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Acute antibody-mediated rejection (AMR) remains a challenge after kidney transplantation (KT). As there is no clear-cut treatment recommendation, accurate information on current therapeutic strategies in real-life practice is needed. KT recipients from the multicenter Swiss Transplant Cohort Study treated for acute AMR during the first post-transplant year were included retrospectively. We aimed at describing the anti-rejection protocols used routinely, as well as patient and graft outcomes, with focus on infectious complications. Overall, 65/1669 (3.9%) KT recipients were treated for 75 episodes of acute AMR. In addition to corticosteroid boluses, most common therapies included plasmapheresis (56.0%), intravenous immunoglobulins (IVIg) (38.7%), rituximab (25.3%), and antithymocyte globulin (22.7%). At least one infectious complication occurred within 6 months from AMR treatment in 63.6% of patients. Plasmapheresis increased the risk of overall (hazard ratio [HR]: 2.89; P-value = 0.002) and opportunistic infection (HR: 5.32; P-value = 0.033). IVIg exerted a protective effect for bacterial infection (HR: 0.29; P-value = 0.053). The recovery of renal function was complete at 3 months after AMR treatment in 67% of episodes. One-year death-censored graft survival was 90.9%. Four patients (6.2%) died during the first year (two due to severe infection). In this nationwide cohort we found significant heterogeneity in therapeutic approaches for acute AMR. Infectious complications were common, particularly among KT recipients receiving plasmapheresis.

BACKGROUND: The impact of pre-transplant social determinants of health on post-transplant outcomes remains understudied. In the United States, poor clinical outcomes are associated with underprivileged status, as assessed by the Social Adaptability Index (SAI), a composite score of education, employment status, marital status, household income, and substance abuse. Using data from the Swiss Transplant Cohort Study (STCS), we determined the SAI's predictive value regarding two post-transplant outcomes: all-cause mortality and return to dialysis. METHODS: Between 2012 and 2018, we included adult renal transplant patients (aged ≥ 18 years) with pre-transplant assessment SAI scores, calculated from a STCS Psychosocial Questionnaire. Time to all-cause mortality and return to dialysis were predicted using Cox regression. RESULTS: Of 1238 included patients (mean age: 53.8 ± 13.2 years; 37.9% female; median follow-up time: 4.4 years [IQR: 2.7]), 93 (7.5%) died and 57 (4.6%) returned to dialysis. The SAI's hazard ratio was 0.94 (95%CI: 0.88-1.01; p = .09) for mortality and 0.93 (95%CI: 0.85-1.02; p = .15) for return to dialysis. CONCLUSIONS: In contrast to most published studies on social deprivation, analysis of this Swiss sample detected no significant association between SAI score and mortality or return to dialysis. ispartof: CLINICAL TRANSPLANTATION vol:35 issue:4 ispartof: location:Denmark status: published

To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p 180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Background Ventricular assist devices (VAD) are valuable options for patients with heart failure awaiting cardiac transplantation. We assessed the impact of pre-transplant VAD implantation on the incidence of post-transplant infections in a nationwide cohort of heart transplant recipients. Methods Heart transplant recipients included in the Swiss Transplant Cohort Study between May 2008 and December 2012 were analyzed. Cumulative incidence curves were used to calculate the incidence of bacterial or Candida infections (primary endpoint) and of other infections (secondary endpoint) after transplant. Cox regression models treating death as a competing risk were used to identify risk factors for the development of infection after transplant. Results Overall, 119 patients were included in the study, 35 with a VAD and 84 without VAD. Cumulative incidences of post-transplant bacterial or Candida infections were 37.7 % in VAD patients and 40.4 % in non-VAD patients. In multivariate analysis, the use of cotrimoxazole prophylaxis was the only variable associated with bacterial/Candida infections after transplant (HR 0.29 [95 % CI 0.15-0.57], p

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus-positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.

Most countries exclude human immunodeficiency virus (HIV)-positive patients from organ donation because of concerns regarding donor-derived HIV transmission. The Swiss Federal Act on Transplantation has allowed organ transplantation between HIV-positive donors and recipients since 2007. We report the successful liver transplantation from an HIV-positive donor to an HIV-positive recipient. Both donor and recipient had been treated for many years with antiretroviral therapy and harbored multidrug-resistant viruses. Five months after transplantation, HIV viremia remains undetectable. This observation supports the inclusion of appropriate HIV-positive donors for transplants specifically allocated to HIV-positive recipients.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. Background. Polymorphisms in IFNL3 and IFNL4 the genes encoding interferon ?3 and interferon ?4 respectively have been associated with reduced hepatitis C virus clearance. We explored the role of such polymorphisms on the incidence of cytomegalovirus (CMV) infection in solid organ transplant recipients. Methods. White patients participating in the Swiss Transplant Cohort Study in 2008 2011 were included. A novel functional TT/ G polymorphism (rs368234815) in the CpG region upstream of IFNL3 was investigated. Results. A total of 840 solid organ transplant recipients at risk for CMV infection were included among whom 373 (44) received antiviral prophylaxis. The 12 month cumulative incidence of CMV replication and disease were 0.44 and 0.08 cases respectively. Patient homozygous for the minor rs368234815 allele ( G/ G) tended to have a higher cumulative incidence of CMV replication (subdistribution hazard ratio [SHR] 1.30 [95 confidence interval {CI}. 97 1.74]; P =. 07) compared with other patients (TT/TT or TT/ G). The association was significant among patients followed by a preemptive approach (SHR 1.46 [95 CI 1.01 2.12]; P =. 047) especially in patients receiving an organ from a seropositive donor (SHR 1.92 [95 CI 1.30 2.85]; P =. 001) but not among those who received antiviral prophylaxis (SHR 1.13 [95 CI. 70 1.83]; P =. 6). These associations remained significant in multivariate competing risk regression models. Conclusions. Polymorphisms in the IFNL3/4 region influence susceptibility to CMV replication in solid organ transplant recipients particularly in patients not receiving antiviral prophylaxis.

Contains fulltext : 153038.pdf (Publisher’s version ) (Closed access) BACKGROUND: Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS: Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. RESULTS: Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1beta (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and beta-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1beta and tumor necrosis factor alpha secretion by PBMCs. CONCLUSIONS: Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification.

Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, comprehensive data of SARS‐CoV‐2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS‐CoV‐2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%) and diarrhea (33%). Ninety‐five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow‐up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS‐CoV‐2 infection in middle‐aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts.

Background Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of transplantation occurring in the setting of immunosuppression and oncogenic viral infections. However, little is known about the cumulative incidence, histological subtypes, risk determinants and outcome of PTLD in solid organ transplant (SOT) recipients in Switzerland. Methods This retrospective observational study investigated adult SOT recipients from two sequential cohorts, the pre-SCTS (Swiss Transplant Cohort Study) series, with data collected from January 1986 to April 2008, and the STCS series, with data collected from May 2008 to December 2014 in Switzerland. SOT recipients were cross-referenced with the data of all the patients with a lymphoma diagnosis in each transplant centre and with the data of the Swiss Transplant Cohort Study (STCS) to determine the cumulative incidence of PTLD, pre-therapeutic clinical features, clinical course and outcome. Kaplan-Meier analysis was performed for overall survival after PTLD. Results We identified 79 cases of PTLD during the study period in the two cohorts: pre-STCS from 1986 to 2008 (n = 62) and STCS from 2008 to 2014 (n = 17). Histological subgroups included: early lesions (pre-STCS n = 2, STCS n = 0); polymorphic PTLD (pre-STCS n = 8, STCS n = 7); monomorphic PTLD (pre-STCS n = 47, STCS n = 10), and Hodgkin's lymphoma (pre-STCS n = 5, STCS n = 0). Median time to PTLD diagnosis was 90 months (range 3-281 months) and 14 months (range 2-59 months) in the pre-STCS and STCS cohorts, respectively. Median follow-up after transplantation was 141 months for the pre-STCS patients and 33 months for the STCS patients. Cumulative incidences of PTLD during the STCS period at 0.5, 1 and 5 years were 0.17% (95% confidence interval 0.07-0.46%), 0.22% (0.09-0.53%) and 0.96% (0.52-1.80%), respectively. For the pre-STCS case series, it was not possible to estimate the incidence rate of PTLD. Survival after PTLD diagnosis was 80% (68-87%) at 1 year and 56% (42-68%) at 5 years for the pre-STCS and STCS cohorts combined. Conclusions At 5 years, the cumulative incidence of PTLD, regardless of the organ transplanted, was only 0.96% in the STCS cohort, which is lower than that reported in the literature.

Bone disease contributes to relevant morbidity after solid organ transplantation. Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends on the endocrine function of both, liver and kidney. Our study assessed key markers of bone metabolism at time of transplantation and 6 months after transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients 25-OH vitamin D levels did not differ significantly between peri-transplant (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272). Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300% (from 9.1 to 36.5ng/l; P