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Rituximab is an effective treatment for steroid-dependent/ frequently-relapsing nephrotic syndrome (SDFRNS) in children. However, the optimal rituximab regimen remains unknown. To help determine this we conducted an international, multicenter retrospective study at 11 tertiary pediatric nephrology centers in Asia, Europe and North America of children 1-18 years of age with complicated SDFRNS receiving rituximab between 2005-2016 for 18 or more months follow-up. The effect of rituximab prescribed at three dosing levels: low (375mg/m 2 ), medium (750mg/m 2 ) and high (1125-1500mg/m 2 ), with or without maintenance immunosuppression (defined as concurrent use of corticosteroids, mycophenolate motile or calcineurin inhibition at first relapse or for at least six months following the rituximab treatment) was examined. Among the 511 children (median age 11.5 year, 67% boys), 191, 208 and 112 received low, medium and high dose rituximab, respectively. Within this total cohort of 511 children, 283 (55%) received maintenance immunosuppression. Renal biopsies were performed in 317 children indicating the predominant histology was minimal change disease (74%). Without maintenance immunosuppression, low-dose rituximab had a shorter relapse-free period and a higher relapse risk (8.5 months) than medium (12.7 months; adjusted hazard ratio, 0.62) and high dose (14.3 months; adjusted hazard ratio, 0.50; all significant). With maintenance immunosuppression, the relapse-free survival in low-dose rituximab (14 months) was similar to medium (10.9 months; adjusted hazard ratio, 1.23) and high dose (12.0 months; adjusted hazard ratio, 0.92; all non-significant). Most adverse events were mild. Thus, children receiving low-dose rituximab without maintenance immunosuppression had the shortest relapse-free survival. Hence, both rituximab dose and maintenance immunosuppression have important effects on the treatment outcomes., (Copyright © 2019 International Society of Nephrology. All rights reserved.)

The International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) is an organization of more than 500 physicians and scientists focused on the treatment of cutaneous malignancies following solid organ transplantation and in other forms of immunosuppression. It is well known that solid organ transplant recipients (SOTRs) have an approximate 100-fold increase in the risk of developing skin cancer with consensus guidelines recommending these patients be managed as high risk for local recurrence and metastasis associated with poor outcomes. In September 2018, ITSCC and its European counterpart, the Skin Care in Organ Transplant Patients-Europe (SCOPE), held their biennial scientific retreat in Essex, MA to discuss novel findings in the pathogenesis of cutaneous malignancy including new treatment and prevention strategies in this at-risk population for significant morbidity and mortality from their cutaneous disease. This meeting report is a summary of the novel findings discussed., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Hepatitis E virus (HEV) infection is a pandemic with regional outbreaks, including in industrialized countries. HEV infection is usually self-limiting but can progress to chronic hepatitis E in transplant recipients and HIV-infected patients. Whether other immunocompromised hosts, including rheumatology and internal medicine patients, are at risk of developing chronic HEV infection is unclear. Methods: We conducted a retrospective European multicenter cohort study involving 21 rheumatology and internal medicine patients with HEV infection between April 2014 and April 2016. The underlying diseases included rheumatoid arthritis ( n = 5), psoriatic arthritis ( n = 4), other variants of chronic arthritis ( n = 4), primary immunodeficiency ( n = 3), systemic granulomatosis ( n = 2), lupus erythematosus ( n = 1), Erdheim⁻Chester disease ( n = 1), and retroperitoneal fibrosis ( n = 1). Results: HEV infection lasting longer than 3 months was observed in seven (33%) patients, including two (40%) patients with rheumatoid arthritis, three (100%) patients with primary immunodeficiency, one (100%) patient with retroperitoneal fibrosis and one (100%) patient with systemic granulomatosis. Patients with HEV infection lasting longer than 3 months were treated with methotrexate without corticosteroids ( n = 2), mycophenolate mofetil/prednisone ( n = 1), and sirolimus/prednisone ( n = 1). Overall, 8/21 (38%) and 11/21 (52%) patients cleared HEV with and without ribavirin treatment, respectively. One patient experienced an HEV relapse after initially successful ribavirin therapy. One patient (5%) was lost to follow-up, and no patients died from hepatic complications. Conclusion: Rheumatology and internal medicine patients, including patients treated with methotrexate without corticosteroids, are at risk of developing chronic HEV infection. Rheumatology and internal medicine patients with abnormal liver tests should be screened for HEV infection.

Introduction: The first renal transplantation was completed in 1991 at the University of Debrecen. In 2013 Hungary joined Eurotransplant., Aim: The authors retrospectively compared the trends., Method: Comparison between Period A (from January 1, 2008 to August 31, 2013) and Period B (from September 1, 2013 to October 22, 2015)., Results: The proportion of living transplants rose from 3.5% to 9.1 %. During period B over 25% of utilized donors were over 60 years of age. Recipients with body mass index above 30 kg/m(2) increased from 12% to 31%. Prevalence of diabetes among recipients rose twofold. Uretero-neocystostomy was used during period A (99%) while in period B end to side uretero-ureteral anastomosis has also gained popularity (68%). In 2013 the authors introduced routine use of induction treatment. Acute rejection rate decreased from 34% to 8%. The rate of surgical complications did not change. Acute bacterial infections decreased from 41% to 33%. Cumulative renal allograft 1, 3 and 5 year survival rates were 86.6%, 85% and 82.7% in group A vs. projected rates 88%, 84% and 84% in group B, respectively., Conclusions: Despite the growing proportion of expanded criteria donors, the authors were able to maintain a low incidence of delayed graft function and a favorable graft survival. Since 2013 the authors introduced treatments for acute humoral rejection according to international standards.

This study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0-12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen-matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0·18). Event-free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0·001). Ninety-one of 167 patients (55%) failed front-line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up-front (P 0·017). Rejection was 2% for MFD HSCT and HSCT post-IST failure (P 0·73). Acute graft-versus-host disease (GVHD) grade II-IV was 8% in MFD graft vs. 25% for HSCT post-IST failure (P < 0·0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post-IST failure (P < 0·0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first-line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option., (© 2015 John Wiley & Sons Ltd.)

The overall success of organ transplantation in the 21st century has been predicated, in part, on the use of newer, more potent, and selective immunosuppressive agents. However, the high cost of lifelong immunosuppression represents a financial burden for many patients. In the past 15 years, regulatory agencies in Europe and America have approved several generic immunosuppressants. One concern is whether the conversion between innovator and generic immunosuppressants will prove to be problematic. This manuscript aims to compare and contrast the bioequivalence requirements among regulatory authorities in the USA, Europe, and Canada, evaluate published studies of generic immunosuppressants in transplant recipients, summarize consensus statements made by transplant organizations and discuss how to engage patients in discussion regarding the choice between innovator and generic immunosuppressants.

Background: Beta-human papillomavirus (betaPV) may play a role in the development of cutaneous squamous cell carcinoma (SCC). However betaPV is highly prevalent, and it may only be people with a higher viral load who have increased risk of SCCs. We therefore examined the association between betaPV load and SCCs., Methods: We recruited 448 immunocompetent cases with SCCs and 464 controls from Italy and Australia and 497 immunosuppressed organ transplant recipients (OTR; 179 cases and 318 controls) from Europe. We used reverse hybridization to genotype 25 betaPV types in eyebrow hair follicles and determined the viral load for eight selected types using quantitative PCR. We used logistic regression to assess associations between type-specific and cumulative viral load and SCCs., Results: Australian and OTR participants in the highest cumulative load tertile were at significantly higher risk of SCCs than those in the lowest tertile. Those with more than four betaPV types in the high load tertile were at approximately three-fold increased risk of SCCs. In Australia, HPV23 and 36 loads were significantly associated with SCCs, with borderline associations for HPV5 and 38. In OTR, HPV8 and 38 loads were significantly associated and HPV20 and 36 were borderline. We found little evidence for an association between load and SCCs in Italy., Conclusions: High viral load may be associated with risk of cutaneous SCCs, with total load seemingly more important than the load of any specific type., Impact: Our findings lend weight to the hypothesis that HPV plays a role in skin carcinogenesis.

Organ transplant recipients (OTR) are at increased risk of cutaneous squamous cell carcinoma, which may be related to reactivation of human papillomavirus (HPV) infections. Measurement of change in HPV antibodies after transplantation would help to explore this hypothesis. We measured antibodies to 34 HPV types on up to six occasions over 18 months in 441 OTRs from five European countries. At baseline (mean 24 days after transplantation), 80% of all OTRs were seropositive to at least one HPV type. The beta HPV genus had the highest seroprevalence (45%). For most HPV genera baseline seroprevalence peaked between 40 and 59 years old. Most OTRs retained their serostatus over time and antibody levels were stable. Seroprevalence in immunosuppressed OTRs is stable in the 18 months immediately after transplantation. Thus there is no short-term evidence that immunosuppression leads to new or reactivated skin infection with HPV sufficient to induce antibodies., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Hepatitis E virus (HEV) is an important cause of acute hepatitis in humans worldwide, both as epidemic and sporadic disease. Since the virus was identified in 1983, epidemics have occurred regularly in many countries across South and Southeast Asia when seasonal floods have contaminated drinking water supplies and in Africa during humanitarian crises among refugee populations without access to clean water. In addition, sporadic cases and small clusters of HEV infections have been recognized throughout the world in developed countries over the past couple of decades. This review will focus on emerging evidence of HEV infection as an under-recognized pathogen in Europe, the USA and other industrialized countries. We will discuss some of the issues associated with the recognition, diagnosis and treatment of these sporadic cases. We will also summarize the recent literature on autochthonous HEV infection among populations in developed countries in industrialized Europe, the USA, Japan and other industrialized Asian countries. We will review recent reports of acute and chronic HEV infections among transplant recipients and other immunocompromised individuals including HIV/AIDS patients.

Heart transplantation was performed firstly in 1967, but it became a valuable option in the 1980s, due to the availability of cyclosporine and of the technique for rejection monitoring by means of serial endomyocardial biopsies. Post-transplant survival improved over the years, mainly due to a reduction in early mortality for infection or acute rejection. Expected 1-year and 5-year survivals are around 85% and 70%, respectively. During the past 20-30 years, better therapies for heart failure have been developed, leading to restriction of heart transplant candidacy to truly refractory heart failure. On the contrary, the criteria for donor acceptance have been liberalized, due to the discrepancy between heart transplant candidates and available organs. It must be kept in mind that renal and/or hepatic insufficiency that may be a consequence of heart failure, pulmonary hypertension, and donor age, all remain risk factors for mortality after transplantation. In order to maintain and possibly improve the results of heart transplantation, effective strategies to increase safely the donor pool are of utmost importance. Moreover, long-term post-transplant recipients present new challenges to research and clinical practice. Mechanical circulatory support devices represent a surgical bridge or an alternative to transplantation; their expansion is limited by costs, organizational burden, and by patient difficulties in accepting this therapy.

Objective: To evaluate the feasibility of haematopoietic stem cell transplantation (HSCT) in vasculitis., Methods: This is a retrospective analysis of patients who had received HSCT for vasculitic diseases and have been reported to the European League Against Rheumatism autoimmune disease or European Bone Marrow Transplantation ProMISe databases. Information about the disease and outcome was obtained by a questionnaire sent to the referring centres. Response of the disease to HSCT was defined as partial or complete responses according to the ability to reduce immunosuppression after HSCT. In addition, the Medline database was searched for reports on HSCT in patients with vasculitis., Results: Detailed information was obtained for 15 patients, whose median age at HSCT was 37 years. The diagnoses were cryoglobulinaemia in four patients, Behçet's disease in three patients, Wegener's granulomatosis in three patients, and undifferentiated vasculitis, Churg-Strauss angiitis, polychondritis, Takayasu arteritis and polyarteritis nodosa in one patient each. 14 patients received autologous HSCT and 1 an allogeneic HSCT as the first transplant. In three patients, further transplantation was given because of relapse. The overall response, including all consecutive transplantations (HSCT/patient, n = 1-3, median 1.3) to HSCT, was 93%, with 46% complete responses and 46% partial responses; median (range) duration of response at the time of reporting was 45 (16-84) months. Three patients died, one from advanced disease, one from cancer and one from graft-versus-host disease. The Medline search showed five other patients who were effectively treated with HSCT for vasculitic diseases., Conclusion: This retrospective study suggests that autologous HSCT is feasible for vasculitis. Its value remains to be tested in prospective controlled studies.

The agent that causes tick-borne fever (TBF) in sheep was first described in 1940, 8 years after the disease was first recognized in Scotland. The same agent was soon shown to cause TBF in sheep and pasture fever in cattle in other parts of the UK, Scandinavia, and other parts of Europe. After the initial use of the name Rickettsia phagocytophila, the organism was given the name Cytoecetes phagocytophila to reflect its association with granulocytes and its morphological similarity with Cytoecetes microti. This name continued to be used by workers in the UK until the recent reclassification of the granulocytic ehrlichiae affecting ruminants, horses, and humans as variants of the same species, Anaplasma phagocytophilum. TBF and pasture fever are characterized by high fever, recurrent bacteremia, neutropenia, lymphocytopenia, thrombocytopenia, and general immunosuppression, resulting in more severe secondary infections such as tick pyemia, pneumonic pasteurellosis, listeriosis, and enterotoxemia. During the peak period of bacteremia as many as 90% of granulocytes may be infected. The agent is transmitted transtadially by the hard tick Ixodes ricinus, and possibly other ticks. After patent bacteremia, sheep, goats, and cattle become persistently infected "carriers," perhaps playing an important role in the maintenance of infection, in the flock/herd. Little is known about how efficiently ticks acquire and maintain infection in ruminant populations or whether "carrier" domestic ruminants play an important role as reservoirs of infection, but deer, other free-living ruminants, and wild rodents are also potential sources of infection. During the late 1990s serological evidence of infection of humans was demonstrated in several European countries, creating a renewed interest and increased awareness of the zoonotic potential of TBF variants. More recently, a few cases of human granulocytic anaplasmosis (HGA) have been reported in some European countries, but it remains to be established whether the variants causing HGA in Europe are genetically and biologically different from those causing TBF in ruminants. TBF is readily diagnosed by demonstrating intracytoplasmic inclusions in peripheral blood granulocytes or monocytes of febrile animals or by detecting specific DNA by polymerase chain reaction (PCR), and TBF variants of A. phagocytophilum can be cultivated in tick cell lines, but the differentiation of TBF variants from HGA variants awaits further investigations.

Multiple sclerosis is a relatively common and seriously disabling disease of autoimmune pathogenesis, for which there is currently no cure. Available therapies include immunomodulating agents and standard-dose immunosuppressants, which may be helpful but are not curative. Recently, studies in animal models have indicated that control of autoimmune disease can be obtained by high-dose immunosuppression followed by hematopoietic stem cell transplantation (rescue). Autologous transplants for severe and refractory multiple sclerosis were proposed in 1997 and have been performed ever since in selected patients and in the context of phase I/II trials. To date, more than 200 patients have been treated worldwide, and similar results were obtained in different centers: high-dose therapy suppresses inflammation in the brain to a degree superior to any other conventional therapy and seems to delay significantly clinical disease progression. There is, however, a procedure-related mortality risk of 1.5-5%, requiring careful patient selection before transplant. The treatment should be reserved for patients having high chance of response, i.e., young patients with low disability scores but rapidly progressing disease, having inflammatory rather than neurodegenerative changes in the central nervous system. The mechanism of action of transplantation is unclear. The initial concept of immune ablation by high-dose therapy and reconstitution of normal immunity from transplant-derived lymphocyte progenitors has given way to the concept of "resetting" the immune system and of bringing the disease to a lower level of activity. One could also speculate on a tissue repair effect, given the ability of human hematopoietic stem cells to migrate also into the central nervous system. The clinical effect of transplantation remains to be demonstrated in a randomized study. The Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation has launched such a trial, comparing transplantation to the currently best available therapy, i.e., mitoxantrone, and in about 5 years we should know whether transplantation offers more than the benefit of a transient immunosuppressive effect.

In Germany the number of kidney transplantations has increased rather slowly during recent years. While living donations increased, the number of postmortal donations decreased during the same time. In order to lower the number of patients on the waiting lists in Germany, the rate of postmortal or living donations as well as the number of marginal donors must be increased. Furthermore, risk factors related to the development of coronary heart disease or chronic allograft nephropathy, have to be strictly controlled in order to improve graft survival and, thus, reduce the waiting lists. In addition to the well established risk factors for graft survival such as HLA-missmatch, ischemia, coronary artery disease, metabolic diseases, or recipient/donor age others such as recipient/donor gender, social status, and patient education also influence graft survival. Screening for malignant tumors is crucial as donor and recipient age is increasing. Whether newer immunosuppressive substances such as mycophenolat mofetil (MMF), sirolimus, Il-2 receptor antagonists, or FTY720 prolong long term graft survival, has to be investigated in future clinical trials.

As of December 31, 2003, more than 21,000 pancreas transplants had been reported to the IPTR, >15,000 in the US and >5,000 outside the US. An era analysis of US cases from 1987 to May 15, 2003 showed a progressive improvement in outcome (p<0.04), with pancreas transplant graft survival rates (GSRs) going from 76% at one year for 1987-92 to 85% for 2001-2003 SPK cases, from 57%-79% for PAK cases, and from 55%-76% for PTA cases. The improvements were due both to decreases in technical failure rates (from 15%-10% in SPK, 21%-13% in PAK, and 24%-8% in PTA) and immunological failure rates (going from 6%-1% for SPK, from 23%-4% for PAK, and from 28%-7% for PTA cases). The proportion of recipients >45 years old increased from 11% in all 3 recipient categories in 1987-92 to 32-36% for 2001-2003 cases, and the improved outcomes encompassed the older patients as well. Contemporary pancreas transplant outcomes were calculated separately for January 1, 1999- May 15, 2003 US and non-US cases. The results of the US analysis are summarized first. US patient survival rates at one year were >95% in each recipient category, with one-year primary pancreas GSRs of 85% for SPK (n=3,775), 79% for PAK (n=951), and 78% for PTA (n=403) (p<0.0001). The immunological graft failure rates for 1996-2002 technically successful SPK, PAK and PTA cases were 2% (n=3,437), 5% (n=854), and 7% (n=356) at one year (p=0.0001). There was a progressive increase in the use of ED (as opposed to BD) for duct management. For 1999-2003 US primary pancreas transplants, ED was used in 78% of SPK, 60% of PAK and 49% for PTA cases. Of the ED transplants, venous drainage via the portal system was used for 23% of SPK, 27% of PAK and 44% of PTA cases. Pancreas GSRs were nearly identical for 1999-2003 ED (n=2,898) and BD (n=798) SPK transplants (85% for both at one year), nor was there a significant difference (p>0.17) in pancreas GSRs for systemic (n=2,218) versus portal (n=680) venous drained ED SPK transplants (84% vs 87% at one year). Kidney GSRs were not significantly different for ED versus BD SPK cases, 93% and 92% at one year (p=0.24). Pancreas GSRs for PAK transplants were 82% at one year for BD (n=360; all systemic venous drainage) versus 77% for ED with systemic (n=398) versus 74% for ED with portal (n=150) venous drainage (p=0.03 overall, and 0.02 for ED portal vs ED systemic). For PTA cases, one-year GSRs were 81% with BD (n=196; all systemic venous drainage) versus 69% for ED with systemic (n=99) versus 80% for ED with portal (n=90) venous drainage (p > or = 0.08 overall, and 0.11 for ED portal vs ED systemic). BD transplants were associated with a 12-14% conversion rate to ED by 2 years after transplantation in the 3 recipient categories. The age of US pancreas transplant recipients made little difference for outcome in the SPK category, with one-year pancreas GSRs ranging from 80-85% for patients grouped by age in decades from 10-19 to 60-69 years. In the PAK category, one-year GSRs tended to increase with age, going from 71% for those 20-29 to 89% for those 60-69 years old. Likewise, in the PTA category one-year GSRs were higher in older than younger donors, age, being only 50% in 10-19 year-old and 87% in 40-49 year-old recipients. Pancreas GSRs were identical (85% at one year) for 1999-2003 US SPK recipients reported to have Type 1 (n=3,479) or Type 2 (n=231) diabetes (6% classified as Type 2). TAC+MMF was the dominant maintenance immunosuppressant for 1999-2003 US cases (approximately two-thirds) and with this regime one-year GSRs were >81% in all 3 recipient categories. The results were very similar (> or = 79% one-year GSR) in patients (approximately 10%) treated with sirolimus under various protocols. HLA-B locus matching had a significant effect on pancreas transplant outcome in the PTA category. For 1999-2003 cases the one-year rejection loss rate was 15% in recipients mismatched for 2 B-locus antigens (n=28) versus 3% and 4% for those mismatched for one (n=114) or zero (n=82) antigens. The proportion of 1999-2003 US pancreas grafts that were retransplants was <2% in the SPK and only 9% in the PTA categories, but 23% in the PAK category. The majority of the latter were done after isolated failure of a pancreas graft in SPK recipients. Pancreas retransplant GSRs at one year were 69% in the SPK (n=60), 77% in the PAK (n=288) and 73% in the PTA (n=39) categories, significantly lower than for primary grafts only in the SPK category (p=0.001). In regard to non-US pancreas transplants, even in 1999-2003 the overwhelming majority were in the SPK category (n=1,833), with one-year patient, kidney and pancreas survival rates of 98%, 94% and 89%, slightly but significantly higher than those for US cases done during the same period. Non-US PAK (n=55) GSR at one year was 88%, similar to that for US cases done during this period, but the non-US PTA (n=80) GSR at one year was lower at 66%. In summary, with modern immunosuppression (TAC + MMF for maintenance) 1999-2003 US pancreas transplant graft survival rates were > or = 80% at one year in all categories of recipients (SPK, PAK, PTA), as was the case for non-US SPK and PAK transplants.

Based on a review of the literature on human herpesvirus-8 (HHV8) and Kaposi's sarcoma (KS) and on the distribution of KS in Italy (Veneto region particularly), we hypothesize that the bite of bloodsucking arthropods is a cofactor in the seroconversion to HHV8 positivity and probably in the pathogenesis of KS. The bloodsucking arthropod releases with saliva powerful antihaemostatics and immunomodulators which may favour the replication and the establishment of the pathogen. Transmission would depend on the close contact of the child with a seropositive mother (or relatives) whose infective saliva is used to relieve itching and scratching at the arthropod bite's sites. During any deregulation of the immune system (e.g. ageing), local immune responses to new insect bites may induce virus activation which could prelude KS insurgence. The pathogen is not directly transmitted by the arthropod which merely prepares the cutaneous microenvironment for the virus. We have therefore introduced a new category of medically important arthropods, "promoter arthropods", besides those already defined as biological or mechanical vectors. Promoter arthropods are species able to induce in the host long-lasting, immediate or delayed-type hypersensitivity responses as well as local immunosuppression due to substances injected with their saliva. The striking variability of ORF-K1 gene of HHV8 could be due to the adaptation of the virus to the specific microenvironments resulting from the immune response to the salivary antigens characteristic of the bloodsucking arthropod species prevalent in each geographical area. It is worth noting that other viruses (especially Hepatitis B Virus) may exploit the same non-sexual transmission route.

The rate of the clinical adoption of the so-called pre-emptive transplantation is widely different among countries. In North America it represents 25 % of the total living donor transplantations; in Norway and Sweden it is 15 % and 9 %, respectively, of all grafts performed; in Italy it is less than 1%, whilst in countries like Austria, Germany and Ireland pre-emptive transplantation is nonexistent. Some concern on this type of transplantation was raised in the Seventies and were mainly based on the evidence that uraemia has an immunosuppressive effect, which could be weaker in the pre-dialysis period. Several clinical observations in the pre- cyclosporin era supported this assumption. Starting from the Eighties, however, several studies have demonstrated that pre-emptive transplantation may yield better recipient and graft survival. Moreover, a recent retrospective study, based on higher than 8000 living donor grafts that included both treated and untreated by long-term dialysis before transplantation, showed in the pre-emptive cohort a 52 % reduction in graft losses after the first year and also a lower incidence of acute rejections. Among the advantages of pre-emptive transplantation we find better rehabilitation and especially a lower risk of job loss. The risk of poorer patient compliance, as initially pointed out, has no longer been reported and can be overcome by adequate psychological preparation of the patient. Most centres performing pre-emptive transplantation favour the use of living donor because of the general shortage of cadaver kidney vs. the increasing number of dialysed patients on the waiting list. Nevertheless, in special circumstances (national programs with short waiting lists, uremic type I diabetics, children, primary type I hyperoxaluria), some AA also recommend the use of the cadaver donor.

The number of living donations is increasing in Europe and especially in Germany. The reasons seem to be a continuous shortage of cadaveric organs, better results after living related and living unrelated donation, and a high willingness in the population to donate. Various legal prerequisites have to be fulfilled in different countries. In general, careful donor evaluation is necessary to avoid excessive risk in the donor. Nephrectomy for transplantation can be performed via various approaches; microinvasive surgical techniques have been introduced, but are not yet established. Immunosuppression in living related donation is no different from that in cadaveric transplantations. In conclusion, living donation seems to be an adequate alternative to cadaveric donation. Moreover, results are twice as good as cadaveric donation with regard to long-term function.

Problem: Clinical trials of the use of intravenous immunoglobulin (IvIg) in the treatment of recurrent spontaneous abortion (RSA) in Europe were reported and discussed., Method of Study: A search of the published literature, combined with our own published and unpublished results, was performed., Results: Two placebo-controlled trials have been concluded in Europe. One trial found high but equal success rates in both the IvIg and the placebo group. Another trial found that IvIg treatment may increase the success rate by 24% compared with placebo but that the result was not statistically significant, which might be due to the small number of patients. Reasons for the diverse results of the two trials were discussed., Conclusion: More and larger placebo-controlled trials of IvIg treatment in RSA are needed before drawing definitive conclusions.

Recognition that allogeneic transfusion associated immunomodulation can increase morbidity in allogeneically transfused individuals has become a major concern for those involved in transfusion medicine. However, whether allogeneic blood transfusions predispose recipients to increased risk for cancer recurrence or to bacterial infections is still unproven. In contrast, data from studies in experimental animal models suggest that allogeneic blood transfusion associated immunomodulation is an immunologically mediated biological effect which is associated primarily with the infusion of allogeneic leukocytes. Moreover, the available experimental animal data suggest that pre-storage leukoreduction, as opposed to post-storage leukodepletion, is effective in ameliorating this tumor growth-enhancing effect of allogeneic blood. While considerable data have accumulated in an attempt to unravel the mechanism of the immunomodulatory effect of allogeneic blood transfusions, the precise mechanism of this effect has not yet been elucidated.

In recent years, mass mortalities among seals and dolphins have been attributed to infections with different morbilliviruses. In all cases, these marine top predators were exposed to high levels of persistent lipophilic environmental contaminants accumulated through the food chain. This observation led to the hypothesis that a contaminant-related suppression of the immune system might have contributed to the severity of the virus outbreaks. We conducted a semi-field feeding experiment, in which we fed two groups of harbour seals (Phoca vitulina) fish with different levels of contaminants. During a period of 2 1/2 years, blood samples were taken at regular intervals, and the functioning of different compartments of the immune system was monitored and compared. We found impaired natural killer (NK) and specific T cell responses in the seals fed contaminated fish. This is the first demonstration of immunosuppression in mammals following chronic exposure to environmental contaminants at ambient environmental levels.

Tricholoma populinum is widely distributed in Europe and North America. In the GDR 110 localities have been recorded, ranging from sea level to 470 m s.m. It is associated with many Populus spp. on acidic and neutral ground; its frequency has locally increased by recultivation of slap-dumps and waste land with poplars. Maximum of fructification is in the first decade of October. Investigations, stimulated by empiric observations on immunosuppressive effects of the mushroom in allergic diseases of man, lead to isolation of ergosterol peroxide as one substance responsible for these effects.

Clinical pancreas transplantation is a procedure being applied with increasing effectiveness for the treatment of diabetes. The authors examine, through the Pancreas Transplant Registry, all known cases of islet transplantation since 1970 and all pancreas transplantation since 1977 and then summarize their own work on pancreas transplants at the University of Minnesota.

This review has indicated that there is decreased activity in research of experimental lung transplantation and a virtual cessation of lung transplants in man. Several groups are continuing active research in various aspects of the lung transplantation problems, but it is suspected that a greater effort will be required before transplantation of the lung will become commonplace for human patients. In the appendix attached to the bibliography, we have attempted to identify groups of investigators by geographic locations in the hope of allowing a better comprehension of where and by whom research and lung transplantation is being conducted so that better communication can be established among workers in the field.

1. The realization of the two main goals of the Eurotransplant Organization have been enhanced during the period between 1981 and 1985 by two factors: A reliable HLA-A, -B and -DR typing of kidney donors and recipients, reflected in this analysis by the Hardy-Weinberg analysis but also by the results of the regular tissue typing quality controls. The number of patients who received a kidney without HLA-DR mismatches was 53% (N = 2,904). A significant difference with the 390 of 5,535 (7%) patients who received a kidney with two HLA-DR mismatches. 2. Treatment with cyclosporine increases kidney graft survival significantly in recipients of a first cadaveric transplant which is in agreement with the results of many other groups. Also a significant improvement in kidney graft survival with cyclosporine treatment was observed in recipients of a cadaveric retransplant, an observation in contrast with those of UCLA. 3. Although no significant influence of HLA-A and -B matching was observed in patients treated with or without cyclosporine, the best matched patients had the best graft survival. As stated many times before, the beneficial effect of HLA-A and -B matching is best demonstrated four or five years posttransplantation. 4. The effect of HLA-DR matching on kidney graft survival is highly significant, regardless of whether cyclosporine has been used or not. This finding is also in accordance with those of other investigators. 5. Prolonged cold ischemia periods in cyclosporine-treated patients resulted in a significant decrease of kidney graft survival. This is in contrast with the observations in non-cyclosporine-treated recipients.(ABSTRACT TRUNCATED AT 250 WORDS)