Asociacion Medica de Puerto Rico
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Asociacion Medica de Puerto Rico
B LETIN Médico-Científico de la Asociación Médica de Puerto Rico Coronary Levels Of Angiotensin-Ii And Endothelin-I In Diabetic Patients With And Without CoronaryArtery Disease Interventional Nephrology In Puerto Rico: A Four Year Experience Brugada Syndrome In Puerto Rico: A Case Series Primary Venous Thromboembolism And Malignancy, Is There Any Relationship? Intravenous Ascorbic Acid And Hydrogen Peroxide In The Management Of Patients With Chikungunya Quality Of Life In Patients With Differentiated Thyroid Cancer At The General Endocrinology Clinics Of The University Hospital Of Puerto Rico Clinical And Radiological Indicators Of Severity In Patients With Acute Pancreatitis Celiac Trunk And Branches Dissection Due To Energy Drink Consumption And Heavy Resistance Exercise: Case Report And Review Of Literature Worsening Gradient Of Aortic Stenosis With Treatment Of Pulmonary Arterial Hypertension In Scleroderma Uncommon Cause Of Life-Threatening Retroperitoneal Hemorrhage In A Healthy Young Hispanic Patient:Splenic Arte Artery Aneurysm Rupture Atraumatic Bilateral Femoral Neck Fractures In A Premenopausal Female With Hypovitaminosis D (Cover Pic) Small Cell Carcinoma Of The Uterine Cervix: A Case Report And Literature Review Handlebar Hernia: Case Report And Literature Review Should We Revisit Anticoagulation Guidelines During Thyroid Storm? Año 107 Nro. 1 BOLETIN CONTENIDO Médico Científico de la Asociación Médica de Puerto Rico Año 107 Número 1 - Enero a Marzo de 2015 3 President’s Message Wanda Velez Andujar MD Original articles 5 Coronary Levels Of Angiotensin-Ii And Endothelin-I In Diabetic Patients With And Without Coronary Artery Disease Pablo I. Altieri Md, José M. Marcial Md, Héctor L. Banchs Md, Nelson Escobales Phd, María Crespo Phd, Wilma González Bs 8 Interventional Nephrology In Puerto Rico: A Four Year Experience Rafael Baez Md, Jose Betancourt Md, Hector J. Diaz Md, Anmelys Rivera Md, Javier Monserrate Md, Tania Ramírez Md, Martin Gorrochategui, Md, Carlos Rivera Bermudez Md, Francisco Torre Leon Md, Jose L. Cangiano Md, Facp, Fah 12 Brugada Syndrome In Puerto Rico: A Case Series Héctor Banchs-Viñas Md, Norwin Rivera Md , Héctor Banchs-Pieretti Md, Pablo Altieri Md 16 Primary Venous Thromboembolism And Malignancy, Is There Any Relationship? Luis Cotto Santana Md, William Caceres Perkins Md 20 Intravenous Ascorbic Acid And Hydrogen Peroxide In The Management Of Patients With Chikungunya Victor Marcial-Vega Md, Idxian Gonzalez-Terron, Thomas Edward Levy Md 25 Quality Of Life In Patients With Differentiated Thyroid Cancer At The General Endocrinology Clinics Of The University Hospital Of Puerto Rico Mónica A. Vega-Vázquez Md, Loida González-Rodríguez Md, Eduardo J. Santiago-Rodríguez Mph,Anette Garcés-Domínguez Md,Lee-Ming Shum Md, Maribel Tirado-Gómez Md, Margarita Ramírez-Vick Md 33 Clinical And Radiological Indicators Of Severity In Patients With Acute Pancreatitis Jorge Álvarez Md,Pablo Castro Md, Maria Fernández Md, Beatriz Mcmullen Md, Carmen Rodríguez Md, Jorge Vera Md Case Report Medicine is a science. Keeping people healthy is an art. Over a decade reaching this balance. 38 Celiac Trunk And Branches Dissection Due To Energy Drink Consumption And Heavy Resistance Exercise: Case Report And Review Of Literature Wilma González Bs, Pablo I. Altieri Md, Enrique Alvarado Md, Héctor L. Banchs MdEdgar Colón MdNelson Escobales Ph, María Crespo Phd 41 Worsening Gradient Of Aortic Stenosis With Treatment Of Pulmonary Arterial Hypertension In Scleroderma Daniel A. Pietras Md, Francisco R. Lopez Md, Reynerio Pérez Md, Angel López-Candales Md, Jean Elwing Md 45 Uncommon Cause Of Life-Threatening Retroperitoneal Hemorrhage In A Healthy Young Hispanic Patient: Splenic Artery Aneurysm Rupture Luis A. Figueroa-Jiménez Md, Amy Lee González-Márquez Md, Luis Negrón-García Md, Francisco Rosas-Soler, Md, Aixa Dones-Rodríguez Md, Mayknoll De La Paz-López, Md; Mónica Santiago-Casiano Md, Edwin Rodrίguez-Cruz Md, William Cáceres-Pérkins, Facp; Luis Báez-Díaz, Facp 51 Atraumatic Bilateral Femoral Neck Fractures In A Premenopausal Female With Hypovitaminosis D Giovanni Paraliticci Md, David Rodríguez-Quintana Md, Ariel Dávila Md, Antonio Otero-López Md 55 Small Cell Carcinoma Of The Uterine Cervix: A Case Report And Literature Review Pilar E. Silva-Meléndez Md, Pedro F. Escobar Md, Héctor Silva Md, Sylvia Gutiérrez Md, Manuel Rodríguez Md 58 Handlebar Hernia: Case Report And Literature Review Luisa Angel Buitrago Md, Humberto Lugo-Vicente Md 62 Should We Revisit Anticoagulation Guidelines During Thyroid Storm? Andrew W. Petersen Md, Gisela D. Puig-Carrión Md, Angel López-Candales Md Catalogado en Cumulative Index e Index Medicus Listed in Cumulative Index and Index Medicus No. ISSN-0004-4849. Registrado en Latindex -Sistema Regional de Información en Línea para Revistas Científicas de América Latina, el Caribe, España y Portugal OFICINAS ADMINISTRATIVAS: Asociación Médica de Puerto Rico PO Box 9387 • SANTURCE, Puerto Rico 00908-9387 Tel 787-721-6969 • Fax: 787- 724-5208 - Email: [email protected] ANUNCIOS EN BOLETIN, WEBSITEy NEWSLETTER: Tel.: (787) 721-6939 Ext. Informártica - [email protected] - Web Site: www.asocmedpr.org Ilustración digital de cubierta y diseño gráfico realizados por Juan Laborde-Crocela en la Oficina de Informática de la AMPR. Impreso en los talleres gráficos digitales de la Asociación Médica de Puerto Rico - E-mail:[email protected] Asociacion Medica de Puerto Rico Junta de Directores 2014/2015 Dra. Wanda G. Vélez Andújar President Dr. Ricardo Marrero Santiago President Elect Dr. Natalio J. Izquierdo Encarnación Inmediate Past President Dr. Luis A. Román Irizarry Treasurer Dra. Ilsa Figueroa Secretary Dr. Arturo Arché Matta Vicepresident Dr. Raúl A. Yordán Rivera Vicepresident Dr. Jaime M. Díaz Hernández Vicepresident Dr. Benigno López López House of Delegates President Dr. Eliud López Vélez House of Delegates Vicepresident Dr. Gonzalo González Liboy AMA Delegate Dr. Rolance G. Chavier Roper AMA Delegate Dr. Luis A. Lugo Medina Alt. Delegate AMA Dr. Rafael Fernández Feliberti Alt. Delegate AMA Dra. Mildred R. Arché Central District President Dr. Pedro J. Zayas Santos East District President Dr. Rubén Rivera Carrión South District President Council of Political and Legislative Issues Luis J. Lugo Vélez, MD Affiliation and Credentials Committee Rafael Fernández Feliberti, MD President’s Message The Health Systems in the United States and Puerto Rico will transform itself through fostering Health Information Technology (HIT), which the Federal Government is implementing. To accomplish this endeavor the Electronic Health Records (EHR) need to be implemented. This system will provide for medical services patient oriented, well-coordinated and focused on prevention. Right now we are close to the deadline for physicians to use Electronic Health Records (EHR) if they participate of Medicare and/or Medicaid. For the past immediate years the Federal Government has been promoting the EHR’s use and awarded incentives to stimulate all physicians involved to become knowledgeable on the subject and to acquire adequate meaningful use. After the deadline, Medicare will penalize providers not using EHR appropriately. To make a wise decision to select which EHR is best suitable for you, it is imperative that you know which criteria apply to your specialty, your needs and your responsibilities to guarantee privacy and secured information about your patients. You must know that Electronic Health Records are above Electronic Medical Records. The EHR System allows you to interchange, integrate and process patient’s information with different providers caring for the patient with the same privacy, accuracy and information protection of regular records in compliance with the Health Insurance Portability and Accountability Act, HIPAA. Given that we as physicians are the ultimate responsible for our patient’s health, it is imperative we assume leadership on the matter and give our patient’s the opportunity to benefit of participating of the EHR System. The Puerto Rico Medical Association has much expertise on the matter. We have been very much involved in the HIT-EHR System from the very beginning. It will be our pleasure to give any and all of you the assistance you might still need on the subject. Do not forget, the EHR is here to stay. It is indispensable in the 21st Century Medical Practice. There is no turning back! Institute of Continuing Medical Education Judith Román, MD BOLETIN Editors Board Chief Rafael Rodríguez Mercado MD Wanda G Vélez Andújar, MD PRMA President BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 3 ROYAL MASTERPIECE TERRA PINK NATURAL Original Articles/Articulos Originales CORONARY LEVELS OF ANGIOTENSIN-II AND ENDOTHELIN-I IN DIABETIC PATIENTS WITH AND WITHOUT CORONARY ARTERY DISEASE Department of Medicine and Physiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico. b Cardiovascular Center of Puerto Rico and the Caribbean, San Juan, Puerto Rico. *Corresponding author: Pablo I. Altieri MD - Box 8387, Humacao, Puerto Rico 00792. E-mail: [email protected] a Pablo I. Altieri MDab*, José M. Marcial MDa, Héctor L. Banchs MDab, Nelson Escobales PhDa, María Crespo PhDa, Wilma González BSa ABSTRACT Two groups of patients were studied to find out the levels of angiotensin-II and endothelin-I in the coronary and peripheral circulation. Group A consisted of eight patients with diabetes mellitus Type 2 and coronary artery disease; and Group B with diabetes mellitus without coronary artery disease. Significant differences were found between Group A and B in the levels of both peptides peripherally and intracoronary. This shows the importance of these peptides in the origin of coronary artery disease and progression of the disease in diabetics with coronary artery disease. Index words: coronary, level, angiotensin, endothelin, diabetic, artery, disease INTRODUCTION For more than a century, the path to understand coronary artery disease (CAD) has culminated in a perspective in which inflammation is a fundamental mechanism of the disease. Chronic renin-angiotensin axis (RAS) activation, mainly through the effects of Angiotensin II (Ang-II), leads to hypertension and perpetuates a cascade of pro-inflammatory, prothrombotic, and atherogenic effects associated with end-organ damage. The inhibition of action and reduction in the production of Ang-II has been mainstay therapy to reduce the progression of hypertension and the atherosclerotic process (1-16). ¡Así soy! Natural. Por eso selecciono Master Paints, con su línea EcoPure que refleja mi naturalidad. Además, EcoPure de Master Paints tiene Bio-Pruf® que mantiene la superficie de la pintura libre de hongos y no contiene VOC para la tranquilidad y seguridad de mi familia. masterpaintspr www.mastergroup-pr.com Ang-II will activate Endothelin-I (ET1) release by endothelial cells (17). This peptide is a potent vasoconstrictor, but also induces leukocyte adhesion, monocyte chemotaxis, platelet aggregation, stimulate the production of cytokines, promotes differentiation processes in vascular cells and has marked mitogenic properties that facilitate proliferation of endothelial and vascular muscle cells (18). Both plasma Ang-II and ET1 levels are elevated in patients with advanced atherosclerosis and congestive heart failure. There exists a possibility in the future that peripheral plasma AngII and ET1 levels might serve as practical clinical as well as pathogenetic markers for the extent of coronary disease. However, no experiments have explored the levels of these peptides in the human coronary artery circulation itself. The association between Ang-II, ET and progression of CAD suggest that these peptides could play an even more active role in the etiology of coronary atherosclerosis inside the coronary arteries. The objectives of our study were to quantify Ang-II and ET-1 levels in the coronary artery circulation in diabetic patients with CAD, and correlate these levels with the degree of CAD and compare with similar patients without CAD. MATERIALS AND METHODS Two groups were studied and compared the levels of the two peptides with CAD. Group A consisted of eight patients with Diabetes Mellitus Type 2 (DMT2) and Coronary Heart Disease (CHD). Group B consisted of ten patients with DMT2, but without CAD (control group). Right heart catheterization was done, a catheter was positioned at the level of the origin of the coronaries arteries and another at the end of the coronary sinus (CS) considered the coronary artery efflux. 10 ml of blood was collected and immediately centrifuged. The plasma was kept at -20ºC of the temperature. Analysis of the ET1 was done using radioimmunoassay and angiotensin II using Immunoassay techniques. This was followed by coronary angiography. CAD was categorized as mild, moderate or severe. Mild was defined as less than 50% of obstruction in any major artery. Moderate to severe was defined as more than 50% of obstruction in any major artery or previous history of interventional or surgical management. Variables were compared using the student’s t-test. The Ang-II and ET1 levels were reported as mean and standard deviation. Significant values were considered with a p < 0.05. RESULTS In Group A, the levels of Ang-II in BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 5 the CS were similar to those in the aorta (46 ± 18 pg/ml vs. 35 ± 15 pg/ml, respectively) and non-significant. These values were significantly higher when compared to Group B levels (10 ± 2 pg/ml, P <0.001) when the patients were grouped according the severity of coronary disease. The Ang-II levels were 42% lower in the mild disease group when compared to those with moderate to severe disease (29 ± 2 vs. 52 ± 8 pg/ml, respectively). The ET1 levels of Group A at the aortic and CS were similar (13 ± 6; 14 ± 4 pg/ml). The levels in Group B at the aortic and CS were (3 ± 1; 5 ± 2 pg/ml). This difference was statistically significant P<0.001. DISCUSSION The RAS is a complicated and essential system in the regulation of vascular homeostasis (1-16). Angiotensin II (Ang-II) is cleaved from angiotensin I (Ang-I) by angiotensin converting enzyme (ACE), which is localized on the surface of endothelial cells and in the media and adventia of the aorta (16); a soluble form of ACE is also found in plasma. Ang-I is formed from angiotensinogen, which is secreted from the liver and cleaved by renin, which in turn is found in the juxtaglomerular cells in the kidney. The traditional RAS inhibitors, angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB), target the main RAS axis described above. However, there are additional enzymes associated with the production of Ang-II, such as Cathepsin-G (7), as well as other. More novel angiotensin molecules that serve as potential therapeutic targets: the ACE2/Ang (1–9) axis is a new and important pathway to compensate for the vasoconstrictive and hyper proliferative RAS axis. A direct mechanism implicated in the production of these distinctive angiotensin molecules involves ACE2, a novel component of the RAS that converts Ang-I to Ang-(1-9) and AngII to Ang-(1-7), a peptide with vasodilator and anti-proliferative properties. The induction of ACE2 not only holds therapeutic promise by producing the anti-inflammatory Ang-(1-7), but also by reducing Ang-II levels, thereby conferring a twofold protection against cardiovascular remodeling from ongoing hypertension and inflammation (116). Concomitant to the progression of the RAS, hyperglycemia promotes the deposition of advanced glycation end products (AGEs) that are formed from the non-enzymatic glycation of proteins and lipids after contact with reducing sugars (17). The accumulation of AGEs is an important factor in the development and progression of vascular injury in diabetes-associated atherosclerosis (9). Both hyperglycemia and induction of the main RAS axis will increase oxidative stress and increase the rate of the atherosclerotic process that ultimately end in apoptosis and necrosis of myocytes (9), hence propagating the deleterious effects of inflammation, insulin resistance and endothelial dysfunction (15). The inhibition of the RAS by ACE inhibitors and ARBs has been mainstay therapy to reduce the onset and/or progression of hypertension, left ventricular dysfunction, diabetic renal disease and atherosclerosis (18). For example, inhibitors of the RAS seem to be more effective than other medications in stopping the progression of dilated cardiomyopathy in hamsters that have an inherited mutation that predisposes to such a disease. In rodents, pharmacological or genetic disruption of RAS action prevents weightgain, promotes insulin sensitivity and relieves hypertension (8-9), suggesting that ACE inhibitors or ARBs may present an effective treatment for MetS in humans. In addition, when obese individuals lose weight, both adipose tissue mass and systemic RAS activity are reduced. An increase in adipose tissue angiotensinogen has been reported in diet-induced obesity: further evidence that lifestyle changes are integral to targeting the underlying mechanisms of MetS (9-10). 6 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico Systemic inflammation (15) is a fundamental process in the development of cardiovascular disease in patients with MetS. This process starts with the activation of the neuro-hormonal system. Data shows elevated intra-coronary levels of Ang-II and endothelin-I (E-I) in some patients with Diabetes Mellitus Type 2 (DMT2). We measured these peptides in 8 patients with DMT2 and concomitant MetS, normal coronary arteries and sub-normal ejection fraction (49 ± 5%), and discovered that the levels of Ang-II and E-I were elevated in the CS (coronary efflux) and aorta of these patients when compared to the control group, which consisted of 10 cases with DMT2 but without MetS that were catheterized and found to have normal coronary arteries and a normal ejection fraction. In the former, MetS group, Ang-II levels inside the coronary sinus and aorta were 46 ± 18 and 35 ± 15 pg/ ml, respectively, while Ang-II levels were 10 ± 2 pg/ml inside both chambers of the control group (P < 0.001). Furthermore, in the group with MetS, the E-I levels inside the coronary sinus and aorta were elevated at 14 ± 4 and 13 ± 6 pg/ml in both chambers, respectively, compared to 3 ± 1 pg/ml inside both chambers of the control group (P < 0.001). This shows that some diabetic Type 2 patients with Mets the activation of Ang-II and E-1 are a primordial process leading to atherosclerotic heart disease leading to severe coronary artery disease with its consequences. This brings the idea that these peptides have an extremely important role, in the origin of the atherosclerotic process, more pronounced in diabetic patients, especially producing inflammation that is a crucial mechanism in the progression of this disease. Also, we are in process of evaluating the role of essential fatty acids (resolving, protectins, maresins) in the atherosclerotic process. REFERENCES (1) Rocha VZ, Libby P. Obesity, inflammation and atherosclerosis. Nat Rev. Cardiol. 2009; 6: 399-409. (2) Fukai T. Endothelial GTPCH in ENOS uncoupling and atherosclerosis. Artherioscler Thromb Vasc Biol 2007; 27: 1493-5. (3) Ridker PM. Inflammation C-reactive protein and cardiovascular disease. Cir Res. 2014; 114: 594-595. (4) Tedqui A, Mallat Z. Cytokines in atherosclerosis pathogenic and regulatory pathways. Physiol Rev 2006; 86: 515-81. (5) Hussein AA, Gottdiener JS, Bartz TM, Sotoodehnia N, et al. Heart rhythm 2013; 10: 1425-1432. (6) Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammations in women. N Engl J Med 2000; 342: 836-43. (7) Fuster V, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and acute coronary syndrome. N Engl J Med. Part 1 and 2, 1992: 326, 242-50, 310-8. (8) de Kloet, AD, Krause EG, Wood SC. The renin angiotensin system and metabolic syndrome. Physiol Behav 2010; 100: 525534. (9) Boustany CM et al. Activation of the systemic in rats with diet-induced obesity and hypertension Am J Physiology 2004; 287: 943-49. (10) Altieri P, Alvarado S, Banchs H, Escobales N, Crespo M. The role of angiotensin II and endothelin I in the cardiomyopathy of diabetic patients. J Investigative Med 2012; 81. (11) Heeneman S, Sluimer J, Daeman Mat Jap. Angiotensin converting enzyme and vascular remodeling. Circ Res. 2007; 101: 441-45. (12) Highsmith RF. Endothelin-molecular biology, physiology and pathology. Humana Press- 1998. (13) Ferri C, et al. Angiotensin II increases the release of endothelin cells, but does not regulate its circulating levels. 1999; 96: 261-270. (14) Patel VB, Robbins MA & Topol EJ. C-reactive protein: a ‘golden marker’ for inflammation and coronary artery disease. Cleve Clin J Med 2001; 68: 521-524, 527-534. (15) Hansson, GK. Inflammation, atherosclerosis and coronary disease. N Engl J Med 2005; 352: 1685-1695. (16) Ferrario, CM. Role of angiotensin II in cardiovascular disease therapeutic implications of more than a century of research. J Renen Angiotensin Aldosterone Syst 2006; 7: 3-14. (17) Iwanaga Y, et al. Differential effects of angiotensin II versus endothelin-1 inhibitions in hypertrophic left ventricular myocardium during transition to heart failure. Circulation 2001; 107: 606612. (18) Luscher, TF & Burton, M. Endothelins and endothelin receptors antagonists: therapeutic consideration for a novel class of cardiovascular drugs. Circulation 2000; 102: 2434-2440. (19) Roig E. et al. Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur Heart J 2000; 21: 53-57. (20) Zouridakis, EG, et. al. Increased plasma endothelin levels in angina patients with rapid coronary artery disease progression. Eur Heart J 2001; 22: 1578-1584. (21) Zeiher, AM, Ihling, C, Pistorius, K, et al. Increased tissue endothelin immunoreactivity in atherosclerotic lesion associated with acute coronary syndromes. Lancet 1994; 344: 1405-1406. (22) Bannenberf G, Serham C IV. Specialized pro-resolving lipid mediator in the inflammatory response: An update. Biochim Biophys Acta 2010; 1801(12):1260-73. RESUMEN Dos grupos de pacientes fueron estudiados para encontrar los niveles de angiotensina II y endotelina I en la circulación coronaria y periférica. El Grupo A consistió de ocho pacientes con diabetes mellitus Tipo 2 y enfermedad coronaria; y el Grupo B 10 pacientes con diabetes mellitus sin enfermedad coronaria. Se encontraron diferencias significativas entre el grupo A y B en los niveles de ambos péptidos periféricamente e intra-coronaria. Esto muestra la importancia de estos péptidos en el origen de la enfermedad coronaria y progresión de la enfermedad en diabéticos con enfermedad coronaria. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 7 INTERVENTIONAL NEPHROLOGY IN PUERTO RICO: A Four Year Experience Nephrology Section, Internal Medicine Department, University of Puerto Rico School of Medicine, San Juan, Puerto Rico. b Internal Medicine Residency Program, University of Puerto Rico School of Medicine. c University of Puerto Rico School of Medicine d Vascular Access Unit, Auxilio Mutuo Hospital, San Juan, Puerto Rico. *Corresponding author: Jose L. Cangiano MD 313 Domenech Avenue, Suite 101, San Juan, Puerto Rico 00918. E-mail: jlcangiano@ yahoo.com a Rafael Baez M,Jose Betancourt MDb, Hector J. Diaz MDb, Anmelys Rivera MDb, Javier Monserrate MDc, Tania Ramírez MDa, Martin Gorrochategui, MDd, Carlos Rivera Bermudez MDa, Francisco Torre Leon MDa, Jose L. Cangianoa* MD, FACP, FAHA ABSTRACT Puerto Rico is one of the most prevalent areas covered by Medicare in need of renal replacement therapy for which interventional procedures are performed. A cumulative analysis of this management is reported in patients during the period between June 2007 and August 2010. Experience accumulated with 3755 surgical patients revealed that 58% had intravascular catheters, 28% had arteriovenous fistulas, 15% had arteriovenous grafts, and 2% without vascular access. Procedures performed in these patients were: catheter introduction in 1990 cases (33%), angioplasty in 751 cases (20%), angiography in 450 cases (12%), thrombectomy in 413 cases (11%) and venous mapping in 151 cases (4%). The success rates of these procedures were evaluated by analysis of the Society of Interventional Radiology (SIR) criteria for Lifeline Vascular Access. Using SIR definition of success rate for at least one session that includes “declots”, placement of catheters and angioplasty, our results revealed an average of 98.2% overall success rate greater than the standard value KDOQI/SIR (> 85% ). This study has documented for four years the success rate of Vascular Interventional Nephrology Center at Auxilio Mutuo Hospital. In order to maintain this success rate is necessary to further evaluate its effectiveness and, most importantly, the development of an educational program for vascular access in patients with chronic kidney disease prior to placement in dialysis units. Index words: interventional, nephrology, Puerto Rico, experience INTRODUCTION Puerto Rico continues to be one of the most prevalent areas covered by Medicare in need of renal replacement therapy. In 2009, a report from the Network Council on Renal Disease of New Jersey, revealed that in Puerto Rico 4470 cases received dialysis with a prevalent rate of 1,126 persons per million (ppm); a total growth of +3.58%. On the other hand, the incidence rate was reported to be 345 ppm with 1,370 new cases (1). The total growth for 2000-2009 was +2.41% (USA it was +2.0%). The main causes of End Stage Renal Disease (ESRD) in Puerto Rico are diabetes mellitus and hypertension. Of the 1370 new cases, 911 (67%) were diabetic and 200 (15%) hypertensive. An increased frequency has been reported with diabetes +3.04% and hypertension +3.75%. Additionally, one of the main concerns of this report was the high mortality in Puerto Rico as compared to USA mainland (23.4% vs. 20.3% respectively). In looking for solutions to this vexing problem in our island, the Network Council has provided great support to identify the reasons involved for disparity in mortality outcome. Several recommendations have been provided to strengthen the renal community in Puerto Rico. Among them the Network has strengthened support for the development of Centers of Excellence for procedures needed in this type of patients, such as Vascular Access 8 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico Units. With this purpose in mind, on February 2005 an Interventional Nephrology Unit for Vascular Access was established in Auxilio Mutuo Hospital in San Juan, Puerto Rico. An initial report of this experience has been published (2). It was the first and has remained the only unit to be serviced by a group of interventional nephrologists on an outpatient basis. Before its establishment, vascular access problems were referred mainly to vascular surgeons and/ or interventional radiologists. It is now accepted that nephrologists are well suited for training and development of skills for performing invasive procedures because of their knowledge of renal replacement therapy. In addition, one of the main advantages of the interventional progress by nephrologists is that it has minimized delays in performing the procedures, hospitalizations and the use of temporary catheters therefore improving the quality of care for the chronic kidney disease patient. At present, there are three trained interventional nephrologists with excellent procedural skills participating in this program. The procedures performed at this center include angiograms, percutaneous balloon angioplasty, thrombectomies, tunneled hemodialysis catheter placement and venous mapping. A cumulative analysis is herein reported in 3755 patients intervened for the period between June 2007 to August 2010. Our data was compiled and analyzed by Lifeline Vascular Access. RESULTS Our four year experience in an Interventional Nephrology Vascular Access unit in San Juan in 3755 patients intervened revealed that 58% of the patients had intravascular catheters, 28% arteriovenous fistulas, 15% arteriovenous grafts and 2% no vascular access. The procedures performed in these patients included: 1990 (33%) catheter placement, 751 (20%) angioplasty, 450 (12%) angiogram, 413 (11%) thrombectomy, and 151 (4%) vein mapping (see Figure 1). Figure 2 shows the reasons for referrals in our group of patients. Catheter exchange (29%) was the most common reason, followed by clotted arteriovenous fistula (23%), malfunctioning fistula (21%), change of modality (17%), arteriovenous fistula stenosis (6%), vein mapping (3%) and no vascular access (1%). Figure 3 depicts the procedure success rate as analyzed by SIR (Society of Interventional Radiology) criteria from Lifeline Vascular Access. Using SIR definition of success rate for at least one session including declots, catheter placements and angioplasties, our results revealed an average of 98.2% of overall success rate exceeding the KDOQI/SIR standard Figure 1: Shows the procedures performed. Each column depicts the number of patients with the respective percentage. 53% 1990 20% 12% 11% 4% 751 450 413 151 Figure 2: Shows the reason for referral of the 3755 patients in the study. Each column depicts the number of patients with the respective percentage. 21% 794 29% 23% 857 1091 17% 636 6% 220 1% 36 value (= or > 85%). Taking into consideration the SIR threshold for complications being 5%, we observed a minimal complication rate in our procedures of 0.45%, which is significantly below the established threshold. DISCUSSION This retrospective study reports the four-year experience in an 3% 121 Interventional Nephrology Vascular Access Unit in San Juan Puerto Rico after establishment in 2004. A total of 3,755 cases were performed during the study period from 2007 to 2010.The period studied was from 2007 to 2010. The procedures were catheter placement, angioplasty, angiograms, thrombectomy, and vein mapping. Most of the complications of tunneled catheter placement are related to the experience BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 9 Figure 3: Shows the procedure success rate. Each column depicts the number of patients with the respective percentage. disease patients prior to placement in dialysis units. 99% REFERENCES SIR/KDOQI = 85% 98% of the operator and the use of ultrasound guidance for cannulation of the vein. Blind insertion may result in complication rates as high as 5.9% (4). Complications observed include pneumothorax, hemothorax, hemomediastinum, recurrent laryngeal nerve palsy, or bleeding which may require exploration and/or blood transfusion. Our Vascular Unit uses ultrasonogram and fluoroscopic guidance for cannulation of veins and the success rate was 95.4%. The complication for tunneled catheters was acceptable with minimal complications were observed, most of them mild or moderate hematomas. Venous stenosis may be a hazardous lesion to treat. Angioplasty is not always successful. The main complication associated to angioplasty is venous rupture (5,6) with an incidence between 1.7% to 3.8% (7,8). The most common lesion producing venous stenosis is intimal fibromuscular dysplasia. The interventionist must be careful in avoiding the tear of veins. In our study, no episodes of venous rupture were reported and the majority of complications were minimal, mostly related to the development of grade 1 and 2 hematomas. Thrombectomy was also successful in our team. Large series of thrombectomies have reported a success ratio of 95% in 1176 98% 98% cases (9,10). However, success rates for cardiovascular thrombectomies have been from 62% to 95% (11,12). The most common complication associated to thrombectomy has been vein rupture resulting in hematomas. On the other hand, the major complication related to thrombectomy is peripheral vascular embolization. Some studies have reported this complication to be as high as 6% (13). In our current experience, no peripheral arterial embolization was reported. The safety and efficacy of vascular access related procedures were also demonstrated in our study. Complications were minimal and reported as 0.45% not affecting the well being of the patient. The overall success rate of 98.2% by the SIR criteria is well above the standard SIR criteria of 85% and compares to many Vascular Centers throughout the United States. In conclusion, this four-year study has documented the success rate of the Interventional Nephrology Vascular Center at the Auxilio Mutuo Hospital. This progress has been well accepted by our nephrologists and patients. In order to maintain this successful rate we need to continue assessing its effectiveness and, most important, develop a vascular access educational program with chronic kidney 10 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico 1.Report from Network Council on Renal Disease of New Jersey. Puerto Rico Data; 2009 2. Torre León F, Rivera Bermúdez C, Hernández V, Silva J, Santiago Delpín E. Interventional Nephrology in Puerto Rico. Semin Dial 2006;19:176-9 3. Sacks D, McClenny TE, Cardella JF, Lewis CA, Society of Interventional Radiology Clinical Practice Guidelines J Vasc Interv Radiol 2003; 14:S199–S202 4. Bour ES, Weaver AS, Yang HC, Gifford RR. Experience with the double lumen Silastic catheter for hemoaccess. Surg Gynecol Obstet. 1990 Jul;171(1):33-9. 5. Beathard GA. Management of complications of endovascular dialysis access procedures Semin Dial. 2003 JulAug;16(4):309-13 6. Pappas JN, Vesely TM. Vascular rupture during angioplasty of hemodialysis raft-related stenosis J Vasc Access. 2002 Jul-Sep;3(3):120-6 7. Rundback JH, Leonardo RF, Poplausky MR, Rozenblit G. Venous rupture complicating hemodialysis access angioplasty: percutaneous treatment and outcomes in seven patients AJR Am J Roentgenol. 1998 Oct;171(4):1081-4 8. Raynaud AC, Angel CY, Sapoval MR, Beyssen B, Pagny JY, Auguste M. Treatment of hemodialysis access rupture during PTA with Wallstent implantation J Vasc Interv Radiol. 1998 MayJun;9(3):437-42 9. Beathard GA, Welch BR, Maidment HJ. Mechanical thrombolysis for the treatment of thrombosed hemodialysis access grafts Radiology. 1996 Sep;200(3):711-6 10. Sharafuddin MJ, Kadir S, Joshi SJ, Parr D. Percutaneous balloon-assisted aspiration thrombectomy of clotted hemodialysis access grafts J Vasc Interv Radiol. 1996 Mar-Apr;7(2):177-83. 11. Overbosch EH, Pattynama PM, Aarts HJ, Schultze Kool LJ, Hermans J, Reekers JA. Occluded hemodialysis shunts: Dutch multicenter experience with the hydrolyser catheter Radiology. 1996 Nov;201(2):485-8. 12. Trerotola SO, Vesely TM, Lund GB, Soulen MC, Ehrman KO, Cardella JF. Treatment of thrombosed hemodialysis access grafts: Arrow-Trerotola percutaneous thrombolytic device versus pulsespray thrombolysis. Arrow-Trerotola Percutaneous Thrombolytic Device Clinical Trial. Radiology. 1998 Feb;206(2):403-14 13. Lazzaro CR, Trerotola SO, Shah H, Namyslowski J, Moresco K, Patel N. Modified use of the arrow-trerotola percutaneous thrombolytic device for the treatment of thrombosed hemodialysis access grafts. J Vasc Interv Radiol. 1999 Sep;10(8):1025-31. RESUMEN Puerto Rico es una de las zonas de mayor prevalencia de enfermedad crónica renal, cubiertas por Medicare, en necesidad de intervenciones quirúrgicas. Un análisis acumulativo de estas intervenciones y tratamientos se informa en este documento en 3,755 pacientes durante el período comprendido entre junio de 2007 y agosto de 2010. Nuestra experiencia en 3,755 pacientes reveló que al 58% se le realizó inserción de catéteres intravasculares, 28% creación de fístulas arteriovenosas, y 15% tuvieron injertos arteriovenosos. Los procedimientos realizados en estos pacientes fueron los siguientes: implantación de catéter en 1990 casos (33%), angioplastia en 751 casos (20%), angiograma en 450 casos (12%), trombectomía en 413 casos (11%) y mapa venoso en 151 casos (4%). La tasa de éxito de los procedimientos se evalúa por análisis de SIR (Sociedad de Radiología Intervencional) por criterios de Acceso Vascular “Lifeline”. Usando la definición SIR nuestros resultados revelaron un promedio de 98.2% de tasa de éxito global superior al valor KDOQI/SIR estándar (> 85%). Este estudio ha documentado la tasa de éxito del Centro Vascular Intervencionista de Nefrología del Hospital Auxilio Mutuo superando lo establecido por SIR. Con el fin de mantener esta tasa de éxito es necesario seguir evaluando su eficacia y, lo más importante, el desarrollo de un programa educativo de acceso vascular en pacientes con enfermedad renal crónica antes de admitirse en las unidades de diálisis. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 11 BRUGADA SYNDROME IN PUERTO RICO: A Case Series Héctor Banchs-Viñas MDa Norwin Rivera MDb Héctor Banchs-Pieretti MDa Pablo Altieri MDa* University of Puerto Rico School of Medicine, Department of Medicine, Cardiology Section. San Juan, Puerto Rico. Veterans Affairs Caribbean Healthcare System, Department of Medicine, San Juan, Puerto Rico. *Corresponding author: Pablo I. Altieri MD - Box 8387, Humacao, Puerto Rico 00792. E-mail: [email protected] a b ABSTRACT Brugada syndrome (BrS) is characterized by ST-segment changes in the right precordial ECG leads and a high incidence of sudden death in patients with structurally normal hearts. Life-threatening ventricular arrhythmias are the hallmark of Brugada syndrome. The incidence and prevalence of BrS in Puerto Rico, to our knowledge, has never been studied and there is only one case report of BrS in Puerto Rico in the literature. We review three cases of BrS in Puerto Rican patients who presented to our institution with syncope reviewing the literature. Index words: brugada, syndrome, Puerto Rico, case, series INTRODUCTION Brugada Syndrome (BrS) is a hereditary cardiac channelopathy that predisposes affected individuals to ventricular arrhythmias. BrS is associated with sudden cardiac death in otherwise healthy individuals and is characterized by ST-segment elevation in the right precordial ECG leads and a high incidence of sudden death in patients with structurally normal hearts [1]. It is difficult to estimate the true prevalence of the disease in the general population because the ECG pattern can be dynamic and is often concealed [2]. The clinical diagnosis of BrS is made when a type 1 BrS ECG pattern occurs in association with a personal history of syncope secondary to ventricular tachycardia (VT) or ventricular fibrillation (VF), or a history of aborted sudden cardiac death. This diagnostic electrocardiographic pattern has a worldwide prevalence in the general population of 1 of 1,000 individuals, representing a relevant health care issue [3]. The mainstay treatment in BrS is implantation of a cardioverter defibrillator (ICD). The incidence and prevalence of BrS in Puerto Rico, to our knowledge, has never been studied and there is only one case report of BrS in Puerto Rico in the literature [1]. We review three cases of BrS in Puerto Rican patients who presented to our institution with syncope reviewing the literature. Case History 1 A 62 year-old man with past history of arterial hypertension and type 2 diabetes mellitus was at a pre-operative evaluation for elective non-cardiac surgery when he had sudden onset of cramping pain on his left shoulder followed by loss of consciousness for approximately one minute. Vital signs after the event were normal except for a temperature of 39°C. ECG performed after he regained consciousness revealed ST segment elevation in leads V1-V3 (see Figure 1), and he was taken emergently to the cardiac catheterization laboratory due to suspected STEMI. Coronary angiography showed normal coronary arteries with no obstructive lesions. The left ventriculogram showed preserved left ventricular systolic function. Transthoracic echocardiography showed no structural abnormalities with normal Figure 1. Electrocardiogram showing coved ST segment elevations from v1-v3 consistent with type 1 Brugada pattern 12 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico left ventricular ejection fraction. Upon further questioning he denied past episodes of syncope, loss of consciousness, seizure activity, a history of arrhythmias and family history of sudden cardiac death. He also denied alcohol, cigarette or drug abuse. Laboratory studies, including complete blood count, serum chemistries, hepatic and renal function tests, were within normal limits. Troponin I, CK-MB and myoglobin levels were also within normal limits. Based on clinical presentation and electrocardiographic findings Figure 2: Initial ECG showing type 1 Brugada pattern with coved ST-seghe was diagnosed with Brugada ment elevation descend with upward convexity, T-wave inversion and ≥ syndrome and an ICD was im- 2mm J-point elevation in V2-V3. planted. He was discharge home without complications. Case History 2 A 29-year-old man with history of bronchial asthma presented to the emergency department with retrosternal chest pain of three hours duration and loss of consciousness. Pain was described as 10/10 in intensity, oppressive, and non-radiating. Chest pain started after an episode of emotional stress, after which he suddenly lost consciousness for approximately three minutes, regaining consciousness spontaneously. By the time he arrived to the emergency department all symptoms had resolved. Review of systems was remarkable for three episodes of sudden loss of consciousness in the past year. These episodes were not associated with exertion and he did not seek medical care at that time. He denied palpitations, history of heart disease, cardiac surgery, shortness of breath, diaphoresis, seizures, or family history of SCD. He admitted to recent cocaine abuse including the day of the event. Physical examination and vital signs were unremarkable. Initial complete blood count and serum chemistries were within normal limits, including potassium levels. Troponin, creatine kinase (CK-MB) and myoglobin were all negative. A 12-lead ECG (see Figure 2) showed ST-segment elevation in the right precordial leads Figure 3: Follow up ECG showing resolution if the Brugada pattern (V1-V3), initially diagnosed as an antero-septal acute myocardial infarction. Closer inspection showed coved ST-segment elevation of more than 2 mm in the right precordial leads (V1-V3) with T-wave inversion compatible with type 1 Brugada pattern. A follow up ECG (see Figure 3) showed resolution of the Brugada pattern. 2D-Echocardiogram showed normal left ventricle systolic and diastolic function with 60% ejection fraction, normal cardiac chambers dimensions with no structural abnormalities. Due to history of recent and recurring syncope of unexplained cause, and the presence of type 1 Brugada pattern on ECG, an implantable cardioverter-defibrillator (ICD) to treat ventricular arrhythmias and prevent SCD was offered but he declined this option. Case History 3 A 62 year-old man with past history of multiple myeloma was brought to the emergency department after experiencing an episode of sudden loss of consciousness while driving in heavy traffic. A bystander started cardiopulmonary resuscitation until paramedics arrived, intubated him and took him to the nearest emergency department. Upon arrival to the emergency room ECG revealed coved ST elevations in leads V1-V3 (see Figure 4). He had six episodes of ventricular tachycardia with hemodynamic deterioration that required electrical cardioversion. He was transferred to our institution with a suspected STEMI for emergent cardiac catheterization. Coronary angiography showed no significant lesions and transthoracic BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 13 Figure 4. Marked coved ST segment elevations and negative T wave of right precordial leads in a patient with Brugada Syndrome. Figure 5: The 3 recognized ECG patterns seen in Brugada Syndrome. echocardiography revealed no structural abnormalities and normal left ventricular ejection fraction. Medical history was negative for previous episodes of syncope, arrhythmias and family history of sudden cardiac death. Laboratory workup revealed mild leukocytosis and Troponin I elevation with normal serum chemistries, renal and liver function. Based on the ECG findings and a history of syncope and ventricular tachycardia the diagnosis of BrS was made and the patient received an ICD for secondary prevention. He was extubated without complications and discharged home in stable condition. DISCUSSION Brugada syndrome (BrS) was first described in 1992 as a disease that predisposes apparently healthy individuals to sudden cardiac death [3]. It is as an autosomal dominant inherited arrhythmic disorder characterized by ST elevation with successive negative T waves in the right precordial leads without structural cardiac abnormalities [4]. The ECG changes can be dynamic and sometimes are concealed and may be observed only in certain situations, such as fever, intoxication, vagal stimulation, electrolyte imbalance and with some drugs 14 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico (sodium channels blockers) that may unmask a Brugada pattern [5]. There are three recognized ECG patterns seen in BrS, but only the type 1 pattern is considered diagnostic (see Figure 5). In individuals presenting with patterns 2 and 3 provocative maneuvers must be performed in order to unmask the type 1 pattern. Although most cases of BrS display right precordial ST-segment elevation, isolated cases of ST-segment elevation in the inferior and left precordial leads have been reported in Brugada-like syndromes [2]. It is important to recognize the Brugada ECG pattern and to be aware that patients with BrS may be initially diagnosed with STEMI. Life-threatening ventricular arrhythmias are the hallmark of Brugada syndrome and are thought to arise as a result of accelerated inactivation of the sodium channels and predominance of transient outward potassium current to generate a voltage gradient in the right ventricular layers. This gradient triggers VT/VF possibly through a phase 2 reentrant mechanism [5,9]. Patients are at risk for sudden cardiac death (SCD) due to ventricular arrhythmias, which can be the first manifestation of the disease, and often occur at rest and at night [2]. The syndrome manifests predominantly in men in the third and fourth decades of life [10]. Roughly 15% to 20% of the patients with BrS have mutations at the alpha subunit of the sodium channel gene (SCN5A) but recent studies have linked the syndrome to mutations in the genes that encode the α and β subunit of the calcium channel and the gene that encodes glycerol-3-phosphate dehydrogenase 1-like enzyme (GPD1L)[6,7]. Brugada phenotype has been reported to be up to 8 to 10 times more prevalent in men than in women and hormonal influence might play a role in the phenotypic manifestations of BrS [6]. Patients with BrS have an increased incidence of atrial arrhythmias with atrial fibrillation being the most common, found in 11% to 14% of patients [4,7]. Enhanced duration of atrial action potential and increased intra-atrial conduction time may contribute to the genesis of atrial arrhythmias in BrS [7]. In patients with BrS and a history of aborted SCD or syncope secondary to VT/VF, an implantable cardioverter defibrillator (ICD) is the first line therapy and is the only proven effective treatment for the disease [2]. For patients with recurrent VT/VF and ICD shocks, adjunctive medical with quinidine may be required for suppression of ventricular arrhythmias [4]. REFERENCES 1. Martínez H, Montano L, Rodríguez-Ospina L, et al. A case of Brugada Syndrome in a 63 y/o man with chest pain. Bol Asoc Med PR. 2008 Oct-Dec: 100(4):86-8 2. Antzelevitch C, Brugada P, Borggrefe M, et al.Brugada Syndrome: Report of the Second Consensus Conference: Endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation. 2005; 111:659-670. 3. Priori SG, Gasparini M, Napolitano C, et al. Risk Stratification in Brugada Syndrome. Results of the PRELUDE Registry. J Am Coll Cardiol.2012;59:37-45. 4. Mizusawa Y, Wilde AA. Brugada Syndrome. Circ Arrhythm Electrophysiol. 2012;5:606-616. 5. De Luna AB, Brugada J, Baranchuk A, et al. Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report. J Electrocardiol. 2012; 45: 433-442. 6. Benito B, Sarkozy A, Mont L, et al. Gender Differences in Clinical Manifestations of Brugada Syndrome. J Am Coll Cardiol 2008; 52: 1567-73. 7. Francis J, Antzelevitch C. Atrial Fibrillation and Brugada Syndrome. J Am Coll Cardiol.2008;51:1149-53. 8. Wilde AA, Antzelevitch C, Borggrefe M,et al.Proposed Diagnostic Criteria for the Brugada Syndrome Consensus Report. Circulation.2002;106:2514-2519. 9. Nagase S, Kusano KF, Morita H, et al. Longer Repolarization in the Epicardium at the Right Ventricular Outflow Tract Causes Type 1 Electrocardiogram in patients with Brugada Syndrome. J Am Coll Cardiol 2008; 51:1154-61. 10. Prystowsky EN, Padanilam BJ, Joshi S, Fogel RI. Ventricular Arrhythmias in the Absence of Structural Heart Disease. J Am Coll Cardiol. 2012;59:1733-44. RESUMEN El Síndrome de Brugada es un desorden cardiaco hereditario que causa arritmias ventriculares en personas sin enfermedad estructural cardiaca. Este síndrome puede causar muerte súbita y tiene un patrón hereditario autosómico dominante causando mutaciones en los canales de iones del corazón, predisponiendo a los individuos con la mutacion a arritmias ventriculares. El tratamiento para esta condición consiste en la implantación de un desfibrilador cardiaco. El Síndrome de Brugada no ha sido estudiado en Puerto Rico y a nuestro entender solo existe en la literatura un reporte de caso del Síndrome de Brugada en Puerto Rico. En este artículo presentamos tres casos de Sindrome de Brugada que fueron atendidos en el Centro Cardiovascular de Puerto y hacemos una revisión de la literatura. AMPR App Aplicación gratuita para su celular y i-pad que le permite estar conectado a la información que produce la Asociación Médica, además de proveerle otras herramientas útiles. Links para la descarga gratuita de la aplicación BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 15 Primary venous thromboembolism and malignancy, is there any relationship? Department of Internal Medicine San Juan City Hospital, San Juan, Puerto Rico. Hematology-Oncology Department, VA Caribbean System and San Juan City Hospital, San Juan, Puerto Rico. *Corresponding author: Luis Cotto Santana MD – Internal Medicine Department, San Juan City Hospital, San Juan, Puerto Rico 00926. E-mail: luiscottosantana@gmail. com a b Luis Cotto Santana MDa* William Caceres Perkins MDb ABSTRACT Deep venous thrombosis and pulmonary embolism can be the first manifestation of cancer. In light of this association screening for cancer has been proposed in patients with primary VTE to identify an undiagnosed malignancy. Method: Descriptive, retrospective record review that includes 3244 patients from VA San Juan Caribbean system with diagnosis of lung (small and non-small cell), prostate, colon, rectum, liver, stomach, esophagus, pancreas and breast cancer, lymphoma or leukemia from 2005 to 2010 evaluated for primary VTE during five years prior to their malignancy diagnosis. Secondary outcomes evaluated were age and staging at the time of VTE diagnosis. The inclusion criteria were veterans with age 21 years old or more and with diagnosis of the above mentioned malignancies. The exclusion criteria were pregnancy five years to the diagnosis of malignancy, history of coagulopathy or use of anticoagulation at moment of the diagnosis of malignancy. Results: 3244 records were reviewed. From the 2858 that met the inclusion criteria 22 (8%) had history of VTE five years before their malignancy, most of them (14%) with diagnosis of pancreatic malignancy. After we studied VTE by site of malignancy: 7% of pancreatic, 0.8% of prostate, 0.5% of colon, 0.6% of bladder, 0.8% of liver, 0.4% of lung, 1.1% of rectal cancer patients but none with leukemia, stomach, esophagus, breast cancer had VTE. Regarding patients with advanced metastatic cancer at the moment of their diagnosis, only 13% had a prior event of VTE. Conclusion: Although at this point there is no clear indication to screen for malignancy in patients presenting primary VTE our results point out an increased number of VTE in patients with subsequent pancreatic cancer. More research is needed before further recommendations on cancer screening in patients with VTE. Index words: primary, venous, thromboembolism, malignancy INTRODUCTION Deep venous thrombosis and pulmonary embolism, collectively termed venous thromboembolism (VTE), can be the first manifestation of cancer. It has been speculated that the development of VTE result from interactions between multiple genetic and environmental risk factors. Unprovoked (or primary) VTE is defined as a principal diagnosis of VTE during admission in patients without history of cancer or hospitalization in the previous six months. Provoked (or secondary) VTE is defined as a diagnosis of VTE that occur during hospitalization or in patients requiring hospitalization within 90 days of one surgical procedure, trauma or hospitalization, patients with immobilization for more than 7 days, using oral contraceptive or hormone replacement therapy as well as those in the postpartum period (1, 2). Several inherited or acquired coagulation defects have been identified as VTE risk factors over the past year (3). On the other hand and in light of its association with malignancies, a more extensive screening for cancer has been proposed in patients with primary VTE. Identifying previously undiagnosed cancer in patients with VTE may be important for several reasons 16 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico including diagnosis at a curable stage (4). Some retrospective studies suggested that limited cancer screening (careful medical history, physical examination and basic blood work) was adequate to detect most cases of undiagnosed cancer in patient with VTE (3). They also found that the highest percent of diagnosis of cancer was six month after an episode of VTE (3). The main objective of this research is to identify the most common type of malignancies that present after a primary VTE in order to establish screening guidelines for those patients. METHOD Data and study sample The IRB office at Veterans Affair Caribbean System in San Juan, Puerto Rico approved this study. The tumor data registry center in VA Hospital, San Juan P.R. was reviewed for veterans 18 years of age or older with diagnosis of lung (small and non-small cell), prostate, colon, rectum, liver, stomach, esophagus, pancreas and breast cancer, lymphoma and leukemia from January 1, 2005 to December 31, 2010. Those electronic medical records were evaluated for an admission diagnosis of primary VTE during five years prior to the diagnosis of malignancy. Primary VTE was defined as a VTE in patients without history of cancer or hospitalization in the previous 6 months. Provoked (or secondary) VTE was defined as a VTE during a hospitalization or in patients requiring hospitalization within 90 days of a surgical procedure, trauma or hospitalization, patients with immobilization for more than 7 days, using oral contraceptive or hormone replacement therapy as well as those in the postpartum period. Patients were excluded if they had a diagnosis of malignancy prior to January 1, 2005, history of coagulopathy or pregnancy five years prior to the diagnosis of malignancy. excluded based on exclusion criteria. One hundred fourteen were on anticoagulation at moment of the diagnosis of malignancy and 272 had a prior diagnosis of malignancy between 2005 and 2010. Of the 2859 patients that met the inclusion criteria, 1559(54%) had prostate cancer, 432(15%) colon cancer, 234(8%) lung cancer, 164(5%) bladder cancer, 17(5%) breast cancer, 132(4%) hepatic cancer, 82(2%) gastric cancer, 42(1%) pancreatic cancer, 89(3%) rectal cancer, 44(1%) esophageal cancer and 64(2%) had leukemia. (see Figure 1) Twenty-one cases (0.7%) of primary VTE were identified from those patients meeting our inclusion criteria. They occurred as follows: 13 (0.83%) of those with prostate cancer, 2(0.5%) of those with colon cancer, 1(0.6%) of those with bladder cancer, 1(0.8%) of those with hepatic cancer, 3(7%) of those with pancreatic cancer, 1(1.1%) of those with rectal cancer and none of those with gastric, lung, esophageal, breast cancer or leukemia patients had an event of primary VTE in the five years prior their diagnosis of malignancy (see Figure 2). Figure 1. Number of patients evaluated by type of malignancies included in the research. Validation of diagnosis Diagnosis of primary VTE was confirmed after reviewing anticoagulation clinics record and/or imaging studies. Statistics Descriptive statistics were used to analyze the collected data. RESULTS Three thousand two hundred forty four patients had a diagnosis of lung (small and non-small cell), prostate, colon, rectum, liver, stomach, esophagus, pancreas and breast cancer, lymphoma and leukemia within January 1, 2005 to December 31, 2010. Three hundred eighty six (12%) were Figure 2. Percent of patients with VTE within five years prior to their diagnosis of malignancy BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 17 Most patients with primary VTE (95%) presented lower extremity deep vein thrombosis (DVT) and 1 (5%) had atrial thrombi. There was no upper extremity DVT or pulmonary embolism identify in our population. Regarding time of presentation of VTE before the diagnosis malignancy, 9 patients (43%) were diagnosed at 0-6 months interval, none within 7-12 months, 3(14%) within 13-18 months, 2(9%) within 19 to 24 months, 2(9%) within 25 to 36 months, 3(14%) within 37 to 48 months and 2(9%) 49 to 60 months interval prior to their diagnosis of malignancy (see Figure 3). Staging at the time of diagnosis of malignancy confirmed metastasis in 4 (19%) patients with previous primary VTE and none in 16(76%) patients. One (5%) patient had no documented metastatic status (see Figure 4). 6- Chew, H. et al; Incidence of venous thromboembolism and its effect on survival among patients with common cancers, Annals of Internal medicine, vol. 166, Feb 2006, pags. 458 – 464. 7- Nordstrom M, Lindblad B, Anderson H, et al Deep venous thrombosis and occult malignancy: an epidemiological study. 8- Cornuz J, Pearson SD, Creager MA, et al. Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis. RESUMEN Figure 3. Percent of number of patients by time interval between diagnosis of primary VTE and malignancy DISCUSSION White R. et al described an increase in primary VTE in patients with leukemia, non-Hodgkin lymphoma and pancreatic, ovarian, stomach, renal cell and lung cancer, most of them within four months prior to the diagnosis of malignancy (1). In accordance with their findings, most of primary VTE in our population occurred in patients with pancreatic cancer. Interestingly, the time interval from the primary VTE and the diagnosis of malignancy also occurred within six months. On the contrary the metastatic status of our population at moment of diagnosis was much lower in relation with the patients studied by White (1). This finding and the low percent of patients with malignancy who had a previous diagnosis of primary VTE in our population are most likely related to our small sample population. Other researchers previously studied other secondary outcomes of our study. For example, although some suggest that an upper extremity DVT is a common presentation in patients with malignancy (5), there were Figure 4. Percent of patient metastatic status at moment of diagnosis of malignancy in patient with primary VTE. no events of upper extre mity DVT reported in our population. Chew et al, (6) report a high prevalence of pulmonary embolism (PE) associated with abdominal cavity malignancies particularly ovarian, biliary or stomach cancer. In contrast to their finding there were no cases of pulmonary embolism in our population. Although some author recommend an aggressive and extensive screening for cancer in patients that present with a primary VTE(2) more studies are needed before establish guidelines or recommend screening studies for malignancy (7, 8). 18 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico REFERENCES 1- White R. et al; Incidence of Idiopathic Deep Venous thrombosis and secondary thromboembolism among ethnic groups in California, Annals of Internal Medicine, Vol 128, Num 9, Pags 737-740. May 1998 2- White R. et al; Incidence of venous thromboembolism in the year before the diagnosis of cancer in 528 693 adults, Annals of Internal Medicine, Vol 165, Aug 8/22, 2005, pags 1782-1787 3- Jan-Leedert P, Nic J., Veeger, et al; The pathogenesis of venous thromboembolism: Evidence for multiple interrelated causes. Annals of internal medicine 2006, vol 145, number 11, pags 807-815 4- Carrier M., Le Gal M., Wells P. et al; Systematic reviews: The trousseau syndrome revised: should we screen extensively for cancer in patients with venous thromboembolism?, Annals of internal medicine, vol 149, num 5, pags. 323-333. 5- Kucher, Nils MD; Deep-vein thrombosis of the upper extremities, The new England journal of medicine 2011; 364:8619, pags 861-869 Trombosis venosa profunda y embolia pulmonar, llamados colectivamente tromboembolismo venoso (TEV), puede ser la primera manifestación de cáncer. Dada esta asociación se ha tratado de proponer un método de cernimiento para malignidad en pacientes que presentan con un TEV con el propósito de identificar alguna malignidad no diagnosticada. Método: Es un estudio descriptivo, retrospectivo, monocéntrico de revisión de expedientes clínicos que incluyó 3244 pacientes del Hospital Veterano en San Juan P.R. con diagnósticos de cáncer de pulmón (de célula pequeña y no pequeña), próstata, colon, recto, hígado, estómago, páncreas, seno, linfoma y leucemia entre 2005 y 2012. Dichos expedientes se evaluaron para un evento de TEV en los cinco años previos a su diagnóstico de malignidad. Resultados secundarios del estudio fueron edad y estadio de la enfermedad al momento de su diagnóstico. Los pacientes debían ser veteranos, mayores de 21 años con un diagnóstico de cáncer de los previamente mencionados entre 1 de enero de 2005 y 31 de diciembre de 2010. Los criterios de exclusión fueron un estado de embarazo en los 5 años previos a su diagnóstico de malignidad, historial previo de alguna coagulopatía, alguna malignidad preexistente o tratamiento de anticoagulación al momento del diagnóstico de la malignidad. Resultados: Se evaluaron 3244 expedientes. De los 2858 expedientes que cumplieron los criterios de inclusión 22 (0.8%) tuvieron un evento de TEV en los cinco años previos a su diagnóstico de malignidad; la mayoría (14%) con un diagnóstico de cáncer de páncreas. Al evaluar los casos de TEV según la malignidad: 7% de páncreas, 0.8% de próstata, 0.5% de colon, 0.6% de vejiga, 0.8% de hígado, 0.4% de pulmón y 1.1% cáncer de recto, pero ninguno de los pacientes con cáncer de estómago, esófago, seno o leucemia tuvieron un evento de TEV. En relación al estadio metastático al momento de diagnóstico, sólo 13% de los pacientes con historial previo de TEV tenían un estado metastático avanzado al momento de su diagnóstico de malignidad. Conclusión: Aunque en este momento no existe una indicación clara para recomendar cernimiento de malignidad en pacientes que presentan con un TEV, nuestros resultados apuntan a un numero aumentado de paciente con TEV a los cuales subsecuentemente se le diagnostica cáncer de páncreas. Se necesitan mas investigaciones para establecer guías de cernimiento para cáncer en los pacientes que presentan con un TEV. Una completa red de servicios: Website https://asocmedpr.org con información en texto y video de interés para los profesionales de la salud. AMPRAPP Aplicacion para smart phones y i-pad con acceso a nuestro website, eventos, agenda e interesantes servicios adicionales. Grupo Facebook con información directa al instante de producirse. Newsletter semanal por email. BOLETIN médico científico, peer review, con exclusivos artículos, en hardcopy y digital. Actividades sociales, cine, confraternización, arte, música, torneos y salidas. Educación médica continua. Cursos especiales. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 19 INTRAVENOUS ASCORBIC ACID AND HYDROGEN PEROXIDE IN THE MANAGEMENT OF PATIENTS WITH CHIKUNGUNYA Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico. San Juan Bautista School of Medicine, School of Public Health, Caguas, Puerto Rico. c Memorial Hospital, Colorado Springs, Colorado. Corresponding author: Victor Marcial-Vega MD - 122 Eleanor Roosevelt, Interior, San Juan, Puerto Rico, 00918. E-mail: [email protected] a b Victor Marcial-Vega MDa* Idxian Gonzalez-Terronb Thomas Edward Levy MDc Authors acknowledge Solynet Baez, Alin Blanchet, Milagros Monge, RN, for their care of the patients in this study ABSTRACT Chikungunya is a viral illness characterized by severe joint pains, which may persist for months to years. There is no effective treatment for this disease. We treated 56 patients with moderate to severe persistent pains with a single infusion of ascorbic acid ranging from 25-50 grams and hydrogen peroxide (3 cc of a 3% solution) from July to October 2014. Patients were asked about their pain using the Verbal Numerical Rating Scale-11 immediately before and after treatment. The mean Pain Score before and after treatment was 8 and 2 respectively (60%) (p < 0.001); and 5 patients (9%) had a Pain Score of 0. The use of intravenous ascorbic acid and hydrogen peroxide resulted in a statistically significant reduction of pain in patients with moderate to severe pain from the Chikungunya virus immediately after treatment. Index words: intravenous, ascorbic, acid, hydrogen, peroxide, chikungunya INTRODUCTION Chikungunya is a viral illness characterized by an acute viral syndrome, typically lasting a few days to a week, followed by a chronic and extremely painful involvement of the joints which can last four months to 5 years in up to 33% of the patients. There is no cure for this disease and the only available treatment is symptomatic and supportive [1-6]. The Puerto Rico Department of Health has reported by November 2014 (10th Month of epidemic) 18,109 suspected cases and 3,385 confirmed cases (total of 21,494) with most cases reported during the month of July. No effective treatment has been reported for this condition [7]. The purpose of this work was to determine whether intravenous vitamin c and hydrogen peroxide were effective against the pain caused by the Chikungunya virus. During the beginning of the present epidemic of Chikungunya in Puerto Rico, we administered intravenous ascorbic acid and hydrogen peroxide to 56 patients complaining of severe pains due to their clinical diagnosis seen at Marcial Integrative Medical Center. This is a review of the results of the pain control in this population. All 22 patients with influenza who received intravenous 3 cc of 0.3% solution of hydrogen peroxide followed by 20 grams of ascorbic acid, including a suspected case of viral meningo-encephalitis, have responded dramatically within three hours with complete resolution of at least 50% of symptoms, and with no side effects[8]. The use of ascorbic acid as an effective antiviral has been documented as early as 1949 when 20 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico Frederick R. Klenner, MD, the first doctor to publish in peer reviewed journals, documented the ability of vitamin C to reliably cure many different acute infectious diseases and reliably neutralize any toxin treated, when sufficiently dosed and administered for a long enough period of time [9], the cure of 60 out of patients with polio within 4 days of ascorbic acid administration intramuscularly and orally [10], and the cure of advanced polio and its associated flaccid paralysis with ascorbic acid in 1951 [11]. The purpose of this review was to determine whether the administration of intravenous vitamin C and hydrogen peroxide is associated with a reduction and/or elimination of the chronic persistent pain due to Chikungunya immediately after treatment. MATERIALS AND METHOD Study design All patients came to the Marcial Integrative Medicine Center in San Juan during the 2014 Chikungunya epidemic in Puerto Rico. They all had the initial acute clinical picture, which included all or some of the following symptoms: fevers, chills, rash, weakness, malaise, fatigue, headaches. All patients had the most important clinical feature of persistent, moderate to severe joint pains that interfered significantly with activities of daily living. for each patient indicating that this was not a proven method of treatment for this condition and the possible side effects of it. We have observed from experience that the most common side effect is hypoglycemia that can be prevented in all patients by instructing them to eat before and during the infusion. Statistical Analysis We used the SPSS IBM 22 statistics package. The relation between Vitamin C + hydrogen peroxide and Pain score was plotted in two histograms and frequency tables. Comparison of parameters before and after the treatment was performed by Wilcoxon Signed Rank 2 sample test. A p value ≤ 0.001 was considered as statistically significant. They underwent an evaluation that included review of blood-work, history taking, pertinent physical exam and detailed determination of the pain in each joint using the Numeric Rating Scale-11. Each patient had a RESULTS calculated average Pain Score that was obtained adding all individual A total of 56 patients were available areas of pain and dividing among the number of affected sites. All patients were instructed to eat within two hours before the infusion and to snack liberally during the procedure. for analysis. They were 14 males (25%) and 42 females (75%). Patients at the 25 percentile of Pain Score, or who reported lesser intensity pain had a pre-treatment score of 7. This was reported as a 2 Post treatment for a reduction on the Pain Score of 71%. The median pre-treatment Pain Score for the group was 8 and this was reduced to 2 post-treatment for a reduction of 75%. The average Pain Score pre-treatment for at the 75 Percentile, or associated with more severe pain was 8 and to a reduction post-treatment of 4 for a reduction of the Pain Score of 60%. The range of reduction of the Pain Score was from 60-71% for the most and least affected patients respectively. Five of the patients (5/56) or 9% had a complete response to treatment or complete disappearance of pain after treatment. Three of the patients, or 5%, had no response to treatment (see Table 1). Effect of Vitamin C and hydrogen peroxide on Chikungunya patients Two infusions were injected in 56 patients: 100 cc Normal Saline with 3 cc of a 3% solution of hydrogen peroxide, 500 mg of magnesium chloride and 1000 micrograms of methylcobalamin followed by 500 cc of sterile water or lactated Ringer’s solution with 20 to 50 grams of ascorbic acid, B complex (thiamine 100 mg, riboflavin 2mg, pyridoxine 2mg, dexpanthenol 2mg, niacinamide 100 mg), 100 milligrams of thiamine and 100 milligrams of pyridoxine. All were slowly infused intravenously over a 2-4 hour period. Patients were then evaluated after the infusion to determine their overall Pain Score post-treatment using the Verbal Numerical Rating Scale-11. The evaluated variable was the pain intensity from a scale of 0-10 (0 meaning no pain and 10 the worst pain experienced). Forty-two (42/56=75%) of the patients received 25-30 grams of ascorbic acid. Seven, 6, 5 and 3 patients received 30 grams, 20 grams, 50 grams and 40 grams respectively. Written informed consent was obtained Table 1 Frequency Table of Pain Score before and after treatment. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 21 No patients discontinued their participation in the study because of adverse reactions to the treatment. No adverse side effects were observed in any patient. The scores of pain showed significant improvement (p < 0.001) after the treatment (see Figure 1). The results of the Wilcoxon Signed Rank test show that this treatment improves quality of life in patients with Chikungunya (see Figure 2). Figure 2: Results of Wilcoxon Signed Rank test. DISCUSSION Our protocol has shown that the use of intravenous hydrogen peroxide and ascorbic acid is safe and strongly associated with a more than 61% post-infusion reduction of pain in patients affected with Chikungunya virus related arthralgias. These results are consistent with previous in-vitro research which has shown that ascorbic acid inactivates the polio [21], herpes Figure 1A: Histogram of Pain Score before the treatment [22], vaccinia [24], tobacco mosaic [25], bacteriophage [26-29], entero [30], influenza [31] and rabies [32] viruses. They are also consistent with previous clinical research showing ascorbic acid can resolve polio [9-11,33,34], its associated flaccid paralysis [10], acute hepatitis [35-38], viral encephalitis [39-42], measles (simple and complicated) [43], mumps (simple and complicated) [44], chickenpox [45], influenza [46] and rabies in guinea pigs. Since there is no effective treatment for severe debilitating Chikungunya related pains [47], and because there is an epidemic in Puerto Rico at the present moment, intravenous vitamin C and hydrogen peroxide may be considered as a safe and viable alternative to manage these patients effectively. Randomized controlled studies need to be done to further explore this question. We are in the process of reviewing our clinical data to determine the longer range apparent effect of Figure 2B: Histogram of Pain Score after the treatment. this modality on Pain Scores 22 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico and to determine if more infusions and/or higher doses will be more effective. REFERENCES 1. Pialoux G, Gaüzère BA, Jauréguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis. 2007;7:319–27 2. Fourie ED, Morrison JG. Rheumatoid arthritic syndrome after chikungunya fever. S Afr Med J. 1979; 56:130–2. 3. Kennedy AC, Fleming J, Solomon L. Chikungunya viral arthropathy: A clinical description. J Rheumatol. 1980; 7:231–6. 4. Brighton SW, Prozesky OW, de la Harpe AL. Chikungunya virus infection. A retrospective study of 107 cases. S Afr Med J. 1983; 63:313–5. 5. Sam IC, AbuBakar S. Chikungunya virus infection. Med J Malaysia 2006; 61:264-9. 6. Mohan A. Chikungunya fever: clinical presentation and principles of management. Indian J Med Res 2006 (in press). 7. Puerto Rico Department of Health, Weekly Report of (October 22-28, 2014) of Chikungunya Epidemic (Week 43) 8. Marcial-Vega, VA, 2013, Presented at the XIIth Health Symposium of the Ana G Mendez University System, July 19, 2013, Marriott Hotel, San Juan, Puerto Rico, Integrative Medicine: Its Role in The Management of Cancer, Autism, Degenerative Neurological Conditions, Influenza and other Chronic Conditions: A New Paradigm In Medicine, (In Press) 9. Frederick R. Klenner, M.D., F.C.C.P, Journal of Applied Nutrition Vol. 23, No’s 3 & 4, Winter ,1971, 1, Observations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range Of A Vitamin In Human Pathology Frederick R. Klenner, M.D., F.C.C.P. 10. Klenner, F.R., The Treatment of Poliomyelitis and Other Viral Diseases with Vitamin C, Southern Medicine and Surgery, July1949, 209 11. Klenner, F.R. Massive Doses of Vitamin C and the Virus Diseases, Journal of Southern Medicine and Surgery, April 1951, Vol.113, No.4, pp.101-107 12. Wilson MK, Baguley BC, Wall C, Jameson MB, Findlay MP. Review of high-dose intravenous vitamin C as ananticancer agent. Asia Pac J Clin Oncol. 2014 Mar; 10(1):22-37. doi: 10.1111/ ajco.12173. Review. PubMed PMID: 24571058. 13. Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 2014 Feb 5; 6(222):222ra18. 14. Parrow NL, Leshin JA, Levine M. Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics. Antioxid Redox Signal. 2013 Dec 10; 19(17):2141-56. doi: 10.1089/ ars.2013.5372. Epub 2013 Jun 19. Review. PubMed PMID: 23621620; 15. Efficacy of improved hydrogen peroxide against important healthcare-associated pathogens. Rutala WA, Gergen MF, Weber DJ. Infect Control Hosp Epidemi ol. 2012 Nov; 33(11):1159-61. 16. [Hydrogen peroxide treatment for vaginal trichomoniasis. 1955]. González Ramos M. Ginecol Obstet Mex. 2010 Jun; 78(6):329-31. 17. Marcial-Vega, VA, 2013, Presented at the XIIth Health Symposium of the Ana G Mendez University System, July 19, 2013, Marriott Hotel, San Juan, Puerto Rico, Integrative Medicine: It’s Role in The Management of Cancer, Autism, Degenerative Neurological Conditions, Influenza and other Chronic Conditions: A New Paradigm In Medicine. (Submitted for publication) 18. Marcial-Vega, VA, 2014, Integrative Medicine in the Management of Breast and other Cancers, Presented at the First Multidisciplinary Breast Symposium of the Sociedad Puertorriqueña de Senología, Aug.23, 2014, Embassy Suites Hotel, Carolina, Puerto Rico. 19.A naturopathic cause of portal venous gas embolism. Hydrogenperoxide ingestion causing significant portal venous gas and stomach wall thickening.Fok MC, Zwirewich C, Salh BS. Gastroenterology. 2013 Mar; 144(3):509, 658-9. 20. Shallenberger, Frank, M.D, President of the American Academy of Ozonetherapy, Nov. 2014, Personal Communication 21. Jungeblut, CW, Inactivation of Poliomyelitis virus in vitro by crystalline vitamin C (ascorbic acid): J Exp Med. 1935 Sep 30; 62(4):517-19. 22. Holden; Molloy: Further experiments on the inactivation of herpes virus by vitamin C (l-ascorbic acid). Journal of Immunology 33:251-257, 1937 23. Kligler and Bernkopf: Inactivation of vaccinia virus by ascorbic acid and glutathione. Nature 139:965-966, 1937, 24. Turner G (1964) Inactivation of vaccinia virus by ascorbic acid. J Gen Microbiol 35:75-80 25. Lojkin M (1936) A study of ascorbic acid as an inactivating agent of tobacco mosaic virus. Contr B o y c e Thompson Inst Pl Res 8:455 26. Lominski (1936) Inactivation du BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 23 bacteriophage par l’acide delta containing single-stranded DNA by ascorbic acid. J Nutr Sci Viascorbique. C r Seanc Soc Biol 122:176 27. Murata, A, : Mechanism of inactivation of bacteriophage deltaA containing single-stranded DNA by ascorbic acid. J Nutr Sci Vitaminol (Tokyo). 1975;21(4):261-9. 28. Morgan, AR (1976) The mechanism of DNA strand breakage by vitamin C and superoxide and the protective roles of catalase and superoxide dismutase. Nucleic Acids Res. 1976 May;3(5):1139-49. 29. Richter, HE (1982) Rapid inactivation of bacteriophage T7 by ascorbic acid is repairable. Biochim Biophys Acta. 1982 Apr 26;697(1):25-30. 30. Salo, RJ (1978) Inactivation of enteroviruses by ascorbic acid and sodium bisulfite. Appl Environ Microbiol. 1978 Jul;36(1):68-75. 31. Cheng, LL (2012) [An in vitro study on the pharmacological ascorbate treatment of influenza virus]. [Article in Chinese] Zhonghua Jie He He Hu Xi Za Zhi. 2012 Jul;35(7):520-3. 32. Amato G (1937) Azione dell’acido ascorbico sul virus fisso della rabia e sulla tossina tetanica. Giornale di Batteriologia, Virologia et Immunologia (Torino) 19:843-847 33. Greer, 1955, Med Times. 1955 Nov; 83(11):1160-1. Vitamin C in acute poliomyelitis. 34. Baur, H, Poliomyelitis therapy with ascorbic acid: Helv Med Acta., 1952 Oct; 19(4-5):470-4. 35. Dalton, WL, Massive Doses of Vitamin C in the treatment of Viral Diseases: J Indiana State Med Assoc., 1962 Aug; 55:1151-4. 36. Cathcart, 1981 [7321921] (Reported that he never had a single case of acute viral hepatitis fail to respond to properly dosed IVC, and that he never had a VC-treated hepatitis patient subsequently develop chronic hepatitis) 37. Orens, S, Hepatitis B—A ten Day “Cure”. A personal History: Bull Phila Cty Dent Socc., 1983 Mar; 48(6):4-5. 38. (1974) Klenner FR. Significance of high daily intake of ascorbic acid in preventive medicine. Journal of the International Academy of Preventive Medicine 1:45-69 Vitamin C repeatedly cured cases of viral encephalitis, many presenting in coma: 39. (July 1949) Klenner FR. The treatment of poliomyelitis and other virus diseases with vitamin C. Southern Medicine & Surgery 111:209-214 [18147027] 40. (April 1951) Klenner FR. Massive doses of vitamin C and the virus diseases. Southern Medicine & Surgery 103:101-107 [14855098] 41. (1953) Klenner FR. Observations of the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology. Journal of Applied Nutrition 23:61-88 43. Klenner, FR : The Treatment of Poliomyelitis and Other Virus Diseases With Vitamin C, South Med Surg. 1949 Jul;111(7):209-14. 44. Herpes infections, acute (chickenpox) Dainow, 1943 68 197; Zureick, 1950 [14908970]; (1974) Klenner 1: 45 45. Influenza (flu, including H1N1 swine flu); 60 Minutes report, New Zealand, 2010); see www.peakenergy.com 46. Banic, S, ; Prevention of Rabies By Vitamin C, Nature. 1975 Nov 13;258(5531):153-4. 47. Centers for Disease Control and Prevention: Chikungunya virus http://www.cdc.gov/chikungunya/symptoms/index.html Ehr Timeline RESUMEN Chikungunya es una enfermedad viral caracterizada por dolor severo en el área de las coyunturas que puede persistir por meses o años. Manejamos56 pacientes con dolor moderado-severo persistente con una infusión sencilla de ácido ascórbico entre rangos de 25-50 gramos y peróxido de hidrógeno (3 cc de una solución de 3%) entre Julio a Octubre del 2014. A los pacientes se les preguntó acerca de su dolor utilizando la Escala de Valoración Numérica Verbal-11 inmediatamente antes y después del tratamiento. La Puntuación de Dolor promedio antes y después del tratamiento fue 8 y 2 respectivamente (60%) (p < 0.001) y en 5 pacientes (9%) la Puntuación de Dolor bajó a 0. El uso de ácido ascórbico y peróxido de hidrógeno intravenoso está asociado con una reducción estadísticamente significativa de dolor en pacientes con dolor moderado a severo debido al virus del Chikungunya inmediatamente después de la infusión. QUALITY OF LIFE IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AT THE GENERAL ENDOCRINOLOGY CLINICS OF THE UNIVERSITY HOSPITAL OF PUERTO RICO University of Puerto Rico Medical Sciences Campus, Department of Medicine, Endocrinology, Diabetes and Metabolism Section, San Juan, Puerto Rico. b Puerto Rico Clinical and Translational Research Consortium. c University of Puerto Rico Medical Sciences Campus, Department of Internal Medicine, San Juan, Puerto Rico. d University of Puerto Rico Medical Sciences Campus, Department of Medicine, Hematology and Oncology Section, San Juan, Puerto Rico. *Corresponding author: Margarita Ramírez-Vick, MD- PO Box 365067 San Juan, Puerto Rico 00936-5067. Email: [email protected] Presented during the poster session of the 83rd Annual Meeting of the American Thyroid Association held in San Juan, Puerto Rico. a ABSTRACT Differentiated thyroid cancer (DTC) can compromise the quality of life of patients. Our purpose is to investigate if the quality of life, in a cohort of patients in Puerto Rico, is affected by the diagnosis and/or treatment modalities received for DTC. Methods: This is a cross-sectional study of 75 subjects with DTC. A Spanish version of the University Of Washington Quality Of Life Questionnaire was used, including multiple aspects of physical and social functioning. Descriptive and bivariate analysis between domain scores and variables of interest were performed. Results: 82.7% of the patients reported that their health was the same or better than it was before treatment. The mean composite score obtained was 82.3, reflecting an overall little effect on quality of life. Patients diagnosed with DTC at an age of ≥45 years reported a significantly better score on the pain domain when compared with those diagnosed earlier (p < 0.05). Patient who received >150 mCi of radioiodine had a tendency towards a worse score on the same domain (p=0.05). Conclusions: Our cohort reported an overall minimal effect on the quality of life of patients with DTC. Future treatment strategies should include periodic quality of life evaluations, in order to tailor therapy in this growing population. Index words: quality, life, differentiated, thyroid, cancer, University, Hospital, Puerto Rico INTRODUCTION Thyroid carcinoma is the most common malignancy of the endocrine system [1-4]. Thyroid cancer can be classified according to its histological features [4], with the most common type being the differentiated thyroid carcinoma (DTC). Arising from thyroid follicular epithelial cells, DTC includes papillary carcinoma, follicular carcinoma, and the less frequently found Hurthle cell carcinoma. It is more common in females and is often asymptomatic. The age of diagnosis is an important prognostic factor; thyroid cancer in older persons (more than 45 years of age 24 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico Mónica A. Vega-Vázquez MDa Loida González-Rodríguez MDa Eduardo J. Santiago-Rodríguez MPHb Anette Garcés-Domínguez MD0 Lee-Ming Shum MDc Maribel Tirado-Gómez MDd Margarita Ramírez-Vick MDa* is associated with a worse prognosis [4,5]. Other important risk factors include a history of head and neck irradiation, male gender, large nodule size, focal tumor fixation or invasion to lymph node and the presence of metastasis, among others [4,5]. The incidence of thyroid cancer is rising worldwide [6]. Within the United States, the incidence of thyroid cancer has increased from 3.6 to 8.7 per 100,000 from 1973 to 2002, representing a 2.4-fold increase [7]. Further studies found that this was mostly due to the diagnosis of papillary thyroid cancer, although its mortality has remained stable during this period [7]. An estimate reported by the American Cancer Society in 2014 resulted in 62,980 new cases of thyroid cancer in the United States [8]. The explanation for this increasing trend is still under investigation; however it is thought that it could be related to new diagnostic modalities, such as the introduction of ultrasound and fine needle aspiration of thyroid gland [7,9]. Data gathered from the Central Cancer Registry of Puerto Rico revealed that the overall incidence rate for thyroid cancer in Puerto Rico has also increased from 3.0 to 7.0 per 100,000 population, with an annual percentage change of 5.3% during BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 25 years 1985 to 2004 [10]. neck cancer settings [23,24]. The treatment for DTC mainly consists of surgical management, in some cases it is followed by the use of radioactive iodine (I131 ) [11] and lifelong supplementation with levothyroxine at a dose to suppress thyrotropin levels [12-16]. Although treatment for thyroid cancer is generally well tolerated, it can often result in multiple short and long term complications. Complications reported with thyroidectomy mainly include physical or functional impairments, including voice and discomfort during swallowing and recurrent laryngeal nerve injury [17]. Radioactive iodine ablation therapy has also been associated with acute and long-term complications within thyroid cancer patients. Acute risks associated with radioactive iodine include nausea, vomiting, ageusia, salivary swelling and pain [18]. Long-term complications include recurrent sialoadenitis, xerostomia, dental caries, pulmonary fibrosis, nasolacrimal outflow obstruction and second primary malignancy [18]. Given the repercussions that the diagnosis and treatment of thyroid carcinoma may have in our patients, and its worldwide increase in prevalence, several researchers have taken the task to study the impact on the quality of life in different populations with variable outcomes. Although DTC generally has a favorable prognosis with long-term survival rate of 90% [5,20,25], the primary goal of our study is to investigate, through the UW-QOL questionnaire, if the quality of life of patients with the diagnosis of DTC is affected in a cohort of patients within Puerto Rico. To our knowledge this is the first study in the Puerto Rican population to assess the quality of life of patients with DTC. Quality of life questionnaires are useful tools developed to evaluate patient well-being, mainly throughout the individual’s own perception of life [19,20]. Among the tools developed for quality of life assessment in patients with cancer, the University of Washington Quality of Life (UW-QOL) questionnaire is a validated, accurate and internationally accepted survey instrument [21]. The UW-QOL was first described in 1993 by Hasan and Weymuller [22] and was specifically designed to assess quality of life in patients with head and neck malignancy. The questionnaire provides a simple measurement of health-related quality of life and it has been shown to be suitable for use in a wide variety of head and Each patient underwent a face-toface interview in order to obtain sociodemographic information, past and present medical history. Other data including weight, height, body mass index, thyroid stimulating hormone (TSH) level, cancer histopathology type, tumor size, time of diagnosis, remission state, and treatment received for cancer were obtained by reviewing the medical records. Tumor staging at the time of cancer diagnosis, was classified according to American Joint Cancer Committee (AJCC) TNM system [26]. PATIENTS AND METHODS A cross-sectional study of 75 consenting subjects attending the General Endocrinology Clinics of the University Hospital of Puerto Rico was performed. Subjects meeting the inclusion criteria were invited to participate on our study after their follow-up medical evaluation. In order to participate, subjects must have met the following inclusion criteria: 1) should be 21 years or older; and 2) must have been previously diagnosed with differentiated thyroid cancer. Subjects were excluded from the study if: 1) were unable to complete the questionnaire, and 2) if they had history of other types of head and neck cancer. The Institutional Review Board of the University of Puerto Rico, Medical Sciences Campus approved this study. After data collection, subjects were asked to complete a Spanish version of the UW-QOL questionnaire [27]. The first part of the UW-QOL 26 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico questionnaire consists of 12 multiple choice questions, designed to address the following domains: pain, appearance, activity, recreation, chewing, swallowing, speech, shoulder, taste, saliva, humor and anxiety [3, 21,23]. Scores for these questions can range from 0 to 100, with 100 indicating the best level of function. Scores for the questionnaire were done according to the UW-QOL questionnaire guidance; higher scores reflect a better QOL and higher functioning. An overall composite score was calculated using the mean of all domains included in the questionnaire. Two additional subscale scores were computed, which included the physical function and the social function subscale. The physical subscale includes the average scores for the domains of chewing, swallowing, speech, taste, saliva, and appearance; and the social-emotional function subscale includes the average score for anxiety, mood, pain, activity, recreation and shoulder domains. As a general agreement for scoring, from 75-100 will be graded as having little effect in quality of life, from 50-74 having a relative effect on quality of life and less than 50 points as having an important effect on quality of life [21]. The UW-QOL questionnaire also includes three additional questions concerning patients’ perception of global health-related quality of life. The statistical analysis was performed using the statistical package Stata 12.1 version. A descriptive analysis of the demographic, clinical and treatment variables, as well as the quality of life scores was performed. Categorical variables were reported as frequencies and percentages, and continuous variables were reported as mean ± standard deviation. To assess the relationship between each of the twelve domains on the UW-QOL questionnaire and independent variables, such as age of diagnosis, sex, type of surgery, radioiodine treatment and tumor size, the Mann-Whitney or Kruskal-Wallis tests were used. Results were considered significant at p values below 0.05. RESULTS A total of 75 subjects with differentiated thyroid cancer were recruited for the study cohort. The mean age of the group was 51.5 ± 13.3 years (range, 24-87 years) and 84% were female. Forty-eight percent of patients were diagnosed with cancer at an age younger than 45 years old and 52% were diagnosed at an age older than 45 years. The most frequently encountered histopathology type of thyroid cancer was the papillary carcinoma, seen in 96% of the subjects; followed by follicular thyroid cancer, reported in 2.7% of the study population. At the time of diagnosis, 70.7% of the subjects were classified as Stage I, 6.7 % as Stage II, 12% as Stage III and 5.3% as Stage IV. As documented in the medical records, the size of the tumor was reported as less than 1 cm in 25 subjects (37.3%), between 1 and 2 cm in 25 subjects (37.3%) and larger than 2 cm in 17 individuals (25.4%). Table 1 summarizes the demographics and characteristics of our study population. Most of our study subjects underwent total thyroidectomy (98.7%). Adjuvant lymph node dissection was done only in twenty-four subjects (32%). Sixty-eight (90.7%) patients received levothyroxine for TSH suppression therapy. Sixty-six (88%) subjects in the cohort received radioactive iodine treatment for adjuvant remnant ablation therapy. Patients receiving radioactive therapy were then divided into low-dose (150 mCi or less, n=40) and high-dose (more than 150 mCi, n= 14) of the total therapeutic dose of radioiodine received, defined as the summation of all doses greater than 30 mCi. The elapsed period of time since the radioiodine therapy was also Table 1: Demographics and Clinical classified into recent exposure in the study (12 months or less, n= 15) and long-time exposure (more than 12 associated variables (see Table 3), months, n= 51). Table 2 summariz- the age of diagnosis had an effect es treatment-related characteris- on the pain domain score. Subtics of our cohort. jects diagnosed younger (less than 45 years old) showed significantly In the evaluation of the relationship worse scores on the domain than between the quality of life domains their counterparts (p=0.02). Meanwith clinical profile and treatment while patients who received high Profile of the 75 subjects included therapeutic radioiodine doses had a tendency toward a worse score on the same domain (p=0.05). Of the subjects diagnosed with DTC at an age younger than 45 years, 36.1% underwent treatment with radioiodine at a cumulative dose higher than 150 mCi, while 2.6% BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 27 of those diagnosed at 45 years of age or older received a cumulative radioiodine doses higher than150 mCi (Fisher’s exact test: p<0.001); which could account for the unexpectedly lower scores seen in the pain domain for the patients diagnosed younger. In regard to the relationship among the other quality of life domains with clinical profile and treatment variables, no other significant association was found. Regarding the UW-QOL question on overall health-related quality of life, 82.7% of the patients reported that their health was the same or better than it was before treatment. The calculated UW-QOL mean composite score was 82.3 ± 15.1. For the physical subscale the mean score was 87.9 ± 14.1. The social-emotional subscale mean score was 77.0 ± 19.4. (see Figure 1). These computed results are all associated with an overall little effect on the cohort quality of life. DISCUSSION The purpose of this study was to evaluate quality of life in a cohort of DTC patients in Puerto Rico. We found that the overall quality of life score, assessed by the UWQOL questionnaire, was minimally affected after the diagnosis and treatment for differentiated thyroid cancer in our cohort; although we did found a slightly lower overall composite score than the one reported by Almeida et al [21]. In our study, patients who were diagnosed at an age younger than 45 years showed significantly worse scores on the pain domain than their counterparts. Meanwhile patients who received a cumulative therapeutic radioiodine dose of more than 150 mCi had a tendency toward a worse score on the same domain. In our cohort, the patients who received higher cumulative radioiodine doses were those diagnosed before 45 years of age, which could account for the unexpectedly lower scores seen in the pain domain of the subjects diagnosed younger. In general, patients with DTC usually received radioiodine therapy for remnant or Table 3: Bivariate analysis of the relationship between quality of life domains with clinical profile and treatment associated variables Table 2: Differentiated thyroid cancer treatment-related characteristics of the 75 subjects included in the study adjuvant ablation of residual tissue. However, appropriate patient selection and therapeutic doses used for radioiodine therapy are still uncertain and recently have been under debate. Especially in the low risk for recurrence population 28 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico and because higher cumulative doses of RAI have been associated to acute and long term complications, the minimum effective dose, if any, should be given. We did not observe the significant reduction in quality of life in the recreation domain described by Dingle et.al, among patients exposed to higher cumulative doses of radioiodine [3]. Nor did we observe the effect of higher cumulative radioiodine doses with worse scores on the domains of swallowing, chewing, speech, shoulder, taste or anxiety reported by Almeida et.al [21]. In our study population, we did not find any association between gender, tumor size, type of surgery, or time since radioiodine therapy with the twelve domains scores included in the UW-QOL questionnaire. cross-sectional design, thus no baseline questionnaire before treatment or during follow up period was obtained. Second, the questionnaire was given in a faceto-face setting which could have introduced some information bias, as patients’ answers might be exThere are some limitations in aggerated in an attempt to seek our study. First, our study had a more physician attention at the BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 29 Figure 1: Composite score, physical and social-emotional subscales. The composite score is the average score of the twelve domains included in the University of Washington Quality of Life Questionnaire. The physical subscale is the average of the domains of chewing, swallowing, speech, taste, saliva, and appearance; and the social subscale includes the average scores for anxiety, mood, pain, activity, recreation and shoulder domains. clinic. Third, some clinical data was obtained from medical chart, which are not designed for research purposes and may have had missing information. Fourth, TSH levels and thyroglobulin panel were not measured the same day that the questionnaire was administered, thus we were unable to make associations between quality of life domains with TSH levels or thyroglobulin presence. Given the low mortality associated to thyroid cancer, health care providers tend to regard differentiated thyroid cancer somewhat indifferently when compared with other types of cancer [1]. However a systematic review from 1997 to 2010 done by Husson et.al has shown that patients with differentiated thyroid cancer can have a similar or slightly worse health related quality of life compared with the normative population [6]. Thyroid cancer survivors have reported some specific medical problems after cancer treatment and follow-up tests, which can have a direct negative impact on their current and long-term quality of life [6]. Although the treatment of differentiated thyroid cancer is generally associated with a good prognosis, some studies have shown that quality of life domains can be affected by treatment and its side effects. Future treatment strategies should include periodic quality of life assessment and evaluation of long-term side effect of therapies, in order to tailor therapy in this growing population of patients. The multidisciplinary approach in a cancer patient 30 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico should not only target cancer remission and/or increasing patient survival, but should also attempt to preserve or provide an adequate quality of life for these patients and their families. It should be mandatory to investigate potential factors that may affect quality of life in thyroid cancer patients, in order to develop tools that may help improve their quality of life in the nearby future within this population. REFERENCES [1] Tagay S, Herpertz S, Langkafel M, Erim Y, Freudenberg L, Schopper N, Bockisch A, Senf W, Gorges R 2005 Health-related quality of life, anxiety and depression in thyroid cancer patients under short-term hypothyroidism and TSH suppressive levothyroxine treatment. Eur J Endocrinol 153 (6):755-763. [2] Dagan T, Bedrin L, Horowitz Z, Chaushu G, Wolf M, Kronenberg J, Talmi YP 2004 Quality of life of well-differentiated thyroid carcinoma patients. J Laryngol Otol 118(7):537-542. [3] Dingle IS, Mishoe AE, Nguyen SA, Overton LJ, Gillespie MB 2013 Salivary morbidity and quality of life following radioactive iodine for well-differentiated thyroid cancer. Otolaryngol Head Neck Surgery 148(5): 746-752. [4] Larry-Jameson J, Weetman AP 2010 Disorders of the Thyroid Gland. In: Larry-Jameson J (eds) Harrison’s Endocrinology, 2nd edition. The McGraw-Hill Companies, China pp 91-98. [5] Schlumberger MJ, Torlontano M. 2000 Papillary and follicular thyroid carcinoma. Baillieres Best Pract Res Clin Enocrinol Metab 14(4): 601-613. [6] Husson O, Haak H, Oranje W, Mols F, Reemst P, Van de Poll-Franse L 2011 Health-related quality of life among thyroid cancer survivors: a systematic review. Clinical Endocrinology 75:544-554. [7] Davies L, Welch HG 2006 Increasing Incidence of Thyroid Cancer in the United States, 1973-2002. JAMA 295:21642167. [8] American Cancer Society, Inc. 2014 Thyroid cancer Available at http://www. cancer.org/Cancer/ThyroidCancer/DetailedGuide/thyroid-cancer-key-statistics. Accessed April 6, 2014. [9] Kent WDT, Hall SF, Isotalo PA, Houlden RL, George RL, Groome PA 2007 Increased incidence of differentiated thyroid cancer and detection of subclinical disease. CMAJ 177 (11):1357-136. [10] Ramirez-Vick M, Nieves-Rodriguez M, Lugaro-Gómez A, Perez-Irizarry J 2011 Increasing Incidence of Thyroid Cancer in Puerto Rico, 1985-2004. PRHSJ 30 (3) 109-115. [11] Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJG, Tennvall J, Bombardieri E 2008 Guidelines for Radioiodine Therapy of Differentiated Thyroid Cancer. Eur J Nucl Med Mol Imaging 35:1941-1959. [12] Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzarerri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM 2006 The American Thyroid Association Guideline Taskforce. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16:109-142. [13] Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzarerri EL, McIver B, Pacini F, Schlumberger M, Sherman, SI, Steward DL, Tuttle RM 2009 The American Thyroid Association Guideline Taskforce. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167-1214. [14] Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JWA, Wiersinga W and the European Thyroid Cancer Taskforce 2006 European consensus for the management of patients with differentiated thyroid carcionma of the follicular epithelium. Eur J Endocrinol 154: 787-803. [15] Cobin RH, Gharib H, Bergman DA, Clark OH, Cooper DS, Daniels GH, Dickey RA, Duick DS, Garber JR, Hay ID, Kukora JS, Lando HM, Schorr AB, Zeiger MA, Thyroid Carcinoma Task Force 2001 AACE/ AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma. Endocr Pract 7(3):202-220. [16] Paz-Filho G, Graf H, Sterian-Ward L 2013 Comparative analysis of the new guidelines and consensues for the manangement of hypothyroidism, thyroid nodules, and differentiated thyroid cancer. Arq Bras Endocrinol Metab 57(4): 233-239. [17] Ryu J, Ryu YM, Jung YS, Kim SJ, Lee YJ, Lee EK, Kim SK, Kim TS, Kim TH, Lee CY, Park SY, Chung KW 2013 Extent of thyroidectoym affects vocal and throat functions: a prospective observational study of lobectomy versus total thyroidectomy. Surgery 154(3):611-620. [18] Lee SL 2010 Complications of RAI treatment of thyroid carcinoma. J Natl Compr Canc Netw 8(11): 1277-1286. [19] Crevenna R, Zettinig G, Keilani M, Posch M, Schmidinger M, Pirich C, Nuhr M, Wolzt M, Quittan M, Fialka-Moser V, Dudczak R 2003 Quality of life in patients with non-metastatic differentiated thyroid cancer under thyroxine supplementation therapy. Support Care Cancer 11(9):597603. [20] Giusti M, Melle G, Fenocchio M, Mortara L, Cecoli F, Caorsi V, Ferone D, Minuto F, Rasore E 2011 Five-year longitudinal evaluation of quality of life in a cohort of patients with differentiated thyroid cancer. J Zhejiang Univ Sci B 12(3):163173. [21] Almeida JP, Vartanian JG, Kowalski LP 2009 Clinical predictors of quality of life in patients with initial differentiated thyroid cancers. Arch Otolaryngol Head Neck Surg 135 (4):342–346. [22] Hassan SJ, Weymuller EA 1993 Assessment of quality of life in head and neck cancer patients. Head Neck 15 (6): 485-496. [23] Laraway DC, Rogers SN 2012 A structured review of journal articles reporting outcomes using the University of Washington Quality of Life Scale. Br J Oral Maxillofac Surg 50: 122-131. [24] Rogers SN, Gwanne S, Lowe D, Humphris G, Yueh B, Weymuller EA Jr 2002 The addition of mood and anxiety domains to the University of Washington quality of life scale. Head Neck 24(6): 521-529. [25] Tala H, Tuttle RM 2010 Contemporary post surgical management of differentiated thyroid carcinoma. Clin Oncol 22(6):419-429. [26] Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A 2010 AJCC Cancer Staging Manual, 7th ed. Springer-Verlag, New York. [27] Nazar G, Garmendia ML, Royer M, McDowell JA, Weymuller EA Jr, Yueh B 2010 Spanish validation of the University of Washington Quality of Life questionnaire for head and neck cancer patients. Otolaryngol Head Neck Surg 143(6):801807. ACKNOWLEDGMENTS This publication was made possible by grants from the National Center for Research Resources (U54 RR 026139) and the National Institute on Minority Health and Health Disparities (8U54 MD 007587-03), a component of the National Institutes of Health. RESUMEN El propósito de nuestro estudio es investigar si la calidad de vida, de un grupo de pacientes en Puerto Rico, se ve afectada por el diagnóstico y/o modalidades de tratamiento recibido luego del diagnóstico de cáncer diferenciado de tiroide. Métodos: Se trata de un estudio transversal de 75 sujetos con cáncer diferenciado de tiroide, donde se utilizó una versión en español del cuestionario de calidad de vida de la Universidad de Washington. Este instrumento incluye múltiples aspectos del funcionamiento físico y social que impactan la calidad de vida de los sujetos. Se realizó un análisis descriptivo y bivariado de las puntuaciones obtenidas en el cuestionario y las variables de interés relacionadas al cáncer diferenciado de tiroide. Resultado: 82.7% de los pacientes informaron de que su salud era igual o mejor de lo que era antes del diagnostico y tratamiento del cáncer diferenciado de tiroide. El promedio de la puntuación compuesta obtenida en el cuestionario fue de 82.3, lo que refleja un efecto mínimo sobre la calidad de vida en estos pacientes. Sin embargo, los sujetos diagnosticados con cáncer diferenciado de tiroide a una edad de ≥45 años reportaron una puntuación significativamente mejor en el dominio del dolor en comparación con los diagnosticados a edades mas tempranas (p < 0.05). Los paciente que recibieron > 150 mCi de yodo radiactivo mostraron una tendencia hacia una peor puntuación en la misma categoría de dolor (p= 0.05). Conclusiones: Nuestro grupo de pacientes con cáncer diferenciado de tiroide reportaron en general un efecto mínimo en su calidad de vida. Sin embargo, futuras intervenciones de tratamiento deben incluir instrumentos que de forma periódica evalúen la calidad de vida de estos pacientes. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 31 CLINICAL AND RADIOLOGICAL INDICATORS OF SEVERITY IN PATIENTS WITH ACUTE PANCREATITIS Bella Vista Hospital Family Medicine Program, Mayaguez, Puerto Rico. *Corresponding author: Beatriz McMullen MD – 1201 NW 16th Street, Miami, Florida, USA 33125. E-mail: [email protected] a Jorge Álvarez MDa Pablo Castro MDa Maria Fernández MDa Beatriz McMullen MDa* Carmen Rodríguez MDa Jorge Vera MDa ABSTRACT The purpose of this study was to estimate the degree of association between clinical (Ranson criteria) and radiological variables (Abdominal CT scan) with degree of severity in patients with a diagnosis of acute pancreatitis. Method: All patients discharged with the diagnosis of acute pancreatitis from January 1, 2010 through December 31, 2012 in a community hospital were selected (N = 174). The following variables were studied: sex; age; weight; height; admission and discharge dates; presence of several chronic conditions; laboratory results included in Ranson criteria; abdominal CT category; outcome, including fatality, surgery, and other complications. Analysis included descriptive statistics and Risk-Ratios for complications for different groups of subjects, using clinical and radiological criteria. Results: The incidence rate of complications, including fatality, surgery and organ failure was 36.2%. Factors that showed significant associations with the risk of complication on crude analysis were gallbladder disease with a RR = 1.78 (95% CI: 1.22, 2.60) and abnormal abdominal CT with a RR = 1.85 (95% CI: 1.11, 3.07). With multivariate analysis, gallbladder disease, abnormal abdominal CT, and presence of 3 or more Ranson’s criteria showed increased risk for complications, but the results did not reach statistical significance. Discussion: The factors that seemed to be associated with increased rate of complications in subjects with acute pancreatitis were gallbladder disease, abnormal abdominal CT, and 3 or more Ranson’s criteria. The results did not show statistical significance probably because of low statistical power of the study. Index words: clinical, radiological, indicators, severity, acute, pancreatitis INTRODUCTION emboli, hypoperfusion, vasculitis), accounts for a significant percentcystic fibrosis, and Reye’s syn- age of admissions to hospitals. At Acute pancreatitis is an inflamma- drome. (4). Bella Vista Hospital between 2010 tion of the pancreas that usually and 2012, there were 24,768 hosoccurs as a result of gallstones or This is a disease capable of wide pitalized patients; acute pancreatialcohol abuse. These are the two clinical variation, ranging from mild tis was responsible for 1% of those most common causes of acute pan- discomfort to severe pain and pros- admissions. creatitis, accounting for 60-80% of tration. Moreover, the inflammatocases. Other causes include blunt ry process may remain localized in There are currently controversies trauma to the abdomen, iatrogenic the pancreas, spread to regional regarding which factors or criteria trauma (postoperative trauma or tissues, or even involve remote or- are better predictors of a poor outprocedures like endoscopic retro- gan systems. (5) The majority of come from this disease. The most grade cholangiopancreatography), cases of acute pancreatitis do not common method of assessing sehypertriglyceridemia, hypercalce- cause complications nonetheless verity and prognosis of patients mia, drugs such as rosuvastatin a small percentage may develop with acute pancreatitis is the use of and sitaglipin (1, 2), infections such an illness with complications that clinical criteria that were described as mumps or leptospirosis (3), require intensive care. In all cas- by Ranson as far back as 1974 (6). congenital anomalies (pancreas es it is essential to determine the These clinical criteria are used to divisum, choledochocele), ampul- cause and if at all possible to try to calculate a severity score based lary or pancreatic tumors, vascular prevent acute pancreatitis and its on factors identified at admisabnormalities (atherosclerotic complications. Acute pancreatitis sion (age, white blood cell count, BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 33 blood glucose, AST, LDH) and within 48 hours of admission (serum calcium, hematocrit change, oxygen, BUN, base deficit, and fluid sequestration). More recently, Balthazar described a system of classifying the severity of acute pancreatitis, based in findings of an abdominal CT scan. According to this system: Class A = normal pancreas; Class B = enlargement of pancreas; Class C = inflammatory changes in pancreas; Class D = ill-defined single fluid collection; Class E = two or more poorly defined fluid collections. (7) The objective of this study was to describe the characteristics of patients admitted with acute pancreatitis in a community hospital and to estimate the degree of association between clinical (Ranson criteria) and radiological variables (Abdominal CT scan) with prognosis in patients with a diagnosis of acute pancreatitis. METHOD This was a retrospective cohort study conducted in a community hospital located in Mayagüez, Puerto Rico. The investigators obtained all necessary authorizations from the hospital’s administration and from Ponce School of Medicine and Health Sciences’ Institutional Review Board (IRB 130312-II). All patients discharged with the diagnosis of acute pancreatitis from January 1, 2010 through December 31, 2012 in the mentioned hospital were selected (N = 174). Investigators systematically reviewed the hospital records of these subjects and extracted data including the following variables: sex; age; weight; height; admission and discharge dates; presence of diabetes mellitus, arterial hypertension, chronic obstructive pulmonary disease, and cholelithiasis; evidence of excessive alcohol intake; Laboratory test results on admission, including white blood cell count, blood glucose, AST, serum calcium, pO2, hematocrit, blood urea nitrogen, serum creatinine, and blood CO2; and outcome, including fatality, surgery, organ failure or death. Abdominal computed tomography (CT) scan findings were classified in four groups according to criteria defined previously by Balthazar (7) Normal abdominal CT scans were classified as “A”. Abnormal abdominal CT scans were classified as “B” if only pancreatic swelling was reported. A “C” classification was given when the scan showed fluid collection, and “D” was used when there was evidence of severe abnormalities such as hemorrhage. Investigators did the data analysis using Epiinfo®, which is a statistical software produced by the Centers for Disease Control (CDC). Statistical analysis included distribution frequencies of demographic variables and co-morbid conditions. Means and frequency distributions for different laboratory abnormalities and abdominal CT categories were estimated. The analysis also included estimation of risks for several complications and comparison of these risks for different groups of subjects. These comparisons were expressed in terms of risk-ratios and their respective 95% confidence intervals. The adjusted hazard ratios of complications for different factors were calculated using a Cox Proportional Hazards model. RESULTS Figure 1 shows the sex distribution of the 174 subjects in the study, of which 51% were female and 49% were male. The mean age was 59.5 years (SD = 17.8), with a median age of 63 years and a range of 17-94 years. Figure 2 shows the age distribution by groups; the majority of subjects were 60 years of age or older. Figure 3 shows the distribution of subjects by groups according to their Body Mass Index (BMI). The majority of subjects were overweight or obese. The mean number of days of hospital stay was 7 days (SD = 5.1) with a median stay of 5 days and a range of 1-32 days. A total of 36 subjects (21%) were admitted from 7-14 days; 13 subjects (7%) were admitted for more than 14 days. hypertension, 46.0% for diabetes mellitus and 31.0% for gallbladder disease. Table 1 shows these results and the prevalence rates of other conditions. Results of abdominal CT scans were classified in four categories as described in the Method section. Figure 4 shows the distribution of abdominal CT scan results by group. Only 114 subjects had abdominal CT scans. For the remaining data analysis all abnormal CT scans (categories B, C and D) were grouped together. The prevalence rate of abnormal abdominal CT’s was 35.1%. Table 2 shows the prevalence rates in the study subjects of different clinical criteria, including abnormal laboratory results that have been implicated in the past as having prognostic value in patients with pancreatitis. These criteria are among those described by Ranson but not all of these criteria were available in this study population. Table 3 shows the incidence rate of different complications. The most frequent complication was surgery (20.1%) followed by renal failure (9.8%). Four subjects in this study died during the course of hospitalization, for a case-fatality rate of 2.3%. The combined incidence rate for any complication was 36.2%. Individuals with complications had a mean hospital stay of 8.6 days (SD = 5.8); individuals without complications had a mean hospital stay of 6.0 days (SD = 4.5). The difference of their mean stays was 2.6 days (95% CI: 0.9, 4.3), which was statistically significant. Table 4 shows results from the crude analysis of the risk of having an outcome with complications comparing groups of individuals with and without different exposures. Factors that showed significant associations with the risk of complication on crude analysis were gallbladder disease with a RR = 1.78 (95% CI: 1.22, 2.60) and abnormal abdominal CT with a RR = 1.85 (95% CI: 1.85). Having three or more of the clinical RanPrevalence rates of chronic con- son’s criteria present also showed ditions were 63.2% for arterial a tendency for increased risk of 34 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico Figura 2 Figura 1 Figura 4 Figura 3 Tabla 1 Tabla 2 complications, although the result was not statistically significant, with a RR = 1.58 (95% CI: 0.66, 3.74). Since many of these clinical and radiological factors may coexist in the same individuals and serve as confounders one another, these three factors were included in a multivariate analysis or Cox Proportional Hazards Model in order to estimate their adjusted Hazard Ratios for complications. In this analysis, the three factors included continued to show a tendency for increased risk for complications, but the results did not reach statistical significance. These results are shown in Table 5. DISCUSSION Tabla 3 The incidence of acute pancreatitis varies in different countries and can be developed as the results of many factors. In the United States the incidence of this disease ranges from 13 to 45/100,000 persons, per year. Causal factors of acute pancreatitis are many, but the most BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 35 RESUMEN frequent causes are gallstones and alcohol (8). Studies suggest that the incidence of pancreatitis has increased in Europe and USA in the past years (9). The patient profile of the subjects in this study reveals a similar prevalence of both sexes. The majority of patients were 60 years or older. There was a high prevalence of co-morbidities such as obesity, hypertension, and diabetes mellitus. The overall incidence of complications was 36.2%. These complications included necrosis, hemorrhage, infection, organ failure and death. As anticipated, patients with complications had longer hospital stays than patients without complications. Ranson’s criteria and other severity scoring systems such as Computed Tomography (CT) Severity Index have been developed to predict the likelihood of adverse outcomes, including fatality, in patients with acute pancreatitis. Early evaluation and risk stratification for patients with acute pancreatitis are important to differentiate patients with mild versus severe disease and those who need intensive care treatment (10). Attempts have been made to determine whether clinical or radiological criteria are better predictors of poor prognosis in these patients. Bollen and collaborators found that the Balthazar system of abdominal CT classification was a better predictor of poor prognosis than other classification systems based on CT findings, but they did not find a difference between this system and several others based on clinical criteria in their ability to predict severity (11). Bota and her co-investigators developed a clinical severity score system – they called Prediction Pancreatic Severity Score – that was able to predict a poor outcome with 75% accuracy (12). In another recent study C- Reactive Protein (CRP) levels were found to be good predictors of pancreatic necrosis and Ranson scores were better Tabla 4 Tabla 5 predictors of case fatality (13). In a very recent study, Brand and collaborators established that contrast-enhanced abdominal CT was useful to predict a poor outcome, but the study included only subjects with necrotizing pancreatitis (14). In our study the factors that showed a tendency to be associated with the risk of complications were the presence of three or more Ranson’s criteria’s and abnormalities in Abdominal CT Scan. However, none of the associations were statistically significant, more likely due the size of the group and subsequent lack of statistical power. Another limitation of this study was that not all of Ranson’s criteria were available in the medical records. REFERENCES 1. Chintanaboina JK, Gopavaram D. Recurrent Acute Pancreatitis Probably Induced by Rosuvastatin Therapy: A Case Report. Case Reports in Medicine. 2012: 2012: 4 pages (E pub) 2. Sue M , Yoshihara A, Kuboki K, Hiroi N, Yoshino G. A case of severe acute necrotizing pancreatitis after administration of sitagliptin. Clin Med Insights Case Rep. 2013; 6:23-7. 3. Popa D , Vasile D, Ilco A. Severe acute pancreatitis - a serious complication of leptospirosis. J Med Life. 2013 Sep 15;6(3):307-9. 4. Tenner S. Baillie J, DeWitt J, Vege SS. American College of Gastroenterology Guideline: Management of Acute Pancreatitis. Am J Gastroenterol 2013; 108:1400–1415. 5. Bradley EL. A Clinically Based Classification System for Acute Pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, GA, 36 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico September 11 through 13, 1992. Arch Surg 1993;128:586–90. 6. Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet. 1974 Jul;139(1):69-81. 7. Balthazar E. Acute pancreatitis: Assessment of severity with clinical and CT evaluation. Radiology 2002; 223:603-613. 8. Dhiraj Yadav and Albert B. Lowenfels, The Epidemiology of Pancreatitis and Pancreatic Cancer, Gastroenterology. Jun 2013; 144(6): 1252–1261. 9. Roberts SE, Akbari A, Thorne K, Atkinson M, Evans PA, The incidence of acute pancreatitis: impact of social deprivation, alcohol consumption, seasonal and demographic factors, Alimentary Pharmacology and Therapeutic. 2013 Sep; 38(5): 539-48. 10. Carroll J, Herrick B, Gipson T, Lee S., Acute Pancreatitis: Diagnosis, Prognosis, and Treatment, American Family Physician. 2007 May 15; 75(10):1513-1520. 11. Bollen TL , Singh VK, Maurer R, Repas K, van Es HW, Banks PA, Mortele KJ. A comparative evaluation of radiologic and clinical scoring systems in the early prediction of severity in acute pancreatitis. Am J Gastroenterol. 2012 Apr;107(4):612-9. 12. Bota S, Sporea I, Sirli R, et al. Predictive factors for severe evolution in acute pancreatitis and a new score for predicting a severe outcome. Annals of Gastroenterology 2013; 26: 156-162 13. Khanna AK, Meher S, Prakash S, Tiwary SK, Singh U, Srivastava A, Dixit VK. Comparison of Ranson, Glasgow, MOSS, SIRS, BISAP, APACHE-II, CTSI Scores, IL-6, CRP, and Procalcitonin in Predicting Severity, Organ Failure, Pancreatic Necrosis and Mortality in Acute Pancreatitis. HPB Surgery 2013; 2013: 10 pages (E pub) 14. Brand M , Götz A, Zeman F, Bet al. Acute necrotizing pancreatitis: laboratory, clinical, and imaging findings as predictors of patient outcome. AJR Am J Roentgenol. 2014 Jun;202(6):1215-31. Continue... El propósito de este estudio fue estimar el grado de asociación entre criterios clínicos (Ranson) y radiológicos (TC abdominal) con el grado de severidad en pacientes con pancreatitis aguda. Método; Todos los pacientes dados de alta con un diagnóstico de pancreatitis aguda en un hospital de comunidad entre el 1ro de enero de 2012 al 31 de diciembre de 2012 fueron seleccionados (N = 174). Las siguientes variables fueron estudiadas: sexo, edad, peso, estatura, fechas de admisión y alta, presencia de varias condiciones crónicas, resultados de laboratorio, categoría de TC abdominal, letalidad, cirugía y otras complicaciones. El análisis incluyó estadísticas descriptivas y razones de riesgo para diferentes complicaciones para diferentes grupos de sujetos, usando criterios clínicos y radiológicos. Resultados: La tasa de incidencia de complicaciones, incluyendo letalidad, cirugía y fallo de órganos fue 36.2%. Factores que tuvieron asociaciones significativas con el riesgo de complicaciones al hacer análisis crudos fueron enfermedad de la vesícula con un RR = 1.78 (IC 95%: 1.22, 2.60) y una TC abdominal anormal con un RR = 1.85 (IC 95%: 1.11, 3.07). Con análisis multivariado, la enfermedad de la vesícula, una TC abdominal anormal y la presencia de 3 o más criterios de Ranson tuvieron una tendencia a un mayor riesgo de complicaciones, pero los resultados no fueron estadísticamente significativos. Discusión: Los factores que parecieron estar asociados con un aumento en riesgo de complicaciones en sujetos con pancreatitis aguda fueron enfermedad de la vesícula, una TC abdominal anormal y la presencia de 3 o más criterios de Ranson. Los resultados no demostraron significación estadística probablemente por un poder estadístico bajo del estudio. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 37 Case Report/Reporte de Casos CELIAC TRUNK AND BRANCHES DISSECTION DUE TO ENERGY DRINK CONSUMPTION AND HEAVY RESISTANCE EXERCISE: Case Report and Review of Literature Wilma González BSa Pablo I. Altieri MDac* Enrique Alvarado MDb Héctor L. Banchs MDac Edgar Colón MDb Nelson Escobales PhDa María Crespo PhDa A Department of Medicine and Physiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico. b Department of Diagnostic Radiology, University of Puerto Rico, School of Medicine, Medical Sciences Campus, San Juan, Puerto Rico. c Cardiovascular Center of Puerto Rico and the Caribbean, San Juan, Puerto Rico. *Corresponding author: Pablo I. Altieri MD - Box 8387, Humacao, Puerto Rico 00792. E-mail: [email protected] a ABSTRACT Higher doses and consumption of energy drinks leads to cardiovascular effects and potential consequences. Principal components found in energy drinks such as caffeine, guarana and taurine has been related to dilatation, aneurysm formation, dissection and ruptures. There is no evidence showing an integration of these components and its effects in endothelium and aortic walls due to higher levels of pressure during exercises. We report a case of a 44 years male with celiac trunk and branches dissection due to long-term consumption of energy drinks and intense exercise routine. Our proposition relates cell and vessel walls alterations including elasticity in endothelial wall due to higher blood pressure, resistance by intense exercise routine and long-term consumption of energy drinks. Index words: celiac, trunk, branches, dissection, energy, drink, consumption, exercise INTRODUCTION Energy drinks (ED) consumptions have been related in recent years to cardiovascular disease events but little evidence exists showing its hemodynamic side effects (1). Critical analysis has been studied to present the effects of ED components with extensive exercise routine and its cardiovascular effects. We present a case of a 44 years old male with a history of long-term ED consumption and intense exercise routine that used cross training and heavy resistance bands. Case History The patient is a 44 years old male with no previous history of any cardiovascular disease, presenting severe epigastric pain and dizziness. The pain started during exercise while using weight training and heavy resistance bands in a cross training program, persisting for several hours. Prior to exercise, the patient drank an ED based on caffeine and guarana as stimulants. A computed tomography angiography (CTA) of the abdomen and pelvis was performed during his evaluation (see Figure 1). It showed a small linear filling defect (intimal flap) in the celiac trunk, approximately 1.2 cm distal to the origin, with a fusiform aneurysmal dilatation and tortuosity of the vessel distal to the identified flap. The CTA showed also tortuous dilatation of the common hepatic artery and a stenotic region with discontinuity of lumen in the proximal splenic artery, 1.6 cm distal to its origin, with distal reconstitution by collateral circulation. No abdominopelvic solid organ abnormalities were presented. The patient was observed closely. Follow up CTA showed no further changes. The patient was advised to stop using of ED and 38 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico B Figure 1. Abdominopelvic CT angiogram (CTA) showing dissection of the celiac trunk. (a) Axial maximum intensity projection (MIP) image at the level of the celiac trunk showing a linear filling defect (yellow arrow) representing the intimal flap. Note the large caliber of the common hepatic artery (blue arrow). The splenic artery (black arrow) shows an area of proximal severe stenosis and discontinuity of the lumen. (b) 3-dimensional volume rendering frontal image of the upper abdominal aorta showing an area of severe stenosis and discontinuity in the proximal splenic artery (white arrow). (CA: celiac artery, CH: common hepatic artery, SMA: superior mesenteric artery, RRA: right renal artery, LRA: left renal artery). stop the intensive exercise routine. DISCUSSION Higher aortic wall stress involved in strenuous exercise routine could lead to aortic dilatation, aneurysm formation, aortic dissection, and ruptures (2). This associations are based on higher levels of pressure over 300 mmHg versus normal level between 180-220 mmHg presented in heavy trainings that deteriorate properties of the aortic lumen and increases the risk to dissects (3). The necessity to enhance performance in heavy training routine exercises has improve the usage of stimulants such as energy drinks (ED), but its consumption could lead to potential health consequences. These relations are based on ED principal content of excessive caffeine, taurine, and guarana doses, long-term exposure, and its biochemical effects BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 39 . The use of caffeine has been related to cell swelling, catecholamine excess, endothelium-dependent flow mediated dilatation, modulation of glucose levels, higher cholesterol, arterial hypertension, cell wall and arterial stiffness, cardiac arrhythmias, coronary artery disease, abnormal stimulation of the central nervous system, and death (4-7). Combination of principal components in ED may lead to apoptotic cell pathways such as lower basal levels of free radical generation, membrane blebbing, cell shrinkage, catecholamine excess, cleaved caspase-3 positivity, removal of intracellular reactive oxygen species, acid-base disorders, seizure, and insulin sensitivity (89). ED’s principal components have been related with aortic dissection and aortic aneurysm (10, 11), but there’s no evidence showing this effects by the integration of ED’s components, consumption of high doses of caffeine, and the stress in vessel walls during extensive exercise routine. The effect of these additives has been reported to increase epinephrine and endurance during exercise (12). Thus, higher doses of ED has not been reported as a secondary factor during exercise routines that could contribute to stress limit in vessel walls. During exercise, acute rises in BP has been related to vessel walls by deteriorating aortic wall and producing aneurysmal enlargement (3). Riles & Lin (13) have reported a 45-year-old man with arterial dissection, similar to our patient’s, related to weight lifting and its effects in blood pressure. Also, the relation between root dilatation during weight training routines in youth population (11) and acute aortic dissection activity due to weight lifting (10) has been reported. The main factors related to aortic dissection have been reported as degeneration in the intima media thickness related to collagen content, elastin, and hypertensive activity (14). We proposed a relationship in the intervention of elasticity in endothelial vessel walls, strengthen by ED’s effects in higher blood pressure, and a combination of cell and vessel wall alterations due to the pressure exerted by heavy resistance bands with long term consumption of caffeine-based ED. Individuals who show aneurysmal formation or aortic dilatation should be warned to the use of these components in heavy training. Also, those who are using heavy training exercises should consider prior screening and a broader knowledge of possible side effects of these additives. REFERENCES and clinical understanding provide an opportunity to save young lives. J Cardiovasc Surg (Torino) 2010; 51(5): 669-81. (12) Heckman MA, Sherry K, De Mejia EG. Energy drinks: an assessment of their market size, consumer demographics, ingredients profile, functionality, and regulations in the United States. Compr Rev Food Sci Food Saf 2010; 9: 303–17. (13) Riles TS, Lin JC. Celiac artery dissection from heavy weight lifting. J Vasc Surg 2011; 53(6): 1714-5. (14) Aziz F, Penupolu S, Alok A, Doddi S, Abed M. Peripartum acute aortic dissection: A case report & review of literature. J Thorac Dis 2011; 3(1) 65-7. (3) Mayerick C, Carré F, Elefteriades J. Aortic dissections and sport: physiologic and clinical understanding provide an opportunity to save young lives. J Cardiovasc Surg 2010; 51(5): 669-81. (4) Wolk BJ, Ganetsky M, Babu KM. Toxicity of energy drinks. Curr Opin Pediatr 2012; 24(2): 243-51. (5) Dworzański W, Opielak G, Burdan F. Side effects of caffeine. Pol Merkur Lekarski 2009; 27(161): 357-61. (6) Eudy AE, Gordon LL, Hockaday BC, et al. Efficacy and safety of ingredients found in preworkout supplements. Am J Health Syst Pharm 2013; 70(7): 577-88. (7) Doerner J, Kuetting D, Naehle CP, Schild HH, Thomas DK. Caffeine and taurine containing energy drink improves systolic left-ventricular contractility in healthy volunteers assessed by strain analysis using cardiac magnetic resonance tagging (CSPAMM). Radiological Society of North America 2013, Chicago, USA. (8) Zeidán-Chuliá F, Gelain DP, Kolling EA, et al. Major components of energy drinks (caffeine, taurine, and guarana) exert cytotoxic effects on human neuronal SH-SY5Y cells by decreasing reactive oxygen species production. Oxid Med Cell Longev 2013; 2013:791-795. (9) Trabulo D, Marques S, Pedroso E. Caffeinated energy drink intoxication. Emerg Med J 2011; 28: 712-14. (10) Hatzaras I, Tranquilli M, Coady M, Barrett PM, Bible J, Elefteriades JA. Weight lifting and aortic dissection: more evidence for a connection. Cardiology 2007; 107(2): 103-6. (11) Mayerick C, Carré F, Elefteriades J. Aortic dissection and sport: physiologic 40 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico Department of Internal Medicine, University of Cincinnati, College of Medicine, Cincinnati, Ohio. b Cardiovascular Division, University of Cincinnati, College of Medicine, Cincinnati, Ohio. c Pulmonary Division, University of Cincinnati, College of Medicine, Cincinnati, Ohio. d Cardiovascular Medicine Division, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico. *Corresponding author: Angel López-Candales, MD, PO Box 365067, San Juan, Puerto Rico 00936-5067. Email: [email protected] a Daniel A. Pietras MDa Francisco R. Lopez MDb Reynerio Pérez MDc Angel López-Candales MDc* Jean Elwing MDd ABSTRACT (1) Jonjev ZS, Bala G. High-energy drinks may provoke aortic dissection. Coll Antropol 2013; 37 Suppl 2: 227-9. (2) Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection. Eur Heart J 2001; 22(18): 1642-81. WORSENING GRADIENT OF AORTIC STENOSIS WITH TREATMENT OF PULMONARY ARTERIAL HYPERTENSION IN SCLERODERMA RESUMEN Dosis altas y el consumo de bebidas energéticas conduce a efectos cardiovasculares con sus posibles consecuencias. Componentes principales en las bebidas energéticas como la cafeína, guaraná y taurina se ha relacionado con la dilatación, formación de aneurismas, disección y rupturas; aunque no existe evidencia mostrando una integración de estos componentes y sus efectos en endotelio y paredes aórticas debido a altos niveles de presión en los ejercicios. Divulgamos un caso de un varón de 44 años con disección del tronco celíaco y sus ramas debido al largo plazo de consumo de bebidas energéticas y rutina de ejercicio intenso. Nuestra propuesta refiere a la célula y alteraciones de las paredes de los vasos arteriales incluyendo la elasticidad en la pared endotelial debido a la presión arterial más alta, resistencia de rutina de ejercicio intenso y consumo a largo plazo de energía bebidas Systemic sclerosis (SSc) can cause interstitial lung and pulmonary vascular disease that can induce pulmonary arterial hypertension (PAH). It is well known that severe PAH may reduce left ventricular preload and decrease diastolic filling with the potential of reducing forward flow. We present a case in which a patient with SSc and symptomatic PAH required direct pulmonary vasodilator therapy for treatment of elevated pulmonary pressures. On follow-up echocardiogram, while improvement in right ventricular function and reduction in estimated pulmonary pressures were noted; worsening of aortic valve gradients was also found. Cardiac hemodynamics of pulmonary vasodilator therapy is discussed and the literature is reviewed. Index words: gradient, aortic, stenosis, pulmonary, hypertension, scleroderma INTRODUCTION Pulmonary arterial hypertension is a frequent complication of systemic sclerosis. Even though survival in systemic sclerosis complicated by pulmonary arterial hypertension remains poor; early diagnosis and treatment may improve outcomes since worsening hemodynamic factors are associated with reduced survival. In this case report we review treatment with a pulmonary vasodilator resulting in improvement in right sided function; however, uncovered the true severity of a previously unrecognized valvular abnormality. Further evidence is provided to review cardiac hemodynamics and explain why aortic stenosis was uncovered while treating this patient. Case History A 58-year-old male with systemic sclerosis (SSc) presented with dyspnea on exertion, lethargy, and fatigue. A transthoracic echocardiogram (TTE) showed normal left ventricular systolic function, pulmonary arterial hypertension (PAH) and mild aortic stenosis (AS) with a mean valve gradient of 16 mmHg. A right heart catheterization confirmed severe elevation in pulmonary artery (PA) pressures (70/25 mmHg with mean PA 45 mmHg), decreased pulmonary capillary wedge pressure (PCWP) (8 mmHg), high pulmonary vascular resistance (453 dyn·s/cm5) and increased transpulmonary gradient (37 mmHg) were noted, confirming an intrinsic right-sided cause for this patient pulmonary hypertension. Pre-capillary etiology of PH was further supported by exercise hemodynamics (supine bike) with 23 mmHg increase in mPA without increase in wedge and a mild AS gradient. Vasodilator therapy was initiated. A repeat echocardiogram obtained eight months after starting PA vasodilator therapy showed a decreased in PA systolic pressures of nearly 50% from baseline (36 mmHg) while the mean aortic valve gradient had increased from 21 to 32 mmHg as seen in Figure 1. As expected, RV systolic function had significantly improved as demonstrated by the increase in strain generation using velocity vector imaging (Figure 2A and B). Similarly, left ventricular myocardial systolic velocities as well as strain generation were also significantly increased by the velocity vector imaging technique as seen in Figure 2C-F. DISCUSSION PAH is a frequent complication of SSc and likely due to proliferative arterial pulmonary microangiopathy (1-4). Even though survival in SSc complicated by PAH remains poor, despite currently available treatment options, and the prognosis for patients with interstitial lung disease associated PAH is particularly grim, early diagnosis and treatment may improve outcomes since worsening hemodynamic factors are associated with reduced survival (5). BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 41 Figure 2: (A) Velocity vector imaging of RV segments during the initial study and (B) on the follow up study. Please note the significant increase in peak systolic RV strain generation. (C) Baseline and (D) follow-up velocity vector imaging of LV segments demonstrating velocity curves. Please note how the systolic velocity has doubled (solid arrow). (E) Baseline and (F) follow-up velocity vector imaging curves showing strain generation of the same LV segments. Similarly, please note that the peak systolic LV strain generation has also doubled (broken arrow). Figure 1: Initial and follow-up aortic, peak aortic and LVOT systolic velocities as well as tricuspid regurgitation Doppler signals. Please note, a significant increase in aortic velocity when compared to LVOT, suggesting worsening aortic stenosis calculation as a result of increased forward flow in the follow-up study. In addition, the follow-up study shows a lower maximal velocity of the tricuspid regurgitation signal, suggesting improvement in pulmonary hypertension as a result of therapy. This particular case not only highlights a basic hemodynamic principle between improved right ventricular ejection as a result of vasodilator therapy; thus increasing forward flow; but also of enhanced myocardial mechanics. Not only we speculate that these two mechanisms directly contributed to unmasking the true AS severity; but provide direct proof of this hemodynamic and mechanical principle. The latter can be clearly appreciated with the use of velocity vector imaging. The use of direct pulmonary vasodilator therapy significantly improved myocardial dynamics as seen in Figure 2. Specifically, a significant increase in peak systolic strain generation not only was documented in the RV, but also in the LV. It is well known that systole and diastole result in shortening and elongation of the myocardium, respectively. This cyclical change in shape (deformation) allows the use of strain to quantify cardiac function. Lagrangian strain, or simply strain, is defined as the change in myocardial fiber length and it has been used to objectively quantitative myocardial contractility (6). Lack of recognition of this basic mechanical principle proven by velocity vector imaging could have been wrongly interpreted as PAH progression and/or therapy failure if there was any reappearance of symptoms. In our patient, there we no new symptoms; worsening of the aortic valve gradients was simply discovered on a follow-up surveillance study. Therefore, no 42 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico additional changes were done to his PAH regimen and at that time no other intervention was recommended as development of severe AS was not anticipated given the advanced nature of his underlying condition. To our knowledge not only this is the first case reporting documentation of worsening in AS severity as a direct result of improving right and left ventricular mechanics with direct pulmonary vasoactive therapy; but also of the objective documentation of improvement myocardial mechanics with this form of therapy. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 43 REFERENCES 1. Sitbon O, Humbert M, Jais X, et al. Longterm response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005;111:3105-3111. 2. Hachulla E, Gressin V, Guillevin L, et al. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum 2005;52:3792–3800. 3. Mukerjee D, St George D, Coleiro B, et al. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis 2003;62:1088– 1093. 4. Phung S, Strange G, Chung LP, et al. Prevalence of pulmonary arterial hypertension in an Australian scleroderma population: screening allows for earlier diagnosis. Intern Med J 2009;39:682–691. 5. Mathai SC, Hummers LK, Champion HC, Wigley FM, Zaiman A, Hassoun PM, Girgis RE. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis Rheum 2009;60:569-577. 6. Huang SJ, Orde S. From speckle tracking echocardiography to torsion: research tool today, clinical practice tomorrow. Curr Opin Crit Care. 2013;19:250-257. RESUMEN La esclerosis sistémica puede causar enfermedad pulmonar intersticial y de la vasculatura pulmonar produciendo hipertensión pulmonar arterial. Se reconoce que esta hipertensión pulmonar puede reducir la precarga ventricular izquierda y disminuir la presión diastólica de llenado reduciendo el flujo del corazón. Discutimos el caso de un paciente con esclerosis sistémica e hipertensión pulmonar sintomática que requirió terapia vasodilatadora directa pulmonar para el manejo de su presión pulmonar elevada. En ecocardiogramas de seguimientos mientras se noto una mejora en la función ventricular derecha y reducción en la presión pulmonar, ocurrió un deterioro en el gradiente de presión de la válvula aortica. La hemodinámica cardiaca de la terapia de vasodilatación pulmonar se discute y la literatura en esta condición se revisa. Asociación Médica de Puerto Rico UNCOMMON CAUSE OF LIFE-THREATENING RETROPERITONEAL HEMORRHAGE IN A HEALTHY YOUNG HISPANIC PATIENT: SPLENIC ARTERY ANEURYSM RUPTURE Internal Medicine Department, San Juan City Hospital, San Juan, Puerto Rico. b Hematology–Medical Oncology Section, VA Caribbean Healthcare System and San Juan City Hospital, San Juan, Puerto Rico. c Interventional Vascular Section,Cardiovascular Medical Center of Puerto Rico, San Juan, Puerto Rico *Corresponding author: Luis A. Figueroa-Jiménez MD - Internal Medicine Department, San Juan City Hospital, CMMS #79 PO Box 70344, San Juan, Puerto Rico 00936-8344. Email: [email protected] a Objetivos La Asociación Médica de Puerto Rico es fundada en el año de 1902, cuando por aquel entonces, el insigne doctor Manuel Quevedo Báez ve la necesidad de aglutinar a la profesión médica puertorriqueña en un núcleo para la defensa de la colectividad y así fomentar el contínuo progreso de la ciencia y el arte de la medicina y el mejoramiento de la salud del pueblo de Puerto Rico. Tras vencer incontables dificultades e inconvenientes naturales de la época, se celebró la asamblea constituyente el día 21 de septiembre de 1902, en el salón de sesiones de la Cámara de Delegados en la ciudad de San Juan. MEMBRESIAS ABSTRACT Splenic artery aneurysms (SAA) are a rare life threatening clinical diagnosis. We present a case of a young Hispanic woman with an aneurysm of the middle branch of the splenic artery and active leakage. The defect was embolized with complete resolution of the retroperitoneal bleeding. Physicians should be aware of this rare entity especially when female patients presents complaining of severe epigastric pain with associated hypovolemic shock. Index words: retroperitoneal hemorrhage, young Hispanic, women, splenic, artery, aneurysm, rupture INTRODUCTION FARES (US dollars) ACTIVE MEMBER a. Not resident b. Special member c. Government $ 150 $ 100 $ 60 $ 100 AFILIATE MEMBER a. Internal $ 60 b. Resident $ 60 STUDENT FREE Documentos requeridos • • • • • • Solicitud (ver próxima página) Copia de licencia para la práctica medica Retrato 2” x 2” Si es médico del gobierno, evidencia. Si es estudiante de medicina, deberá incluir evidencia de estudios. Pago de cuota según señalado en clasificación de socios y cuotas, por medio de cheque. Enviar los documentos requeridos por correo a: ASOCIACION MEDICA DE PUERTO RICO MEMBRESIAS P.O.BOX 9387 SAN JUAN, PR 00908-9387 44 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico Luis A. Figueroa-Jiménez MDa*, Amy Lee González-Márquez MDa, Luis Negrón-García MDb, Francisco Rosas-Soler, MDa, Aixa Dones-Rodríguez MDa, Mayknoll De la Paz-López, MDb; Mónica Santiago-Casiano MDb, Edwin Rodrίguez-Cruz MDc, William Cáceres-Pérkins, FACPb; Luis Báez-Díaz, FACPb present a case of a young Hispanic woman with an aneurysm of the Splenic artery aneurysms (SAA) middle branch of the splenic artery are a rare life-threatening clinical and active leakage. diagnosis. They may either be due to congenital defects or acquired Case History conditions such as atherosclerosis formation (1). The specific etiolog- A 19-year-old woman without hisic factors are in relation with an- tory of any systemic illness was giodysplasia, portal hypertension, brought to the urgency room with pregnancy and atherosclerosis (2). the complaint of diffuse abdominal The prevalence of SAA ranges from pain of 24 hours of evolution. She 0.1% to 2% (3). Although SAA are described the pain as of sudden considered rare, they remain the onset, initially located in the left upmost common (50%–75%) among per quadrant, blunt in quality, gradall visceral aneurysms. Predomi- ually progressing to 10 out of 10 in nance among women is found with intensity, radiating to the back. Exa ratio of 4:13. SAA are important acerbated by movement and parto recognize, considering that in tially alleviated by the supine posiacute settings, patients who pres- tion. There was no association to ent with ruptured or symptomatic food ingestion, sick contacts, drug SAA, are exposed to a life-threat- use, or trauma. Pain was accomening condition with hemodynamic panied by the sensation of abdomcollapse and high mortality. Up to inal fullness. She denied allergies, 25% may be complicated by rup- fever, chills, night sweats, nausea ture (2). Retrospective studies or vomiting, and changes in bowel have shown that women with SAA or voiding habits. No past similar rupture are exposed to a high mor- episodes of abdominal pain were tality rate of 70% to 90% (3). We reported. She had no previous hospitalizations or any past surgeries. Did not travel recently, nor was sexually active. Family history was non-contributory. Except for occasional spontaneous bruising, mild gum bleeding and self-limited epistaxis, the rest of the review of systems was negative. On physical examination, patient was in acute distress and ill appearing. She was alert and fully oriented. Vital signs were remarkable for hypotension (98/60 mmHg) and tachycardia (96 bpm). Conjunctival pallor and dry oral mucosa were evident. No extra-heart sounds, murmurs or gallops were noted. Lung fields were clear to auscultation. Abdominal auscultation revealed hypoactive bowel sounds. Percussion was dull in both upper abdominal quadrants. Palpation of a bulging or mass-like area located to the left upper quadrant elicited severe pain 10/10 in intensity. Spleen size could not be determined. Scrutiny was negative as well as Murphy’s sign, McBurney’s point tenderness, illiopsoas sign, Rovsing’s sign, and BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 45 Cullen’s sign. Scattered discrete ecchymosis were found in bilateral lower extremities. There was no evidence of any gross neurological deficits. Laboratories showed a complete metabolic panel within normal limits. Complete blood count disclosed WBC count of 15,000/μL, hemoglobin 9.4g/dL, hematocrit 27.2%, and platelet count of 235,000/ μL. Coagulation panel; PT, PTT and INR were within normal limits, except for a prolonged bleed- Figure 1: Abdominopelvic CT Scan: Large left retroperitoneal hematoing time. Urine analysis revealed ma, causing severe mass effect upon the adjacent celiac trunk, splenic microscopic hematuria. Follow up artery/vein, pancreas, spleen and left kidney. laboratories revealed hemoglobin levels in decreasing trend; from 9.4 g/dL to 5.3 g/dL in a period of 24 hours. The patient received analgesia and multiple packed RBCs transfusions. An abdominopelvic CT-scan revealed the presence of a large left retroperitoneal space hematoma causing severe mass effect upon the adjacent celiac trunk, splenic artery and vein, pancreas, spleen and left kidney (see Figure 1). Findings were suggestive of a small outpouching of the distal splenic vein or artery with an acute over chronic left retroperitoneal hematoma, worrisome for the pos- Figure 2: Abdominopelvic MRI: Large encapsulated retroperitoneal sibility of aneurysmal rupture with hemorrhage active bleeding. In addition, a left perinephric space hemorrhage and distal transverse colon wall hematoma were described. Due to these life-threatening findings an immeFigure 3: Abdiate more extensive workup was dominal arperformed besides clinical and heteriogram: modynamic stabilization of the paDownward tient. displacement into the pelvic An abdominal MRI revealed findregion of the ings compatible with a large 18 cm left kidney and in craniocaudal dimension and 15 adjacent struccm in transverse dimension encaptures with comsulated hemorrhage in the left side promise of of the abdomen, which could be blood flow secretroperitoneal in location or disondary to mass secting within the mesentery (see effect. (upper Figure 2). The source of bleeding arrow: towards was not identified. Abdominal ultrathe right kidney, sound disclosed a large left retroarrow below: peritoneal mass with thick septapointing out the tions and avascular compartments, displacement of findings suggested a lymphovasthe left kidney) cular malformation. 46 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico Figure 4: Abdominal arteriogram: Identification of the splenic artery aneurysm located in the middle splenic branch. Figure 5: Abdominal arteriogram/ Catheterism: Figure 6: Splenic catheterism: Status-post emCatheter device reached the splenic aneurysm, bolization of the middle and 3rd branch of splenic artery. Disclosed blockade of splenic aneuready for embolization techniques. rysm leakage and blood flow after placement of vascular plugs proximal to the aneurysm (Amplatzer® vascular occluders; St. Jude MedicalMN, USA). Radiographic findings prompted immediate surgical evaluation. General surgery, as well as interventional radiologist specialists analyzed the case, however invasive strategies were disregarded upon consideration of a possible concomitant coagulopathic process. Also, considering the worrisome findings in the history of spontaneous self-limited mucosal bleeding in addition to a prolonged bleeding time, the possibility of a bleeding disorder was very likely. However, von Willebrand factor, ristocetin cofactor activity, factor VII, VIII activity, D-dimers and fibrinogen levels were all within normal limits, so a hemostasis disorder was excluded. performed by cardiovascular intervention service revealing an aneurysm of the middle branch of the splenic artery with active leakage (see Figure 4). Embolization with Amplatzer® vascular occluders (St. Jude Medical- MN, USA) were done to the middle and third branch of the splenic arteries with complete resolution of the retroperAn abdominal arteriogram was itoneal bleeding (see Figure 6). BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 47 The patient was discharge home within one-week with follow up at outpatient clinics. Re-evaluation with imaging studies disclosed persistence of the large capsulated retroperitoneal hematoma but the patient remains asymptomatic. No further medical actions have been taken. DISCUSSION Splenic artery aneurysms (SAA) are rare and remain an insidious entity. Retrospective reviews of nonselective angiograms have provided the most reliable incidence estimate of approximately 0.8% (3). The pathogenesis of SAA has only been partially elucidated. Histologic examinations have variously demonstrated internal and external lamina disruption, fibrodysplasia of the media, subendothelial thickening, and accretion of glycosaminoglycans in the subintimal layer and media (4). Commonly listed risk factors and associated diseases include atherosclerosis, autoimmune conditions (eg, lupus, vasculitides), collagen vascular diseases, pancreatitis, and portal hypertension (2). There is a higher prevalence of SAA among women. The influence of hormonal factors on arterial structure has been speculated but not confirmed (4, 5). Retrospective analysis suggests there is an inverse correlation of SAA calcification and initial aneurysm size. The more calcification presents in the SAA, the smaller the SAA at presentation (6). However, calcification cannot be correlated with SAA rupture, a protective role against aneurysm growth may exist. One study suggests that may be that eggshell calcification early in aneurysm development will prevent expansion of the aneurysm (6). Rupture is the most fatal clinical presentation of SAA. Life-threatening rupture results in severe abdominal pain and hypovolemic shock as we reported in our case presentation. There is an absence of convincing evidence predicting the risk of SAA rupture. Size of the SAA is not clearly associated with risk of rupture (3). Data shows that cases with rupture SAA presented with massive blood collection within peritoneal cavity and retroperitoneal space. These cases usually undergo exploration laparotomy, to identify the source of bleeding and further splenectomy is performed following the ligation of the splenic artery proximal to the lesion (7). SAA may be treated via open or endovascular methods. The treatment of SAA depends on its location over the splenic artery. The favored method of treatment at present is embolization (5). When embolization is difficult or contraindicated by the proximity of the aneurysm to the spleen (with risk of splenic infarction) the options are open or laparoscopic surgery with ligation of the splenic artery, excision of the aneurysm with re-anastomosis of the artery or splenectomy with removal of the aneurysm (5). In our case embolization was successfully done after the patient was hemodynamically stable. Embolization of the SAA could be performed when preservation of the native artery is not required (8). The goal is to achieve complete occlusion of the vessel beyond the aneurysmal neck first and then proximal to the lesion to avoid back bleeding into the lesions through gastroepiploic, pancreatic, or gastric collaterals (8). In summary, treatment options are dictated by the anatomic location, the age of the patient, the physiologic and clinical conditions (9). SAA rupture may become a relevant differential diagnosis of intraperitoneal hemorrhage and sudden death, respectively. Physicians should be aware of this rare entity, especially when patients present to the emergency department complaining of severe epigastric pain with associated hypovolemic shock more concerning in the female population. Future studies must continue to focus on risk factors for rapid growth and further delineation of SAA natural history, which could ultimately identify patients who would benefit from early prophylactic intervention. alimenta REFERENCES 1. Betal D, Khangura JS, Swan PJ, Mehmet V: Spontaneous ruptured splenic artery aneurysm: a case report, Cases Journal 2009;2:7150. tu vida 2. Abbas MA, Stone WM, Fowl RJ: Splenic artery aneurysms; Two decades experience at Mayo Clinic, Ann Vasc Surg 2002;16:442-449. 3. Berceli SA: Hepatic and splenic artery aneurysms, Semin Vasc Surg 2005;18:196-201. “Ensure me brinda los nutrientes que necesito todos los días para ayudar a mantenerme activa y con energía.” 4. Sadat U, Dar O, Walsh S, Varty K: Splenic artery aneurysms in pregnancy: a systematic review, Int J Surg 2008;6:261265. 5. Matsumoto K, Ohgami M, Shirasingi N, Nohga K, Kitajima M: A first case report of the successful laparoscopic repair of a splenic artery aneurysm, Surgery 1997;121:462–4. 6. Lakin RO, Bena JF, Sarac TP, et al: The contemporary management of splenic artery aneurysms, J Vasc Surg 2011;53:95865. 7. Trastek VF, Pairolero PC, Joyce JW, Hollier LH, Bernatz PE: Splenic artery aneurysms, Surgery 1982; 91:694-9. 8. Zhu X, Tam MDBS, Pierce G, et al: Utility of the Amplatzer vascular plugs in splenic artery embolization: comparison in conventional coil technique, Cardiovasc Intervent Radiol 2011;34:522-531. 9. Ikeda O, Tamura Y, Nakasone Y, et al: Nonoperative management of unruptured visceral artery aneurysms: treatment by transcatheter coil embolization, J Vasc Surg 2008;47:1212-1219. C M Y CM MY CY CMY K RESUMEN Aneurismas en la arteria esplénica son un raro y potencialmente diagnóstico mortal clínico. Presentamos el caso de una mujer joven con un aneurisma de la rama intermedia de la arteria esplénica y sangrado activo. Se realizaron técnicas de embolización de forma exitosa. En este reporte queremos demostrar la importancia de una identificación temprana de esta rara identidad especialmente en mujeres con dolor abdominal y shock hipovolémico. Si consumes 2 botellas * de Vitaminas y Minerales *Del valor diario recomendado de 24 vitaminas y minerales. 48 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico Usarlo como parte de una alimentación saludable y un plan de ejercicios. © 2015 Abbott Laboratories Inc. APR-150270 LITHO en P.R. Mi secreto para ayudar a manejar la diabetes es ATRAUMATIC BILATERAL FEMORAL NECK FRACTURES IN A PREMENOPAUSAL FEMALE WITH HYPOVITAMINOSIS D Department of Orthopedic Surgery, School of Medicine, University of Puerto Rico, Medical Sciences Campus. San Juan, Puerto Rico. *Corresponding author: Antonio Otero-López MD - Department of Orthopedics, UPR Medical Sciences Campus, PO Box 365067, San Juan, Puerto Rico 009365067. E-mail: [email protected] a Giovanni Paraliticci MDa David Rodríguez-Quintana MDa Ariel Dávila MDa Antonio Otero-López MDa* ABSTRACT Bilateral femur neck fractures in young adult patients are very rare in atraumatic circumstances. We report a young premenopausal female with osteomalacia secondary to vitamin D deficiency and spontaneous bilateral femur neck fractures. Patient had no reported risk factors for osteomalacia but hypovitaminosis D was noted on laboratory evaluation. Osteomalacia secondary to low serum levels of vitamin D may lead to stress and fragility fractures. Identification and treatment of at risk patients may decrease the incidence of stress fractures and its possible complications. Index words: atraumatic, bilateral, femoral fractures, premenopausal, female, hypovitaminosis Nutrición Avanzada 3 en 1 Manejo de Azúcar en Sangre con CARB STEADY® ULTRA Salud del Corazón** Apoyo Inmunológico† Disponibles en: Vainilla y Chocolate MARCA E A Toda Hora, Nutrición y Diabetes en Control * Entre los médicos que recomiendan los productos nutricionales a sus pacientes con diabetes. ** Con fitoesteroles a base de plantas † Excelente fuente de antioxidantes (vitaminas C, E y selenio) Use bajo supervisión médica como parte de un plan de manejo de diabetes. © 2014 Abbott Laboratories Inc. APR-140009 Litho en P.R. IC O S ED M R EC OM N # * DA R DA P O INTRODUCTION Bilateral femur neck fractures in premenopausal females or young adult males occur in one of two scenarios, either high-energy trauma or secondary to metabolic disorders. Reports exist of two Japanese individuals with bilateral and unilateral femoral neck fractures secondary to hypovitaminosis D (1, 2). In these cases both patients showed poor dietary habits and alcoholism. Most reports in the literature of atraumatic bilateral femur fractures have documented causes of osteomalacia, including oncogenic osteomalacia, malabsorption, chronic steroid use, pregnancy and alcoholism, among others (3,4,5,6). Low levels of Vitamin D have been documented in normal/healthy individuals as well as in the orthopedic patient population seen on everyday orthopedic practice (7). We present a young adult premenopausal female with atraumatic bilateral femoral neck fracture. This patient had normal laboratory values except for very low serum level of vitamin D3. Our patient was notified and consented for presentation of her case in the literature. Case History femoral neck fractures she was then referred to our clinic for further This is the case of a 46-year-old evaluation and management. female patient with progressive bilateral hip pain. Her hip symp- The patient was 160 cm tall and toms began twenty-two days prior her weight was 66 kg (body mass to presenting at our clinic at the index; 25.9). She had a past medPuerto Rico Medical Center. She ical history of hypothyroidism that reported her bilateral hip pain as was well controlled with levothydeveloping insidiously and asso- roxine sodium 50 micrograms daiciated with gradual bilateral knee ly (TSH – 2.04). She denied other pain. Symptoms did improve after medical conditions or medication a short course of physical therapy treatments. She had no history of and non-steroidal anti-inflammato- trauma, seizures, or bone metary drugs. Given some improvement bolic diseases. Both her family and in her pain she continued with her dietary history were also unremarkPT regimen as directed by her pri- able. mary physician who documented negative findings on pelvis and bi- Upon arrival at our clinic patient had lateral knee radiographs. pain on inguinal area upon ambulation and associated antalgic gait. During this second stage of phys- Both hips had decreased range of ical therapy she developed wors- motion secondary to pain. Radioening bilateral thigh pain with ra- graphs and computerized tomodiation to both her gluteal and hip gram (CT) showed possible stress regions. At this time, her hip pain fractures of bilateral femoral necks was 7/10 on visual analogue scale and no looser’s zones on pubic (VAS) with marked limitation of her rami or femoral cortex (see Figures daily activities. At this time, her pri- 1 & 2). Pelvic MRI did show evimary physician ordered further ra- dence of non-displaced acute bilatdiographic workup, which included eral femoral neck stress fractures radiographs, computerized tomog- (see Figure 3). Dual-energy x-ray raphy (CT) scan, and pelvic mag- absorptiometry showed lumbar netic resonance imaging (MRI). Af- spine Z score -1.4, femoral neck Z ter imaging results showed bilateral score 1.3, totals hip Z score -0.1. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 51 FRAX score for major osteoporotic Figure 1: Preoperative anteroposterior radiograph of the bilateral hip fracture and hip fracture were 2.6% joints. There are no looser’s zones in the pubic rami or stress fractures and < 0.1% respectively. apparent in this examination. Laboratory results displayed normal values of total serum calcium (9.6 mg/dL; reference range, 9-10.5 mg/dL), serum phosphorus (3.7 mg/dL; reference range, 3-4.5 mg/dL), and alkaline phosphatase (71 IU/L; reference range, 36-92 IU/L). Serum level of 1,25(OH)2vitamin D3 was decreased (18.3 pg/ mL; reference range, 15-80 pg/mL). The serum albumin was normal (4.1 g/dL; reference range, 3.5-5.1 g/dL). Her PTH level at most recent follow up was 23pq/ml (reference range, 16-64pq/mL). Given previous failure of conservative management and symptoms of severe bilateral hip pain we recommended and internal fixation with two cannulated hip screws for both hips (see Figures 4). Decision for internal fixation versus arthroplasty was made given the non-displaced nature of the fractures. At the time of surgery and given the possibility of osteomalacia a tricortical biopsy of the ilium was obtained. It showed no histologic evidence of osteomalacia. She was started on daily oral calcium and vitamin D supplements (50,000 Units). Partial weight bearing was allowed with assistive devices 60 days postoperatively. Complete weight bearing was not allowed until 90 days postoperatively at which time patient had complete radiographic healing apparent on radiographs. Follow up laboratories showed improvement in hypovitaminosis D (Vitamin D3 = 47.26 ng/mL) following two months of oral supplements. Our patient was able to return to her activities of daily living without assistance three months post operatively. DISCUSSION Vitamin D has received considerable attention in recent years, because of studies demonstrating inadequate levels in otherwise healthy populations (5,6). Recent recommendations of the International Osteoporosis Foundation and Osteoporosis Canada show that optimum levels vitamin D Figure 2: Preoperative coronal (a) and sagittal (b) tomographic images showing bilateral femoral necks with vertical sclerotic lesions. Noted how lesions are on tension side of the bone. Figure 3: Preoperative T1 (a) and T2 Fat Suppression (b) magnetic resonance imaging (MRI) showing bilateral femoral neck fractures Hypovitaminosis D may result in osteomalacia, a metabolic bone condition resulting in weak demineralized bone. Long termed hypovitaminosis D may result in spontaneous fractures secondary to this poorly mineralized weakened bone. Multiple risk factors for hypovitaminosis D exist such as: decrease sun exposure, obesity, 52 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico dietary deficiency, malabsorption, medication-induced, breast-feeding, cholesterol-lowering agents, genetic disorder, anti-seizure medication, and hyperthyroidism. None of these risk factors were identified in our patient. Orthopedic surgeons and physicians in general should be aware of these increasing trends in Vitamin D deficiency. Similar to the American Academy of Orthopedic Surgeons move towards better osteoporosis awareness and prevention of fragility fracture, screening and early recognition of high risk patients with vitamin D deficiency and osteomalacia can decrease the incidence of morbid hip fractures. Figure 4: Postoperative radiograph showing bilateral cannulated screw fixation of femoral neck fractures. In the present case, the patient had no history of major trauma or any known risk factors for osteomalacia. Her presenting symptoms of insidious atraumatic bilateral thigh/ inguinal pain imply a fragility fracture secondary to possible bone mineral deficiency. Laboratory data did not demonstrate any abnormality in the serum levels of calcium, phosphorus, or bone alkaline phosphatase, but she did have a low serum level of 1,25 (OH)2vitamin D3. Moreover, radiographs did not show typical features of osteomalacia such as Looser's zone, but addition of CT scan did show sclerotic vertical lines on both femoral necks implying healing stress fractures. Given normal dietary and other lifestyle habits the cause of the low serum level of vitamin D in this case is still not clear. To our knowledge, a previous report exists in the literature of bilateral femur fractures in a patient with low levels of vitamin D. This report was in an Asian patient with dietary deficiencies and alcoholism (1). Our patient underwent bilateral internal fixation with cannulated screws given the early recognition and non-displaced fracture pattern. Further delay in treatment may have led to displacement of the fractures and hip replacement surgery. With this, we think that prevention and early diagnosis seem of paramount importance to prevent occurrence and displacement of hip stress fractures on patients with osteomalacia. The increasing incidence of hypovitaminosis D in the general population will lead to an increase in reported incidence of fragility fractures.. Femoral neck fractures, as in this case, require early diagnosis to prevent morbidities associated with fragility fractures. Given the previously reported elevated rate of undiagnosed hypovitaminosis D, preventive medicine with screening and oral vitamin D supplementation should be implemented by primary care physicians and orthopedic specialists. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 53 REFERENCES RESUMEN 1. Nagao S1, Ito K, Nakamura I. Spontaneous bilateral femoral neck fractures associated with a low serum level of vitamin D in a young adult. J Arthroplasty. 2009 Feb; 24(2):322.e1-4. 2. Ohishi H1, Nakamura Y, Kishiya M, Toh S. Spontaneous femoral neck fracture associated with a low serum level of vitamin D. J Orthop Sci. 2013 May; 18(3):496-9. 3. Rajeev A. Bilateral spontaneous inter-trochanteric fractures of proximal femurs. Int J Surg Case Rep. 2014; 5(5):246-8. 4. Baki ME1, Uygun H, Arı B, Aydın H. Bilateral femoral neck insufficiency fractures in pregnancy. Eklem Hastalik Cerrahisi. 2014 5. Carter T1, Nutt J, Simons A. Bilateral femoral neck insufficiency fractures secondary to vitamin D deficiency and concurrent corticosteroid use--a case report. Arch Osteoporos. 2014;9:172 6. Sivas F1, Günesen O, Ozoran K, Alemdaroğlu E. Osteomalacia from Mg-containing antacid: a case report of bilateral hip fracture. Rheumatol Int. 2007 May;27(7):679-81 7. Patton CM1, Powell AP, Patel AA. Vitamin D in orthopedics. J Am Acad Orthop Surg. 2012 Mar; 20(3):123-9. 8. Hanley DA, Cranney A, Jones G, Whiting SJ, Leslie WD, Guidelines Committee of the Scientific Advisory Council of Osteoporosis Canada: Vitamin D in adult health and disease: A review and guideline statement from Osteoporosis Canada (summary). CMAJ 2010; 182():1315-1319. 9. Dawson-Hughes B, Mithal A, Bonjour J-P, et al: IOF position statement: Vitamin D recommendations for older adults. Osteoporos Int 2010; 21():11511154. 10. Caro Y, Negron V, Palacios C. Association between Vitamin D Levels and Blood Pressure in a Group of Puerto Ricans. PR Health Sci J.Sep 2012; 31(3):123-129. Las fracturas bilaterales de cuello femoral en jóvenes adultos son inusuales en circunstancias no traumáticas. En este reporte presentamos un paciente con osteomalacia sin factores de riesgo por historial y fracturas bilaterales de cuello femoral. En nuestra evaluación preoperatoria se identificaron niveles disminuidos de vitamina D. Osteomalacia secundaria a niveles bajos de vitamina D puede llevar a fracturas de estrés o fragilidad. El tratamiento de esta condición debe ser preventivo. La identificación con tratamiento temprano de pacientes a riesgo puede prevenir complicaciones mayores asociadas con fracturas de estrés en la cadera. SMALL CELL CARCINOMA OF THE UTERINE CERVIX: A Case Report and Literature Review St. Luke Episcopal Hospital and the Ponce School of Medicine, Ponce, Puerto Rico. *Corresponding author: Pedro F. Escobar MD - 100 Grand Paseos Blvd, Suite 112, PMB 236 San Juan, PR 00926. Email: [email protected] a Pilar E. Silva-Meléndez MDa Pedro F. Escobar MDa* Héctor Silva MDa Sylvia Gutiérrez MDa Manuel Rodríguez MDa ABSTRACT Small cell carcinoma of the uterine cervix is a rare and aggressive extra-pulmonary variant of small cell tumors. This carcinoma of the cervix comprises less than 5% of all cervical carcinomas and is known to be highly undifferentiated. It is associated with a poor prognosis and characterized by premature distant nodal involvement. The survival rate at all stages ranges from 17% to 67%. We describe the case of a 41 years old female patient with a rare, and aggressive, clinical stage IB2 small cell neuroendocrine carcinoma of the cervix. The goal of this case report is to describe this rare pathology and contribute information to the scant available data. Index words: small, cell, carcinoma, uterine, cervix INTRODUCTION CONVIERTASE EN PROVEEDOR DE EDUCACION MEDICA CONTINUA PRMA - ACCME Validez U.S. y P.R. Asociación Médica de Puerto Rico Acreditador exclusivo de ACCME (787) 721-6969 Dra. Victoria Michelen 54 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico Small cell carcinoma of the uterine cervix (SCC) is a highly malignant extra-pulmonary variant of small cell malignancy (1, 2). This rare uterine cervix carcinoma variant is histopathologically indistinguishable from its pulmonary counterpart (1). The incidence is estimated to be around 3% of all uterine cervix malignancies. The exact numbers are not precise due to nomenclature disagreement leading to histopathologic misdiagnoses. The diagnosis of small cell carcinoma of the uterine cervix might be overestimated. However, Reagan established specific histopathologic criteria for its classification. These are: predominance of uniformly organized small basophilic cells, high nuclear-cellular ratio, presence of opaque or coarsely granular chromatin, cell and nuclear size uniformity, and elevated mitotic index (3). Small cell carcinoma of the cervix is known to be highly undifferentiated and with a poor prognosis. The tumor is characterized by increased invasion of lymphatics, distant metastasis, and dismal survival rates. Weed et al found dis- studied patients, with a 93% mortality rate 5 years after diagnosis (2). Chemotherapy has been used for metastatic disease in multiple combinations with some response. However, the regimen, timing and duration of chemotherapy remain controversial (1). Some authors also argue in favor of prophylactic brain irradiation due to high risk of brain metastases. Small case series of patients with adequate small cell carcinoma diagnosis are not sufficient to establish a standard of care. Current treatments have been extrapolated from pulmonary small cell carcinoma treatment regimens (4). We describe the case of a 41 years old female patient with a rare, and aggressive, clinical stage IB2 small cell neuroendocrine carcinoma of the cervix. The goal of this case report is to describe this rare pathology and contribute information to the scant available data. The study design is a retrospective record review analysis. The medical records available at the Saint Luke's Episcopal Hospital and private clinic were reviewed and proceed with data collection in accordance to HIPAA regulations. The Ponce School of Medicine Review Board (IRB) approved the study. Case History This is the case of a 41 yearsold-female G3P3A0 with the chief complaint of foul smelling, bloody, vaginal discharge, inter-menstrual bleeding, and pelvic discomfort of four months duration. She denies fever or chills. The patient had regular menstrual cycles and no previous history of similar episodes. She is currently sexually active. Five years ago she was treated with a loop electrosurgical excision procedure for a cervical intraepithelial neoplasia grade 3. Two years later she had cryosurgery of the cervix due to a lowgrade lesion. The subsequent Pap smear evaluations were negative. The last evaluation was one year prior to current complains. Upon examination, a 4 centimeters exophytic, necrotic mass on the posterior cervical lip was identified (see Figure 1). Cervical punch biopsies were taken and reported as small cell carcinoma of the cervix (see Figure 2). Endometrial biopsy was performed and reported as normal proliferative endometrium. The clinical staging for this patient BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 55 DISCUSSION Figure 1. Uterine cervix exophytic mass. Pioneer studies of cervical cancer were performed by Reagan classifying uterine cervix cancer into three groups based on histopathology. These were: keratinizing carcinoma, large cell non-keratinizing carcinoma, and small cell carcinoma. The latter has distinct and specific histopathologic findings. The lack of standardization for differentiating between the groups led Reagan, in 1959, to establish specific histopathologic criteria for identifying a small cell carcinoma of the uterine cervix. Our case meets these criteria, presenting with predominance of uniformly organized small basophilic cells, high nuclear-cellular ratio, and elevated mitotic index (see Figure 2a) (3). The immunohistochemistry favored a small cell carcinoma diagnosis with positive staining for the characteristic immunohistochemical markers: synaptophysin, Chromogranin A, neurofilament, and neuron-specific enolase (Figure 2b, 2c, 2d, and 2e). Although immunohistochemical markers are not part of the criteria for diagnosis of small cell carcinoma of the cervix, they are frequently used to guide it. The most frequent markers used are: Chromogranin A, synaptophysin, and neuron-specific enolase (5). In addition, immunohistochemical staining was positive for ki-67, which correlates with the characteristic high mitotic rate of this malignancy (see Figure 2f). Figure 2. Histopathology of Small cell carcinoma. a) Hematoxylin and Eosin stain, b)Synaptophysin, c)Chromogranin A, d)Neurofilment, e)Neu- The incidence of small cell carcinoma of the cervix is rare, comrospecific enolase, and f)Ki-67. prising less than 5% of all cervical is IB2. Abdomino-pelvic CT scan three cycles of Cisplastin and Etopo- carcinomas (1). Moreover, this evaluation showed inhomogenous side. Upon follow up evaluation with malignancy comprises 0.9% of all solid mass in the right adnexa as Abdomino-Pelvic CT scan showed invasive cervical carcinomas (5). well as multiseptated cystic lesion enlarged bilateral periaortic and peri- It is an extra-pulmonary variant of in the left adnexa with prominent caval lymph nodes with largest lymph small cell carcinoma and it is hisuterine cervix and retroperitoneal nodes along psoas muscle extend- topathologically indistinguishable lymphadenopathy. Physical exam, ing from renal vessels into the pelvis, from its pulmonary counterpart. imagining and pathologic findings pelvic large conglomeration of lymph Extensive studies have been perguide our referral to chemothera- nodes and cervix with thick mucosa formed to determine adequate py and radiotherapy. She received and presence of inhomogeneous management, but the scarcity of 56 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico cases limits the investigations. Due to these previously mentio ned limitations, extrapolation of treatment regimens used in the treatment of lung small cell carcinoma is currently being used for the treatment of small cell carcinoma of the uterine cervix. The role of surgery in this type of malignancy is a cause for dispute. Various retrospective analysis have found increased survival rates with either radical hysterectomy or hysterectomy alone (4,8). In contrast, large studies investigated the role of surgery and found no change in outcome, but did find decreased survival in the surgical management group (7). Furthermore, several studies have found increased brain metastases and many argued in favor of prophylactic brain irradiation due to high risk of brain metastases. Liao et al. studied prognostic factors for this type of carcinoma and identified the positivity of chromogranin, an advanced FIGO stage, and increased tumor mass as poor prognostic factors of survival (6). Cohen et al. found that early-stage disease is an independent prognostic factor (4). However, the survival is dismal even in early stage disease with a 5-year survival of 37%. Human papilloma virus (HPV) has a well-known role in development of carcinoma of the cervix. The emerging data suggests that HPV also has a role in the development of small cell carcinoma of the cervix, with HPV genotypes 16 and 18 being most commonly associated. Interestingly, genotype 18 seems to be more prevalent in small cell carcinoma in contrast to squamous cell carcinoma (5). Our patient did not present with high-risk HPV serotypes. In conclusion, the main outcome of this case report is reinforcing the need to have more studies and case reports of small cell carcinoma of the uterine cervix in order to develop the most appropriate guidelines of treatment and a standard of care for this rare malignancy. Additional data is still needed in order to establish standardized and effective treatment modalities for this pathology. Consideration should be given to this rare malignancy aiming to identify effective treatment modalities. REFERENCES 1. Viswanathan AN, Deavers MT, Jhingran A, et al. Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence. Journal of Gynecology Oncology. 2004;93:27-33. 2. Weed JC, Graff AT, Shoup B, et al. Small Cell Undifferentiated (Neuroendocrine) Carcinoma of the Uterine Cervix. Journal of the American College of Surgeons. 2003;197:44-51. 3. Wentz WB, Reagan JW. Survival in cervical cancer with respect to cell type. Cancer. 1959; 12: 384-388. 4. Cohen JG, Kapp DS, Shin JY, et al. Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients. American Journal of Obstetrics and Gynecology. 2010; 203: 347 e1-e6. 5. Atienza-Amores M, Guerini-Rocco E, Soslow RA, et al. Small cell carcinoma of the gynecologic tract: A multifaceted spectrum of lesions. Journal of Gynecology Oncology. 2014;134:410-418. 6. Liao LM, Zhang X, Ren YF, et al. Chromogranin A (CgA) as poor prognostic factor in patients with small cell carcinoma of the cervix: results of a retrospective study of 293 patients. PLOS ONE. 2012; 7(4):e33674. 7. Wang KL, Chang TC, Jung SM, et al. Primary treatment and prognostic factors of small neuroendocrine carcinoma of the uterine cervix: A Taiwanese Gynecologic Oncology group study. European Journal of Cancer. 2012; 48:1484-1494. 8. Boruta II DM,Schorge JO, Duska LA, et al. Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine cervix. Journal of Gynecology Oncology. 2013; 129: 135-139. RESUMEN El carcinoma de células pequeñas en el cuello del útero es raro y agresivo, es una variante extra-pulmonar de los carcinomas de células pequeñas. Este tipo de carcinoma del cuello del útero compone menos de 5% de todas las malignidades del cuello del útero, se conoce por ser altamente no diferenciado. Se asocia con un pronóstico pobre y es caracterizado por invasión a distancia del sistema linfático. La sobrevida en todos los estadíos va de un 17% a un 67%. El caso presentado es de una fémina de 41 años de edad con un carcinoma de células pequeñas en el cuello del útero. La meta de este reporte de caso es compartir la presentación clínica, hallazgos y evolución de la enfermedad para contribuir a entender mejor esta rara malignidad del cuello del útero. WWW.ASOCMEDPR.ORG solid lesion. Patient was schedule to change chemotherapy regimen but was lost to follow-up. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 57 HANDLEBAR HERNIA: Case Report and Literature Review Luisa Angel Buitrago MDa Humberto Lugo-Vicente MDa* Department and Residency of Pediatrics, San Juan City Hospital, San Juan, Puerto Rico. bSection of Pediatric Surgery, Department of Surgery, UPR School of Medicine, San Juan, Puerto Rico. *Corresponding author: Humberto Lugo-Vicente MD – PO Box 10426, San Juan, Puerto Rico 00922. E-mail: [email protected] a ABSTRACT Handlebar hernia is a rare traumatic abdominal wall hernia occurring after blunt trauma. We report a case of an adolescent patient with a traumatic rectus muscle abdominal wall hernia produced by injury with the bicycle handlebar. The skin abrasion caused by the trauma and a swelling reproduced after a Valsalva maneuver suggested the diagnosis. Traumatic wall hernias after blunt trauma should be repaired primarily to avoid complications. Index words: handlebar, hernia, rectus, abdominis INTRODUCTION Traumatic abdominal wall hernias caused by bicycle handle are rare. The criteria to identify a traumatic hernia include absence of previous hernia in the same area, evidence of abdominal wall injury and immediate or delayed development of a hernia. There are approximately forty cases reported in the literature [1,2]. This abdominal wall injury is caused by a direct trauma with an object with small surface area like a bicycle handlebar with sufficient force to damage the abdominal wall, but not the skin. We present a case of an adolescent male with a traumatic handlebar hernia after a fall from a bicycle. Case History This is a 14-year-old-male patient with no history of systemic illness presenting to the emergency department one day after losing control of his bicycle and falling into the handlebar. He complained of a lump on his right abdomen with mild intermittent non-radiating pain in the area of the protruding bulge with coughing. In general the patient was in no acute distress with normal vital signs for age, clear lung to auscultation, normal heart rate and rhythm no murmur or gallop. At abdominal evaluation the patient had a right supra-umbilical abrasion, with an obvious abdominal wall hernia visualized in his right rectus abdominal muscle after a Valsalva maneuver, with no rebound or tenderness to palpation (see Figure 1 & 2). Laboratories (CBC, BMP, PT, PTT, INR) were within the normal range. Abdominal Ultrasound followed by a CT-Scan of abdomen with contrast showed a rectus abdominal wall rupture with omental protrusion within the defect (see Figure 3 & 4). During surgery a five cm defect due to rupture of the transverse fascia of the right rectus abdominis was identified (see Figure 5). The hernial defect was repaired using approximation of the medial rectus muscle to the midline with anterior fascia transverse closure using interrupted absorbable sutures (see Figure 6). He followed an uneventful postoperative course. identified the relationship of blunt injury with the handlebar of the bicycle and the development of an abdominal hernia in 1980 [3,7]. DICUSSSION There are three types of TAWH categorized in 1988 by Wood and Robyn; Type I is a small defect caused by blunt injury of low energy trauma such as a bicycle handlebar. Type II is a larger defect caused by high-energy blunt trauma from motor vehicles crash or from a height, and type III is a larger defect involving intraabdominal bowel herniation as described in deceleration injuries [1,4,5]. Most traumatic abdominal wall hernias in children are Type 1, also called handlebar hernias due to the common nature of the accident. The criteria to identify a traumatic hernia include absence of previous hernia in the same area, evidence of abdominal wall injury and immediate or delayed development of a hernia, with or without presence of peritoneum [1]. Traumatic abdominal wall hernias (TAWH) are caused by a force strong enough to damage the abdominal wall, but not to damage the more elastic skin [1-8]. Selvy first described TAWH in 1906, and the term handlebar hernia was introduced when Dimyan and Robb There are approximately forty cases of TAWH reported in the literature, the more common presentation is a hernia in the lower abdomen in males with a an average age of 9.5 years (range from 5 to 14 years). Risk factors associated with the development of a TAWH 58 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico in children include risk behavior, not using protective equipment and poor handling experience [2,6,7]. Although the majority of cases reported in the literature have a lower abdominal trauma usually in the right side lateral to the rectus sheath or over the linea alba, a few cases were reported after upper abdominal trauma and even thoracic defects [1,3,6]. Intra-abdominal trauma is more common with upper abdominal trauma and type II TWAH [6,8]. Our case patient was a 14 years adolescent with a supra-umbilical handlebar abrasion and hernia observed when performing the Valsalva maneuver. The diagnosis of handlebar hernia is clinical made by history and physical examination, however some cases reported discovery of a hernial defect during laparoscopy evaluation for blunt abdominal trauma not seen at physical examination [1,5]. Patients usually present to the emergency department with abdominal bulge tender at palpation and overlaying skin contusion or handlebar imprinting abrasion that is not always present, but when is present increased risk of abdominal trauma has been reported [3-6,8,9]. When signs of acute abdomen or hemorrhagic shock are present serious intra-abdominal injury should have to be considered. In our case although the patient has handlebar imprinting abrasion, there were no signs of hemorrhagic shock or acute abdomen such as, abdominal distention, rigidity, absent bowel sound, tenderness with rebound and guarding which make us think about associated intra abdominal injury. Figure 1: Abdominal abrasion caused by handlebar injury. Diagnosis of handlebar hernia should be confirmed with imaging studies. The most important studies are abdominal X-ray, ultrasound and CT scan. Abdominal CT-Scan helps us determine if other intra-abdominal injuries like intestinal perforation, liver, spleen or pancreatic rupture are present [1, 3, 6]. Although laparoscopy repair and conservative management has been reported, the literature recommendsopen surgical repair with closing of all layers and use of prosthetic material when defect is large as definitive treatment to avoid complications like incarceration and bowel ischemia [1, 3, 5, 6, 9-11]. Figure 2: Abdominal bulge caused during Valsalva maneuver. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 59 When CT scan is inconclusive, laparoscopy evaluation of solid organ, diaphragm and small bowel injury is very useful. With intra-abdominal injuries exploratory laparotomy is necessary for repaired of such injuries [1, 4]. In our case abdominal ultrasound and CT scan help confirm the diagnosis of abdominal wall hernia since no intra-abdominal injury was found. Because there were neither clinical signs nor intra-abdominal injury reported on the CT-Scan, laparoscopy was not perform and the defect was closed by primary repair without the need of prosthetic material. Handlebar injury should be included within the differential diagnose at the moment of evaluating abdominal trauma with small surface object. Parent education about adequate cloth and protective equipFigure 3: Ultrasound demonstrating the rectus abdominis wall defect with omen- ment, including using a vest for protecting tum. Figure 4: CT-Scan showing the rectus abdominis wall defect. Figure 5: Hernial defect during surgery 60 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico abdomen when cycling, is a method to prevent and ameliorate such injury. Traumatic wall hernias after blunt trauma should be repaired primarily to avoid future complications. REFERENCES 1. Goliath J., Mittal V. and McDonough J. Traumatic Handlebar Hernia: A Rare Abdominal Wall Hernia pediatric surgery 2004; 1531-5037 2. Klimek P.M., Lutz T., Zanchariou Z., Kessler U., Berger S. Handlebar injuries in children Pediatric Surguery 2013; 29:269-273 3. Rathore A., Simpson B., Diefenbach A. Traumatic abdominal wall hernias: an emerging trend in handlebar injuries Journak of Pediatric Surgery 2012; 47:1410-1413 4. Kubalak G. Hanlerbar hernia: Case repot and review of literature The journal of trauma 1994; 0022-5284 5. Linuma Y., Yamazaki Y., Hirose Y., et al. A case of a traumatic abdominal wall hernia that could not be identified until exploratory laparoscopy was performed Pediatric Surgery int 2005; 21:54-57 6. Yan J., Wood J., Bevan C., Cheng W., Wilson G. Traumatic abdominal wall hernia- a case report and literature review Journal of Pediatric Surgery 2011, 46:1642-1645 7.Ku bota A., Shono J., Yonekura T., et al Handlebar hernia: case report and review of pediatric cases Pediatric Surgery Int. 1999, 15:411-412 8. Mancel B., Aslam A. Traumatic abdominal wall hernia: an unusual bicycle handlebar injury Pediatric Surgery Int 2003; 19:746-747 9. Decker S., Engelmann C., Krettek C., Muller C. Traumatic abdominal wall hernia after blunt abdominal trauma caused by a handlebar in children: A well-visualized case report Surgery 2012; 151:899-900 Figure 6: Surgical closure hernial defect. 10. Matsou S., Okada S., Matsumata T. Successful conservative treatment of a bicycle-handlebar hernia: report of a case Surgery Today 2007; 37(4):349-51 11. Upasani A., Bouhadiba N. Pediatric abdominal wall hernia following handlebar injury: should we diagnose more and operated less? BMJ Case Report 2013; 10.1136 RESUMEN La hernia de manubrio es una hernia abdominal traumática rara que ocurre después de trauma romo. Reportamos el caso de un adolescente con una hernia traumática en su musculo recto luego de trauma romo con el manubrio de su bicicleta. La abrasión en la piel y el abultamiento que ocurrió en el área del recto abdominal con la maniobra de Valsalva sugirieron el diagnostico. Las hernias traumáticas abdominal deben ser reparadas primariamente para evitar futuras complicaciones. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 61 SHOULD WE REVISIT ANTICOAGULATION GUIDELINES DURING THYROID STORM? Andrew W. Petersen MDa Gisela D. Puig-Carrión MDb Angel López-Candales MDc* Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio. b Department of Internal Medicine University of Puerto Rico School of Medicine, San Juan, Puerto Rico. c Cardiovascular Medicine Division , University of Puerto Rico School of Medicine, San Juan, Puerto Rico. *Corresponding Author: Angel López-Candales MD - University of Puerto Rico School of Medicine, Medical Sciences Building, PO Box 365067, San Juan, Puerto Rico 009365067. E-mail: [email protected] a ABSTRACT Thyroid storm is a rare but potentially catastrophic disease expression of thyrotoxicosis with well-recognized cardiovascular manifestations such as heart failure and atrial fibrillation. Even though some studies have found an increased risk of cardiac thrombus formation and subsequent thromboembolism in these patients, the use of anticoagulation to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation remains unclear. We present a patient presenting with new onset dilated cardiomyopathy and resistant atrial fibrillation with thyroid storm that had a large left atrial appendage clot. Case particulars are discussed and the literature reviewed. Index words: anticoagulation, guidelines, thyroid, storm INTRODUCTION and concomitant weight loss. Thyrotoxic (or thyroid) storm (or thyrotoxic crisis) is defined as a life-threatening condition caused by the exaggerated clinical manifestation of thyrotoxicosis. Although it is difficult to estimate the exact incidence of this condition; it is believed that thyroid storm accounts for < 1–2% of hospital admissions (1). If left untreated, it has a high reported mortality, ranging between 20% and 50% (2). On physical exam, her heart rate was 174 and irregular, blood pressure was 126/98 mmHg, respiratory rate was 36 per minute, and temperature was 96.9 F. She was somewhat anxious and diaphoretic, in no distress, and had a slight elevation in her jugular venous pressure noted with bibasilar rales. No ventricular gallops or murmurs were appreciated, but her point of maximal impulse was hyperkinetic and apically displaced. A 2+ bilateral pitting edema was noted as well as horizontal nystagmus and a fine resting tremor. Electrocardiogram showed atrial fibrillation with a rapid ventricular response with a rate of 184. Initial blood workup was unremarkable with the exception of her BNP that was 1277 pg/ml (<450), TSH 0.02 mIU/L (0.45-4.5), Free T4 > 7.0 ng/dl (0.61-1.76). Her thyrotropin receptor antibodies were found to be elevated at 18.91 IU/L (0-1.75) confirming the diagnosis of Grave’s disease. Thyroid storm is mediated not only by an acute and rapid rise in levels of circulating thyroid hormone, but also by enhanced cellular response to thyroid hormone (1). Specific effects of the thyroid hormone on the cardiovascular system have been well characterized. Sinus tachycardia is the most common manifestation of thyrotoxicosis, but atrial fibrillation is the most clinically relevant complication, occurring in an estimated 5% to 15% of patients with hyperthyroidism (3). In contrast, 62 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico transesophageal echocardiogram was performed. This not only confirmed left ventricular dilatation with global hypokinesis and severely reduced ejection fraction (see Figures 1A and 1B), but also identified the presence of a 7 mm thrombus with significant spontaneous echo contrast within the left atrial appendage (see Figures 2A and 2B). Because of the significant risk of embolization intravenous heparin and Warfarin were immediately initiated. The patient responded to standard heart failure therapy with Lisinopril, Toprol XL and required Furosemide as well. She was discharged home and has done remarkably well. On her six month follow-up appointment, she was euthyroid and in normal sinus rhythm. Repeat transesophageal echocardiogram not only showed normal left ventricular cavity size and ejection fraction of 60% (see Figures 3A and 3B); but also showed complete dissolution of her left atrial appendage clot (see Figure 4). DISCUSSION Thyroid hormone is an important regulator of cardiac function and cardiovascular hemodynamics. It is well established that triiodothyronine, (T3), the physiologically active form of thyroid hormone, binds to nuclear receptor proteins and mediates the expression of several important cardiac genes. Genomic pathway alterations include transcriptional activation and repression of target genes encoding structural and functional regulatory proteins of intracellular calcium handling, such as calcium activated ATPase and its inhibitory cofactor phospholamban (6, 7). Thyroid hormone also causes nongenomic alterations of cardiac inotropism and chronotropism, as well as causes an acute reduction in peripheral vascular resistance by promoting relaxation in vascular smooth muscle (8). Excess thyroid hormone causes an increase in sympathetic tone and a decrease in parasympathetic tone resulting in tachycardia and a widened pulse pressure. Through stimulation of erythropoietin secretion there is an increase in overall blood volume and preload. These clinically result in an increase in cardiac output (6, 7). Alterations in tissue responsiveness to catecholamines via modulation of adrenergic receptor expression or possible postreceptor modifications in the submembranic signaling pathways have also been implicated in clinical manifestation of excess thyroid hormone (1). As previously discussed, the development of atrial fibrillation occurs in 5 to 15 percent of patients with hyperthyroidism (7). A higher prevalence of atrial fibrillation is noted among older patients with known or suspected underlying organic heart disease (9). Treatment of hyperthyroidism is frequently associated with reversion to sinus rhythm approximately over a period of 8 to 10 weeks once patients have returned to a euthyroid state (10). This reversibility has resulted in the use of anticoagulation to prevent systemic embolization while in hyperthyroid associated Figure 1A: Transesophageal gastric view taken at the level of the papillary muscles showing the left ventricle in end-diastole. Figure1B: Transesophageal gastric view taken at the level of the papillary muscles showing the left ventricle in end-systole. atrial fibrillation to remain controversial (7). It is well established that while atrial fibrillation increases the risk of stroke; the absolute rate of stroke depends on age and comorbid conditions (11). Furthermore, the use of a classification scheme such as CHADS2 has been validated to help physicians make decisions regarding antithrombotic use in patients with this atrial dysrhythmia (11). Hyperthyroidism However, we believe that the interaction between thyrotoxicosis and cerebrovascular events needs to be revisited, particularly when the thyroid hormone is now known to shorten activated partial thromboplastin time, increase fibrinogen levels, and increase factor VIII and factor X activity (13, 14). These coagulation abnormalities have been linked to stroke in patients with thyrotoxicosis even while in normal sinus rhythm (5). Furthermore, alterations in hemostatic BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 63 mechanisms and platelet activation, as well as inflammation and growth factor changes have been well described in patients with atrial fibrillation (15). Finally, the presence of dilated cardiac chambers and reduced systolic function have also been implicated in the activation of inflammatory and neuroendocrine pathways, leading to endothelial dysfunction and a prothrombotic state with dysregulated platelets and activation of the coagulation cascade (16). Figure 2A: Midesophageal view showing the left atrium and left atrial appendage (LAA). In this view the black arrow demonstrates the presence of a echodense mass, suggestive of a clot within the LAA. Given the significant clot burden that was demonstrated in our patient, it was determined that she would clinically benefit from anticoagulation. She was started on intravenous Heparin and bridged to Warfarin successfully. On follow up, six months after her initial presentation even though she has continued to struggle with alcohol abuse as well as anxiety and depression; her left ventricular function returned to normal and there was complete resolution of the clot. Figure 3A: Transesophageal gastric showing the left ventricle in end-diastole. Early recognition of the clinical manifestations of hyperthyroidism is critical to the proper diagnosis and management of thyroid storm. Similarly important is to recognize the potential for cardiovascular involvement. More importantly, this case highlights an unresolved treatment issue in these patients with regards to anticoagulation in hyperthyroid patients with atrial fibrillation. A large scale prospective study is needed to revisit this critically important clinical dilemma, as in our case, it stands to reason that there was a significant benefit to anticoagulation therapy. REFERENCES Figure 2B: Midesophageal view showing the left atrium and left atrial appendage (LAA). In this view the black arrow shows the clot while the broken white arrow shows the presence of spontaneous echo contrast (sluggish blood flow in early stages of clot formation) within the LAA. In both images, both mitral valve leaflets (denoted by the white arrows) and part of the left ventricle are also seen. 64 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico 1. Sarlis NJ, Gourgiotis L. Thyroid emergencies. Rev Endocr Metab Disord. 2003; 4: 129-136. 2. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993; 22: 263-277. 3. Petersen P, Hansen JM. Stroke in thyrotoxicosis with atrial fibrillation. Stroke 1988;19(1):15-8. 4. Dahl P, Danzi S, Klein I. Thyrotoxic Figure 3B: Transesophageal gastric view showing the left ventricle in end-systole. Please note smaller left ventricular end-diastolic as well as systolic dimensions when compared with Figure 1A and B not only suggestive of resolution of left ventricular cavity dilatation, but also of improvement in left ventricular systolic function. BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 65 RESUMEN Figure 4: Midesophageal view showing the left atrium and left atrial appendage (LAA). In this view there is no spontaneous echo contrast or clot shown suggesting resolution of the blood stasis not that the patient is in normal sinus rhythm. cardiac disease. Curr Heart Fail Rep 2008;5(3):170-6. 5. Traube E, Coplan NL. Embolic risk in atrial fibrillation that arises from hyperthyroidism: review of the medical literature. Tex Heart Inst J. 2011; 38: 225-228. 6. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007 Oct 9;116(15):1725-35 7. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001; 344:501509. 8. Fazio S, Palmieri EA, Lombardi G, et al. Effects of thyroid hormone on the cardiovascular system. Recent Prog Horm Res. 2004; 59: 31-50. 9. Nordyke RA, Gilbert FI Jr, Harada ASM. Graves’ disease: influence of age on clinical findings. Arch Intern Med 1988; 148: 626631. 10. Nakazawa HK, Sakurai K, Hamada N, et al. Management of atrial fibrillation in the post-thyrotoxic state. Am J Med 1982; 72: 903-906. 11. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001; 285: 2864-2870. 12. Petersen P, Hansen JM. Stroke in thyrotoxicosis with atrial fibrillation. Stroke. 1988; 19: 15-18. 13. Franchini M, Montagnana M, Manzato F, et al. Thyroid dysfunction and hemostasis: an issue still unresolved. Semin Thromb Hemost 2009; 35: 288-294. 14. Erem C, Ersoz HO, Karti SS, et al. Blood coagulation and fibrinolysis in patients with hyperthyroidism. J Endocrinol Invest 2002; 25: 345-350. 15. Watson T, Shantsila E, Lip GY. Mechanisms of thrombogenesis in atrial fibrillation: Virchow’s triad revisited. Lancet. 2009; 373: 155166. 16. Bhatia RS, Ouzounian M, Tu JV, et al. Anticoagulation in patients with heart failure. Cardiovasc Hematol Agents Med Chem. 2009; 7: 193-197. 66 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico La tormenta tiroidea es una condición rara pero potencialmente catastrófica en la expresión de tirotoxicosis con reconocidas manifestaciones cardíacas, tales como insuficiencia cardiaca y fibrilación auricular. Aun cuando algunos estudios han documentado un aumento no solamente en el riesgo de formación de trombos; sino también de eventos tromboembólicos de origen cardíaco en estos pacientes, el uso de anticoagulantes para prevenir esta secuelas tromboembólicas en casos de fibrilación auricular asociados tirotóxicosis no están bien definido. Describimos el caso de una paciente fémina que se presenta con cardiomiopatía dilatada, fibrilación atrial resistente y coágulos en su aurícula atrial como consecuencia de tormenta tiroidea. Los particulares del caso se discuten y la literatura actual se revisa. DESCUENTO ESPECIAL A MIEMBROS DE LA AMPR Asociación Médica de Puerto Rico Desde 1902 apoyando a la clase médica y a los futuros profesionales de salud. Creando eventos y jornadas de educación y permitiendo la publicación de investigaciones en nuestro nuest BOLETIN