Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial.

BACKGROUND: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. METHODS: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. RESULTS: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001). CONCLUSIONS: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. CLINICAL TRIALS REGISTRATION: NCT02538172.

Immunogenicity of High-Dose Versus MF59-Adjuvanted Versus Standard Influenza Vaccine in Solid Organ Transplant Recipients: The Swiss/Spanish Trial in Solid Organ Transplantation on Prevention of Influenza (STOP-FLU Trial).

BACKGROUND: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population. METHODS: Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity. RESULTS: A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild. CONCLUSIONS: In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT03699839.

Effects of Physiotherapy on Pain and Mouth Opening in Temporomandibular Disorders: An Umbrella and Mapping Systematic Review with Meta-Meta-Analysis.

The aim of this meta-meta-analysis was to assess the current evidence regarding the effect of physical therapy (PT) interventions on pain and functional variables in temporomandibular disorders (TMD). We conducted an umbrella systematic review (SR) and four meta-meta-analyses (MMA) and created an evidence map to determine the effectiveness of PT on pain intensity and maximum mouth opening in patients with TMD. The quality of the included SR was assessed with the AMSTAR 2, and the risk of bias with ROBIS. Of the 31 SR included in the umbrella SR, only 10 were included in the MMA. The MMA showed moderate effects for manual therapy and therapeutic exercise, and large effects for low-level laser therapy on improving pain intensity and maximum mouth opening in patients with TMD, with a limited to moderate quality of evidence. The overlapping analyses showed only a slight overlap for all the MMA according to the corrected covered area (range from 0.07 to 0.2), 23.1% to 41.6%. This umbrella SR showed that manual therapy and exercise interventions, as well as low-level laser therapy interventions, are effective in the reduction in pain intensity and improvement of maximum mouth opening in TMD. This article presents a synthesis of the available evidence related to the various physical therapy interventions used in patients presenting with temporomandibular disorders. These results could help clinicians to select the optimal intervention for their patients and to reject those that are less useful.

Post-transplant survival with pre-transplant durable continuous-flow mechanical circulatory support in a Swiss cohort of heart transplant recipients.

BACKGROUND: Worldwide, almost half of all heart transplantation candidates arrive today at their transplant operation with durable continuous-flow mechanical circulatory support (CF-MCS). This evolution is due to a progressive increase of waiting list time and hence an increased risk of haemodynamic worsening. Longer duration of CF-MCS is associated with a higher risk of device-related complications with potential adverse impact on post-transplant outcome as suggested by recent results from the United Network of Organ Sharing of the United States. METHODS: A 2-centre Swiss heart transplantation programme conducted a retrospective observational study of consecutive patients of theirs who underwent a transplant in the period 2008-2020. The primary aim was to determine whether post-transplant all-cause mortality is different between heart transplant recipients without or with pre-transplant CF-MCS. The secondary outcome was the acute cellular rejection score within the first year post-transplant. RESULTS: The study participants had a median age of 54 years; 38/158 (24%) were females. 53/158 study participants (34%) had pre-transplant CF-MCS with a median treatment duration of 280 days. In heart transplant recipients with pre-transplant CF-MCS, the prevalence of ischaemic cardiomyopathy was higher (51 vs 32%; p = 0.013), the left ventricular ejection fraction was lower (20 vs 25; p = 0.047) and pulmonary vascular resistance was higher (2.3 vs 2.1 Wood Units; p = 0.047). Over the study period, the proportion of heart transplant recipients with pre-transplant CF-MCS and the duration of pre-transplant CF-MCS treatment increased (2008-2014 vs 2015-2020: 22% vs 45%, p = 0.009; increase of treatment days per year: 34.4 ± 11.2 days, p = 0.003; respectively). The primary and secondary outcomes were not different between heart transplant recipients with pre-transplant CF-MCS or direct heart transplantation (log-rank p = 0.515; 0.16 vs 0.14, respectively; p = 0.81). CONCLUSION: This data indicates that the strategy of pre-transplant CF-MCS with subsequent orthotopic heart transplantation provides post-transplant outcomes not different to direct heart transplantation despite the fact that the duration of pre-transplant assist device treatment has progressively increased.

Atopy as an independent predictor for long-term patient and graft survival after kidney transplantation.

Background: Atopy is a genetic condition predisposing individuals to develop immunoglobulin E (IgE) against common allergens through T-helper 2 (Th2) polarization mechanisms. The impact of atopy on graft survival in solid organ transplantation is unknown. Methodology: We analyzed 268 renal allograft recipients from the Swiss Transplant Cohort Study, a prospective multicenter cohort studying patients after solid organ transplantation, with a 9-year median follow-up (IQR 3.0). We used the Phadiatop assay to measure IgE antibodies against a mixture of common inhaled allergens (grass, tree, herbs, spores, animals, and mites) to identify pre-transplantation atopic patients (>0.35 KU/L). Results: Of 268 kidney transplant recipients, 66 individuals were atopic (24.6%). Atopic patients were significantly younger than non-atopic patients (49.6 vs 58.0 years old, P = 0.002). No significant difference was found for gender, cold/warm ischemia time, preformed donor-specific antibodies (DSA), HLA mismatches, induction and maintenance immunosuppressive therapy, CMV serostatus, or cause of kidney failure. Patient and graft survival at ten years of follow-up were significantly better in the atopic group, 95.2% versus 69.2% patient survival (P < 0.001), and 87.9% versus 60.8% graft survival (P < 0.001), respectively. A multivariate Cox analysis revealed that atopy predicted recipient and graft survival independently of age and living donor donation. Finally, we found similar rates of biopsy-proven acute cellular and antibody-mediated rejections between atopic and non-atopic recipients. Conclusion: Atopy was associated with better long-term patient and graft survival, independently of age and living donor donation after kidney transplantation. Yet, atopy should not be used as a predictor for acute rejection.

Xenotransplantation: A New Era.

Organ allotransplantation has now reached an impassable ceiling inherent to the limited supply of human donor organs. In the United States, there are currently over 100,000 individuals on the national transplant waiting list awaiting a kidney, heart, and/or liver transplant. This is in contrast with only a fraction of them receiving a living or deceased donor allograft. Given the morbidity, mortality, costs, or absence of supportive treatments, xenotransplant has the potential to address the critical shortage in organ grafts. Last decade research efforts focused on creation of donor organs from pigs with various genes edited out using CRISPR technologies and utilizing non-human primates for trial. Three groups in the United States have recently moved forward with trials in human subjects and obtained initial successful results with pig-to-human heart and kidney xenotransplantation. This review serves as a brief discussion of the recent progress in xenotransplantation research, particularly as it concerns utilization of porcine heart, renal, and liver xenografts in clinical practice.

Humoral Responses Against Variants of Concern by COVID-19 mRNA Vaccines in Immunocompromised Patients.

Importance: There are limited comparative data on the durability of neutralizing antibody (nAb) responses elicited by messenger RNA (mRNA) vaccines against the SARS-CoV-2 variants of concern (VOCs) in immunocompromised patients and healthy controls. Objective: To assess the humoral responses after vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines. Design, Setting, and Participants: In this prospective, longitudinal monocentric comparative effectiveness study conducted at the Lausanne University Hospital, binding IgG anti-spike antibody and nAb levels were measured at 1 week, 1 month, 3 months, and 6 months after vaccination with mRNA-1273 (24.6% of participants) or BNT162b2 (75.3% of participants). Interventions: All participants received 2 doses of either mRNA-1273 or BNT162b2 vaccines 4 to 6 weeks apart. Main Outcomes and Measures: The primary outcome of the study was the persistence of nAb responses against the original, nonvariant SARS-CoV-2 (2019-nCoV) and different VOCs at 6 months after vaccination. Key secondary outcomes were associations of the type of mRNA vaccine, the underlying disease, and the treatment with the response to vaccination. Results: Among the 841 participants enrolled between January 14 and August 8, 2021, the patient population comprised 637 participants (mean [SD] age, 61.8 [13.7] years; 386 [60.6%] female), and the healthy control population comprised 204 participants (mean [SD] age, 45.9 [12.0] years; 144 [70.6%] female). There were 399 patients with solid cancers, 101 with hematologic cancers, 38 with solid organ transplants, 99 with autoimmune diseases, and 204 healthy controls. More than 15 000 nAb determinations were performed against the original, nonvariant 2019-nCoV and the Alpha, Beta, Gamma, and Delta variants. The proportions of nAbs and their titers decreased in all study groups at 6 months after vaccination, with the greatest decreases for the Beta and Delta variants. For Beta, the proportion decreased to a median (SE) of 39.2% (5.5%) in those with hematologic cancers, 44.8% (2.7%) in those with solid cancers, 23.1% (8.3%) in those with solid organ transplants, and 22.7% (4.8%) in those with autoimmune diseases compared with 52.1% (4.2%) in healthy controls. For Delta, the proportions decreased to 41.8% (5.6%) in participants with hematologic cancer, 51.9% (2.7%) in those with solid cancers, 26.9% (8.7%) in those with solid organ transplants, and 30.7% (5.3%) in those with autoimmune diseases compared with 56.9% (4.1%) healthy controls. Neutralizing antibody titers decreased 3.5- to 5-fold between month 1 and month 6, and the estimated duration of response was greater and more durable among those participants vaccinated with mRNA-1273. In participants with solid cancers, the estimated duration of nAbs against the Beta variant was 221 days with mRNA-1273 and 146 days with BNT162b2, and against the Delta variant, it was 226 days with mRNA-1273 and 161 with BNT162b2. The estimated duration of nAbs in participants with hematologic cancers was 113 and 127 days against Beta and Delta variants, respectively. Conclusions and Relevance: This comparative effectiveness study suggests that approximately half of patients with hematologic cancers and solid cancers, about 70% of patients with solid organ transplants or autoimmune diseases, and 40% of healthy controls have lost nAbs against the circulating VOCs at 6 months after vaccination. These findings may be helpful for developing the best boosting vaccination schedule especially in immunocompromised patients.

Robotic versus hand-assisted laparoscopic living donor nephrectomy: comparison of two minimally invasive techniques in kidney transplantation.

Robot-assisted donor nephrectomy (RDN) is increasingly used due to its advantages such as its precision and reduced learning curve when compared to laparoscopic techniques. Concerns remain among surgeons regarding possible longer warm ischemia time. This study aimed to compare patients undergoing robotic living donor nephrectomy to the more frequently used hand-assisted laparoscopic nephrectomy (HLDN) technique, focusing on warm ischemia time, total operative time, learning curve, hospital length of stay, donor renal function and post-operative complications. Retrospective study comparing RDN to HLDN in a collaborative transplant network. 176 patients were included, 72 in RDN and 104 in HLDN. Left-sided nephrectomy was favored in RDN (82% vs 52%, p < 0.01). Operative time was longer in RDN (287 vs 160 min; p < 0.01), while warm ischemia time was similar (221 vs 213 secs, p = 0.446). The hospital stay was shorter in RDN (3.9 vs 5.7 days, p < 0.01).Concerning renal function, a slightpersistent increase of 7% of the creatinine ratio was observed in the RDN compared to the HLDN group (1.56 vs 1.44 at 1-month checkup, p < 0.01). The results show that RDN appears safe and efficient in comparison to the gold-standard HLDN technique. Warm ischemia time was similar for both techniques, whereas RDN operative time was longer. Patients undergoing RDN had a shorter hospital stay, this being possibly mitigated by differences in center release criteria. Donor renal function needs to be assessed on a longer-term basis for both techniques.

Increasing prevalence of obesity and diabetes among patients evaluated for liver transplantation in a Swiss tertiary referral center: a 10-year retrospective analysis.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is now the first cause of chronic liver disease in developed countries. We aimed to assess trends in the prevalence of obesity, type 2 diabetes mellitus (T2DM) and NAFLD in patients undergoing liver transplantation evaluation and to assess whether obese patients were less likely to be listed or had an increased drop-out rate after listing. METHODS: We conducted a retrospective study of all consecutive patients who underwent liver transplantation evaluation at a Swiss tertiary referral centre between January 2009 and March 2020. RESULTS: A total of 242 patients were included, 83% were male. The median age was 59 years (IQR, 51-64 years). The most common causes of end-stage liver disease were viral hepatitis (28%), alcoholic liver disease (21%) and NAFLD (12%). Obesity was present in 28% of our cohort, with a significant increase over time. Prevalence of type 2 diabetes mellitus followed the same trend (p = 0.02). The proportions of non-listed and listed obese patients did not differ (21% vs. 30% respectively; p = 0.3). CONCLUSIONS: The prevalence of obesity and type 2 diabetes mellitus significantly increased over our study period. Obese patients had similar chances of being listed. The landscape of liver transplantation indications is shifting towards NAFLD, highlighting the urgent need to prevent NAFLD progression.

Has the profile of heart transplantation recipients changed within the last three decades?

BACKGROUND: Heart transplantation remains the most durable treatment for patients with end-stage heart failure refractory to medical treatment. Central elements of the listing criteria for heart transplantation have remained largely unchanged in the last three decades whereas treatment of heart failure has significantly increased survival and reduced disease-related symptoms. It remains unknown whether the improvement of heart failure therapy changed the profile of heart transplantation candidates or affected post-transplant survival. METHODS: The study investigated a total of 323 heart transplant recipients of the Lausanne University Hospital with 328 transplant operations between 1987 and 2018. Patients were separated into three groups on the basis of availability of heart failure therapy: period 1 (1987-1998; n = 115) when renin-angiotensin system blockade and diuretic treatment were available; period 2 (1999-2010; n = 106) marked by the addition of beta-blocker and mineralocorticoid receptor antagonist treatment in severe heart failure, and the establishment of cardiac defibrillator and resynchronisation therapy; period 3 (2011-2018; n = 107) characterised by the increasing use of ventricular assist devices for bridge to transplantation. RESULTS: The patient characteristics age (all: 53.4 years), male sex (all: 79%) and body mass index (all: 24.5 kg/m2) did not differ between periods. History of arterial hypertension was less prevalent in period 2 (period 1 vs 2 vs 3: 44 vs 28 vs 43%, p = 0.04) whereas other cardiovascular risk factors were equally distributed. Left ventricular ejection fraction, VO2max, and pulmonary vascular resistance were not different between the three periods. The prevalence of ischaemic cardiomyopathy was higher in periods 1 and 3; dilated non-ischaemic cardiomyopathy was more frequent in period 2. Post-transplant 1-year survival was highest in period 3 (1 vs 2 vs 3: 87.2 ± 3.2% vs 70.8 ± 4.4% vs 93.0 ± 2.6%, p always ≤0.02), and the Kaplan-Meier estimates of survivors of the first year post-transplant were not different between the three periods. In descriptive analysis, early mortality was not associated with acknowledged pretransplant predictors of post-transplant mortality. CONCLUSION: Availability of different medical heart failure treatments did not result in greatly different pretransplant characteristics of heart transplantation recipients across the three periods. This suggests that the maintained central criteria of listing for heart transplantation still identify end-stage heart failure patients with a similar profile. This finding can explain the unchanged overall mortality on condition of 1-year survival across the three periods, since pretransplant characteristics are relevant for long-term survival after heart transplantation.

Complement blockade with eculizumab to treat acute symptomatic humoral rejection after heart transplantation.

Antibody-mediated rejection (AMR) is a major barrier preventing successful discordant organ xenotransplantation, but it also occurs in allotransplantation due to anti-HLA antibodies. Symptomatic acute AMR is rare after heart allograft but carries a high risk of mortality, especially >1 year after transplant. As complement activation may play a major role in mediating tissue injury in acute AMR, drugs blocking the terminal complement cascade like eculizumab may be useful, particularly since "standards of care" like plasmapheresis are not based on strong evidence. Eculizumab was successfully used to treat early acute kidney AMR, a typical condition of "active AMR," but showed mitigated results in late AMR, where "chronic active" lesions are more prevalent. Here, we report the case of a heart recipient who presented with acute heart failure due to late acute AMR with eight de novo donor-specific anti-HLA antibodies (DSA), and who fully recovered allograft function and completely cleared DSA following plasmapheresis-free upfront eculizumab administration in addition to thymoglobulin, intravenous immunoglobulins (IVIG), and rituximab. Several clinical (acute onset, abrupt and severe loss of graft function), biological (sudden high-level production of DSA), and pathological features (microvascular injury, C4d deposits) of this cardiac recipient are shared with early kidney AMR and may indicate a strong role of complement in the pathogenesis of acute graft injury that may respond to drugs like eculizumab. Terminal complement blockade should be further explored to treat acute AMR in recipients of heart allografts and possibly also in recipients of discordant xenografts in the future.

Epidemiology and outcomes of medically attended and microbiologically confirmed bacterial foodborne infections in solid organ transplant recipients.

Food-safety measures are recommended to solid organ transplant (SOT) recipients. However, the burden of foodborne infections in SOT recipients has not been established. We describe the epidemiology and outcomes of bacterial foodborne infections in a nationwide cohort including 4405 SOT recipients in Switzerland between 2008 and 2018. Participants were prospectively followed for a median of 4.2 years with systematic collection of data on infections, and patient and graft-related outcomes. We identified 151 episodes of microbiologically confirmed bacterial foodborne infections occurring in median 1.6 years (IQR 0.58-3.40) after transplantation (131 [88%] Campylobacter spp. and 15 [10%] non-typhoidal Salmonella). The cumulative incidence of bacterial foodborne infections was 4% (95% CI 3.4-4.8). Standardized incidence rates were 7.4 (95% CI 6.2-8.7) and 4.6 (95% CI 2.6-7.5) for Campylobacter and Salmonella infections, respectively. Invasive infection was more common with Salmonella (33.3% [5/15]) compared to Campylobacter (3.2% [4/125]; p = .001). Hospital and ICU admission rates were 47.7% (69/145) and 4.1% (6/145), respectively. A composite endpoint of acute rejection, graft loss, or death occurred within 30 days in 3.3% (5/151) of cases. In conclusion, in our cohort bacterial foodborne infections were late post-transplant infections and were associated with significant morbidity, supporting the need for implementation of food-safety recommendations.

Cohort profile: The Swiss Transplant Cohort Study (STCS): A nationwide longitudinal cohort study of all solid organ recipients in Switzerland.

PURPOSE: The Swiss Transplant Cohort Study (STCS) is a prospective multicentre cohort study which started to actively enrol study participants in May 2008. It takes advantage of combining data from all transplant programmes in one unique system to perform comprehensive nationwide reporting and to promote translational and clinical post-transplant outcome research in the framework of Swiss transplantation medicine. PARTICIPANTS: Over 5500 solid organ transplant recipients have been enrolled in all six Swiss transplant centres by end of 2019, around three-quarter of them for kidney and liver transplants. Ninety-three per cent of all transplanted recipients have consented to study participation, almost all of them (99%) contributed to bio-sampling. The STCS genomic data set includes around 3000 patients. FINDINGS TO DATE: Detailed clinical and laboratory data in high granularity as well as patient-reported outcomes from transplant recipients and activities in Switzerland are available in the last decade. Interdisciplinary contributions in diverse fields of transplantation medicine such as infectious diseases, genomics, oncology, immunology and psychosocial science have resulted in approximately 70 scientific papers getting published in peer-review journals so far. FUTURE PLANS: The STCS will deepen its efforts in personalised medicine and digital epidemiology, and will also focus on allocation research and the use of causal inference methods to make complex matters in transplant medicine more understandable and transparent.

Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., ß-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.

Tribute to Professor Stefan Kunz.

It has been a year since Stefan Kunz, a Full Professor since 2017 at the Faculty of Biology and Medicine of the University of Lausanne, Switzerland, passed away [...].

Demographic, psychosocial and health disparities between living and deceased renal allograft recipients in Switzerland.

BACKGROUND: Living donor renal transplantation is widely performed in Switzerland with a superior long-term outcome and lower waiting time compared with deceased renal transplantation. However the chances of receiving a living donor kidney transplant are not the same for all transplant candidates. The current study aimed to identify psychosocial and demographic characteristics that predict lower access to living kidney donation in Switzerland. METHODS: The study was a nationwide multicentre study nested within the Swiss Transplant Cohort Study. Pre-transplant demographic, psychosocial and health characteristics of 1126 deceased and 859 living renal transplant recipients were compared using logistic regression analysis. RESULTS: Transplant candidates with higher age (odds ratio [OR] per 10 years 0.67, 95% confidence interval [CI] 0.60–0.74), lower education (OR 0.46, 95% CI 0.36–0.59), a work capacity of less than 50% (OR 0.48, 95% CI 0.35–0.66), single or formerly married (OR 0.38, 95% CI 0.26–0.53 / OR 0.37, 95% CI 0.26–0.53) or with a higher hospital depression score (OR per 5 points 0.61, 95% CI 0.50–0.74) were less likely to receive an allograft from a living donor. In some regions of Switzerland candidates were more likely to undergo living transplantation than in other regions. No association was found with gender or income. CONCLUSIONS: Interventions to increase access to kidney transplantation from living donors should target transplant candidates of older age, lower education, lower working capacity and not living in a committed relationship. The observed regional differences suggest that additional determinants of living donation may play a role such as population and health professional attitudes toward living donation.

Eculizumab as a New Treatment for Severe Acute Post-infectious Glomerulonephritis: Two Case Reports.

Acute post-infections glomerulonephritis (APIGN) is a frequent cause of glomerulonephritis and represents the most common cause of acute glomerulonephritis in children. It can evolve to severe acute renal failure and chronic kidney disease or even end-stage kidney disease. The precise pathophysiological mechanisms of APIGN are still incompletely understood. The implication of the alternative complement pathway and the potential benefits of C5 blockade have been recently highlighted, in particular in the presence of a C3 Nephritic Factor (C3Nef), anti-Factor B or H autoantibodies. We report two children with severe APIGN, successfully treated with eculizumab. The first patient presented a severe form of APIGN with advanced renal failure and anuria, associated with a decreased level of C3 and an increased level of soluble C5b-9, in the presence of a C3NeF autoantibody. The second case had a severe oliguric APIGN associated with low C3 level. Kidney biopsy confirmed the diagnosis of APIGN in both cases. Eculizumab allowed full renal function recovery and the avoidance of dialysis in both cases. In conclusion, the alternative and terminal complement pathways activation might be common in PIGN, and in severe cases, eculizumab might help.