognostic and predictive potential
of microRNA biomarkers in colorectal cancer. Current Colorectal Cancer
Reports 2012;8(1):22–31.
363. Toiyama Y, Yasuda H, Saigusa S, Matushita K, Fujikawa H, Tanaka K,
Mohri Y, Inoue Y, Goel A, Kusunoki M. Co-expression of hepatocyte
growth factor and c-Met predicts peritoneal dissemination established
by autocrine hepatocyte growth factor/c-Met signaling in gastric cancer.
Int J Cancer 2012;130(12):2912–2921.
364. Tran HT, Liu Y, Zurita AJ, Lin Y, Baker-Neblett KL, Martin AM, Figlin
RA, Hutson TE, Sternberg CN, Amado RG, Pandite LN, Heymach
JV. Prognostic or predictive plasma cytokines and angiogenic factors
for patients treated with pazopanib for metastatic renal-cell cancer:
a retrospective analysis of phase 2 and phase 3 trials. Lancet Oncol
2012;13(8):827–837.
226
365. Ubel PA, Berry SR, Nadler E, Bell CM, Kozminski MA, Palmer JA,
Evans WK, Strevel EL, Neumann PJ. In a survey, marked inconsistency
in how oncologists judged value of high-cost cancer drugs in relation to
gains in survival. Health Aff (Millwood) 2012;31(4):709–717.
366. Vogelzang NJ, Bhor M, Liu Z, Dhanda R, Hutson TE. Everolimus vs.
temsirolimus for advanced renal cell carcinoma: use and use of resources
in the US Oncology network. Clin Genitourin Cancer 2012 Oct 11
367. Williams JC, Hamilton JK, Shiller M, Fischer L, Deprisco G, Boland CR.
Combined juvenile polyposis and hereditary hemorrhagic telangiectasia.
368. Witta SE, Jotte RM, Konduri K, Neubauer MA, Spira AI, Ruxer RL,
Varella-Garcia M, Bunn PA Jr, Hirsch FR. Randomized phase II trial of
erlotinib with and without entinostat in patients with advanced nonsmall-cell lung cancer who progressed on prior chemotherapy. J Clin
Oncol 2012;30(18):2248–2255.
369. Yurgelun MB, Goel A, Hornick JL, Sen A, Turgeon DK, Ruffin MT 4th,
Marcon NE, Baron JA, Bresalier RS, Syngal S, Brenner DE, Boland CR,
Stoffel EM. Microsatellite instability and DNA mismatch repair protein
deficiency in Lynch syndrome colorectal polyps. Cancer Prev Res (Phila)
2012;5(4):574–582.
370. Zurita AJ, George DJ, Shore ND, Liu G, Wilding G, Hutson TE, Kozloff
M, Mathew P, Harmon CS, Wang SL, Chen I, Chow Maneval E, Logothetis CJ. Sunitinib in combination with docetaxel and prednisone in
chemotherapy-naive patients with metastatic, castration-resistant prostate
cancer: a phase 1/2 clinical trial. Ann Oncol 2012;23(3):688–694.
ORAL AND MAXILLOFACIAL SURGERY
371. Wolford LM. Mandibular asymmetry: temporomandibular joint degeneration. In Bagheri SC, Bell RB, Khan HA, eds. Current Therapy in Oral and
Maxillofacial Surgery. St. Louis: Elsevier Saunders, 2012:696–725.
372. Wolford LM, Bourland TC, Rodrigues D, Perez DE, Limoeiro E. Successful reconstruction of nongrowing hemifacial microsomia patients
with unilateral temporomandibular joint total joint prosthesis and orthognathic surgery. J Oral Maxillofac Surg 2012;70(12):2835–2853.
373. Wolford LM, Perez D, Stevao E, Perez E. Airway space changes after
nasopharyngeal adenoidectomy in conjunction with Le Fort I osteotomy.
J Oral Maxillofac Surg 2012;70(3):665–671.
374. Wolford LM, Rodrigues DB. Orthognathic considerations in the young
patient and effects on facial growth. In Preedy VR, ed. Handbook of
Growth and Growth Monitoring in Health and Disease. New York: Springer, 2012:1789–1808.
375. Wolford LM, Rodrigues DB. Temporomandibular joint (TMJ) pathologies in growing patients: effects on facial growth and development. In
Preedy VR, ed. Handbook of Growth and Growth Monitoring in Health
and Disease. New York: Springer, 2012:1809–1828.
376. Wolford LM, Stevo ELL, Alexander CM, Goncalves JR, Rodrigues DB.
Orthodontics for orthognathic surgery. In Miloro M, Ghali GE, Larsen P,
Waite P, eds. Peterson’s Principles of Oral and Maxillofacial Surgery. Shelton,
CT: People’s Medical Publishing House-USA, 2012:1263–1294.
ORTHOPAEDIC SURGERY
377. Atesok K, Mabrey JD, Jazrawi LM, Egol KA. Surgical simulation in orthopaedic skills training. J Am Acad Orthop Surg 2012;20(7):410–422.
378. Brodsky JW, Brajtbord J, Coleman SC, Raut S, Polo FE. Effect of heating on the mechanical properties of insole materials. Foot Ankle Int
2012;33(9):772–778.
379. Brodsky JW, Toppins A. Postsurgical imaging of the peroneal tendons.
Semin Musculoskelet Radiol 2012;16(3):233–240.
380. Daoud AI, Geissler GJ, Wang F, Saretsky J, Daoud YA, Lieberman DE.
Foot strike and injury rates in endurance runners: a retrospective study.
Med Sci Sports Exerc 2012;44(7):1325–1334.
381. Smith SM, Coleman SC, Bacon SA, Polo FE, Brodsky JW. Improved
ankle push-off power following cheilectomy for hallux rigidus: a prospective gait analysis study. Foot Ankle Int 2012;33(6):457–461.
Volume 26, Number 2
OTOLARYNGOLOGY
382. Arosarena O, Ducic Y, Tollefson TT. Mandible fractures: discussion and
debate. Facial Plast Surg Clin North Am 2012;20(3):347–363.
383. Inman J, Ducic Y. Intracranial free tissue transfer for massive cerebrospinal fluid leaks of the anterior cranial fossa. J Oral Maxillofac Surg
2012;70(5):1114–1118.
PATHOLOGY
384. Chen J, Matzuk MM, Zhou XJ, Lu CY. Endothelial pentraxin 3
contributes to murine ischemic acute kidney injury. Kidney Int
2012;82(11):1195–1207.
385. Du Y, An S, Liu L, Li L, Zhou XJ, Mason RP, Mohan C. Serial noninvasive monitoring of renal disease following immune-mediated injury
using near-infrared optical imaging. PLoS One 2012;7(9):e43941.
386. Harbour LN, Koch MS, Louis TH, Fulmer JM, Guileyardo JM. Abdominal apoplexy: two unusual cases of hemoperitoneum. Proc (Bayl
Univ Med Cent) 2012;25(1):16–19.
387. Hutcheson J, Vanarsa K, Bashmakov A, Grewal S, Sajitharan D, Chang BY,
Buggy JJ, Zhou XJ, Du Y, Satterthwaite AB, Mohan C. Modulating proximal cell signaling by targeting Btk ameliorates humoral autoimmunity and
end-organ disease in murine lupus. Arthritis Res Ther 2012;14(6):R243.
388. Hwang SH, Lee H, Yamamoto M, Jones LA, Dayalan J, Hopkins R,
Zhou XJ, Yarovinsky F, Connolly JE, Curotto de Lafaille MA, Wakeland
EK, Fairhurst AM. B cell TLR7 expression drives anti-RNA autoantibody
production and exacerbates disease in systemic lupus erythematosusprone mice. J Immunol 2012;189(12):5786–5796.
389. Kiani AN, Wu T, Fang H, Zhou XJ, Ahn CW, Magder LS, Mohan C,
Petri M. Urinary vascular cell adhesion molecule, but not neutrophil
gelatinase-associated lipocalin, is associated with lupus nephritis. J Rheumatol 2012;39(6):1231–1237.
390. Singh S, Wu T, Xie C, Vanarsa K, Han J, Mahajan T, Oei HB, Ahn C, Zhou XJ,
Putterman C, Saxena R, Mohan C. Urine VCAM-1 as a marker of renal pathology activity index in lupus nephritis. Arthritis Res Ther 2012;14(4):R164.
391. Van Buren P, Velez RL, Vaziri ND, Zhou XJ. Iron overdose: a contributor
to adverse outcomes in randomized trials of anemia correction in CKD.
Int Urol Nephrol 2012;44(2):499–507.
392. Van Vrancken MJ, Guileyardo J. Vertebral artery thrombosis and subsequent stroke following attempted internal jugular central venous catheterization. Proc (Bayl Univ Med Cent) 2012;25(3):240–242.
PHYSICAL MEDICINE AND REHABILITATION
393. Bombardier CH, Fann JR, Tate DG, Richards JS, Wilson CS, Warren AM,
Temkin NR, Heinemann AW; PRISMS Investigators. An exploration of
modifiable risk factors for depression after spinal cord injury: which factors
should we target? Arch Phys Med Rehabil 2012;93(5):775–781.
394. Driver S, Ede A, Dodd Z, Stevens L, Warren AM. What barriers to
physical activity do individuals with a recent brain injury face? Disabil
Health J 2012;5(2):117–125.
395. Kelley E, Sullivan C, Loughlin JK, Hutson L, Dahdah MN, Long MK,
Schwab KA, Poole JH. Self-awareness and neurobehavioral outcomes,
5 years or more after moderate to severe brain injury. J Head Trauma
Rehabil 2012 Dec 15 [Epub ahead of print].
396. Srinivasan R. Patient safety in the rehabilitation of children with traumatic
brain injury and cerebral palsy. Phys Med Rehabil Clin N Am 2012;23(2):
393–400.
397. Stiers W, Hanson S, Turner AP, Stucky K, Barisa M, Brownsberger M, Van
Tubbergen M, Ashman T, Kuemmel A. Guidelines for postdoctoral training in rehabilitation psychology. Rehabil Psychol 2012;57(4):267–29.
398. Warren AM, Williamson M, Erosa NA, Elliott TR. Spinal cord injury.
In The Handbook of Psychology, Volume 9: Health Psychology, 2nd ed. New
York: Wiley, 2012.
PLASTIC SURGERY
399. Beale EW, Rasko Y, Rohrich RJ. A twenty year experience with secondary rhytidectomy: a review of technique, longevity and outcomes. Plast
Reconstr Surg 2012 Nov 8 [Epub ahead of print].
April 2013
400. Bidic SM, Dauwe PB, Heller J, Brown S, Rohrich RJ. Reconstructing
large keloids with neodermis: a systematic review. Plast Reconstr Surg
2012;129(2):380e–382e.
401. Chang S, Lehrman C, Itani K, Rohrich RJ. A systematic review of comparison of upper eyelid involutional ptosis repair techniques: efficacy and
complication rates. Plast Reconstr Surg 2012;129(1):149–157.
402. Cruz RS, O’Reilly EB, Rohrich RJ. The platysma window: an anatomically safe, efficient, and easily reproducible approach to neck contour in
the face lift. Plast Reconstr Surg 2012;129(5):1169–1172.
403. Del Vecchio D, Rohrich RJ. A classification of clinical fat grafting: different problems, different solutions. Plast Reconstr Surg 2012;130(3):
511–522.
404. Eaves FF 3rd, Haeck PC, Rohrich RJ. ASAPS/ASPS position statement on stem cells and fat grafting. Plast Reconstr Surg 2012;129(1):
285–287.
405. Gir P, Brown SA, Oni G, Kashefi N, Mojallal A, Rohrich RJ. Fat grafting:
evidence-based review on autologous fat harvesting, processing, reinjection, and storage. Plast Reconstr Surg 2012;130(1):249–258.
406. Gir P, Oni G, Brown SA, Mojallal A, Rohrich RJ. Human adipose stem
cells: current clinical applications. Plast Reconstr Surg 2012;129(6):
1277–1290.
407. Nguyen AT, Ahmad J, Fagien S, Rohrich RJ. Cosmetic medicine: facial
resurfacing and injectables. Plast Reconstr Surg 2012;129(1):142e–153e.
408. Pessa JE, Rohrich RJ. Aging changes of the midfacial fat compartments: a computed tomographic study. Plast Reconstr Surg 2012;129(1):
274–275.
409. Rasko YM, Beale E, Rohrich RJ. Secondary rhytidectomy: comprehensive review and current concepts. Plast Reconstr Surg 2012;130(6):
1370–1378.
410. Rifkin LH, Stojadinovic S, Stewart CH, Song KH, Maxted MC, Bell
MH, Kashefi NS, Speiser MP, Saint-Cyr M, Story MD, Rohrich RJ,
Brown SA, Solberg TD. An athymic rat model of cutaneous radiation
injury designed to study human tissue-based wound therapy. Radiat
Oncol 2012;7:68.
411. Rohrich RJ. Current concepts in the use of acellular dermal matrices in
surgery. Plast Reconstr Surg 2012;130(5 Suppl 2):1S–3S.
412. Rohrich RJ, Hoxworth RE, Kurkjian TJ. The role of the columellar strut in rhinoplasty: indications and rationale. Plast Reconstr Surg
2012;129(1):118e–125e.
413. Rohrich RJ, Kurkjian TJ, Hoxworth RE, Stephan PJ, Mojallal A. The
effect of the columellar strut graft on nasal tip position in primary rhinoplasty. Plast Reconstr Surg 2012;130(4):926–932.
414. Rohrich RJ, Liu JH. Defining the infratip lobule in rhinoplasty: anatomy,
pathogenesis of abnormalities, and correction using an algorithmic approach. Plast Reconstr Surg 2012;130(5):1148–1158.
415. Saint-Cyr M, Wong C, Oni G, Maia M, Trussler A, Mojallal A,
Rohrich RJ. Modifications to extend the transverse upper gracilis flap
in breast reconstruction: clinical series and results. Plast Reconstr Surg
2012;129(1):24e–36e.
416. Song EH, Shirazian A, Binns B, Fleming Y, Ferreira LM, Rohrich RJ,
Azari K. Benchmarking academic plastic surgery services in the United
States. Plast Reconstr Surg 2012;129(6):1407–1418.
417. Unger JG, Lee MR, Kwon RK, Rohrich RJ. A multivariate analysis of
nasal tip deprojection. Plast Reconstr Surg 2012;129(5):1163–1167.
PULMONOLOGY/SLEEP MEDICINE
418. Gower RG, Lumry WR, Davis-Lorton MA, Johnston DT, Busse PJ.
Current options for prophylactic treatment of hereditary angioedema
in the United States: patient-based considerations. Allergy Asthma Proc
2012;33(3):235–240.
419. Grant JA, White MV, Li HH, Fitts D, Kalfus IN, Uknis ME, Lumry
WR. Preprocedural administration of nanofiltered C1 esterase inhibitor to prevent hereditary angioedema attacks. Allergy Asthma Proc
2012;33(4):348–353.
420. Henry D, Rosenthal L. “Listening for his breath”: The significance of gender and partner reporting on the diagnosis, management, and treatment of
obstructive sleep apnea. Soc Sci Med 2012 Jun 16 [EPub ahead of print].
227
421. Kalfus IN, Gower RG, Riedl M, Bernstein JA, Lumry WR, Frank MM.
Hereditary angioedema: implications of treating a rare disease. Ann
Allergy Asthma Immunol 2012;109(2):150–151.
422. Rosenthal L: Got CPAP? Use it in the hospital! Sleep Breath 2012;16:
945–946.
RADIOLOGY
Note: See also Oncology and other departments in which radiologists were first
authors or coauthors.
423. Barry S, Ha KY, Laurie L. Carcinoma of the breast in men. Proc (Bayl
Univ Med Cent) 2012;25(4):367–368.
424. Barry S, Savage C, Layton KF. Combined endovascular thrombolysis and
uterine fibroid embolization in a patient with dural venous sinus thrombosis and severe metrorrhagia. J Vasc Interv Radiol 2012;23(3):424–426.
425. Barry SK, Schucany WG. Dracunculiasis of the breast: radiological manifestations of a rare disease. J Radiol Case Rep 2012;6(11):29–33.
426. Carter BW. Hermansky-Pudlak syndrome complicated by pulmonary
fibrosis. Proc (Bayl Univ Med Cent) 2012;25(1):76–77.
427. Fitzpatrick MC, Carter BW. Pulmonary mucormycosis complicating
cutaneous blastic plasmacytoid dendritic cell neoplasm. Proc (Bayl Univ
Med Cent) 2012;25(3):287–288.
428. Gibbs WN, Opatowsky MJ, Burton EC. AIRP best cases in radiologicpathologic correlation: cerebral fat embolism syndrome in sickle cell
␤-thalassemia. Radiographics 2012;32(5):1301–1306.
429. Henderson JB, Zarghouni M, Hise JH, Opatowsky MJ, Layton KF.
Dementia caused by dural arteriovenous fistulas reversed following endovascular therapy. Proc (Bayl Univ Med Cent) 2012;25(4):338–340.
430. Islam S, Schucany WG, Hurst DC, Lepe-Suastegui MR. Echinococcus
granulosus infection presenting as right upper-quadrant abdominal pain.
431. Kershen LM, Schucany WG, Gilbert NF. Nora’s lesion: bizarre parosteal
osteochondromatous proliferation of the tibia. Proc (Bayl Univ Med Cent)
2012;25(4):369–371.
432. Layton KJ, Gallichan D, Testud F, Cocosco CA, Welz AM, Barmet C,
Pruessmann KP, Hennig J, Zaitsev M. Single shot trajectory design for
region-specific imaging using linear and nonlinear magnetic encoding
fields. Magn Reson Med 2012 Oct 5 [Epub ahead of print].
433. Layton KJ, Morelande M, Farrell PM, Moran B, Johnston LA. Performance analysis for magnetic resonance imaging with nonlinear encoding
fields. IEEE Trans Med Imaging 2012;31(2):391–404.
434. Levine HR, Ha K, O’Rourke B, Barnett D, Opatowsky MJ. A pictorial
review of complications of acute coalescent mastoiditis. Proc (Bayl Univ
Med Cent) 2012;25(4):372–373.
435. Levine HR, O’Connor J, dePrisco G. Obstetrical emergency: an unusual case
of an ectopic pregnancy. Proc (Bayl Univ Med Cent) 2012;25(1):73–75.
436. McDonald JS, Carter RE, Layton KF, Mocco J, Madigan JB, Tawk RG,
Hanel RA, Roy SS, Cloft HJ, Klunder AM, Suh SH, Kallmes DF. Interobserver variability in retreatment decisions of recurrent and residual aneurysms. AJNR Am J Neuroradiol 2012 Oct 25 [Epub ahead of print].
437. McQuillan B, Carter B, Millard-Hasting B, Ayotte K, Jesinger R, Lichtenberger J. The interventricular septum: a multimodality review of
anatomy and pathology. Am J Roentgen 2012;198(5 Suppl).
438. Patel P, Fischer L, O’Connor J. Retroperitoneal ganglioneuroma incidentally found in a patient presenting with renal colic. Proc (Bayl Univ
Med Cent) 2012;25(3):291–292.
439. Patel P, Schucany G, Wood PB, Hurst D. Paget’s disease of the calcaneus
causing right foot pain. Proc (Bayl Univ Med Cent) 2012;25(2):161–162.
440. Patel P, Schucany WG, Toye L, Ortinau E. Flexor tendon pulley injury
in a bowler. Proc (Bayl Univ Med Cent) 2012;25(3):282–284.
441. Patel P, Schucany WG. A rare case of intraneural ganglion cyst involving
the tibial nerve. Proc (Bayl Univ Med Cent) 2012;25(2):132–135.
442. Ray MJ, Barnett DW, Snipes GJ, Layton KF, Opatowsky MJ. Ruptured intracranial dermoid cyst. Proc (Bayl Univ Med Cent) 2012;25(1):
23–25.
443. Ray MJ, Savage C, Klintmalm GB, Rees CR. Endovascular caudal retraction of the cranial end of a misplaced Viatorr TIPS prior to liver
transplantation. Proc (Bayl Univ Med Cent) 2012;25(4):341–343.
228
444. Saad AF, Opatowsky MJ, Nixon AY, Gilbert SC, Thacker IC. Ruptured
cerebral arteriovenous malformation presenting as intraventricular hemorrhage. Proc (Bayl Univ Med Cent) 2012;25(2):163–164.
445. Sacks J, Ray MJ, Williams S, Opatowsky MJ. Fatal toxic leukoencephalopathy secondary to overdose of a new psychoactive designer drug 2C-E
(“Europa”). Proc (Bayl Univ Med Cent) 2012;25(4):374–376.
446. Schucany WG. Echinococcal infection of the liver causing Budd-Chiari
syndrome. Proc (Bayl Univ Med Cent) 2012;25(1):83–84.
447. Taylor WB III, Lloyd MD, Mendeloff EN, Laird WP, Dockery WD,
Carter BW. Anomalous origin of the right coronary artery from the
pulmonary trunk demonstrated by electrocardiographically gated computed tomography coronary angiography. Proc (Bayl Univ Med Cent)
2012;25(3):289–290.
448. Taylor WB III, Vandergriff CL, Opatowsky MJ, Layton KF. Bowhunter’s
syndrome diagnosed with provocative digital subtraction cerebral angiography. Proc (Bayl Univ Med Cent) 2012;25(1):26–27.
449. Vandergriff C, Opatowsky M, O’Rourke B, Layton K. Papillary tumor of
the pineal region. Proc (Bayl Univ Med Cent) 2012;25(1):78–79.
450. Zarghouni M, Levine H, Layton KF. Intracranial Nocardia in the setting
of AIDS. Proc (Bayl Univ Med Cent) 2012;25(4):381–382.
451. Zarghouni M, Seale TM IV, Ogden E, Savage CM, Carter BW. Benign
endobronchial granular cell tumor resulting in right middle lobe collapse.
452. Zarghouni M, Vandergriff C, Layton KF, McGowan JB, Coimbra C,
Bhakti A, Opatowsky MJ. Chordoid glioma of the third ventricle. Proc
(Bayl Univ Med Cent) 2012;25(3):285–286.
RHEUMATOLOGY
453. Cush JJ, Dao KH. Malignancy risks with biologic therapies. Rheum Dis
Clin North Am 2012;38(4):761–770.
454. Cush JJ, Dao KH. Refining drug safety in rheumatology. Rheum Dis
Clin North Am 2012;38(4):xi–xiv.
455. Dao KH, Herbert M, Habal N, Cush JJ. Nonserious infections:
should there be cause for serious concerns? Rheum Dis Clin North Am
2012;38(4):707–725.
456. Hsia EC, Schluger N, Cush JJ, Chaisson RE, Matteson EL, Xu S,
Beutler A, Doyle MK, Hsu B, Rahman MU. Interferon-␥ release assay
versus tuberculin skin test prior to treatment with golimumab, a human anti-tumor necrosis factor antibody, in patients with rheumatoid
arthritis, psoriatic arthritis, or ankylosing spondylitis. Arthritis Rheum
2012;64(7):2068–2077.
457. Kavanaugh A, Martin G, Cush JJ, Bergman MJ, Fleischmann R,
Troum OM, Strand V, Ruderman EM, Wells AF. Proceedings of the
2012 Rheumatology Winter Clinical Symposia. Semin Arthritis Rheum
2012;41(6):923–926.
458. Petryna O, Cush JJ, Efthimiou P. IL-1 Trap rilonacept in refractory adult
onset Still’s disease. Ann Rheum Dis 2012;71(12):2056–2057.
SURGERY
Note: Most surgery articles are subclassified by specialty, even if general surgeons
were first authors or coauthors.
459. Culp BL, Cedillo VE, Arnold DT. Single-incision laparoscopic cholecystectomy versus traditional four-port cholecystectomy. Proc (Bayl Univ
Med Cent) 2012;25(4):319–323.
460. Stillsmoking K, Jones RC. The changing face of health care education:
a new surgical simulation center at Baylor University Medical Center.
TRANSPLANTATION (ORGAN AND PANCREATIC CELLS)
461. Abouljoud M, Klintmalm G, Whitehouse S. Transplant organizational structures: viewpoints from established centers. Am J Transplant
2012;12(10):2623–2629.
462. Akkina SK, Asrani SK, Peng Y, Stock P, Kim WR, Israni AK. Development
of organ-specific donor risk indices. Liver Transpl 2012;18(4):395–404.
463. Barton FB, Rickels MR, Alejandro R, Hering BJ, Wease S, Naziruddin
B, Oberholzer J, Odorico JS, Garfinkel MR, Levy M, Pattou F, Berney T,
Volume 26, Number 2
464.
465.
466.
467.
468.
469.
470.
471.
472.
473.
474.
475.
476.
477.
478.
479.
480.
Secchi A, Messinger S, Senior PA, Maffi P, Posselt A, Stock PG, Kaufman
DB, Luo X, Kandeel F, Cagliero E, Turgeon NA, Witkowski P, Naji A,
O’Connell PJ, Greenbaum C, Kudva YC, Brayman KL, Aull MJ, Larsen
C, Kay TW, Fernandez LA, Vantyghem MC, Bellin M, Shapiro AM.
Improvement in outcomes of clinical islet transplantation: 1999–2010.
Diabetes Care 2012;35(7):1436–1445.
Carlisle EM, Testa G. Adult to adult living related liver transplantation: where do we currently stand? World J Gastroenterol 2012;18(46):
6729–6736.
Chen S, Shimoda M, Chen J, Matsumoto S, Grayburn PA. Ectopic
transgenic expression of NKX2.2 induces differentiation of adult pancreatic progenitors and mediates islet regeneration. Cell Cycle 2012;11(8):
1544–1553.
Chen S, Shimoda M, Chen J, Matsumoto S, Grayburn PA. Transient
overexpression of cyclin D2/CDK4/GLP1 genes induces proliferation
and differentiation of adult pancreatic progenitors and mediates islet
regeneration. Cell Cycle 2012;11(4):695–705.
Chujo D, Foucat E, Takita M, Itoh T, Sugimoto K, Shimoda M, Yagi
K, Yamagishi M, Tamura Y, Yu L, Naziruddin B, Levy MF, Ueno H,
Matsumoto S. Emergence of a broad repertoire of GAD65-specific T-cells
in type 1 diabetes patients with graft dysfunction after allogeneic islet
transplantation. Cell Transplant 2012;21(12):2783–2795.
Chujo D, Takita M, Tekin Z, Matsumoto S. Chronic graft dysfunction in
allogenic islet cell transplantation. In Berhardt LV, ed. Advances in Medicine and Biology. New York: Nova Science Publishers, 2012:183–201.
Feng S, Trotter JF. Can we stop waiting for Godot? Establishing selection
criteria for simultaneous liver-kidney transplantation. Am J Transplant
2012;12(11):2869–2870.
Itoh T, Iwahashi S, Kanak MA, Shimoda M, Takita M, Chujo D, Tamura
Y, Rahman AM, Chung WY, Onaca N, Coates PT, Dennison AR, Naziruddin B, Levy MF, Matsumoto S. Elevation of high-mobility group box
1 after clinical autologous islet transplantation and its inverse correlation
with outcomes. Cell Transplant 2012 Dec 4. [Epub ahead of print].
Itoh T, Sugimoto K, Takita M, Shimoda M, Chujo D, Sorelle JA, Naziruddin B, Levy MF, Matsumoto S. Low temperature condition prevents
hypoxia induced islet cell damage and HMGB1 release in a mouse model.
Cell Transplant 2012 Apr 10 [Epub ahead of print].
Itoh T, Takita M, Sorelle JA, Shimoda M, Sugimoto K, Chujo D, Qin H,
Naziruddin B, Levy MF, Matsumoto S. Correlation of released HMGB1
levels with the degree of islet damage in mice and humans and with the
outcomes of islet transplantation in mice. Cell Transplant 2012 Apr 26
Jackson AM, Kanak MA, Grishman EK, Chaussabel D, Levy MF, Naziruddin B. Gene expression changes in human islets exposed to type 1
diabetic serum. Islets 2012;4(4):312–319.
Kaneku H, O’Leary JG, Taniguchi M, Susskind BM, Terasaki PI, Klintmalm GB. Donor-specific human leukocyte antigen antibodies of the immunoglobulin G3 subclass are associated with chronic rejection and graft
loss after liver transplantation. Liver Transpl 2012;18(8):984–992.
Klintmalm GB. Treat patients, not statistics. Am J Transplant 2012;
12(3):794.
Matsumoto S, Takita M, Shimoda M, Sugimoto K, Itoh T, Chujo D,
Sorelle JA, Tamura Y, Rahman AM, Onaca N, Naziruddin B, Levy MF.
Impact of tissue volume and purification on clinical autologous islet
transplantation for the treatment of chronic pancreatitis. Cell Transplant
2012;21(4):625–632.
McKenna GJ, Trotter JF. Sirolimus conversion for renal dysfunction
in liver transplant recipients: the devil really is in the details. . . . Am J
Transplant 2012;12(3):521–522.
McKenna GJ, Trotter JF. Sirolimus—it doesn’t deserve its bad Rap(a). J
Hepatol 2012;56(1):285–287.
Naziruddin B, Matsumoto S, Noguchi H, Takita M, Shimoda M, Fujita
Y, Chujo D, Tate C, Onaca N, Lamont J, Kobayashi N, Levy MF. Improved pancreatic islet isolation outcome in autologous transplantation
for chronic pancreatitis. Cell Transplant 2012;21(2–3):553–558.
Naziruddin B, Wease S, Stablein D, Barton FB, Berney T, Rickels MR,
Alejandro R. HLA class I sensitization in islet transplant recipients: re-
April 2013
481.
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487.
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490.
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497.
port from the Collaborative Islet Transplant Registry. Cell Transplant
2012;21(5):901–908.
Noguchi H, Naziruddin B, Jackson A, Shimoda M, Fujita Y, Chujo D,
Takita M, Peng H, Sugimoto K, Itoh T, Kobayashi N, Ueda M, Okitsu
T, Iwanaga Y, Nagata H, Liu X, Kamiya H, Onaca N, Levy MF, Matsumoto S. Comparison of ulinastatin, gabexate mesilate, and nafamostat mesilate in preservation solution for islet isolation. Cell Transplant
2012;21(2–3):509–516.
Noguchi H, Naziruddin B, Jackson A, Shimoda M, Ikemoto T, Fujita Y,
Chujo D, Takita M, Peng H, Sugimoto K, Itoh T, Kobayashi N, Onaca
N, Levy MF, Matsumoto S. Fresh islets are more effective for islet transplantation than cultured islets. Cell Transplant 2012;21(2–3):517–523.
Noguchi H, Naziruddin B, Shimoda M, Chujo D, Takita M, Sugimoto
K, Itoh T, Onaca N, Levy MF, Matsumoto S. A combined continuous
density/osmolality gradient for supplemental purification of human islets.
Cell Med 2012;3(1):33–41.
Noguchi H, Naziruddin B, Shimoda M, Fujita Y, Chujo D, Takita M,
Peng H, Sugimoto K, Itoh T, Kobayashi N, Onaca N, Levy MF, Matsumoto S. Evaluation of osmolality of density gradient for human islet
purification. Cell Transplant 2012;21(2–3):493–500.
O’Connor JK, Trotter J, Davis GL, Dempster J, Klintmalm GB, Goldstein RM. Long-term outcomes of stereotactic body radiation therapy
in the treatment of hepatocellular cancer as a bridge to transplantation.
Liver Transpl 2012;18(8):949–954.
O’Leary JG, Neri MA, Trotter JF, Davis GL, Klintmalm GB. Utilization
of hepatitis C antibody-positive livers: genotype dominance is virally
determined. Transpl Int 2012;25(8):825–829.
Paterno F, Shiller M, Tillery G, O’Leary JG, Susskind B, Trotter J, Klintmalm GB. Bortezomib for acute antibody-mediated rejection in liver
transplantation. Am J Transplant 2012;12(9):2526–2531.
Ruiz R, Klintmalm GB. Renal-sparing regimens employing new agents.
Curr Opin Organ Transplant 2012;17(6):619–625.
Ruiz R, Tomiyama K, Campsen J, Goldstein RM, Levy MF, McKenna
GJ, Onaca N, Susskind B, Tillery GW, Klintmalm GB. Implications
of a positive crossmatch in liver transplantation: a 20-year review. Liver
Transpl 2012;18(4):455–460.
Saxena V, Lai JC, O’Leary JG, Verna EC, Brown RS Jr, Stravitz RT, Trotter JF, Krishnan K, Terrault NA; Consortium to Study Health Outcomes
in HCV Liver Transplant Recipients. Recipient-donor race mismatch for
African American liver transplant patients with chronic hepatitis C. Liver
Transpl 2012;18(5):524–531.
Seven N, Matsumoto S, Takita M, Qin H, De Vol E, Hollander PA.
Metabolic assessment including continuous glucose monitoring for allogenic islet transplantation. Infusystems USA 2012;9(1):4–10.
Sher L, Jennings L, Rudich S, Alexopoulos SP, Netto G, Teperman L, Kinkhabwala M, Brown RS Jr, Pomfret E, Klintmalm G; HCV-3 Study Group. Results
of live donor liver transplantation in patients with hepatitic C virus infection:
the HCV 3 trial experience. Clin Transplant 2012;26(3):502–509.
Shimoda M, Itoh T, Iwahashi S, Takita M, Sugimoto K, Kanak MA,
Chujo D, Naziruddin B, Levy MF, Grayburn PA, Matsumoto S. An
effective purification method using large bottles for human pancreatic
islet isolation. Islets 2012;4(6).
Shimoda M, Itoh T, Sugimoto K, Iwahashi S, Takita M, Chujo D, Sorelle
JA, Naziruddin B, Levy MF, Grayburn PA, Matsumoto S. Improvement
of collagenase distribution with the ductal preservation for human islet
isolation. Islets 2012;4(2):130–137.
Shimoda M, Noguchi H, Fujita Y, Takita M, Ikemoto T, Chujo D, Naziruddin B, Levy MF, Kobayashi N, Grayburn PA, Matsumoto S. Islet
purification method using large bottles effectively achieves high islet yield
from pig pancreas. Cell Transplant 2012;21(2–3):501–508.
Shimoda M, Noguchi H, Fujita Y, Takita M, Ikemoto T, Chujo D,
Naziruddin B, Levy MF, Kobayashi N, Grayburn PA, Matsumoto S.
Improvement of porcine islet isolation by inhibition of trypsin activity
during pancreas preservation and digestion using ␣1-antitrypsin. Cell
Transplant 2012;21(2–3):465–471.
Takita M, Matsumoto S, Noguchi H, Shimoda M, Ikemoto T, Chujo
D, Tamura Y, Olsen GS, Naziruddin B, Purcell K, Onaca N, Levy MF.
229
498.
499.
500.
501.
502.
Adverse events in clinical islet transplantation: one institutional experience. Cell Transplant 2012;21(2–3):547–551.
Takita M, Matsumoto S, Qin H, Noguchi H, Shimoda M, Chujo D,
Itoh T, Sugimoto K, Onaca N, Naziruddin B, Levy MF. Secretory unit
of islet transplant objects (SUITO) index can predict severity of hypoglycemic episodes in clinical islet cell transplantation. Cell Transplant
2012;21(1):91–98.
Takita M, Matsumoto S. SUITO index for evaluation of clinical islet
transplantation. Cell Transplant 2012 Apr 2 [Epub ahead of print].
Takita M, Matsumoto S, Shimoda M, Chujo D, Itoh T, Sorelle JA, Purcell
K, Onaca N, Naziruddin B, Levy MF. Safety and tolerability of the T-cell
depletion protocol coupled with anakinra and etanercept for clinical islet
cell transplantation. Clin Transplant 2012;26(5):E471–E484.
Talukder AH, Bao M, Kim TW, Facchinetti V, Hanabuchi S, Bover L,
Zal T, Liu YJ. Phospholipid scramblase 1 regulates Toll-like receptor
9-mediated type I interferon production in plasmacytoid dendritic cells.
Cell Res 2012;22(7):1129–1139.
Testa G, Carlisle E, Simmerling M, Angelos P. Living donation and
cosmetic surgery: a double standard in medical ethics? J Clin Ethics
2012;23(2):110–117.
HISTORY
503. Fordtran JS, Prince R, Seldin DW. A Dallas doctor who spoke truth
to power: three perspectives. Proc (Bayl Univ Med Cent) 2012;25(3):
254–264.
504. Urschel HC Jr, Urschel BB. Robert R. Shaw, MD: thoracic surgical hero,
Afghanistan medical pioneer, champion for the patient, never a surgical
society president. Ann Thorac Surg 2012;93(6):2111–2116.
INTERVIEWS
505. Barry MJ, Roberts WC. Michael John Barry, MD: a conversation
with the editor on shared decision-making. Proc (Bayl Univ Med Cent)
2012;25(4):383–388.
506. Boden WE, Roberts WC. William Edward Boden, MD: a conversation
with the editor. Am J Cardiol 2012;110(1):145–159.
507. Grayburn PA, Benjamin MM. Paul Arthur Grayburn, MD: an interview by Mina Mecheal Benjamin, MD. Proc (Bayl Univ Med Cent)
2012;25(3):265–270.
508. Libby P, Roberts WC. Peter Libby, MD: a conversation with the editor.
Am J Cardiol 2012;110(5):741–760.
509. Saucedo JF, Roberts WC. Jorge Felix Saucedo, MD, MBA: a conversation
with the editor on optimizing antiplatelet and antithrombotic therapy in
patients having percutaneous coronary intervention for acute coronary
syndromes. Proc (Bayl Univ Med Cent) 2012;25(2):136–138.
EDITORIALS, BOOK REVIEWS, AND MISCELLANEOUS
510. Allday RL, Brooks J, Hosford SL, Owen SF. Tributes to Gordon Hosford,
MD. Proc (Bayl Univ Med Cent) 2012;25(3):274–275.
511. Boland CR. “Irreducible complexity” or “delightful challenge”? Proc (Bayl
Univ Med Cent) 2012;25(2):169–170.
512. Boland CR, Krejs G, Emmett M, Richardson C. A birthday celebration
for John S. Fordtran, MD. Proc (Bayl Univ Med Cent) 2012;25(3):250–
253.
513. Dauwe P, Heller JB, Unger JG, Graham D, Rohrich RJ. Social networks
uncovered: 10 tips every plastic surgeon should know. Aesthet Surg J
2012;32(8):1010–1015.
230
514. Gurevitz SA, Stone MJ. Review of Amyloidosis: Diagnosis and Treatment.
Proc (Bayl Univ Med Cent) 2012;25(2):166.
515. Hasse JM. Editor’s note. Nutr Clin Pract 2012;27(3):319.
516. Hasse JM. Editor’s note. Nutr Clin Pract 2012;27(4):439.
517. Knox S. Review of The Lump. Proc (Bayl Univ Med Cent) 2012;
25(4):399.
518. Kuhn JA. Dissecting Darwinism. Proc (Bayl Univ Med Cent)
2012;25(1):41–47; discussion, 25(2):168–173.
519. Mack MJ. If this were my last speech, what would I say? Ann Thorac Surg
2012;94(4):1044–1052.
520. Matthews CM. Exploring the obesity epidemic. Proc (Bayl Univ Med
Cent) 2012;25(3):276–277.
521. Neubach P, Snoots W. Tributes to George Boswell, MD. Proc (Bayl Univ
Med Cent) 2012;25(2):165.
522. Roberts WC. Facts and ideas from anywhere. Proc (Bayl Univ Med Cent)
2012;25(1):98–107.
2012;25(2):174–183.
2012;25(3):304–313.
2012;25(4):400–410.
526. Roberts WC. Formulating an answerable question, displaying data, illustrating, writing, reviewing, and editing manuscripts for publication
in medical journals. Am J Cardiol 2012;110(2):290–306.
527. Roberts WC. Good books in cardiovascular disease appearing in 2011.
Am J Cardiol 2012;109:1236–1237.
528. Roberts WC. How I prepare a manuscript for publication in a medical
journal. Methodist Debakey Cardiovasc J 2012;8(4):53–54.
529. Roberts WC. Proceedings of the editorial board meeting of the American Journal of Cardiology on March 25, 2012. Am J Cardiol 2012;110(2):316–317.
530. Rohrich RJ, Stuzin JM. Globalization of plastic surgery: the world
of plastic and reconstructive surgery in Brazil. Plast Reconstr Surg
2012;130(4):967–968.
531. Rohrich RJ, Sullivan D. So you want to be a change artist? Plast Reconstr
Surg 2012;129(6):1435–1437.
532. Rohrich RJ, Sullivan D. So you want to get paid for what you do? The
saga continues. Plast Reconstr Surg 2012;130(2):471–473.
533. Rohrich RJ, Weber RA. Are teachers born or do they develop over time?
Plast Reconstr Surg 2012;129(5):1209–1211.
534. Rohrich RJ, Weinstein AG. Connect with plastic surgery: social media
for good. Plast Reconstr Surg 2012;129(3):789–792.
535. Rohrich RJ. Logging in to the PRS iPad app: access made easy. Plast
Reconstr Surg 2012;129(6):1438–1340.
536. Warren B. Review of The Top Five Regrets of the Dying. Proc (Bayl Univ
Med Cent) 2012;25(3):299–300.
537. Winter FD. Review of Genius on the Edge. Proc (Bayl Univ Med Cent)
2012;25(1):95–96.
538. Yager M, Emmett M. How worms’ sex behavior can have a major
impact on understanding human disease. Proc (Bayl Univ Med Cent)
2012;25(4):395–396.
Note: This list (finalized on February 11, 2013) was based on submissions from
medical and allied health staff and on PubMed searches. Although the list is
representative of the year’s publications, some articles and book chapters were
undoubtedly missed, since only a small percentage of researchers respond to the
request for publications. Staff are encouraged to submit their publications each
year. For more information or to submit publications for this list, please contact
Cynthia Orticio ([email protected]).
Volume 26, Number 2
aylor University Medical Center Proceedings welcomes research articles, review articles, case studies, and editorials
from Baylor and non-Baylor authors. Manuscripts containing Baylor data are particularly desired. Send all manuscripts
and editorial correspondence to William C. Roberts, MD, Editor in
Chief, Baylor Scientific Publications Office, 3500 Gaston Avenue, Dallas, Texas 75246; phone: 214-820-9996; fax: 214-820-4064; e-mail:
[email protected].
B
MANUSCRIPT SUBMISSION
Submit the word processing document by e-mail to [email protected]. Large files may be sent using YouSendIt or SendNow.
Cover letter and attachments: According to journal policies outlined
below, list suggested reviewers and discuss potential conflicts of interest
in your cover letter and provide as attachments copies of institutional
review board approval or exemption, written permission for reprinting
tables or figures, copies of any published material that could be considered
duplicative, and release authorization forms for photographs.
Schedule: Deadlines for submission are as follows: January issue, September 1; April issue, December 1; July issue, March 1; and
October issue, June 1. The editorial office cannot guarantee that any
manuscript submitted by these deadlines will be published in the
specified issue; variables include the peer review and revision process
and the number of articles already accepted.
ARTICLE TYPES
In addition to multipatient studies (original research articles),
Proceedings publishes several other article types.
Case studies: Include an abstract, a single-paragraph introduction
(optional with short reports), a case description of 0.5 to 2 doublespaced pages, and a discussion of 1 to 5 double-spaced pages. Up to
25 references are acceptable (although many case reports have 5 to 10).
The maximum number of figures and tables (combined) is 6.
Historical studies: Abstracts are recommended. There is no word
limit, but most historical studies are 1500 to 3500 words.
Editorials: There is no word limit, but most editorials are 800
to 1600 words.
Book reviews: See past issues for format. There is no word limit,
but most book reviews are 800 to 1600 words.
Avocations: Submit an image file for your painting or photograph
or a discussion of your hobby for a maximum of 300 words.
Reader comments (letters to the editor): Both responses to
previously published material and brief reports or observations are
considered for this section. The limit is 1200 words.
MANUSCRIPT PREPARATION
Format: Type manuscripts double spaced, leaving 1-inch margins.
Number all pages, including the title page.
Title page: Include on the first page the article’s title; the authors’
names, highest degree(s), and affiliations; and the name, address, e-mail
address, and phone number of the corresponding author. Acknowledge
any grant support.
Abstract: Provide a one-paragraph double-spaced abstract of 150
to 250 words. Abstracts are required for original articles and case studies and are recommended for reviews and long historical articles.
Conclusions: Conclusion paragraphs at the end of the discussion
section are rarely needed and are often cut if included.
References: Number references according to the order in which
they are cited in the text and type them double spaced at the end of
the manuscript. Do not use the footnote or endnote functions of word
processing software. The numbers in the text should be on line and
in parentheses, such as (14, 16, 17). The references should conform
to the following style, listing all authors:
Journal article: O’Shaughnessy J, Osborne C, Pippen JE, Yoffe
M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C. Iniparib
plus chemotherapy in metastatic triple-negative breast cancer. N
Engl J Med 2011;364(3):205–214.
Book chapter: Ramsay M. Liver transplantation and portopulmonary hypertension. In Milan Z, ed. Cardiovascular Diseases
and Liver Transplantation. New York: Nova Biomedical Books,
2011:83–97.
Book: Gulati G, Filicko-O’Hara J, Krause JR. Case Studies in
Hematology and Coagulation. Chicago, IL: American Society for
Clinical Pathology Press, 2012.
Authors using Endnote can access Proceedings’ reference style by
downloading an EndNote style file, available at http://www.baylorhealth.edu/Research/Proceedings/SubmitaManuscript/Pages/ManuscriptPreparation.aspx. Personal communications and unpublished
data should not be used as references; they should be identified in
parentheses in the text.
Tables and figures: Number tables and figures in the order in
which they are discussed in the text. Include call-outs in the text and
place the tables at the end of the document as Word files using the
Word table function. Figures can be embedded in the text at the end
of the document or provided as separate files, with legends in the Word
file. Provide enough details in titles, footnotes, and legends so that
the tables and figures can be understood apart from the text. Submit
photographs as 350-ppi tiff or jpeg files. Submit graphs and diagrams
as electronic files (EPS format preferred).
Use of color: Color is used in articles only when clinically required (as with certain pathology and radiology images). Avoid
using color when creating charts and graphs. If photographs
(such as those in interviews) are originally in color, they can be converted to black and white during journal production. Articles that use
color are generally grouped together in the issue to decrease overall
printing expenses.
Style issues: Use generic names for drugs; capitalize any trade
names when they are used. Limit the number of abbreviations in
a manuscript to five, and do not abbreviate single words, such as
intravenous. Spell out all abbreviations on first usage. Proceedings
231
follows the style guide of the American Medical Association. As further
guidance, prospective authors are encouraged to consult the “Authors’
submission toolkit” (1) and an article on medical publishing by the
editor in chief (2).
MANUSCRIPT PROCESSING
Peer review: All manuscripts are subject to peer review by editorial
board members or other selected reviewers; however, the final decision
as to which articles are published will be made by the editor in chief. At
the time of manuscript submission, authors are encouraged to suggest
reviewers, within or outside the Baylor Health Care System, and to list
any reviewers they feel should not be used because of potential bias.
If a manuscript was previously reviewed by another journal, authors
should submit those reviews and clearly indicate any revisions that
have been made. Such manuscripts will receive expedited processing,
since they usually will not be sent out for re-review.
Editing: All manuscripts will be edited for clarity and conformity
to Proceedings’ style. The corresponding author will have the opportunity to review editing either before or at the page proof stage.
Reprints: Authors can order reprints using the form provided
through an e-mail link from the printer. Reprints are delivered approximately 4 weeks after the issue comes out. All authors receive a
copy of the printed journal, and PDF files of articles are freely available
to the authors and the general public.
JOURNAL POLICIES
Duplicate publication: When submitting the manuscript, provide a copy of any published or submitted article that is similar to
what is being submitted to Proceedings, so that the editor can judge
whether the manuscript in question would be a duplicate publication.
Once manuscripts are accepted, authors transfer copyright to Baylor
Authorship: All authors listed in the manuscript must have participated in the design or analysis of the project. In addition, all authors
must review the final text and be prepared to take public responsibility
for its content.
Ethical treatment of research subjects: For reports of experimental investigations of human or animal subjects, indicate institutional
review board approval or exemption within the manuscript. Authors
should also explain in the Methods section the procedures followed
to obtain informed consent.
Conflict of interest: Grant support for a particular study must
be indicated on the title page. In addition, authors must communicate to the editor in the cover letter any affiliations that could
be perceived as potential conflicts of interest. Examples include
honoraria, educational grants, participation in speakers’ bureaus,
expert testimony, patent licensing arrangements, consultancies, and
stock ownership.
232
Use of protected health information: Authors should not refer
to patients by name or initials or provide other specific identifying
information, such as Social Security number or medical record number.
Authors are further encouraged to avoid including extraneous social
details about patients. Patient authorization forms are required for all
identifying photographs. For a copy of Proceedings’ full privacy policy,
contact the managing editor.
Permissions: Permission is required for reproduction of any material, including figures and tables, that has been published elsewhere.
When submitting manuscripts, provide written documentation that
permission has been obtained or notify the editorial staff of the need
to request permission (providing all necessary source information). For
photographs in which the subject can be recognized, submit release
authorizations at the time of manuscript submission.
For additional information, please contact Cynthia Orticio, managing editor, at 214-820-9996 or [email protected].
1.
2.
Chipperfield L, Citroma L, Clark J, David FS, Neck R, Evangelista
M, Gonzalez J, Groves T, Magan J, Mansa B, Miller C, Mooney LA,
Murphy A, Shelton J, Wilson PD, Weigl A. Authors’ submission toolkit:
a practical guide to getting your research published. Cur Med Res Open
2010;26(8):1967–1982.
Roberts WC. Formulating an answerable question, displaying data, illustrating, writing, reviewing, and editing manuscripts for publication
in medical journals. Am J Cardiol 2012;110(2):290–306.
MANUSCRIPT SUBMISSION CHECKLIST
— The entire manuscript is double-spaced and in one Word file, in
the following order: title page, abstract, text, references, tables,
figures (either figure legends only or figures embedded plus legends). Page numbers appear on the bottom of each page.
— The title page has required elements: title, authors (with full names
and degrees), affiliations, and address for corresponding author.
— A single-paragraph abstract of 150 to 250 words is included.
— For case studies: After the abstract, the manuscript includes
a single-paragraph introduction (optional), a case discussion
of 0.5 to 2 double-spaced pages, and a discussion of 0.5 to 5
double-spaced pages. The manuscript does not exceed the limit
of 25 references or 6 figures and tables.
— Figures are high-resolution. Photographs are 350-ppi tiff or
jpeg files.
— References include all authors, the full article title, the journal
abbreviation from Index Medicus, the volume and issue number,
and inclusive page numbers. References in the text appear in parentheses, rather than in superscript or footnotes or endnotes.
— All authors have approved the version to be submitted.
Manuscripts that do not meet these requirements may be returned to
authors before peer review is initiated.
Volume 26, Number 2
Volume 26
Number 2
April 2013
Multipatient Studies
95
Model for the cost-efficient delivery of continuous quality cancer care: a
hospital and private-practice collaboration
163
166
168
J. L. Gierman, W. P. Shutze Sr., G. J. Pearl, M. L. Foreman, S. E. Hohmann, and W. P. Shutze Jr.
103
Impact of sham-controlled vertebroplasty trials on referral patterns at two
academic medical centers
High-intensity, occupation-specific training in a series of firefighters during
phase II cardiac rehabilitation
J. Adams, D. Cheng, and R. F. Berbarie
109
116
Quality of life of HIV/AIDS patients in a secondary health care facility,
Ilorin, Nigeria
W. C. Roberts, S. Zafar, and J. M. Ko
120
J. Sobrino and S. Shafi
Baylor University Medical Center, Dallas, Texas
124
Facts and principles learned at the 39th Annual Williamsburg Conference
on Heart Disease
M. M. Benjamin and W. C. Roberts
137
177
179
182
185
Editorials, Tributes, and Book Reviews
194
146
Inflammatory breast cancer
K. Y. Ha, S. B. Glass, and L. Laurie
Pages 93–232
152
156
Recurrent acute inflammatory demyelinating polyradiculoneuropathy
following R-CHOP treatment for non-Hodgkin lymphoma
159
M. J. Van Vrancken, L. Keglovits, and J. Krause
J. J. Liang, P. P. Singh, and T. E. Witzig
M. Zarghouni, M. L. Kershen, L. Skaggs, A. Bhatki, S. C. Gilbert,
C. E. Gomez, and M. J. Opatowsky
To access Baylor’s physicians, clinical services, or
educational programs, contact the Baylor Physician
ConsultLine: 1-800-9BAYLOR (1-800-922-9567)
161
196
A. U. Goldstein and M. A. Ramsay
199
Steve Frost
200
Book review: Making Rounds with Oscar
James Marroquin
From the Editor
202
William C. Roberts
Miscellany
94
158
165
167
187
192
193
212
215
Inguinal lymphadenopathy as the initial presentation of sarcoidosis
J. George, R. Graves, and R. Meador Jr.
B. Allison, C. H. Scheihing, and W. C. Roberts
K. Y. Ha, J. C. Wang, and J. I. Gill
149
Allen B. Weisse
Charles Stewart Roberts
Case Studies
Diagnosis and management of delayed hemoperitoneum following
therapeutic paracentesis
M. J. Katz, M. N. Peters, J. D. Wysocki, and C. Chakraborti
J. I. Ewing, C. A. Denham, C. R. Osborne, N. B. Green, J. Divers, and J. E. Pippen Jr.
A. Saxsena, J. Tarsia, C. Dunn, A. Aysenne, B. Shah, and D. F. Moore
Invited commentary
144
M. Arroyo, A. Z. Fenves, and M. Emmett
191
Thomas B. Gore
M. N. Peters, M. J. Katz, L. A. Howell, J. C. Moscona, T. A. Turnage, and P. Delafontaine
Our experience as a Health Volunteers Overseas–sponsored team in Huế,
Vietnam
A forgotten landmark medical study from 1932 by the Committee on the
Cost of Medical Care
D. Luke Glancy
Historical Studies
142
Congenitally bicuspid aortic valve in brothers: coarctation of the aorta with
a normally functioning aortic valve in one and no coarctation but severe
aortic stenosis in the other
S. Zafar and W. C. Roberts
174
S. I. Bello and I. K. Bello
Review Articles
Ascites with elevated protein content as the presenting sign of constrictive
pericardial disease
B. A. George, G. dePrisco, J. F. Trotter, A. C. Henry III, and R. C. Stoler
171
S. S. Lindsey, D. F. Kallmes, M. J. Opatowsky, E. A. Broyles, and K. F. Layton
106
A. M. Mantas, J. Wells, and J. Trotter
Y. M. Coyle, A. M. Miller, and R. S. Paulson
100
R. Abdul-Karim, C. Ryan, C. Rangel, and M. Emmett
231
Clinical research studies enrolling patients
Avocations: Photograph by Dr. Rosenthal
Avocations: Photograph by Dr. Hoppenstein
Avocations: Photograph by Dr. Khan
Baylor news
Reader comments
In memoriam
2012 publications of the Baylor Health Care System medical
and scientific staff
www.BaylorHealth.edu/Proceedings
Indexed in PubMed, with full text available through PubMed Central

full PDF - Baylorhealth.edu

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