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science 30th September Impacted uterine myoma in a 14 week pregnant patient also Dengue vs. Leptospirosis, diagnosis and treatment from the first contact Recurrent incisional hernia sublay repair with fully reabsorbable monofilament mesh – a case report Dengue, for apparatus and systems Bionic Pancreas and Bionic Organs – how far we are from the success Fragments od bacterial DNA presence in hemodialisis patients’ blood-preliminary report Issue 3/2015 EDITORIAL OFFICE EDITORS-IN CHIEF Krzysztof Zieniewicz MD, PhD (Warszawa, Poland) Michal Wszola MD, PhD Piotr Witkowski (Chicago, USA) Prof. Artur Kwiatkowski MD, PhD Aleksandra Kukla (Mineapolis, USA) Sarah Ferber (Tel-Aviv, Israel) ASSOCIATE EDITORS Yulian Mytsyk (Lviv, Ukraine) Piotr Domagala MD, PhD Antonio Secchi (Milan, Italy) Rafal Kieszek MD, PhD Riccardo Audisio (Liverpool, UK) Karolina Kłoda MD, PhD Monika Bieniasz MD, PhD Jerzy Bednarski MD Jeffrey Eakin MD LINGUISTIC EDITOR Anna Stucky Dennis K. Bielecki (Birmingham, UK) Jeffrey Eakin MD (Salt Lake City, USA) PUBLISHER MEDtube Ltd. Złota 59 street; 00-120 Warsaw, Poland Tel.+4822 2402234 Fax. +4822 2224601 SCIENTIFIC BOARD MEMBERS Stanislav Czudek MD, PhD (Ostrava, Czech Republic) US OFFICE Mohan Desarda MD, PhD (Poona, India) 55 Tiemann Place Takuji Gotoda MD, PhD (Tokyo, Japan) Suite 29; New York, NY 10027, United States Atsushi Irisawa MD, PhD (Fukushima, Japan) Shekhar Kumta MD, PhD (Hong Kong, China) WEBMASTERING AND IT Milan Profant MD, PhD (Bratislava, Slovak Republic) Adrian Fester Shomei Ryozawa MD, PhD (Saitama, Japan) José Pedro da Silva MD, PhD (Sao Paulo, Brasil) COPYRIGHT Pinghong Zhou MD, PhD (Shanghai, China) MEDtube Ltd. 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Adam Dziki MD, PhD (Lodz, Poland) Ireneusz Krasnodębski MD, PhD (Warszawa, Poland) Maciej Michalik MD, PhD (Olsztyn, Poland) Anna Nasierowska – Guttmejer MD, PhD (Warszawa, Poland) Krzysztof Paśnik MD, PhD (Warszawa, Poland) Dariusz Patkowski MD, PhD (Wroclaw, Poland) Piotr Richter MD, PhD (Krakow, Poland) PRINT RUN 500 Witold Rużyłło MD, PhD (Warszawa, Poland) Teresa Starzyńska MD, PhD (Szczecin, Poland) Wiesław Tarnowski MD, PhD (Warszawa, Poland) CONTACT [email protected] Janusz Trzebicki MD, PhD (Warszawa, Poland) Grzegorz Wallner MD, PhD (Lublin, Poland) Marian Zembala MD, PhD (Zabrze, Poland) WEBSITE http://www.medtube.net/science Dear Colleagues, MICHAŁ WSZOŁA MD, PhD Editor in Chief We are pleased to present another issue of MEDtube Science - an open access publication distributed online. MEDtube Science is addressed to all medical professionals – physicians, researchers who are interested in achievements in basic and clinical medical science. MEDtube Science is supposed to satisfy the demand for combining different formats - video and written science in particular. The journal has international scope. It will be published quarterly and exclusively in English. Original articles, reviews, ARTUR KWIATKOWSKI MD, PhD Editor in Chief case reports, rapid communications, special articles and letters to the Editor in both basic and clinical medical research are accepted for publication with particular stress on manuscripts enriched with multimedia such as videos or pictures. We have strong confidence that this new project will be quickly recognized in Medline and other medical bases and will become an indexed journal with impact factor. At the end of our journal you will find information and instructions for authors on how to submit articles. We are also pleased to inform you that in 2014 there will be no fee for accepted articles – so do not waste time – send us your paper. Kindest Regards, Michal Wszola MD, PhD Editor-in Chief Artur Kwiatkowski MD, PhD Editor-in Chief MEDtube Science Sep, 2015; Vol.III (3) TABLE OF CONTENTS Impacted uterine myoma in a 14 week pregnant patient Agnieszka Dobrowolska-Redo, Justyna Teliga-Czajkowska, Ewa Romejko-Wolniewicz et al PAGES 8-10 Dengue vs. Leptospirosis, diagnosis and treatment from the first contact Luis del Carpio Orantes PAGES 11-13 Recurrent incisional hernia sublay repair with fully reabsorbable monofilament mesh – a case report Magdalena Kwapisz, Michał Wszoła, Piotr Domagała et al PAGES 14-20 Dengue, for apparatus and systems Luis del Carpio Orantes PAGES 21-24 Bionic Pancreas and Bionic Organs – how far we are from the success Michal Wszola, Joanna Idaszek, Andrzej Berman et al PAGES 25-27 Fragments od bacterial DNA presence in hemodialisis patients’ blood-preliminary report Marta Serwańska-Świętek, Marzena Sikora, Bożena Interewicz et al PAGES 28-31 MEDtube Science Sep, 2015; Vol.III (3) science 8 Uterine myomas are some of the most frequent neoplasms in women in the reproductive age. Impacted uterine myoma in a 14 week pregnant patient Agnieszka Dobrowolska-Redo1, Justyna Teliga-Czajkowska2#, Ewa Romejko-Wolniewicz1, Julia Zaręba-Szczudlik1, Krzysztof Czajkowski1 1. The 2nd Department of Obstetrics and Gynecology of Warsaw Medical University, Poland 2. Department for Didactics of Gynaecology and Obstetrics, Faculty of Health Sciences, Medical University of Warsaw, Karowa St 2, p.o. box 00-315 Warsaw, Poland. Tel. +48 22 5966 421, Fax +48 22 5966 487 #Corresponding author: Justyna Teliga-Czajkowska e-mail: [email protected] Karowa St 2, p.o. box 00-315 Warsaw, Poland Tel. +48 22 5966 421, Fax +48 22 5966 487 RUNNING TITLE Impacted uterine myoma KEYWORDS myoma, pregnancy, impacted submucosal myoma WORD COUNT 1 437 CONFLICT OF INTERESTS no conflicts of interest No supplemental data have been included with the submission ABSTRACT Uterine myomas are some of the most frequent neoplasms in women in the reproductive age. The frequency of uterine myomas in pregnancy varies between 0.1 and 3.9 %. The pregnancy in a woman with uterine myomas is usually uncomplicated, but in 10% of them, the myomas may cause symptoms. The study presents the case of a pedunculated submucosal myoma impacted in the rectouterine pouch in a woman 14 weeks pregnant. INTRODUCTION U terine myomas are some of the most frequent neoplasms in women in the reproductive age (1,2). The frequency of uterine myomas in pregnancy varies between 0.1 and 3.9 % (2,3,4,5). Most of them appear without any symptoms. The pregnancy in a woman with uterine myomas is usually uncomplicated, but in 10% of them the myomas may cause pain in the small pelvis, miscarriage, bleedings, premature delivery, premature leaking of amniotic fluid (3,4,6,7). During the delivery, the presence of myomas may be conducive towards incorrect position of the fetus, shoulder dystocia, increased risk of delivery with a procedure, and caesarean section. After delivery, myomas may cause bleeding and placental tissue retention (3,4,6,7). Myomectomy during the planned caesarean section seems to be the safe method (8,9), while myomectomy during pregnancy is associated with higher risk of bleeding, increased MEDtube Science Sep, 2015; Vol.III (3) science 9 mortality of mothers, and risk of losing the pregnancy (9). Only 2% of women require an urgent surgical intervention during pregnancy (7). It is believed that surgical intervention should be considered in the case when the pain symptoms persist for 72 hours despite analgesic treatment (5,7). Pedunculated myomas may be particularly dangerous in case they become wedged-in, while their removal bears a lower risk of perioperative bleedings. The study presents the case of a pedunculated submucosal myoma impacted in the rectouterine pouch in a 14 weeks pregnant woman. CASE DESCRIPTION The patient was a 33 year old primigravida, admitted to the hospital while 14 weeks pregnant, as an emergency case, due to the complaints of hypogastric pains intensifying for 3 days, not disappearing after administration of analgesic medications. Until the complaints, the course of pregnancy had been without complications. The ultrasound examination in 6th week of pregnancy presented a living fetus consistent with the pregnancy age. On the posterior wall a pedunculated myoma 99x51 mm was discovered. In a follow-up ultrasound examination in the 12th week of pregnancy, the myoma was found to grow, to the dimensions of 114x74mm. After admitting the patient to the Clinic, her general condition was good, however there appeared strong pains of the hypogastrium radiating to the anus. The blood arterial pressure maintained at the level of 125/85 mmHg, pulse 90/minute, temperature within normal limit. In the gynaecological examination, there was discovered that the vaginal part was behind the pubic symphysis of the length of 2 cm, uterus of correct tone, and at the same time significant muscular pain occurred when moving the uterus. The rectouterine pouch was bulging, tender, filled with a hard tumor of the diameter of about 10 cm – probably an impacted myoma. The patient was informed of indications to an urgent surgical intervention. The abdominal cavity was opened in midline from the pubic symphysis to the navel. During the operation, there was revealed the pulpy body of the uterus, expanded, consistent with the week of pregnancy. Behind the uterus, in the rectouterine pouch, there was discovered an impacted pedunculated submucosal myoma, dimensions 15x8 cm, extruding from the posterior wall from the area of the left horn of the uterus, pulling the uterus posteriorly. The diameter of the peduncle was 2 cm. Apart from that, there were also present two intramural myomas in the anterior wall, each of the diameter of about 2 cm. Due to the difficulty in extracting the impacted myoma, a decision was made during the operation to additionally cut the upper border of the wound, at the angle of 70 degrees, omitting the navel. Through bipolar coagulation, the myoma was removed and the peduncle was fixed with single sutures. The post-operative course was without complications. The patient was discharged on the 8th day, in a good general condition, with live pregnancy. The MEDtube Science Sep, 2015; Vol.III (3) delivery was without complications, natural, at term. DISCUSSION Myomas, in the course of pregnancy, are diagnosed in between 0.1% to even 12.6 women (10,11). Myomas of the size of over 3 cm are discovered in ultrasound examinations in about 4.17% pregnancies (4). As per the research by Muram et al. (12), 42% of myomas are discovered during physical examinations of pregnant women, but in the group of myomas of the size of 3-5 cm, that rate is only 12.5%. It is getting more difficult to locate myomas together with the progress of pregnancy. In many cases, the presence of myoma or myomas, is discovered accidentally during caesarean section (13). According to Muram et al. (12), only in about 41% cases, the presence of myomas is known to the physician supervising the pregnancy. Pregnancy is the period when the uterus becomes significantly enlarged, and the concentrations of hormones - both estrogens and progesterone – are high (14). The impact of pregnancy on changing the size of myomas, is difficult to determine. About 22% to 32% myomas are enlarged during pregnancy, while 7.8% to 19% decrease in volume (15,16). As per the research by Hammoud et al. (2), in the systematic ultrasound examinations between the first half of a pregnancy and its 20th/30th week, a little over one half of myomas shrink, on average in about 35% cases. The remaining myomas (45%) significantly expand in that period, on average by 69%. The changes in volume may depend on the initial size of myomas. A fast growing myoma during pregnancy may cause strong pains, compression on the alimentary canal, and, in additional examinations, look like an oncologically suspicious lesion (17,18). In the case of a polycystic lesion, with uneven echogenicity, it is only possible to distinguish between a necrotic myoma and a sarcoma, on the basis of a microscopic examination. The presence of myomas causes a more frequent occurrence of caesarean sections, by about 25-100% in comparison with other patients (4,6,19,20,21). Coronado et al. (22) analyzed the course of pregnancies of 2065 women with myomas and 4243 without myomas, and discovered that the patients with myomas much more often developed bleedings in early pregnancy (OR=1.82; 95% CI 1.053.20), premature placental abruption (OR=3.87 1.639.17), hydramnion (OR=2.44; 95% CI 1.02-5.84). The authors also recorded disturbances during delivery in the form of incorrect course of delivery (OR=1.85, 95% CI 1.26-2.72), frequency of breech position (OR=3.98; 95% CI 3.07-5.16), percentage of caesarean sections (OR=6.39; 95% CI 5.46-7.50), more frequent deliveries before the 38th week of pregnancy (OR=1.47; 95% CI 1.16-1.87), more children with the mass of < 2500g (OR=1.99; 95% CI 1.51-2.62) and assessed at < 7 points in the Apgar scale in the 5th minute of life (OR=2.49; 95% CI 1.49-4.15). Very similar results in a group of 690 pregnant women with myomas, were presented by Sheiner et al. (23). The operations of removing myomas during pregnan- science cy are conducted relatively rarely, usually due to such reasons as pains, compression on the urinary bladder and urinary retention, fast expansion of the lesion. The main complications of the procedures conducted during pregnancy is premature end of pregnancy (miscarriage, premature labor) and bleeding. However, in the research conducted by Lolis et al., only one miscarriage (5) was recorded among 13 pregnant women subject to myomectomy. However, it should be remembered that the very presence of myomas, may also be conducive to miscarriages and preterm labor (22, 24). Most cases of removal of myomas during pregnancy appear in the case of subserous myomas, between 14th and 19th week of pregnancy (7,9,25). In literature, there are also described cases of extirpating intramural myomas (25). The procedures are performed by laparotomy or laparoscopy (26). The available literature also describes the cases of extirpation of more than one myoma (27). A unique situation occurs when the uterus and myoma are impacted in the small pelvis. A typical symptom is urinary retention and hypogastric pains (28). Similar symptoms appear in the case of a pregnancy with the uterus with permanent retroflexion. In the case described by us, the decision on the surgery was made due to persisting hypogastric pains, not regressing despite administration of analgesic medications. During the surgery, it was discovered that those pains were caused by the herniation of the pedunculated myoma in the rectouterine pouch and the fact that the patient’s uterus was “pulled” posteriorly, thus limiting its mobility and growth. The pain caused by the presence of the myoma, or resulting from its ischemia, may be treated by means other than surgery. The first step should be the attempt to apply opioids, or extradural anesthesia for several days (29, 30, 31). Surgical extirpation of myomas in pregnancy is associated with higher risk of miscarriage and bleeding. Based on the data available, most patients after surgery will deliver the baby in term. The surgical treatment of patients with uterine myomas is a significant challenge, and requires detailed analysis of indications to the surgery and the resulting risks. 10 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. CITE THIS AS 30. MEDtube Science 2015, Sep 3(3), 8 - 10 31. BIBLIOGRAPHY 1. 2. 3. 4. 5. 6. 7. gnancy: a feasible option. J Obstet Gynaecol Res 2009;35(1):173-175. Roman AS, Tabsh KM. Myomectomy at time of cesarean delivery: a retrospective cohort study. BMC Pregnancy Childbirth 2004;16;4(1):14. Umezurike C, Feyi-Waboso P. Successful myomectomy during pregnancy: a case report. Reprod Health 2005;16(2):6. Cooper NP, Okolo S. Fibroids in pregnancy--common but poorly understood. Obstet Gynecol Surv 2005;60(2):132-138. Kolankaya A, Arici A. Myomas and assisted reproductive technologies: when and how to act? Obstet Gynecol Clin North Am. 2006;33(1):145152. Muram D, Gillieson M, Walters JH. Myomas of the uterus in pregnancy: ultrasonographic follow-up. Am J Obstet Gynecol. 1980;138(1):1619. Kaymak O, Ustunyurt E, Okyay RE, Kalyoncu S, Mollamahmutoglu L. Myomectomy during cesarean section. Int J Gynaecol Obstet 2005;89(2):90-93. Ishikawa H, Ishi K, Kakazu R, Bulun SE, Kurita T. Estrogen and progesterone are concurrently required for uterine leiomyomata enlargement in a novel in vivo model. Fertil Sterl 2009; 92(3)Suppl.S43. Aharoni A, Reiter A, Golan D, Paltiely Y, Sharf M. Patterns of growth of uterine leiomyomas during pregnancy. A prospective longitudinal study. Br J Obstet Gynaecol 1988;95(5):510-513. Rosati P, Exacoustos C, Mancuso S. Longitudinal evaluation of uterine myoma growth during pregnancy. A sonographic study. J Ultrasound Med 1992;11(10):511-515. Matsuo K1, Mighty HE, Im DD, Rosenshein NB. A rapid-growing uterine mass during pregnancy: a fast-growing uterine mass complicated a first pregnancy. Am J Obstet Gynecol 2008;199(4):440. Donnez J, Pirard C, Smets M, Polet R, Feger C, Squifflet J. Unusual growth of a myoma during pregnancy. Fertil Steril 2002;78(3):632-633. Davis JL, Ray-Mazumder S, Hobel CJ, Baley K, Sassoon D. Uterine leiomyomas in pregnancy: a prospective study. Obstet Gynecol 1990;75(1):41-44. Katz VL, Dotters DJ, Droegemeuller W. Complications of uterine leiomyomas in pregnancy. Obstet Gynecol 1989;73(4):593-596. Rice JP, Kay HH, Mahony BS. The clinical significance of uterine leiomyomas in pregnancy. Am J Obstet Gynecol 1989;60(5 Pt 1):12121216. Coronado GD, Marshall LM, Schwartz SM. Complications in pregnancy, labor, and delivery with uterine leiomyomas: a population-based study. Obstet Gynecol 2000;95(5):764-769. Sheiner E, Bashiri A, Levy A, Hershkovitz R, Katz M, Mazor M. Obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas. J Reprod Med 2004;49(3):182-186. Mollica G, Pittini L, Minganti E, Perri G, Pansini F. Elective uterine myomectomy in pregnant women. Clin Exp Obstet Gynecol 1996;23(3):168-172. Lozza V, Pieralli A, Corioni S, Longinotti M, Penna C. Multiple laparotomic myomectomy during pregnancy: a case report. Arch Gynecol Obstet 2011;284(3):613-616. Marret H1, Chevillot M, Giraudeau B. A retrospective multicentre study comparing myomectomy by laparoscopy and laparotomy in current surgical practice. What are the best patient selection criteria? Eur J Obstet Gynecol Reprod Biol 2004;117(1):82-86. Lozza V, Pieralli A, Corioni S, Longinotti M, Penna C.. Multiple laparotomic myomectomy during pregnancy: a case report. Arch Gynecol Obstet 2011;284(3):613-616. Chauleur C, Vulliez L, Seffert P. Acute urine retention in early pregnancy resulting from fibroid incarceration: proposition for management. Fertil Steril. 2008;90(4):1198. Hasbargen U, Strauss A, Summerer-Moustaki M et al. Myomectomy as a pregnancy-preserving option in the carefully selected patient. Fetal Diagn Ther;17(2):101-103. Seki H, Takizawa Y, Sodemoto T.Epidural analgesia for painful myomas refractory to medical therapy during pregnancy. Int J Gynaecol Obstet 2003;83(3):303-304. Treissman DA, Bate JT, Randall PT. Epidural use of morphine in managing the pain of carneous degeneration of a uterine leiomyoma during pregnancy. Can Med Assoc J 1982;126(5):505-631. Marshall LM, Spiegelman D, Barbieri RL et al. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet Gynecol. 1997;90(6):967-973. Hammoud AO, Asaad R, Berman J et al. Volume change of uterine myomas during pregnancy: do myomas really grow? J Minim Invasive Gynecol 2006;13(5):386-902. Qidwai GI, Caughey AB, Jacoby AF. Obstetric outcomes in women with sonographically identified uterine leiomyomata. Obstet Gynecol 2006;107(2):376-382. Exacoustos C, Rosati P. Ultrasound diagnosis of uterine myomas and complications in pregnancy. Obstet Gynecol 1993;82(1):97-101. Lolis DE, Klantaridou SN, Makrydimas G et al. Successful myomectomy during pregnancy. Hum Reprod 2003;18(8):1699-1702. Vergani P, Ghidini A, Strobelt N et al. Do uterine leiomyomas influence pregnancy outcome? Am J Perinatol 1994;11(5):356-358. Bhatla N, Dash BB, Kriplani A, Agarwal N. Myomectomy during pre- MEDtube Science Sep, 2015; Vol.III (3) science 11 Dengue infection occurs, without doubt, at high incidence and prevalence rates in endemic tropical areas, including Mexico. Dengue vs. Leptospirosis, diagnosis and treatment from the first contact Luis del Carpio Orantes1 1. Department of Internal Medicine, General Hospital 71, Mexican Institute of Social Security, Veracruz, Veracruz, Mexico #Corresponding author: Luis del Carpio Orantes, E-mail: [email protected]. RUNNING TITLE Dengue vs. leptospirosis KEYWORDS dengue, leptospirosis WORD COUNT 942 CONFLICT OF INTERESTS no conflicts of interest ABSTRACT Dengue infection occurs, without doubt, at high incidence and prevalence rates in endemic tropical areas, including Mexico. Another big issue that physicians from the emergency room are facing, are infections that often simulate dengue symptoms, primarily through the bacterial infection caused by Leptospira, whose rate has increased in some regions. Unfortunately, there is no specific diagnosis done in this matter. Below there is a series of comparisons between the two infections listed. Both clinical and biochemical data has been provided for this cause. D engue infection occurs, without doubt, at high incidence and prevalence rates in endemic tropical areas, including Mexico. Despite primary prevention programs and vector control, the infection is hard to be eradicated and continues to claim lives every year. Yet, different strategies are used to reduce the incidence and mortality. Another big issue that physicians from the emergency room are facing, are infections that often simulate dengue symptoms, primarily through the bacterial infection caused by Leptospira, whose rate has increased in some regions. Unfortunately, there is MEDtube Science Sep, 2015; Vol.III (3) no specific diagnosis done in this matter and consequently, no appropriate subsequent treatment has been introduced to decrease the rate of mortality and lethality in this region. Current medical practice, based on medicine stocks, rather than evidence caused that many doctors do not sufficiently regulate nor standardize practices such as „prophylactic” use of antimicrobials in all patients with dengue or suspected dengue. In such situation it is difficult to avoid failure to diagnose leptospirosis symptoms properly or let it pass unnoticed. One has to remember that patient may not have an accurate serological or microbiological diagnosis, science which can result from iatrogenic allergic reactions , bacterial resistance, use inappropriate and exaggerated antimicrobials, etc. Although the clinical pictures are similar and can often be confused, there are some key points that the doctor should know and understand in his first contact with the patient to skillfully discern the difference. Coexistence cases of dengue infection and Leptospira are virtually not possible to be differentiated. Even though, its existence has not been recorded in the literature, it rarely occurs. Below there is a series of comparisons between the two infections listed. Both clinical and biochemical data has been provided for this cause. Currently, the primary care physician should have the clinical acumen to suspect a possible dengue and differentiate leptospirosis hidden symptoms, for which there are some basics to consider. It is because the clinical picture is very similar in both cases. However in case of Leptospira there are some key symptoms that may arise from the clinical review. These are: data conjunctival hemorrhage, muscle involvement manifested as myalgia and more exaggerated toward the pelvic limbs cramps and jaundice. Typically, the biochemical features of dengue, show hemoconcentration, leucopenia, thrombocytopenia, lymphocytosis, in some cases, the onset of symptoms, which usually indicate free viruses. Yet, in cases of leptospirosis, leukocytosis combined with thrombocytopenia, there is a suspicion of the entity, which is related to a bacterial symptoms. In viruses, there is usually mild transaminasemia (rarely more than two or three times the normal value), rarely jaundice or hiperbilirubinemia, hypoalbuminemia, rarely elevated nitrogenous can be found (reserved for severe cases, or severe hypoperfusion shock) and moves towards gravity are gradual, unless the patient undergoes medical review late. Leptospira infection, in contrast, is often initially depicted with a bulky box and severe hepatic involvement, which in severe cases (Weil’s disease) are more apparent, with transaminasemia severe hiperbilirubinemia and acute kidney injury data with elevation of data nitrogenous and respiratory or cardiac failure (11,17,18). Clinical hospitals often use rapid diagnostic reagents , which help clarify the diagnostic doubt. However, in many rural hospital settings there is a deficiency of resources, which may discern between an entity or other, coupled with basic data clinical laboratory. The problem may be resolved by a study done to measure serum procalcitonine, which normally increases in bacterial or fungal infections, but not in viral conditions. Due to the above factors, it was sometimes decided to start prophylactic or preventive chemotherapy. However it has been shown that those measures have not had a significant impact on the resolution of the pictures and sometimes carry adverse gastrointe- 12 stinal or allergic effects. Similarly, in identified endemic areas and where there is need for humans exposed to these areas, prophylactic doses have been administered, yet with mixed results. For prophylaxis it is recommended to use primarily Doxycycline 200mg per week. There is no increase in gastrointestinal symptoms, mainly nausea and vomiting, and no greater benefit on the incidence, seroconversion or resolution of infection is demonstrated (8,9,10). In our environment, we have chosen to administer parenteral crystalline sodium based penicillin or cephalosporin. However, there are no studies done to support this practice but only to recommend initiation of empirical antibiotic therapy in patients with high suspicion of leptospirosis demonstrated in pictures, which was initially classified as dengue. In this case parameters of high clinical and biochemical suspicion of both entities were advised to be considered. They are summarized in table 1 and 2. While there are pictures of severe dengue with multiorgan involvement that cannot be distinguished clinically or biochemically as leptospirosis, and to keep such critically ill patients is justifiable treating them with empirical antibiotic therapy, then in mild cases , which only show dengue fever or severe dengue, it is not (1,2,3,4,5,6,7). Finally, it needs to be taken into consideration that these infections are associated with atypical paintings, which have rarely been reported in the world literature. Medical contrast images of dengue virus infection with leukocytosis ( some series reported up 4.4%), and worse, coexistence of both infections , dengue, leptospirosis but in one patient at a time , making it extremely difficult to differentiate and treat them separately , especially if it comes to symptoms or mild anicteric leptospirosis , indicating these rare or unusual cases. Antibiotics were used to prevent progression to multiorgan failure and death. Current patterns of prophylaxis in endemic and high incidence of leptospirosis are based on oral doxycycline in weekly doses, and treatment schedules are varied, from use of crystalline sodium penicillin aminopenicillins, cephalosporins 3rd generation, doxycycline, macrolides, quinolones, etc, lasting 7-10 days (12, 13, 14, 15, 16). CITE THIS AS MEDtube Science 2015, Jun 4(3), 11 - 13 LIST OF THE TABLES Tab. 1. Epidemiological and clinical differences Tab. 2. Differences and recommendations MEDtube Science Sep, 2015; Vol.III (3) science 13 TAB. 1. EPIDEMIOLOGICAL AND CLINICAL DIFFERENCES Dengue Infectious agent Transmission Leptospirosis Denguevirus (DEN- 1 to DEN -4) RNA virus, Flavivirus family. Strict aerobic bacteria, spirochetes of the family, and the genus Leptospira. More than 200 infectious serovars. vector, Aedes Egypti mosquito Dermal or mucosal contact with sub-stances or contaminated by the urine of infected species other foods. Sharp sudden fever, headache, muscle aches, abdominal pain, nausea, vomiting. Clinical picture Acute febrile sudden onset accompanied by headache, muscle aches, retro orbital pain, nausea, vomiting, and rash. TAB. 2. DIFFERENCES AND RECOMMENDATIONS * Clinical picture mild anicteric. * Clinical picture with severe hepatic, renal , myocardial and / or neurological (Weil’s Disease) Symptoms and signs of increased likelihood of leptospirosis: exaggerated muscle pain , mainly in calves, Conjunctivitis or conjunctival effusion, or generalized scleral jaundice, hepatalgia , anuria, acute respiratory failure , angina by hemorrhagic myocarditis Suspicion clinical Dengue Acute febrile syndrome accompanied by headache, retro-orbital pain, muscle aches, rash Hemoconcentration (hematocrit ratio / Hb) Lymphocytosis initial, Leukopenia, Thrombocytopenia, Mild transaminemia Leptospirosis Clinically similar to dengue. Spill or conjunctival hemorrhage. Intense muscle aches, leg cramps. Jaundice Anuria. Dyspnea, cyanosis. Angina Leukocytosis combined with thrombocytopenia. Azotemia Transaminemia severe Hyperbilirubinemia. Acute respiratory failure (hypoxemia) Diagnosis Early Detection : * NS1 * IgM and IgG There is no specific treatment. Vigorous hydration. Treatment Symptomatic treatment Advanced life support and critical care (severe). Various antimicrobial * Natural Penicillins (risk of Jarisch- Herxheimer ) . * Aminopenicillins (ampicillin, amoxicillin). * 3rd generation cephalosporins (cefotaxime , ceftriaxone ) * Doxycycline * Macrolides (azithromycin, erythromycin ) * Quinolones Advanced life support and intensive care in severe cases. 1. 2. 3. 4. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. MEDtube Science Sep, 2015; Vol.III (3) Recommendation Not start antimicrobial Start empirical antibiotics, even without waiting for a rapid diagnostic test. BIBLIOGRAPHY 5. * Dark field Microscopy (direct) in blood, CSF or urine. * PCR * Microscopic agglutination test (MAT) * IgM and IgG Suspicion biochemistry Faucher JF, Hoen B, Estavoyer JM. The management of leptospirosis. Expert Opin Pharmacother. 2004 Apr;5(4):819-27. Suputtamongkol Y, Niwattayakul K, Suttinont C, et-al. An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis. Clin Infect Dis. 2004 Nov 15;39(10):1417-24. Griffith ME, Hospenthal DR, Murray CK. Antimicrobial therapy of leptospirosis. Curr Opin Infect Dis. 2006 Dec;19(6):533-7. Phimda K, Hoontrakul S, Suttinont C, et-al. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob Agents Chemother. 2007 Sep;51(9):3259-63. Charan J, Saxena D, Mulla S, et-al. Antibiotics for the treatment of leptospirosis: systematic review and meta-analysis of controlled trials. Int J Prev Med. 2013 May;4(5):501-10. Brett-Major DM, Coldren R. Antibiotics for leptospirosis. Cochrane Database Syst Rev. 2012 Feb 15; 2:CD008264 Guerrier G, D’Ortenzio E. The Jarisch-Herxheimer reaction in leptospirosis: a systematic review. PLoS One. 2013; 8(3):e59266. Guidugli F, Castro AA, Atallah AN. WITHDRAWN: Antibiotics for preventing leptospirosis. Cochrane Database Syst Rev. 2009 Jul 8 ;(3):CD001305 Brett-Major DM, Lipnick RJ. Antibiotic prophylaxis for leptospirosis. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007342. Bhardwaj P, Kosambiya JK, Vikas KD, et-al. Chemoprophylaxis with doxycycline in suspected epidemic of leptospirosis during floods: does this really work? Afr Health Sci. 2010 Jun;10(2):199-200. Vielma, S., Muñoz, M., Pérez.Lo Presti, S. et.al. Hallazgos clínicos y de laboratorio en pacientes con dengue. Revisión de criterios diagnósticos. Revista de la Facultad de Farmacia, Vol. 48 (1) 2006 Cabello MA, Cabral MB, Samudio M. Dengue y leptospirosis compartiendo el mismo nicho ecológico en la localidad ribereña de Carmen del Paraná (Itapúa). Mem. Inst. Investig. Cienc. Salud, Vol. 6(1) Junio 2010: 35-40 Crociati,L.y Onofre de Medeiro Jr, H. Coinfección por leptospirosis y dengue en un paciente de la amazonía brasileña. Rev Pan-Amaz Saude 2010; 1(4):97-99. Navarrete Espinosa, Joel, Acevedo Vales, Juan Antonio, Huerta Hernández, Emilia, et-al. Prevalencia de anticuerpos contra dengue y leptospira en la población de Jáltipan, Veracruz. Salud Pública de México 2006, mayo-junio, 220-228. Gonsalez CR, Casseb J, Monteiro FG, et.al. Use of doxycycline for leptospirosis after high-risk exposure in São Paulo, Brazil. Rev Inst Med Trop Sao Paulo. 1998 Jan-Feb; 40(1):59-61. Edwards CN, Levett PN. Prevention and treatment of leptospirosis. Expert Rev Anti Infect Ther. 2004 Apr; 2(2):293-8. Dengue: Guidelines for treatment, prevention and control. Geneva: World Health Organization, 2009. Simmons, CP., Farrar, JJ., Van Vinh Chau, N., et-al., Dengue. N Engl J Med 2012; 366:1423-32. science 14 Incisional hernia is a common postoperative complication of abdominal surgery, with the incidence ranging from 11% up to 20% of all laparotomy incisions. Recurrent incisional hernia sublay repair with fully reabsorbable monofilament mesh – a case report Magdalena Kwapisz 1, Michał Wszoła1#, Piotr Domagała1, Piotr Góralski 1, Agnieszka Nalewajek 1, Anna Zuchowska2, Andrzej Chmura1, Artur Kwiatkowski1 1. Department of General and Transplantation Surgery, Warsaw Medical University, Warsaw, Poland 2. Department of Clinical Radiology, Warsaw Medical University, Warsaw, Poland # Corresponding author: Michał Wszoła MD, PhD, ul. Nowogrodzka 59 , 02-006 Warsaw, Poland. Phone:+48225021470, e-mail: michal. [email protected] RUNNING TITLE Incisional hernia sublay repair KEYWORDS incisional hernia, recurrent hernia, hernia repair, sublay method, sublay hernioplasty, reabsorbable mesh, phasix WORD COUNT 1 963 CONFLICT OF INTERESTS no conflicts of interest ABSTRACT Incisional hernia is the most common indication for reoperation after abdominal surgery. Mesh hernioplasty is almost a gold standard of treatment, associated with the low recurrence rate. Study presents a case of usage of a fully reabsorbable mesh for successful sublay hernioplasty in recurrent incisional hernia with a past history of many wound complications. INTRODUCTION I ncisional hernia is a common postoperative complication of abdominal surgery, with the incidence ranging from 11% up to 20% of all laparotomy incisions [1, 2] and the most common indication for reoperation after laparotomy [3]. It is defined as a defect occurring through the operative scar, caused by a failure of the lines of closure of abdominall wall. Thereby, it is the only hernia considered to be truly iatrogenic. The most common incision of previous surgery leading to incisional hernia is the infraumbilical or supraumbilical midline incision, followed by Pfannenstiel’s incision, paramedial, lumbar and right subcostal [4, 5]. Not only a closure technique and suture materials have an effect on hernias incidence. Postoperative wound infection and patient factors, such as advanced age, obesity, diabetes mellitus, MEDtube Science Sep, 2015; Vol.III (3) 15 tobacco abuse, hypoproteinemia, corticosteroid use and immunosupresion are esthablished risk factors of hernia formation likewise [4, 6, 7]. Most of incisional hernia require elective surgical repair, because of becoming larger and causing morbidity complications if left untreated. A great variety of surgical techniques have been adopted for the repair of abdominal incisional hernias. Nowaday, the best results are believed to be achieved by the implantation of prosthetic mesh [8] and the use of prosthetic material is almost a standard practise. Fibrous tissue, while growing in the porous mesh, consolidates the abdominal wall and disperses intraabdominal pressure, to prevent a recurrence of hernia. Anatomical repair is associated with recurrence rates about 2350% [9, 10, 11] in comparison to 1,5-10% following prostetic mesh repair [12]. As in general, diabetes mellitus, obesity, smoking, postoperative straining and advanced age are also established risk factors of recurrence [4]. Despite of its significant benefits, a mesh should be treated as a foreign material and susceptible to infection, sinus formation or enteric fistulization [13]. The foreign body implantation may lead to chronic inflammation or excessive fibrosis and may result in increased stiffness and loss of pliability at the site of sewing [10, 14]. There is no general agreement as to the best choice of one of many prosthetic mesh repair techniques that have been proposed. The material can be placed between the subcutaneus tissues of the abdominal wall and the anterior rectus sheath (named onlay method) as well as in the preperitoneal plane created between the rectus muscle and posterior rectus sheath (named sublay method). This study reports a case of usage of a fully reabsorbable Phasix Mesh for sublay hernioplasty of recurrent incisional midline hernia after a primary surgery by Pfannenstiel’s incision and hernioplasty with polypropylene mesh complicated by surgical site infection. CASE REPORT In July 2014, 62 y.o. female admitted to the surgical department with a complaint of the recurrent ventral hernia and the symptoms of pain and movement limitations while performing activities of her daily life. She testified, that she underwent ginecological procedure by Pfannenstiel’s incision few years ago. Her comorbidities were hypertension, diabetes mellitus and obesity (BMI = 35). Her past medical history revealed an incisional hernia repaired with polypropylene mesh in January 2014, complicated with a large hematoma (sized 200 x 120 x 90 mm). Transdermal puncture and drainage with a subsequent antibiotic prophylaxis (ciprofloxacin) were succesfully performed then. In March 2014, control ultrasound examination showed giant multichamber seroma (sized 130 x 70 x 140 mm) in the lower part of anterior abdominal wall tissues. Those MEDtube Science Sep, 2015; Vol.III (3) science abnormal fluid collections remained under medical careful control. In June 2014, another antibioticoterapy (metronidazol and cefuroxime) was administered, but pathological conditions still maintained unhealed. As a result of her first consultation in our department, computer tomography of the abdomen was administered. It revealed a midline gap of hypogastric linea alba, sized 130 x 110 mm, with concomitant inflammatory infiltration of the surrounding adipose tissue. Any pathologic fluid collection within the abdominal cavity wasn’t found. Therapy with cefuroxime was continued with sufficient result. Patient was qualified for operative treatment. In May 2015, direct preoperative examination revealed palpable midline gap sized about 13 x 8 cm [Fig. 1, 2]. Computer tomography showed midline ventral hernia (137 x 112 x 56 mm trans x cc x ap) containing mesenteric adipose tissue and distended loops of small intestine within numerous adhesions. The hernia gate was measured on 104 x 75 mm [Fig. 3]. Under general anesthesia, open sublay hernioplasty (with the mesh placed in the retromuscular space) was performed [Video 1]. Patient was prepared and an antimicrobial-impregnated adhesive drape was placed over the skin of the anterior abdominal wall. The abdomen was accessed through a midline incision, mostly through the previous scar. A single dose of cefazolin (2,0 g intravenously) was administered at the time of skin incision. In a first step, an inflammatory tumor around previous polypropylene mesh was ressected and residual prosthetic material was explanted [Fig. 4]. Peritoneal adhesions were released [Fig. 5]. Then, the sac was delineated [Fig. 6]. Its contents was reduced and discharged into the interior of the abdominal cavity. The fascial defect was identified all around. The preperitoneal dissection of the anterior abdominal wall, allowing for mesh to be extended, began. When the posterior fascia has been released, the edges of the defect were reapproximated with running non-absorbable polydioxanone (size: 1.0) sutures [Fig. 7]. After that, Phasix Mesh sized 4” x 6” (10 x 15 cm) was placed into retromuscular space and anchored by suturing it to the rectus sheath [Fig. 8]. Additional simple sutures were placed on either side laterally to ensure its flat position [Fig. 9]. In the next step, anterior fascia was finally reconstructed over the mesh with a running polydioxanone suture (size: 1.0) [Fig. 10, 11]. Then, hemostasis was attained and two suction drains were placed in subcutaneous plane superficial to the mesh. Next, the excessive skin and subcutaneous tissue were reduced through additional incision needed in Pfannenstiel’s line. Endmost, the wound was closed [Fig.12]. In the postoperative period, patient required analgesic treatment only for 24 hours. The drains were removed in second postoperative day and she was discharged at the third day of hospital stay with no direct postoperative complications. Two weeks later, she attended a clinic as an outpatient with delayed wound healing caused by science seroma in the operated side. She had no fever and microbiological test results were negative. The prophylactic therapy with Sorbact method was carried out to prevent the wound from being infected. Patient remained under ambulatory care with persistent wound exudate and without its adequate healing. After three weeks, Proteus mirabilis was identified in another microbiological tests. Then, woman was hospitalized with diagnosis of wound infection. Intravenous amikacine was administered. Simultaneously, negative pressure therapy was succesfully performed. She was fully recovered at the begining of August 2015 and with no complaints of pain or mesh sensitivity in follow-up 2 months later [Fig. 13, 14]. DISCUSSION The predominance of mesh reinforcement over suture-based repair in incisional hernia surgery has been well established in the literature. Although its incidence rate remains low, the risk of recurrence after meshplasty is not completely eliminated. The best technique to provide a durable correction has not been determined. Moreover, recurrences of abdominal wall hernia as shown by the literature are rarely induced because of failure of the mesh. In most of cases, they occur at the mesh-tissue interface – typically at the cranial edge of the wound in the midline, or at the lateral border of nonmidline hernias [15, 16]. It allows to suggest, that the recurrence arise either due to technical problems with sufficient mesh coverage or next to inadequate coverage of the defect, rather than because of the mesh material itself [17]. The numerous approaches, types of prosthetic materials for repair, and possible locations of mesh placement testify to the lack of unequivocal evidence to promote any of repair technique that have been proposed so far. The sublay method, popularized by Rives [18] and Stoppa [19] in the late 1980s, uses the potential space dissected posterior to the rectus sheath for the mesh placement. It is considered by many surgeons as a gold standard for open abdominal incisional hernia repair [20, 21, 22, 23]. The recurrence rate of preperitoneal (sublay) mesh repair mentioned in different series varies from 2% to less than 10% [24]. Its main advantages in the reconstruction of complex abdominal wall defects are associated with a release of rectus abdominis muscle that provides a 2-layered closure of midline anterior fascia [25]. More importantly, the posterior rectus sheath dissection from the overlying muscle, provides a well-vascularized pocket for mesh placement. In contrast, the anterior sheath is tightly adherent to the tendinous inscriptions of the rectus muscle. It was proved by Binnebosel at collegues on their rabbit model of open incisional hernia repair, that mesh placed in the rectorectus space demostrates more of both type I and type III collagen deposition in a porcine model, when compared with its onlay position [26]. The concern with the open approach to incisional 16 hernias remains wound complications. The dissection required to proper mesh placement and reapproximate the midline can lead to significant wound and mesh infections. In 2010, Venclauskas and colleagues published their results of 1-year follow-up after incisional hernia treatment. That prospective randomized study demonstrated wound complications in 49.1% of onlay patients vs 24% of sublay repairs. Also the incidence of seroma was significantly higher in the onlay technique (45%) when compared with the sublay (24%) [27]. It must be noted, that the rate of wound morbidity after incisional hernia repair depends on not only mesh material or the technique selection, but it is connected with patient comorbidities as well. Prior wound infection, obesity, diabetes mellitus, heart failure, presence of a stoma or malnutrition are well known independent risk factors of surgical site infections [28]. It leads to some difficulties in interpreting and comparing the findings published in the literature. It is believed, that placing the mesh deep in the retrorectus plane prevents the transmittion of infection from subcutaneous tissues down to the mesh [29]. Otherwise, there is a necessity to perform mesh reinforcement in contaminated area in some cases. It significantly affects the success of the operation. When repairing a contaminated abdominal wall defect, the sublay method provides The opportunity of rapid revascularize that prevents a material failure, improve bacterial clearance and long-term success of the repair [30]. Placing a mesh in a poorly vascularized area increases the risk of its early degradation by bacterial collagenase prior to achieving neovascularization and utilization of the native host immune system. Using a bioabsorbable or even biologic grafts in the retrorectus compartment is hypothesized to improve the outcomes related to recurrence rates when contamination is present [28]. Those products significantly raise the cost of the procedure.However, if infectious complications can be avoided, cost would be offset by offering value to the patient. In presented case of recurrent incisional hernia with a previous history of many wound complications, a procedure of sublay reinforcement with fully resorbable mesh implant (Phasix Mesh) was performed. The used material degradates through the processes of hydrolysis and a hydrolytic enzymatic digestive process within 12 to 18 months. There was no recurrence in 4 month follow-up observation. An episode of surgical site infection has been effectively healed with no futher complications. The role of bioabsorbable implants in contaminated cases has not been determined yet, and ongoing prospective studies are indispensable to provide guidance for these difficult patients. The concern for mesh infection must be weighted against the concern of reccurence. MEDtube Science Sep, 2015; Vol.III (3) science 17 CONCLUSIONS FIG. 1. PALPABLE MIDLINE GAP FIG. 2. PALPABLE MIDLINE GAP Retrorectus (sublay) method of mesh reinforcement is preferable in incisional hernia repair, that provides 2-layered closure of the midline fascia to recreate native abdominal wall anatomy. A surgical site infection, as well as implanted foreign body contamination, significantly increases the risk of recurrence. Using the bioabsorbable implants, that completely hydrolyze after providing a support throughout the period of soft tissue healing, is suggested in contaminated area. Despite its encouraging outcomes, a cost factor still existst and futher prospective studies are necessary to establish its position in incisional hernia surgery. CITE THIS AS MEDtube Science 2015, Sep 3(3), 14-20. VIDEO 1. RECURRENT INCISIONAL HERNIA SUBLAY REPAIR WITH FULLY REABSORBABLE MESH Click here to play the video. LIST OF THE FIGURES Fig.1: Palpable midline gap. Fig.2: Palpable midline gap. Fig.3: Midline ventral hernia in preoperative CT scan. Fig.4: Ressection of inflammatory tumour around previous polypropylene mesh. Fig.5: Release of peritoneal adhesions. Fig.6: Hernia sac delineation. Fig.7: Reapproximation of the posterior fascia. Fig.8: Retrorectus mesh placement. Fig.9: Additional suturing to ensure mesh flat position. Fig.10: Reconstruction of anterior fascia over the mesh. Fig.11: Anterior abdominal wall reconstruction visu alised in postoperative CT scan. Fig.12: Excessive skin and subcutaneous tissue reduction through additional Pfannestiel’s incision. Fig.13: Wound appearance in 2 – month follow-up after full recovery. Fig.14: The appearance of anterior abdominal wall in 4 months after procedure. MEDtube Science Sep, 2015; Vol.III (3) FIG. 3. MIDLINE VENTRAL HERNIA IN PREOPERATIVE CT SCAN science FIG. 4. RESSECTION OF INFLAMMATORY TUMOUR AROUND PREVIOUS POLYPROPYLENE MESH FIG. 5. RELEASE OF PERITONEAL ADHESIONS FIG. 6. HERNIA SAC DELINEATION 18 FIG. 7. REAPPROXIMATION OF THE POSTERIOR FASCIA FIG. 8. RETRORECTUS MESH PLACEMENT FIG. 9. ADDITIONAL SUTURING TO ENSURE MESH FLAT POSITION MEDtube Science Sep, 2015; Vol.III (3) 19 FIG. 10. RECONSTRUCTION OF ANTERIOR FASCIA OVER THE MESH FIG. 11. ANTERIOR ABDOMINAL WALL RECONSTRUCTION VISUALISED IN POSTOPERATIVE CT SCAN science FIG. 12. EXCESSIVE SKIN AND SUBCUTANEOUS TISSUE REDUCTION THROUGH ADDITIONAL PFANNESTIEL’S INCISION FIG. 13. WOUND APPEARANCE IN 2 – MONTH FOLLOW-UP AFTER FULL RECOVERY FIG. 14. THE APPEARANCE OF ANTERIOR ABDOMINAL WALL IN 4 MONTHS AFTER PROCEDURE MEDtube Science Sep, 2015; Vol.III (3) science BIBLIOGRAPHY 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. Mudge M, Hughes LE. Incisional hernia: a 10 year prospective study of incidence and attitudes. Br J Surg. 1985;72:70–71. Van ‘t Riet M, Steyerberg EW, Nellensteyn J, et al. Meta-analysis of techniques for closure of midline abdominal incisions. Br J Surg. 2002;89:1350–1356. Pauli EM, Rosen MJ. Open ventral hernia repair with component separation. Surg Clin N Am. 2013;93:1111–1133. Rana KV, Singh G, Deshpande NA, et al. Postoperative complications of mesh hernioplasty for incisional hernia repair and factors affecting the occurrence of complications. Med J DY Patil Univ 2013;6:25-31. Fakhar H, Bashir A, Asrar A, et al. Incisional hernia repair by preperitoneal (sublay) mesh implantation A.P.M.C Vol: 3 No.1 January-June 2009. Yahchouchy-Chouillard E, Aura T, Picone O, et al. Incisional hernias. I. Realted risk factors. Dig Surg 2003;20:3 – 9. Mudge M, Hughes LE. Incisional Henia: A 10 year prospective study of incidence and attitudes. Br J Surg 1985; 72:70-5. Voeller GR, Ramshaw B, Park AE. Incisional hernia. J Am Coll Surg 1999;189:635-7. Luijendijk RW, Hop WC, van den Tol MP, et al. A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med. 2000;343:392–398. Cobb WS, Kercher KW, Heniford BT. The argument for lightweight polypropylene mesh in hernia repair. Surg Innov. 2005;12:63–69. George CD, Ellis H. The result of incisional hernia erpair. A twelve year review. Ann R Coll Surg Engl 1986; 68: 185-7. Bauer JJ, Harris MT, Gorfine SR et al. Rives stoppa repair of giant incisional hernias. Experience with 57 patients. Hernia 2002; 6: 120-3. Basoglu M, Yildirgan MI, Yilmaz I, Balik A, Celebi F, Atamanalp SS, et al. Late complications of incisional hernias following prosthetic mesh repair. Acta Chir Belg 2004;104:425-8. Demirer S, Kepenekci I, Evirgen O, et al. The effect of polypropylene mesh on ilioinguinal nerve in open mesh repair of groin hernia. J Surg Res. 2006;131:175–181. Conze J, Prescher A, Kisielinski K, et al. Technical consideration for subxiphoidal incisional hernia repair. Hernia. 2004;9:84–87. Conze J, Prescher A, Klinge U, et al. Pitfalls in retromuscular mesh repair for incisional hernia: the importance of the “fatty triangle”. Hernia. 2004;8:255–259. Schumpelick V, Klinge U, Junge K, et al. Incisional abdominal hernia: the open mesh repair. Langenbecks Arch Surg. 2004;389:1–5. Rives J. Major incisional hernia. In: chewal JP (ed) Surgery of the abdominal wall. Springer Paris 1987; 116-44. Stoppa RE. The treatment of complicated groin and incisional hernias. World J Surg 1989;13:545-54. Berry MF, Paisley S, Low DW et al. Repair of large complex recurrent incisional hernias with retromuscular mesh and panniculectomy.Am J Surg 2007;194:199-204. Iqbal CW, Pham TH, Joseph A et al. Long term outcome of 254 complex incisional hernia repairs using modified Rives -Stoppa technique. World J Surg 2007; 31: 2398-2404. Martin- Duce A, Noguerales F, Villet AR et al. Modifications to Rives technique for midline incisional hernia repair. Hernia 2001; 5: 70-72. Langer C, Schaper A, Liersch T et al. Prognosis factors in incisional hernia surgery:25 years of experience. Hernia 2005; 9: 16-21. Mc Lana han D, King LT, Weems C et al. Retrorectus prosthetic mesh repair of midline abdominal hernia. Am J Surg 1997; 173: 445-9. Nguyen V, Shistek KC. Separationof anatomic components method of abdominal wall reconstruction – clinical outcome analysis and an update of surgical modifications using the technique. Clin Plastic Surg 2006; 33:247-257. Binnebosel M, Klink CD, Otto J, et al. Impact of mesh positioning on foreign body reaction and collagenous ingrowth in a rabbit model of open incisional hernia repair. Hernia 2010;14:71-77. Venclauskas L, Maleckas A, Kiudelis M. One-year follow-up after incisional hernia treatment: results of a prospective 20 randomized study. Hernia 2010;14:575-582. 28. Rosen MJ, Denoto G, Itani KM, et al. Evaluation of surgical outcomes of retro-rectus versus intraperitoneal reinforcement with bio-prosthetic mesh in the repair of contaminated ventral hernias. Hernia 2013;17:31-35. 29. Bhat Mahabhaleshwar G, Somasundaram Santosh K. Preperitoneal Mesh Repair of incisional Hernia: A seven year retrospective study. Ind J Surg. 2007;69: 95-8. 30. Harth KC, Broome AM, Jacobs MR et al (2011) Bacterial clearance of biologic grafts used in hernia repair: an experimental study. Surg Endosc 25:2224. MEDtube Science Sep, 2015; Vol.III (3) science 21 In daily clinical practice we are all familiar with the word „ dengue „ making us think of an acute febrile illness accompanied by hematologic abnormalities, mainly leukopenia and thrombocytopenia, that may generate plasma leakage to third space. Dengue, for apparatus and systems Luis del Carpio Orantes1 1. Department of Internal Medicine, General Hospital 71, Mexican Institute of Social Security, Veracruz, Veracruz, Mexico #Corresponding author: Luis del Carpio Orantes, E-mail: [email protected]. RUNNING TITLE Dengue KEYWORDS dengue, leptospirosis, diagnosis WORD COUNT 1 361 CONFLICT OF INTERESTS no conflicts of interest ABSTRACT In daily clinical practice we are all familiar with the word „ dengue „ making us think of an acute febrile illness. In order to obtain an overview of the aforementioned, we look closely at and review the damage caused by dengue to various organ systems of human body. I n daily clinical practice we are all familiar with the word „ dengue „ making us think of an acute febrile illness accompanied by hematologic abnormalities, mainly leukopenia and thrombocytopenia, that may generate plasma leakage to third space, however , some-times we face an atypical or unusual cases , that leaves the previous definition useless and, with no knowledge of them, our attention may be diverted to other diseases. lost time for the diagnosis and early treatment are the prerequisites for all medical personnel to be aware that dengue goes beyond a fever and thrombocytopenia , , affecting major organs , what, if not prevented , leads to the death of the patient and no clarification of the cases, most of which often fulfill the criterion of severe dengue , according to the new WHO definition. In order to obtain an overview of the aforementio- MEDtube Science Sep, 2015; Vol.III (3) ned, we look closely at and review the damage caused by dengue to various organ systems of human body, summarized in Table 1. Nervous System. In dengue, the involvement of the nervous system is always constant , starting with a holocranial and persistent headache, , relieved by simple analgesics. Fever in children and sometimes adults may cause seizures, cases of which are reported, as rare or unusual cases include encephalopathy (which may be multifactorial and mental disorders accompanied by acute electrolyte disturbances, etc.), or encephalitis, meningoen-cephalitis; parenchymal and subarachnoid hemorrhage, related to thrombocytopenia have also been reported. The pathophysiology of these disorders lies in the fact that the virus is neurotropic in nature , by capillary bleeding , concomitant metabolic disorders and coag science -ulopathy type CID ( hepatic, renal , etc.) . The rarest neurological manifestations are: Guil-lain Barre Syndrome, myelitis (acute disseminated encephalomyelitis), mononeuropathy and polyneuropathy syndrome. There is an isolated case of phrenic neuropathy with dia-phragmatic paralysis that resolved to cure dengue [4,6,28,29]. Ocular apparatus. It would appear that eyes have no interaction with viral infections, how-ever in dengue, the entities and features unique to this virus have been identified, thus af-fecting primarily the macula, with the so-called dengue maculopathy, multiple case reports and series cases. Rare cases include optic neuropathy, and vitreous retinal hemorrhages, retinal cotonosos infiltrates, foveolitis , among others [12,19,22,24,30]. Breathing apparatus. The most common and not directly related to lung disease, pleural effusion is the demonstration that rarely becomes massive and warrant thoracentesis . However, there are atypical, bleeding and severe cases present with pulmonary hemor-rhage, manifested by hemoptysis to acute respiratory failure, which may cause patient’s death unless prompt measures are taken . In exceptional cases of concomitant pneumonia where theetiological relationship has not been established, primary dengue viral or second-ary bacterial, leveraging inflammation of the lung parenchyma caused by viruses (phenom-enon observed in influenza). Isolated case of diaphragmatic paralysis in relation to phrenic neuropathy [27,28,31]. Circulatory system. The circulatory system is the first to be affected as vascular endotheli-um is directly targeted by the virus , , resulting in thrombocytopenia, plasma leakage and circulatory collapse (shock dengue). Similarly, another of the circulatory system key ele-ments , the heart, is affected mainly as myocarditis, which may manifest itself as anginal syndrome or rhythm disturbances or cardiac conduction. The untrained eye may interpret the symptoms as coronary artery disease or heart disease aggravated by dengue , being a reflection of the same viruses in primary form . There are case reports, which show rise in the enzyme levels and ST -T abnormalities, bradyarrhythmias tachycardia, atrioventricular block in varying degrees, mainly segment as well. Symptoms of myocarditis resemble viral myocarditis and toxic, causing myocardial necrosis, which explains enzymatic and electro-cardiographic abnormalities. Report indicates ephemeral pericardial effusions, that may exist in the context of plasma leakage or a viral serositis at that level [2,17,23,28]. Digestive system. One of the most affected systems after the reticuloendothelial one, some of its organs are of particular importantce (liver and spleen) and hence the close relationship. Always, in all cases of dengue , severe and not severe ones, the liver enzymes rise may be observed (primarily ALT, AST, 22 GGT, LDH) mentioning that the enzyme level is higher than 300 IU TGP are prognostic factors for renal failure , bleeding, and death. On the other hand it has been shown that there exists a discriminating factor between severe and non- severe dengue and hypoalbuminemia as well , not as a manifestation of the ex-pense of liver synthetic function , but capillary plasma leakage and rarely with coagulopathy (which regards whether this alteration in the synthesis function ) , developed serious cases of dengue hepatitis, fulminant hepatic failure or consumptive coagulopathy mainly IDC , which in most cases are mortal. A common manifestation is ascites and acalculous chole-cystitis, that are part of DHF (dengue with warning signs, according to the new WHO classi-fication) and that deserve close scrutiny because they may be the symptoms of develop-ment to a severe or serious condition. In a rare form of mumps, cases of dengue, diarrhea, dengue pancreatitis have been reported and more frequently spontaneous splenic rupture withformation of intra and perisplenitis hematomas. Jaundice, although rare, may also occur in cases of dengue and is not dominant over direct or indirect hyperbilirubinemia. In a cohort study in Veracruz in 2011, 8,559 cases of dengue were studied, of which 67 % had gastrointestinal manifestations, the most common: nausea, abdominal pain, vomiting, he-patomegaly, ascites and gastrointestinal bleeding what leads to the conclusion that gastro-intestinal manifestations are mainly accompanied with fever [3,7,11,13,15,21]. Renal system. The most common renal manifestation is proteinuria, which may be of vary-ing degrees, from microalbuminuria to nephrotic syndrome. secondarily, relative to the degree of shock, acute renal failure may occur. Usually acute renal failure is transient and do not stay long. There have been reports of secondary glomerulonephritis and hemolytic uremic syndrome that is quite uncommon. It is mentioned that greater proteinuria 0.55g/day may lead to the development of a severe hemorrhagic dengue [8,11,14,25]. Locomotor apparatus. The muscular system, which is an important part of the musculoskel-etal system, is primarily affected and symptomatic, since the patient always has the typical “fever bearded”, i.e. from mild to severe muscle aches, which fortunately is usually con-trolled with simple analgesics. However atypical or uncommon manifestations may include myositis, rhabdomyolysis (fortunately rare but in severe forms may contribute to acute renal failure by myoglobinuria) and acute myopathies, severe neuropathies and Guillain Barré syndrome [1,9,10,11,16,18,23]. Hematologic system. Of the major biochemical manifestations of dengue, , hematologic abnormalities are mainly 3 cell lines, it is necessary to monitor hematocrit, hemoglobin, leukocytes and platelets, with typical findings of dengue - elevated hematoMEDtube Science Sep, 2015; Vol.III (3) science 23 crit, which con-firms hemoconcentration, capillary leakage and dehydration, with the subsequent risk of shock, leukopenia and lymphopenia characteristic of viruses, and thrombocytopenia, which is used as a criterion for admission or hospital discharge. In more analytical way, altera-tions in the endothelium have been demonstrated, with increased activation of endothelial cells; high levels of circulating von Willebrand factor and low levels of ADAMTS- 13 (a met-alloprotease and disintegrin regulating partly thrombogenesis) the latter are those that favor severe thrombocytopenia and complications surrounding dengue, mainly thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Another complication mostly seen in children, is the secondary hemophagocytic syndrome, a range in which there is pan-cytopenia with histiocytic infiltrate in bone marrow, which corresponds to class II histiocyto-sis , and clinical courses, in addition to prolonged fever ( which is characteristic ) with ab-dominal pain mainly in school . Isolated cases of purpura fulminans with multiple organ involvement and death. Secondary coagulopathy [5,26,28,32]. Apparatus or system Typical and atypical manifestations Ocular apparatus • • • • • • Conjunctivitis Vitreous Hemorrhage Retinal hemorrhages retinal Departed Foveolitis Maculopathy Breathing apparatus • • • • • • Pleural effusion Hemoptysis Acute respiratory failure Pneumonia Pulmonary hemorrhage Diaphragm Paralysis • • • Acute circulatory collapse - shock Myocarditis (conduction and rhythm disturbances, ST-T) Pericarditis, pericardial effusion. Digestive system • • • • • • • • • • • Nausea and vomiting Ascites Hepatomegaly-hepatalgia Gastrointestinal bleeding Hepatitis for dengue Acalculous cholecystitis Mucositis fulminant hepatic failure Pancreatitis dengue Mumps splenic rupture Renal system • • • • • Proteinuria - nephrotic syndrome Glomerulonephritis Acute renal failure hemolytic uremic syndrome Electrolyte Disorders Locomotor apparatus • • • • Muscle aches Myositis Rhabdomyolysis Acute myopathy • hemoconcentration (hematocrit> 20%, ratio Ht / Hb> / = 3.5) Leukopenia, lymphopenia Thrombocytopenia thrombotic thrombocytopenic purpura hemolytic uremic syndrome Purpura fulminans Circulatory system Dermal system. The skin is not beyond dengue influence on the body . Common skin mani-festation is a skin rash characterized by tiny hypochromic macular lesions on an erythema-tous circular niche, known colloquially as “white islands in a sea of red.” Followed by pruri-tus, petechiae and ecchymosis . Rarely conjunctivitis and mucositis [20,28]. In summary, it is important to note that dengue is not always typical, especially in terms of bleeding or severity, and may be complicated when there is multiorgan involvement, which leads to severe dengue cases with high mortality, that fortunately is still rare in our envi-ronment , but in Asia and the Middle East, is very common. Hematology system CITE THIS AS MEDtube Science 2015, Sep 3(3), 21-24 • • • • • TAB. 1. TYPICAL (UNDERLINED ITALICS) AND ATYPICAL MANIFESTATIONS OF DENGUE • Dermal system • Apparatus or system Dermatitis and rash with „white islands in a sea of red” Itching Typical and atypical manifestations BIBLIOGRAPHY Nervous System • • • • • • • • • • Headache Seizures Mononeuropathies Polyneuropathies Encephalopathy, acute psychosis or dementia encephalitis-meningitis parenchymal hemorrhages Subarachnoid hemorrhage Guillain Barré Syndrome acute encephalomyelitis 1. 2. 3. 4. MEDtube Science Sep, 2015; Vol.III (3) Misra UK , Kalita J , Maurya PK, et al. Dengue -associated transient muscle dysfunction: clinical , electromyography and histopathological changes. Infection . 2012 Apr , 40 (2) :125-30. Yacoub S , Griffiths A, Chau TT, et al. Cardiac function in Vietnamese patients With Different dengue severity grades . Crit Care Med 2012 Feb , 40 (2) :477-83. Bhaskar , E. & Moorthy , S. Spontaneous splenic rupture in dengue fever with non - fatal outcome in an adult . J Infect Dev Ctries 2012 , 6 (4) :369-372. Syed Ahmed Zaki . Acute disseminated encephalomyelitis and dengue fever : Comment. J Vector Borne Dis 49 , March science 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 2012, p. 52-53. Djamiatun K , van der Ven AJAM , de Groot PG, Faradz SMH , Hapsari D , et al. Severe Dengue Consumption Is Associated with von Willebrand Factor of Cleaving Enzyme and Its ADAMTS -13 . PLoS NEGL Trop Dis 2012 , 6 (5): e1628 Ratnayake , EC . , Shivanthan , C. & Wijesiriwardena . BC. Diaphragmatic paralysis : a rare Consequence of dengue fever BMC Infectious Diseases 2012 , 12:46 PM . Ramos -De La Medina A, Remes - Troche JM , GonzálezMedina MF , et al. Abdominal and gastrointestinal symptoms of Dengue fever . Analysis of a cohort of 8559 patients . Gastroenterol Hepatol. 2011 Apr , 34 (4) :243-7. Hutspardol S , Prommalikit O, Upiya N, et al. Heavy proteinuria Following dengue hemorrhagic fever . Southeast Asian J Trop Med Public Health. 2011 May , 42 ( 3) :579 -82. Pimentel LH, de Oliveira GR , do Vale OC , et al. On the spectrum of acute dengue virus myositis . J Neurol Sci 2011 Aug 15 , 307 (1-2) :178-9 . VK Paliwal , RK Garg , Juyal R, et al. Acute dengue virus myositis : a report of seven patients of varying clinical severity including two cases with severe fulminant myositis . J Neurol Sci 2011 Jan 15 , 300 (1-2) :14-8 . Jain , PK . , Sharma AK, Agarwal N., et al. A prospective clinical study of incidence of hematological and hepatorenal complications in dengue fever and management of symptomatic bleed in Bundelkhand region of Northern India with fresh whole blood . Journal of Infectious Diseases and Immunity Vol 3 (7) , pp . 124-133 , July, 2011. Ujiie , M., Ling Moi, M. & Takeda , N. Dengue Maculopathy in a Traveler. Am J Trop . Hyg. , 85 (6), 2011, pp. 965-966. Gonzalez- Fontal, GR . & Henao- Martinez, AF. Dengue hemorrhagic fever complicated by pancreatitis. Braz J Infect Dis 2011, 15 (5):490 -492. Vasanwala , FF . , Puvanendran , R., Fook - Chong , S. et al. Could peak proteinuria determine Whether Patient with dengue hemorrhagic fever Develop dengue / dengue shock syndrome ? A prospective cohort study BMC Infectious Diseases 2011 , 11:212 . Parkash et al. Severity of acute hepatitis and its outcome in patients with dengue fever in a tertiary care hospital Karachi, Pakistan (South Asia) . BMC Gastroenterology 2010, 10:43. Sourya Acharya, Samarth Shukla , S. N. Mahajan, et al. Acute dengue myositis with rhabdomyolysis and acute renal failure . Ann Indian Acad Neurol. 2010 Jul -Sep , 13 ( 3): 221-222 . Lee IK , Lee WH, Liu JW, et al. Acute myocarditis in dengue hemorrhagic fever : a case report and review of cardiac complications in dengue - Affected patients . Int J Infect Dis. 2010 Oct, 14 (10): E919 -22. Sangle SA , Dasgupta A, Ratnalikar SD, et al. Dengue myositis and myocarditis . Neurol India. 2010 Jul -Aug, 58 (4):598-9. Chee E, Sims JL, Jap A, et al. Comparison of Prevalence of dengue maculopathy During Epidemics with two differing predominant serotypes. Am J Ophthalmol . 2009 Dec , 148 (6) :910-913 . Florencio Cortez- Franco. Cutaneous manifestations of dengue. Peruvian Dermatology 2009 , Vol 19 ( 2) , Pg 86-93 . ET Ooi , Ganesananthan S , Anil R, et al. Gastrointestinal manifestations of dengue infection in adults . Med J Malaysia . 2008 Dec , 63 (5) :401-5 . BK Loh , Bacsal K , Chee SP, et al. Associated with Dengue Fever Foveolitis : a case series. Ophthalmologica . 2008 , 222 (5) :317-20 . Pamo R., OG . , L. Knight , J. , Lema O., J. et- al. Myocarditis and Rhabdomyolysis associated with dengue virus infection . Peru Rev Exp Med Public Health . 2008 , 25 (3) :340-42 . Sanjay , S., Wagle , AM . Eong & Au , KG . Optic neuropathy Associated with dengue fever . Eye ( 2008 ) 22 , 722-724 . Lima , EQ . , Gorayeb , FS . , Zanon , JR. et- al. Dengue haemorrhagic fever -induced acute kidney injury without hypotension , haemolysis or rhabdomyolysis . Nephrol Dial Transplant ( 2007 ) 22 : 3322-3326 . DH Karunatilaka , JR De Silva , Ranatunga PK, et al. Idiopathic purpura fulminans in dengue hemorrhagic fever . Indian J Med Sci 2007 Aug , 61 (8) :471-3 . Sharma SK, Gupta BS , Devpura G, et al. Pulmonary haemorrhage syndrome Associated with dengue haemorrhagic fever . J Assoc Physicians India . 2007 Oct ; 55:729-30. 24 28. Gulati , S. & Maheswarih , A. Atypical manifestations of dengue. Tropical Medicine and International Health. volume 12 , No. 9 september 2007 pp 1087-1095. 29. Misra UK , Kalita J , UK Syam , et al. Neurological manifestations of dengue virus infection . J Neurol Sci 2006 May 15 , 244 (1-2 ) :117 -22. 30. Nainiwal S , Garg SP, Prakash G, Nainiwal N. Bilateral vitreous haemorrhage Associated with dengue fever . Eye 2005 , 19 : 1012 . 31. Setlik RF, Ouellette D , Morgan J , et al. Pulmonary hemorrhage syndrome Associated With An autochthonous case of dengue hemorrhagic fever . South Med J. 2004 Jul; 97 (7) :688-91 . 32. Rueda, E. , Méndez , A. and Gonzalez , G. Hemophagocytic syndrome associated with dengue hemorrhagic fever. Biomedical . 2002 , vol. 22 , No. 002 , Pg 160-166. MEDtube Science Sep, 2015; Vol.III (3) science 25 Tissue engineering and regenerative medicine methods are extremely promising, in particular bioprinting of tissues and organs, which begun to develop at the beginning of the XXI century. Currently, medical community, have already transplanted trachea and bladder printed on a 3D printer. Bionic Pancreas and Bionic Organs – how far we are from the success Michal Wszola1,7#, Joanna Idaszek2, Andrzej Berman1, Alicja Kosik2, Lukasz Gorski1, Agnieszka Jozwik1, Agnieszka Dobrzyn3, Agnieszka Cudnoch-Jędrzejewska4, Artur Kaminski5,6, Robert Wrzesien4, Marta Serwanska-Swietek1, Andrzej Chmura1, Artur Kwiatkowski1 and Wojciech Swieszkowski2 1. 2. 3. 4. Department of General and Transplantation Surgery, Warsaw Medical University. Division of Material Engineering, Warsaw University of Technology, Poland. Nencki Insitute of Experimental Biology, Polish Academy of Science, Poland. Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, The Medical University of Warsaw, Warsaw, Poland National Centre for Tissue and Cell Banking, Warsaw, Poland Department of Transplantology and Central Tissue Bank, Medical University of Warsaw, Poland Foundation for Research and Science Development, Otwock, Poland 5. 6. 7. 8. #Corresponding author: [email protected] RUNNING TITLE Bionic organs KEYWORDS bioprinting, 3D-bioprinting, bionic pancreas, bionic organs, artificial organs, islets transplantation WORD COUNT 1 154 CONFLICT OF INTERESTS no conflicts of interest ABSTRACT The progress in the treatment of chronic diseases of civilization that occurred in recent years, led to a significant prolongation of median survival time of the developed countries societies. Organ transplantation has revolutionized medicine as it became possible to replace an irreversibly diseased organ. However, at the moment we can observe a significant shortage of organs for transplantation, which forces doctors to accept those coming from more and more expanding criteria donors. No doubt, the number of donors, at best, will certainly not grow. Tissue engineering and regenerative medicine methods are extremely promising, in particular bioprinting of tissues and organs, which begun to develop at the beginning of the XXI century. Article highlights possible future direction of organ transplantation. MEDtube Science Sep, 2015; Vol.III (3) science T he progress in the treatment of chronic diseases of civilization that occurred in recent years, led to a significant prolongation of median survival time of the developed countries societies [1,2]. Paradoxically, it has raised more medical problems such as increased number of neurodegenerative, cardiovascular diseases [2,3] and increased demand for transplantation organs [4]. In Poland alone, there are more than two and a half million diabetic patients, 200,000 of which are patients with type I diabetes [5]. According to WHO’s statistics, by 2030 these numbers will double [6]. Organ transplantation has revolutionized medicine as it became possible to replace an irreversibly diseased organ. However, at the moment we can observe a significant shortage of organs for transplantation, which forces doctors to accept those coming from more and more expanding criteria donors. No doubt, the number of donors, at best, will certainly not grow. Annually, there are approximately 40 pancreas transplants in Poland. Liver and kidney transplants are more numerous, with 300 and 1000, respectively, organs transplanted each year. Pancreas transplantation has been a successful treatment of patients with diabetic complications for years, limited however to relatively small number of patients not only due to organ shortage but also due to ischemic injury of retrieved organs [7]. Injury is even more pronounced in pancreatic tissue, which is subjected to digestion processes in order to isolate the islets of Langerhans, which are especially sensitive to injury. The digestion process, by stripping the islets of their vasculature and surrounding extracellular matrix in order to isolate them and put into suspension, results in their hypoxic damage. This sequence of deleterious effects is the reason that islet transplantation has not become a common clinical treatment modality [8]. More than 50% of transplanted islets are lost during the first few days post transplant. It is possible that one of the causes of this is IBMIR - instant blood-mediated inflammatory reaction [9], leading investigators search for a new recipient sites for islet transplantation [10,11,14]. Authors have invented, performed study and introduced into clinic as the first in the world, an innovative method of endoscopic gastric submucosa islets transplantation [12,13]. The damage is also caused by deprivation of the islets of their own vasculature and extracellular matrix. “Nude” islets has higher tendency for apoptosis, which further makes that simple procedure very not effective. The medical world is developing several potential paths that can solve the problem of shortage of organs for transplantation: artificial organs [15], xenotransplantation (using organs taken from animals) [16], tissue engineering and regenerative medicine [17]. There have been first visible successes in using artificial organs, such as insulin pumps [15]. But those are not able to inhibit the development of secondary complications of diabetes, which leads to nearly 5 million deaths each year worldwide [18]. Xenotransplantation, as a treatment in humans, cannot be easily brought to the clinical phase due to the still unresolved risk of transmit- 26 ting particularly dangerous zoonotic viral infections together with the cells and organs taken from animals [19]. Therefore, the development of new approaches to protect newly transplanted pancreatic islets/betacells from oxidative and inflammatory stress is critical and urgently needed. Dobrzyn et al. recently showed that endocanabinoid system, stearoyl-CoA desaturase and Wnt singnaling play a critical role in keeping pancreatic beta-cell identity and islet architecture and might be used for injury treatment [20-22]. Tissue engineering and regenerative medicine methods are extremely promising, in particular bioprinting of tissues and organs, which begun to develop at the beginning of the XXI century [23]. Currently, medical community, have already transplanted trachea and bladder printed on a 3D printer [24,25]. In addition, beyond the obvious purpose of transplantation, we may use bioprinted proteins, cells, tissues, and organs in in vitro drug trials (toxicity tests), in clinical trials and in „personalized medicine”, adapting the drug dosage to the biological capabilities of the potential patient’s tissues. Possible rebuilding extracellular matrix, with bioprinting, for islets and creating a stable, well oxygenated scaffold might effectively improve islet transplants survival, make this treatment available for a wider population of patients and influence positively survival and quality of life of millions of diabetic patients. Building scaffolds for clinical use [32-34] in orthopaedics and oncologic surgery is also developing. Recently, there has been a significant progress in the development of scaffolds, that could constitute building blocks for organs culture with a use of stem cells [26-28]. There have been attempts to built scaffolds for islets transplantation that could solve problems of lack of ECM after isolation [29]. It has been proved by Authors of this proposal and other team independently, that islets encapsulated in special hydrogels could be used as a “bioink” in 3D bio-fabrication [29-30]. Nevertheless there are several weak points to be solved if one wants to achieve a 3Dprinted scaffold with pancreatic islets, which will be ready for transplantation (and with islets responding to glucose stimulus). To print islets they have to be immersed in some kind of gel, which will have a viscosity that allows of 3D printing but on the others hand glucose will be able to easily go through the matrix material. This situation only will allow islets to response properly for glucose stimuli. So far bioengineered hydrogels like alginate, polyglicane and many others allow to print islets and allow to keep them alive but function of this islets are limited [29]. Another problem that should be solved is the lack of vasculature. All attempts are being done with islets suspended in the hydrogel, suggesting that after transplantation, the vasculature will ingrow into the islets somehow. Unfortunately by the time the vasculature in-grows into the islets, most of them are already dead, because of lack of proper nutrition. The only answer for that problem might be engineering scaffold with vasculature in it and with using proper ECM for bioprinting. It is not an easy MEDtube Science Sep, 2015; Vol.III (3) science 27 task, but it seems that lately there has been a small breakthrough. Researchers managed to 3D - bioprint vessels with diameter of 0,5 mm diameter, which were physiologically active – nutrients and oxygen were possible to be transported through the wall and cells of endothelium of that vessels produced steady junction between them [31]. Such vessels would be appropriate for islets nutrition within printed scaffolds. Improving of 3D bioprinting technology might help to build scaffolds that will be able to be used in clinical medicine. Of the most importance seems to be engineering an Human Bionic Pancreas with islets and extracellular matrix which could help become an islet transplantation a method of treatment for definitely larger group of patients with diabetes then it is now. Implementation of such Bionic pancreas could lower costs paid on the treatment of diabetes mellitus and its complication and may reverse negative trends which says that diabetes will be one of the most common cause of death by the end of 2030 [2]. Results of that programme will give definitely a great progress in prevention of diabetic complications and help in treatment. CITE THIS AS MEDtube Science 2015, Sep 3(3), 25-27 BIBLIOGRAPHY 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. WHO Global InfoBase. https://apps.who.int/infobase Mathers CD, Loncar D.Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006 Nov;3(11):e442. WHO. The global burden of disease: 2004 update. Geneva: World Health Organization, 2008. US Dep. Health Hum. Serv. Donate the Gift of Life Statistics and Figures. US Dep Health Hum Serv; Washington, DC: 2014. The need is real: data. retrieved February 26, 2014http:// www.organdonor.gov/ about/data.html Patterson CC, Dahlquist GG, Gyurus E, et al. Incidence trends for childhood type 1 diabetes in Europe during 1989Y2003 and predicted new cases 2005Y20: a multicentre prospective registration study. Lancet 2009; 373: 2027. Imperatore G, Boyle JP, Thompson TJ, et al., SEARCH for Diabetes in Youth Study Group. Projections of type 1 and type 2 diabetes burden in the U.S. population aged G20 years through 2050. Diabetes Care 2012; 35: 2515. Michalak G., Kwiatkowski A, Czerwinski J, Chmura A, Wszola M et al. Surgical Complications of Simultaneous Pancreas–Kidney Transplantation: A 16-Year-Experience at One Center Transplant Proc. 2005 Oct;37(8): 3555-3557. Fiorina P, Shapiro J, Ricordi C, Secchi A. The clinical impact of islets transplantation. Am J of Transplantation 2008;8:1990-97. O. Korsgren, T. Lundgren et al.: Optimising islet engraftment is critical for successful clinical islet transplantation. Diabetologia 2008; 51:227–232. Merani S, Tosso C, Emammauelle J, Shapiro J. Optimal implantation site for pancreatic islets transplantation. British Journal of Surgery 2008:95;1449-1461. Wszola M, Berman A, Fabisiak M et al. TransEndoscopic Gastric SubMucosa Islet Transplantation (eGSM-ITx) in pigs with streptozotocine induced diabetes - technical aspects of the procedure - preliminary report. Ann Transplant. 2009 Apr-Jun;14(2):45-50. Wszola M, Kwiatkowski A, Berman A et al. Case of successful Endoscopic Pancreatic Islets auto-transplantation into gastric sub-mucosa in patient with chronic pancreatitis - preliminary report. Transplantation 2013 September 27, 2013 - Volume 96. Wszola M, Kwiatkowski A, Berman A et al. Early results and technical aspects of endoscopic islets autotransplantation in a patient with contraindication to transplantation into the portal vein. Medtube Science Dec.2013; 1(1), 6-9. Echeverri GJ, McGrath K, Bottino R, Hara H, Dons EM, van der Windt DJ, Ekser B, Casu A, Houser S, Ezzelarab M, Wagner R, Trucco M, Lakkis FG, Cooper DK. Endoscopic gastric submucosal transplantation of islets (ENDO-STI): technique and initial results in diabetic pigs. Am J Transplant. 2009 Nov;9(11):2485-96.Russel SJ, El-Khatib FH, sinha M et al. Outpatient glycemic control with a bionic pancreas in MEDtube Science Sep, 2015; Vol.III (3) type 1 diabetes. N Engl J Med. 2014 Jul 24;371(4):313-25. 15. Russel SJ, El-Khatib FH, sinha M et al. Outpatient glycemic control with a bionic pancreas in type 1 diabetes. N Engl J Med. 2014 Jul 24;371(4):313-25. 16. Wolf E, Braun-Reichhart C, Streckel E, Renner S. Genetically engineered pig models for diabetes research. Transgenic Res. 2014 Feb;23(1):27-38. 17. Chaudhury K, Kumar V, Kandasamy J, RoyChoudhury S. Regenerative nanomedicine: current perspectives and future directions. Int J Nanomedicine. 2014 Sep 1;9:4153-4167. eCollection 2014. 18. Global health risks. Mortality and burden of disease attributable to selected major risks. Geneva, World Health Organization, 2009. 19. Wilson CA. Porcine endogenous retroviruses and xenotransplantation. Cell Mol Life Sci. 2008 Nov;65(21):3399-412. 20. Malenczyk K, Jazurek M, Keimpema E, Silvestri C, Janikiewicz J, Mackie K, Di Marzo V, Redowicz MJ, Harkany T, Dobrzyn A.: CB1 cannabinoid receptors couple to focal adhesion kinase to control insulin release. J Biol Chem (2013) 288(45):32685-99 21. Janikiewicz J, Hanzelka K, Dziewulska A, Kozinski K, Dobrzyn P, Bernas T, Dobrzyn A: Inhibition of SCD1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cells. J Lipid Res (2015) 56(10):1901-11. 22. Malenczyk K, Keimpema E, Piscitelli F, Calvigioni D, Björklund P, Mackie K, Di Marzo V, Hokfelt TGM, Dobrzyn A, Harkany T.: Fetal endocannabinoids orchestrate the organization of pancreatic islet microarchitecture. Proc Natl Acad Sci U S A. (2015) – in press 23. Roth EA et al. Inkjet printing for high-throughput cell patterning Biomaterials 25 (2004) 3707–3715 24. Chang JW, Park SA, Park JK et al. Tissue-engineered tracheal reconstruction using three-dimensionally printed artificial tracheal graft: preliminary report. Artif Organs. 2014 Jun;38(6):E95-E105. 25. Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 2006;367:1241–6. 26. Karina H. Nakayama, Cynthia A. Batchelder, Chang I. Lee and Alice F. Tarantal. Decellularized Rhesus Monkey Kidney as a Three-Dimensional Scaffold for Renal Tissue Engineering. Tissue Engineering: Part A Volume 16, Number 7, 2010. 27. Sullivan DC, Sayed-Hadi Mirmalek-Sani, Deegan DB et al. Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system. Biomaterials 33 (2012) 7756-7764. 28. Saik-Kia Goh, Bertera S, Olsen P et al. Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering. Biomaterials 34 (2013) 6760-6772. 29. Marchioli G, van Gurp L, van Krieken PP et al. Fabrication of threedimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation. Biofabrication. 2015 May 28;7(2):025009 30. Wszola M, Constantini M, Berman A et al. Using human pancreatic islets as a bioink for 3D bioprinting for bioengineering an artificial pancreas-preliminary report. IPITA report, Transplantation 2015. 31. Vivian K. Lee, Diana Y. Kim, Haygan Ngo, Young Lee, Lan Seo, Seung -Schik Yoo, Peter A. Vincent, Guohao Dai Creating perfused functional vascular channels using 3D bio-printing technology. Biomaterials (2014), Volume 35, Issue 28, Pages 8092-8102. 32. IdaszekJ, Zinn M, Bruinink A, Obarzanek-Fojt M, Święszkowski W. Materials Science and Enginerring C: Materials for Biological Applications; Vol. 33:7 (2013), 4352–4360 33. Idaszek J, Zell V, Bruinink A, Swieszkowski W.: PCL-based scaffolds with degradation profiles tuned to various treatment strategies of bone; European Cells and Materials; Vol. 26, Suppl. 4, 2013. 34. Biomechanical properties of native and tissue engineered heart valve constructs. Hasan A, Ragaert K, Swieszkowski W, Selimović S, Paul A, Camci-Unal G, Mofrad MR, Khademhosseini A. J Biomech. 2014 Jun 27;47(9):1949-63. 35. Fehily D., Uhrynowska-Tyszkiewicz I., Creusvaux H., Pariente-Khayat A., Kaminski A et al. Vigilance: lessons learned from the tissue and cell experience in the European Union. Part 1: reporting and communication. Organs Tissues & Cells, 16(3): 165-173, 2013. science 28 In 54 among 59 investigated DNA blood samples from HD patients we were able to detect a DNA fragment about 790 bp in length, consistent with the presence of 16sRNA bacterial DNA. Fragments od bacterial DNA presence in hemodialisis patients’ blood-preliminary report Marta Serwańska-Świętek1#, Marzena Sikora3, Bożena Interewicz3, Waldemar L Olszewski3, Andrzej Rydzewski2,4, Marek Durlik3,4 1. 2. 3. 4. Department of General and Transplantation Surgery, Warsaw Medical University, Nowogrodzka 59th Street, 02-006 Warsaw, Poland. Department of Internal Medicine, Nephrology and Transplantology, Central Clinical Hospital of Ministry of Internal Affairs, Warsaw, Poland Department of Gastrointestinal Surgery and Transplantology, Central Clinical Hospital of Ministry of Internal Affairs, Poland Institute of Experimental and Clinical Medicine, Polish Academy of Sciences, Warsaw, Poland #Corresponding author: Marta Serwańska-Świętek, Department of General and Transplantation Surgery, Warsaw Medical University, Nowogrodzka 59th Street, 02-006 Warsaw, Poland, Tel: +48225021113, Fax: +48225022155, E-mail: [email protected] RUNNING TITLE Bacterial DNA in hemodialysis patients KEYWORDS bacterial DNA, hemodialysis, inflammation, atherosclerosis WORD COUNT 787 CONFLICT OF INTERESTS no conflicts of interest ABSTRACT Cardiovascular disease (CVD) accounts for most of morbidity and mortality in patients with end-stage renal disease treated by chronic hemodialysis. The idea that inflammation state present in uremia plays an important role in the development of atherosclerosis has enjoyed much attention. We have investigated therefore possible presence of bacterial DNA in the blood of chronically hemodialyzed patients. There were retrospectively studies of 59 patients without any signs of active infection, who had been undergoing intermittent HD. In 54 among 59 investigated DNA blood samples from HD patients we were able to detect a DNA fragment about 790 bp in length, consistent with the presence of 16sRNA bacterial DNA. Bacterial DNA could not be detected in any of the samples from control subjects. We were not able to detect bacterial DNA in any of 9 investigated dialysate samples although in 4 blood samples of these patients bacterial DNA encoding ribosomal RNA was observed. Bacterial DNA is detectable in blood of HD patients. This might be one of the inflammatory stimuli. MEDtube Science Sep, 2015; Vol.III (3) science 29 INTRODUCTION C ardiovascular disease (CVD) accounts for most of morbidity and mortality in patients with end-stage renal disease treated by chronic hemodialysis (1). Even proper management of those patients, which helps to prevent hypertension, does not fully answer the problem (2). Traditional risk factors do not adequately explain excess CVD observed in ESRD patients, and paradoxically some of them are inversely related to prevalence of CVD a phenomenon called “reverse epidemiology” (3). Thus the idea that inflammation state present in uremia plays an important role in the development of atherosclerosis has enjoyed much attention (4,5). This notion has found support in reports of association between markers of inflammation (CRP, pro-inflammatory cytokines) and increased mortality. It was found that 30-60% of HD patients have evidence of activation of inflammation (6). The stimulus or stimuli for such a response were not found however. Several of them were proposed such as reduced renal clearance of cytokines, accumulation of AGE’s, occult inflammatory processes or infections, bioincompatibility of dialysis membranes and exposure to endotoxins and unspecified pro-inflammatory substances present in dialysis fluid (7,8). Schindler et al. have reported on the presence of short bacterial fragments in dialysate and induction of cytokines and TLR9 by them (9). These fragments were of sufficient small size to pass through dialyzer membrane. We have investigated therefore possible presence of bacterial DNA in the blood of chronically hemodialyzed patients. MATERIAL AND METHODS There were retrospectively studies of 59 patients without any signs of active infection, who had been undergoing intermittent HD (tab. 1). DNA samples isolated from whole blood, which were stored at -20C as a part of an ongoing prospective study on the CRP gene polymorphism effect on the CVD prevalence, were randomly selected. DNA samples was also isolated from dialysate of 9 different dialysis machines.100ml of dialysate and 5 ml of whole blood anticoagulated with 0.48% citric acid, 1.32% sodium citrate 1.47% glukose were withdrawn before HD session. Microbiological purity of water and dialysate was monitored according to Polish Pharmacopeia VI regulations. Control subjects - 109 healthy volunteers (hospital staff) donated blood for DNA isolation. DNA was isolated using Macherey-Nagel kit according to the manufacturer procedure after pretreatment of samples by three enzymatic digestions (Fig.1) PCR was performed with universal primers for 16sRNA bacterial gene: forward 5’ AGT TTG ATC CTG GCT CAG and reverse 5’ GAA CTA CCA GGG TAT CTA AT (Oligo Poland), 5 ng of DNA, Fast Start MEDtube Science Sep, 2015; Vol.III (3) Taq DNA polymerase Kit, GC rich (Roche) and PCR Anty-Inhibitor (DNA Gdańsk, Gdańsk, Poland), in final volume of 25 µl. Amplifications were performed in MJ Research thermocycler. We established following conditions: 95°C for 15min, 60°C for 45s, 72°C for 10s, (95°C for 45s ,60°C for 45s, 72°C for 1 min) 35 times, and finally 72°C for 10 min. As a negative controls we used: reaction mixture without template and DNAse treated reaction mixture. All procedures were performed in sterile condictions to minimalise even minor contamination of PCR mixture with exogenous template DNA. As a positive control Staphylococcus aureus 1/1W, Staphylococcus epidermidis 23/GS, Staphylococcus epidermidis 78/GS, Staphylococcus epidermidis 96/GS, Enterococcus 6/WO3, Enterococcus 1/2/WO3 and Escherichia Coli B2 strains were used (own collection). Products of amplification were electrophoresed on 12.5% poliacrylamide gels (ExelGel, Amersham Biosciences) and silver stained (DNA Silver Kit, Amersham Biosciences). Expected bands 789bp were compared to 100bp ladder (Amarsham Biosciences) with the use of GeneTools software (Syngene, England) (Fig.2). RESULTS In 54 among 59 investigated DNA blood samples from HD patients we were able to detect a DNA fragment about 790 bp in length, consistent with the presence of 16sRNA bacterial DNA. Observed bands were differing slightly in length and density suggesting different bacterial species as a DNA source and different concentrations in blood (Fig. 3). Bacterial DNA could not be detected in any of the samples from control subjects. We were not able to detect bacterial DNA in any of 9 investigated dialysate samples although in 4 blood samples of these patients bacterial DNA encoding ribosomal RNA was observed. CONCLUSION Bacterial DNA is detectable in blood of HD patients. This might be one of the inflammatory stimuli. There are several possible sources of bacterial DNA in blood of HD patients: passing of oligonucleotides through dialyzer membrane, endogenous sources (from atherotic plaques, paradontium, nasal sinuses, veins wall, aortic wall, dialysis fistula) or repeated introduction of bacteria into bloodstream during puncturing of dialysis fistula. Normal skin is colonized predominantly by Gram-positive bacteria, like Staphylococcus spp., Micrococcus spp., and coryneforms, whereas only Acinetobacter spp. are only Gram-negative bacteria regularly colonizing normal skin. External factors, like topical antiseptics, however may promote skin colonization by Gram-negative bacteria. Due to preliminary nature of this work we were not able to ascertain neither the source DNA nor bacterial science 30 species involved. CITE THIS AS MEDtube Science 2015, Sep 3(3), 28-30 LIST OF THE FIGURES Fig. 1. DNA isolation Fig. 2. ELEKTROPHORESIS Fig. 3. Bacterial 16S rRNA gene UNIVERSAL - HIGHLY CONSERVED REGION OF DNA FIG. 1. DNA ISOLATION FIG. 2. ELEKTROPHORESIS FIG. 3. BACTERIAL 16S RRNA GENE UNIVERSAL - HIGHLY CONSERVED REGION OF DNA Broad-range bacterial PCR is based on the use of primers that recognize conserved sequences of bacterial chromosomal genes encoding ribosomal RNA (rRNA) The resulting amplified rRNA sequences also include variable regions that provide an alternative approach for identifying theoretically all bacterial species, including those that cannot be cultivated by classical methods. MEDtube Science Sep, 2015; Vol.III (3) science 31 TAB. 1. CHARACTERISTIC OF PATIENT male gender (%) 54 age of years 62,5 Median value of CRP (ng/ ml) 6,4 median period of HD (months) 40,4 Frequency per week 3 Lenght of HD (h) fistulae 4-5 native arteriovenous, the double-needle technique machines ultrafiltration controllers dialysers low-flux modyfied cellulose dialysate bicarbonate-buffered The enrolment criteria excluded patients • • • • • • • diabetes SLE malignancy, HIV severe liver disease colitis ulcerosa Crohn desease BIBLIOGRAPHY 1. 2. 3. 4. 5. 6. 7. 8. 9. Daugirdas, John T. Handbook of Dialysis 5th Edition, Wolters Kluwer 2014 Prystacki T, Kloda K, Safranow K, Dziedziejko V, Domanski L. Modern Management of Dialysis Center has an impact on patients’ blood pressure and calcium-phosphorus metabolism. MEDtube Science Dec 2013; 1(1), 19-21. Tsirpanlis G, Boufidou F, Zoga M, Triantafyllis G, Fatourou A, Nicolaou C. Low cholesterol along with inflammation predicts morbidity and mortality in hemodialysis patient. Hemodial Int. 2009 Apr;13(2):197-204. Al Aly Z, Edwards JC. Vascular biology in uremia: insights into novel mechanisms of vascular injuryAdv Chronic Kidney Dis. 2004 Jul;11(3):310-8. Review. Wszola M, Kwiatkowski A, Nosek R et al. Chlamydia pneumoniae infection and ischemic heart disease in hemodialysis patients. Transplant Proc. 2006 Jan-Feb;38(1):31-4. Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, Jogestrand T: Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 1999;55:1899-1911. Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C: Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999;55:648-658. Gupta J, Mitra N, Kanetsky PA, Devaney J, Wing MR, Reilly M, Shah VO, Balakrishnan VS, Guzman NJ, Girndt M, Periera BG, Feldman HI, Kusek JW, Joffe MM, Raj DS: Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC. Clin J Am Soc Nephrol 2012;7:1938-1946. Schindler R, Beck W, Deppisch R, Aussieker M, Wilde A, Göhl H, Frei U. Short bacterial DNA fragments: detection in dialysate and induction of cytokines. J Am Soc Nephrol. 2004 Dec;15(12):3207-14. MEDtube Science Sep, 2015; Vol.III (3) science 32 INSTRUCTIONS FOR AUTHORS MEDtube Science is an open access journal of MEDtube community and is addressed to all medical professionals – doctors, clinicians, scientists who are interested in achievements in basic and clinical medical science. The journal has the international scope. It is published quarterly and exclusively in English. 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