Infectious Disease Burden after Solid Organ Transplantation (SOT) in the Swiss Transplant Cohort Study (STCS).

Infectious diseases (ID) are a major cause of morbidity and mortality after SOT. Since May 2008, the STCS has registered 95% of all SOT recipients in Switzerland. The extensive data set includes pre- and post-transplant variables that are prospectively collected at transplantation, 6 months post-transplant, and yearly thereafter. All ID events are recorded using internationally validated defi nitions. We obtained data from 1101 patients (79 heart, 685 kidney, 29 kidney-pancreas, 212 liver, and 96 lung transplants). So far the median observation times were 0.8 (IQR 0.3-1.4; heart); 1.1 (0.6-1.8, kidney); 1.1 (0.6-1.9, kidney-pancreas); 1.0 (0.5-1.7, liver); and 0.9 years (0.5-1.5, lung). The highest rates of proven or probable ID events were seen in lung (76%), followed by liver (64%), heart (62%), kidney-pancreas (62%), kidney (58%). During the observation period, ID was the cause of death in 19 patients (1.7%). Rates of infections per person-years according to pathogen and type of transplantation are shown in Figure 1. The data indicate that virus infections are only second after bacteria whereas fungi occur at relatively low rates. This prospective and standardized long-term collection of all ID events will allow a comprehensive assessment of the burden of ID across all SOT types in Switzerland. Regular analysis will identify new trends, serve as a quality control and help design anti-infectious interventions aiming at increasing safety and improving overall transplantation outcome.

Quality of life in simultaneous pancreas-kidney transplant recipients

Currently, simultaneous pancreas-kidney transplantation (SPK Tx) is the treatment of choice in selected patients with type 1 diabetes mellitus (DM1) and terminal kidney failure (TRF). A functioning SPK transplant allows dialysis and insulin therapy to be discontinued and stabilizes or improves the complications of DM1. Nevertheless, to a greater or lesser degree, these complications (physical and psychological alterations, secondary effects of immunosuppressive therapy and the need for lifelong medication and medical follow-up) can persist after SPK Tx. Health professionals have mainly investigated the clinical features of transplant recipients. However, in the last few years, interest in analyzing perceived health and health-related quality of life (QoL) has increased. This latter concept includes the features of QoL most closely associated with a particular disease, its treatment and follow-up and therefore those elements most susceptible to modification by the health system. The general aim of this study was to measure health-related QoL in our population with SPK Tx and to determine whether there are significant differences between these patients and those with DM1 and TRF who continue to receive renal replacement therapy (RRT) and insulin therapy. More specific aims were to evaluate whether there are significant differences between the study groups and the means of the Spanish reference population in the distinct dimensions of a QoL questionnaire and whether other variables such as age, sex, years" duration of DM1, length of dialysis, and time since SPK Tx significantly affect health-related QoL.

Quality of life in simultaneous pancreas-kidney transplant recipients

Currently, simultaneous pancreas-kidney transplantation (SPK Tx) is the treatment of choice in selected patients with type 1 diabetes mellitus (DM1) and terminal kidney failure (TRF). A functioning SPK transplant allows dialysis and insulin therapy to be discontinued and stabilizes or improves the complications of DM1. Nevertheless, to a greater or lesser degree, these complications (physical and psychological alterations, secondary effects of immunosuppressive therapy and the need for lifelong medication and medical follow-up) can persist after SPK Tx. Health professionals have mainly investigated the clinical features of transplant recipients. However, in the last few years, interest in analyzing perceived health and health-related quality of life (QoL) has increased. This latter concept includes the features of QoL most closely associated with a particular disease, its treatment and follow-up and therefore those elements most susceptible to modification by the health system. The general aim of this study was to measure health-related QoL in our population with SPK Tx and to determine whether there are significant differences between these patients and those with DM1 and TRF who continue to receive renal replacement therapy (RRT) and insulin therapy. More specific aims were to evaluate whether there are significant differences between the study groups and the means of the Spanish reference population in the distinct dimensions of a QoL questionnaire and whether other variables such as age, sex, years" duration of DM1, length of dialysis, and time since SPK Tx significantly affect health-related QoL.

Quality of life in simultaneous pancreas-kidney transplant recipients

Currently, simultaneous pancreas-kidney transplantation (SPK Tx) is the treatment of choice in selected patients with type 1 diabetes mellitus (DM1) and terminal kidney failure (TRF). A functioning SPK transplant allows dialysis and insulin therapy to be discontinued and stabilizes or improves the complications of DM1. Nevertheless, to a greater or lesser degree, these complications (physical and psychological alterations, secondary effects of immunosuppressive therapy and the need for lifelong medication and medical follow-up) can persist after SPK Tx. Health professionals have mainly investigated the clinical features of transplant recipients. However, in the last few years, interest in analyzing perceived health and health-related quality of life (QoL) has increased. This latter concept includes the features of QoL most closely associated with a particular disease, its treatment and follow-up and therefore those elements most susceptible to modification by the health system. The general aim of this study was to measure health-related QoL in our population with SPK Tx and to determine whether there are significant differences between these patients and those with DM1 and TRF who continue to receive renal replacement therapy (RRT) and insulin therapy. More specific aims were to evaluate whether there are significant differences between the study groups and the means of the Spanish reference population in the distinct dimensions of a QoL questionnaire and whether other variables such as age, sex, years" duration of DM1, length of dialysis, and time since SPK Tx significantly affect health-related QoL.

Development of the endocrine pancreas and novel strategies for β-cell mass restoration and diabetes therapy

Diabetes mellitus represents a serious public health problem owing to its global prevalence in the last decade. The causes of this metabolic disease include dysfunction and/or insufficient number of β cells. Existing diabetes mellitus treatments do not reverse or control the disease. Therefore, β-cell mass restoration might be a promising treatment. Several restoration approaches have been developed: inducing the proliferation of remaining insulin-producing cells, de novo islet formation from pancreatic progenitor cells (neogenesis), and converting non-β cells within the pancreas to β cells (transdifferentiation) are the most direct, simple, and least invasive ways to increase β-cell mass. However, their clinical significance is yet to be determined. Hypothetically, β cells or islet transplantation methods might be curative strategies for diabetes mellitus; however, the scarcity of donors limits the clinical application of these approaches. Thus, alternative cell sources for β-cell replacement could include embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. However, most differentiated cells obtained using these techniques are functionally immature and show poor glucose-stimulated insulin secretion compared with native β cells. Currently, their clinical use is still hampered by ethical issues and the risk of tumor development post transplantation. In this review, we briefly summarize the current knowledge of mouse pancreas organogenesis, morphogenesis, and maturation, including the molecular mechanisms involved. We then discuss two possible approaches of β-cell mass restoration for diabetes mellitus therapy: β-cell regeneration and β-cell replacement. We critically analyze each strategy with respect to the accessibility of the cells, potential risk to patients, and possible clinical outcomes.

METABOLIC EFFECT OF PANCREATICODUODENAL TRANSPLANTATION IN DIABETIC RATS

Outbred Wistar rats were randomly assigned to three experimental groups: GI, 10 nondiabetic control rats; GII, 10 alloxan-diabetic control rats; GIII, 25 alloxan-diabetic rats that received pancreaticoduodenal transplantation (PDT) from normal donor Wistar rats and were immunosuppressed with cyclosporin A. For 7 prior and 4, 7, 14, 21, and 30 days posttransplantation (during which the animals were housed in metabolic cages for periods of 24 hours) body weight, water and food intake, urine output, blood and urinary glucose, plasma insulin, and glucagon were recorded. These parameters were also concurrently recorded for diabetic and nondiabetic control rats. Animals were sacrificed after 30 days and histological and immunohistochemical studies of the pancreas were performed. Pancreatic transplants consistently and significantly improved the metabolic abnormalities of the diabetic rat (P < 0.01) by restoring body weight gain, and by immediate relief of hyperglycemia, glucosuria, polyuria, polydipsia, and also the low levels of plasma insulin. The plasma glucagon, elevated in diabetic control rats, did not change after transplant.

Pancreatic islet transplantation

Abstract Background No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR) from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects. Conclusion Human islet transplantation should be regarded as an intervention that can decrease the frequency of severe hypoglycemic episodes and improve glycemic control in selected patient for whom benefits of 4-5 years duration would be very valuable. Its limitations, however, indicate that the procedure in its current format is not suitable for all patients with type 1 diabetes.

Prevalence of cholecystolithiasis and its management among kidney/pancreas-transplanted type 1 (insulin-dependent) diabetic patients

BACKGROUND: Simultaneous pancreas/kidney transplantation (SPK) should be the procedure of choice for (pre)uremic patients with type 1 diabetes. All standard immunosuppressive protocols for SPK include a calcineurin-inhibitor. Both calcineurin inhibitors, cyclosporine (CyA) and probably tacrolimus (FK506) too, are associated with the occurrence of cholelithiasis due to their metabolic side effects. PATIENTS AND METHODS: We evaluated the prevalence of cholelithiasis in 83 kidney/pancreas transplanted type I-diabetic patients (46 males, 37 females, mean age 42.8 +/- 7.5 years) by conventional B-mode ultrasound 5 years after transplantation. 56 patients received CyA (group 1) and 27 received tacrolimus (group 2) as first-line-immunosuppressive drug. Additional immunosuppression consisted of steroids, azathioprine or mycophenolate mofetil. Additionally, laboratory analyses of cholestasis parameters (gamma-GT and alcalic phosphatasis) were performed. RESULTS: In total, 23 patients (28%) revealed gallstones and 52 patients (62%) revealed a completely normal gallbladder. In eight patients (10%) a cholecystectomy was performed before or during transplantation because of already known gallstones. No concrements in the biliary ducts (choledocholithiasis) could be detected. In group 2 the number of patients with gallstones was slightly lower (22%) compared with group 1 patients (30%), but without statistical significance. - Cholestasis parameters were not increased and HbA1c values were normal in both groups of patients. CONCLUSION: The prevalence of biliary disease in kidney/pancreas transplanted type I-diabetic patients with 28% is increased in comparison to the general population (10-15%). Lithogenicity under tacrolimus seems to be lower as under cyclosporine based immunosuppressive drug treatment. We recommend regular sonographical examinations to detect an acute or chronic cholecystis as early as possible, which may develop occultly in these patients.

[Knowledge, attitude and reservations of medical students about organ transplantation: results of a survey during the first year of study]

AIM: Establish a list of first year medical students' attitudes, doubts, and knowledge in the fields of organ transplantation and donation. METHOD: Anonymized questionnaire handed out to students during class lectures. RESULTS: 183 questionnaires were distributed and 117 returned (participation: 64%). The average age of the students was 21.6 +/- 2.7 years (range 18 to 38 years); the sample included 71 women (60.7%) and 48 men (39.3%). Only 2 students (2%) were not interested in the subject of organ donation. The students knew very little of the legal aspects of organ donation and 1/4 of them thought there was even a Federal law regarding organ transplantation. When asked if they knew whether a law existed in the Canton of Berne, 44% replied yes, but only 24 (20%) knew that this is contradictory. There was no gender difference in the answers to these question. From 57 students (48%) 246 individual comments on doubts and concerns were analyzed. In this respect, the students mainly questioned whether the donor was truly dead when donation took place (n = 48), if illegal transplantation could be eliminated (n = 44) and if transplantation was truly necessary (n = 43). Some also mentioned religious/ethical doubts (n = 42). In regard to organ donation by a living individual, 27 students were concerned about the health of this donor. 20 students had doubts regarding the pressure possibly applied by family members and friends and as many voiced doubts in regard to premature diagnosis of brain death of potential donors. Only 2 students were concerned about the post-mortem presentation. 45 students (48%) indicated discomfort with the donation of certain organs. They ranked the kidney as the first organ to donate, followed by the pancreas, heart, cornea, intestine, lung and liver. CONCLUSION: The interest in organ donation and transplantation is already strong in fist year medical students in the pre-clinical stage. However, differences from lay public are not readably detectable at this stage of medical training. Adequate information could influence future physicians in their mediatory role.

Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver

The ability to identify, isolate, and transplant progenitor cells from solid tissues would greatly facilitate the treatment of diseases currently requiring whole organ transplantation. In this study, cell fractions enriched in candidate epithelial progenitor cells from the rat pancreas were isolated and transplanted into the liver of an inbred strain of Fischer rats. Using a dipeptidyl dipeptidase IV genetic marker system to follow the fate of transplanted cells in conjunction with albumin gene expression, we provide conclusive evidence that, after transplantation to the liver, epithelial progenitor cells from the pancreas differentiate into hepatocytes, express liver-specific proteins, and become fully integrated into the liver parenchymal structure. These studies demonstrate the presence of multipotent progenitor cells in the adult pancreas and establish a role for the liver microenvironment in the terminal differentiation of epithelial cells of foregut origin. They further suggest that such progenitor cells might be useful in studies of organ repopulation following acute or chronic liver injury.

Sinonasal Disorders In Hematopoietic Stem Cell Transplantation.

hematopoietic stem cell transplantation (HSCT) is associated with more respiratory infections due to immunosuppression. this study aimed to verify the frequency of rhinosinusitis after HSCT, and the association between rhinosinusitis and chronic graft vs. host disease (GVHD) and type of transplantation, clinical treatment, surgical treatment, and survival. this was a retrospective study in a tertiary university hospital. A total of 95 patients with hematological diseases undergoing HSCT between 1996 and 2011 were selected. chronic myeloid leukemia was the most prevalent disease. The type of transplant most often performed was the allogenic type (85.26%). The frequency of rhinosinusitis was 36%, with no difference between the autologous and the allogenic types. Chronic GVHD occurred in 30% of patients. Patients with GVHD had a higher frequency and recurrence of rhinosinusitis, in addition to more frequent need for endoscopic sinusectomy and decreased overall survival. there was a higher frequency of rhinosinusitis in HSCT and GVHD. The type of transplant does not appear to predispose to the occurrence of rhinosinusitis. GVHD seems to be an aggravating factor and requires a more stringent treatment.

Influence Of Cyclosporine On The Occurrence Of Nephrotoxicity After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review.

Cyclosporine, a drug used in immunosuppression protocols for hematopoietic stem cell transplantation that has a narrow therapeutic index, may cause various adverse reactions, including nephrotoxicity. This has a direct clinical impact on the patient. This study aims to summarize available evidence in the scientific literature on the use of cyclosporine in respect to its risk factor for the development of nephrotoxicity in patients submitted to hematopoietic stem cell transplantation. A systematic review was made with the following electronic databases: PubMed, Web of Science, Embase, Scopus, CINAHL, LILACS, SciELO and Cochrane BVS. The keywords used were: bone marrow transplantation OR stem cell transplantation OR grafting, bone marrow AND cyclosporine OR cyclosporin OR risk factors AND acute kidney injury OR acute kidney injuries OR acute renal failure OR acute renal failures OR nephrotoxicity. The level of scientific evidence of the studies was classified according to the Oxford Centre for Evidence Based Medicine. The final sample was composed of 19 studies, most of which (89.5%) had an observational design, evidence level 2B and pointed to an incidence of nephrotoxicity above 30%. The available evidence, considered as good quality and appropriate for the analyzed event, indicates that cyclosporine represents a risk factor for the occurrence of nephrotoxicity, particularly when combined with amphotericin B or aminoglycosides, agents commonly used in hematopoietic stem cell transplantation recipients.

Unusual Erythrocyte Split Chimerism In Pregnancy After Allogeneic Stem Cell Transplantation.

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Robotic Resection of Intraductal Neoplasm of the Pancreas

Background: Minimally invasive techniques have been revolutionary and provide clinical evidence of decreased morbidity and comparable efficacy to traditional open surgery. Computer-assisted surgical devices have recently been approved for general surgical use. Aim: The aim of this study was to report the first known case of pancreatic resection with the use of a computer-assisted, or robotic, surgical device in Latin America. Patient and Methods: A 37-year-old female with a previous history of radical mastectomy for bilateral breast cancer due to a BRCA2 mutation presented with an acute pancreatitis episode. Radiologic investigation disclosed an intraductal pancreatic neoplasm located in the neck of the pancreas with atrophy of the body and tail. The main pancreatic duct was enlarged. The surgical decision was to perform a laparoscopic subtotal pancreatectomy, using the da Vinci (R) robotic system (Intuitive Surgical, Sunnyvale, CA). Five trocars were used. Pancreatic transection was achieved with vascular endoscopic stapler. The surgical specimen was removed without an additional incision. Results: Operative time was 240 minutes. Blood loss was minimal, and the patient did not receive a transfusion. The recovery was uneventful, and the patient was discharged on postoperative day 4. Conclusions: The subtotal laparoscopic pancreatic resection can safely be performed. The da Vinci robotic system allowed for technical refinements of laparoscopic pancreatic resection. Robotic assistance improved the dissection and control of major blood vessels due to three-dimensional visualization of the operative field and instruments with wrist-type end-effectors.