Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020–June 19, 2020) and late 2020 (June 20, 2020–December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46–0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.
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.
Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p < .001), hypertension (69% vs. 44%, p = .001), HIV (7% vs. 1.4%, p = .024), and peripheral vascular disorders (19% vs. 8%, p = .018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p = .13), length-of-stay (sHR: 0.91.11.4, p = .5), or mortality (sHR: 0.10.41.6, p = .19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non-SOT (median [IQR] 4 [3–4]) (p = .042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.760.810.86, p < .001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.
Recently published studies have found an impaired immune response after SARS-CoV-2 vaccination in solid organ recipients. However, most of these studies have not assessed immune cellular responses in liver and heart transplant recipients. We prospectively studied heart and liver transplant recipients eligible for SARS-CoV-2 vaccination. Patients with past history of SARS-CoV-2 infection or SARS-CoV-2 detectable antibodies (IgM or IgG) were excluded. We assessed IgM/IgG antibodies and ELISpot against the S protein 4 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. Side effects, troponin I, liver tests and anti-HLA donor-specific antibodies (DSA) were also assessed. A total of 58 liver and 46 heart recipients received two doses of mRNA-1273 vaccine. Median time from transplantation to vaccination was 5.4 years (IQR 0.3–27). Sixty-four percent of the patients developed SARS-CoV-2 IgM/IgG antibodies and 79% S-ELISpot positivity. Ninety percent of recipients developed either humoral or cellular response (87% in heart recipients and 93% in liver recipients). Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation. Local and systemic side effects were mild or moderate, and none presented DSA or graft dysfunction after vaccination. Ninety percent of our patients did develop humoral or cellular responses to mRNA-1273 vaccine. Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation, highlighting the need to further protect these patients.
Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.
Vaccine-preventable viral infections are associated with increased risk of morbidity and mortality in post-transplant patients on immunosuppression regimens. Therefore, we studied rates of immunity against vaccine-preventable viruses in lung transplantation (LTx) candidates and their associations with underlying lung disease and clinical characteristics. We retrospectively studied 1025 consecutive adult patients who underwent first-time evaluation for LTx at a single center between January 2016 and October 2018. Viruses studied included varicella zoster (VZV), measles, and mumps. Young age (17–48 years old) was negatively associated with immunity for VZV (OR 4.54, p < .001), measles (OR 15.45, p < .001) and mumps (OR 3.1, p < .001), as compared to those 65+. Many LTx candidates with cystic fibrosis (CF) had undetectable virus-specific antibody titers including: 13.5% for VZV, 19.1% for measles, and 15.7% for mumps with significant odds of undetectable titers for VZV (OR 4.54, p < .001) and measles (OR 2.32, p = .010) as compared to those without CF. Therefore, a substantial number of patients undergoing LTx evaluation had undetectable virus-specific antibody titers. Our results emphasize the importance of screening for immunity to vaccine-preventable infections in this population and the need for revaccination in selected patients to boost their humoral immunity prior to transplantation.
COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors’ liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool.
Long-term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L-CsA-i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double-blind, placebo-controlled, multi-center Phase 3 study, 180 LT recipients in BOS grade 0 were planned to receive L-CsA-i or placebo in addition to triple-drug immunosuppression. L-CsA-i was administered twice daily via an Investigational eFlow nebulizer to recipients of single (SLT) and bilateral lung transplants (BLT) within 6–32 weeks posttransplant, and continued for 2 years. The primary endpoint was BOS-free survival. 130 patients were enrolled before the study was prematurely terminated for business reasons. Despite a 2-year actuarial difference in BOS-free survival of 14.1% in favor of L-CsA-i in the overall study population, the primary endpoint was not met (p = .243). The pre-defined per protocol analysis of SLT recipients (n = 24) resulted in a treatment difference of 58.2% (p = .053). No difference was observed in the BLT (n = 48) subpopulation (p = .973). L-CsA-i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L-CsA-i in lung transplant recipients.
Liver function is measured regularly in liver transplantation (LT) candidates. Currently, these previous disease development data are not used for survival prediction. By constructing and validating joint models (JMs), we aimed to predict the outcome based on all available data, using both disease severity and its rate of change over time. Adult LT candidates listed in Eurotransplant between 2007 and 2018 (n = 16 283) and UNOS between 2016 and 2019 (n = 30 533) were included. Patients with acute liver failure, exception points, or priority status were excluded. Longitudinal MELD(-Na) data were modeled using spline-based mixed effects. Waiting list survival was modeled with Cox proportional hazards models. The JMs combined the longitudinal and survival analysis. JM 90-day mortality prediction performance was compared to MELD(-Na) in the validation cohorts. MELD(-Na) score and its rate of change over time significantly influenced patient survival. The JMs significantly outperformed the MELD(-Na) score at baseline and during follow-up. At baseline, MELD-JM AUC and MELD AUC were 0.94 (0.92–0.95) and 0.87 (0.85–0.89), respectively. MELDNa-JM AUC was 0.91 (0.89–0.93) and MELD-Na AUC was 0.84 (0.81–0.87). The JMs were significantly (p < .001) more accurate than MELD(-Na). After 90 days, we ranked patients for LT based on their MELD-Na and MELDNa-JM survival rates, showing that MELDNa-JM-prioritized patients had three times higher waiting list mortality.
A landmark 2002 study identified Black liver transplant (LT) recipients as having lower post-LT survival compared to other races. While persistent disparities exist, changes over time and mediating factors are understudied. Capturing LT recipients between 2002 and 2018 in UNOS, we used logistic regression and Cox proportional-hazard models to calculate differences in post-LT mortality among races. We examined interactions between transplant year and race. A mediation analysis assessed biologic and environmental factors potentially associated with race differences in post-LT survival. The cohort included 46,997 LT recipients (3898 Black;36,560 White;6539 Hispanic). In most years, Black (vs. White) LT recipients had a higher probability of age-adjusted mortality, not observed among Hispanics. In multivariable analysis, Blacks (vs. Whites) had higher (aHR = 1.15, 95% CI 1.07–1.24), whereas Hispanics had lower (aHR = 0.78, 95% CI 0.72–0.83) risk of mortality. Differences in post-LT mortality among Blacks (vs. Whites) narrowed between 2002 and 2009, were similar between 2010 and 2013, and may have worsened between 2014 and 2018. Race differences were larger for mortality beyond 1-year post-LT (vs. within 1-year), and among non-HCV (vs. HCV). Alcohol-associated liver disease (ALD) was the strongest mediator (13.9%, 95% CI 8.7–32.7%) of the Black–White disparity in 2010–2018. Our analyses suggest disparities may worsen with longer follow-up, as HCV recedes with elimination efforts, and with further increases in ALD.
Minimally invasive approaches are increasingly being applied in surgeries and have recently been used in living donor hepatectomy. We have developed a safe and reproducible method for minimally invasive living donor liver transplantation, which consists of pure laparoscopic explant hepatectomy and pure laparoscopic implantation of the graft, which was inserted through a suprapubic incision. Pure laparoscopic explant hepatectomy without liver fragmentation was performed in a 60-year-old man with alcoholic liver cirrhosis and hepatocellular carcinoma. The explanted liver was retrieved through a suprapubic incision. A modified right liver graft, procured from his 24-year-old son using the pure laparoscopic method, was inserted through a suprapubic incision, and implantation was performed intracorporeally throughout the procedure. The time required to remove the liver was 369 min, and the total operative time was 960 min. No complications occurred during or after the surgery. The patient recovered well, and his hospital stay was of 11 days. Pure laparoscopic living donor liver transplantation from explant hepatectomy to implantation was performed successfully. It is a feasible procedure when performed by a highly experienced surgeon and transplantation team. Further studies with larger sample sizes are needed to confirm its safety and feasibility.
Opportunities continue to be lost with a high rate of kidneys recovered for transplant but not utilized, particularly those considered less than ideal quality. The Organ Procurement and Transplantation Network (OPTN) Organ Center is tasked with allocating arguably the most difficult-to-place kidneys, and we hypothesized an accelerated placement pathway would increase utilization of kidneys placed by the Organ Center. The Kidney Accelerated Placement (KAP) project, implemented by the Organ Center from July 18, 2019 to July 15, 2020, aimed to offer kidneys with a high kidney donor profile index to programs that had a history of accepting such organs. We compared OPTN kidney match run, donor, and transplant recipient data during the project period and 1 year prior. There was no statistically significant change in the percentage of KAP-eligible donors accepted during the project period (16.4%) compared to the prior year (17.5%). Conversion from acceptance to transplant was higher under KAP (72.7% vs. 71.2%), though not significant. Waiting to accelerate placement after kidneys have been declined by multiple transplant programs locally and regionally is an intervention that may come too late to effectively increase utilization. Transplant rates of nationally shared and marginal kidneys remain a challenge, and future iterations of this project should be investigated.
Pediatric en bloc kidney transplants (EBKs) from small deceased pediatric donors are associated with increased early graft loss and morbidity. Yet, urologic complications post‐EBK and their potential impact on graft survival have not been systematically studied. We retrospectively studied urological complications requiring intervention for 225 EBKs performed at our center January 2005 to September 2017 from donors ≤20 kg into recipients ≥18 years. Overall ureteral complication incidence after EBK was 9.8% (n = 22) (12% vs 2% for EBK donors 10 vs 10 kg, respectively [P = .031]). The most common post‐EBK urologic complication was a stricture (55%), followed by urine leak (41%). In all, 95% of all urologic complications occurred early within 5 months posttransplant (median, 138 days). Urologic complications could be successfully managed nonoperatively in 50% of all cases and had no impact on graft or patient survival. In summary, urologic complications after EBK were common, associated with lower donor weights, occurred early posttransplant, and were often amenable to nonoperative treatment, without adversely affecting survival. We conclude that the higher urologic complication rate after EBK (1) should not prevent increased utilization of small pediatric donor en bloc kidneys for properly selected recipients, and (2) warrants specific discussion with EBK recipients during the preoperative consent process. 相似文献
The kidney is a notable site of glycolysis, gluconeogenesis, and fatty acid oxidation. Loss of a kidney after kidney donation might, therefore, affect the glucose and lipid metabolism of the donors. This matched cohort study investigated the effect of nephrectomy on glucose and lipid metabolisms using Bayesian hypothesis testing. There were 77 pairs of matched donor-control pairs in the present study. Clinical and laboratory data of the participants, at baseline and 1-year, were extracted from electronic medical records. Comparisons between donor and control groups were performed using the Bayesian independent samples t-test or Bayesian Mann–Whitney test. The Bayes Factor for alternative hypothesis over null hypothesis (BF10) was used to compare the two competing hypotheses. The BF10 of 3 or more was considered evidence for the alternative hypothesis. Comparing changes from baseline to 1-year between donors and controls, the BF10 of triglycerides, high-density lipoprotein cholesterol (HDL-C), triglyceride-glucose (TyG) index of insulin resistance, and estimated glomerular filtration rate (eGFR) were 7.95, 3.96, 30.13, and 1.32 x 1041, respectively signifying that the change of these variables in the donors differed from those in the controls (alternative hypothesis). Triglyceride, HDL-C, and TyG index of the donors increased more than those of the controls while eGFR of the donor decreased more than that of the controls. Our data suggest that triglycerides and insulin resistance increase after donor nephrectomy. Kidney donors should be informed about these metabolic changes and should adhere to lifestyle recommendations that may mitigate insulin resistance.
Catheter-related bloodstream infection (CRBI) is an important complication of catheter use for haemodialysis, but it remains unclear whether clinical outcomes following CRBI are influenced by organism type. This study aims to compare clinical outcomes following CRBI from Gram-positive and non-Gram-positive organisms. This was a retrospective cohort study of patients with kidney failure receiving haemodialysis (HD) via vascular catheters who had a documented episode of CRBI in Western Australia between 2005 and 2018. The associations between organism type, likelihood of hospitalization, catheter removal and death from CRBI were examined using adjusted logistic regression models. There were 111 episodes of CRBI in 99 patients (6.1 episodes per 1000-catheter-days at risk). Of the study cohort, 53 (48%) were male and 38 (34%) identified as Aboriginal or Torres Strait Islander. Gram-positive organisms were identified in 73 (66%) CRBI episodes, most commonly Staphylococcus aureus. Of those with non-Gram-positive CRBI, 9 (24%) were attributed to Pseudomonas aeruginosa. One-hundred and two (92%) episodes of CRBI required hospitalization and 15 (13%) patients died from CRBI. Compared with non-Gram-positive CRBI, Gram-positive CRBI was associated with an increased risk of hospitalization and catheter removal, with adjusted odds ratio of 9.34 (95% CI 1.28–68.03) and 3.47 (95% CI 1.25–9.67), respectively. There was no association between organism type and death from CRBI. Staphylococcus aureus remains the most common organism causing CRBI in HD patients. CRBI is associated with substantial morbidity, particularly CRBI attributed to Gram-positive organisms.
The cover image is based on the Original Article The application of the Limberg flap repair technique in the surgical treatment of pilonidal sinus disease by Yaoyao Song et al., https://doi.org/10.1111/iwj.14105 .
Polyomavirus BK (BKV) is the cause of polyomavirus‐associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV. 相似文献
Although antiviral prophylaxis has reduced cytomegalovirus (CMV) DNAemia and disease in seronegative solid organ transplant (SOT) recipients (R-) receiving seropositive donor organs (D+), its impact on CMV transmission is uncertain. Transmission, defined as CMV antigenemia/CMV DNAemia and/or seroconversion by year 2, and associated demographic risk factors were studied retrospectively in 428 D+/R- and 429 D-/R- patients receiving a SOT at our center. The cumulative transmission incidence was higher for lung (90.5%) and liver recipients (85.1%) than heart (72.7%), kidney (63.9%), and pancreas (56.2%) recipients (p < .001) and was significantly lower in living (50.1%) versus deceased donor (77.4%, p < .001) kidney recipients despite identical antiviral prophylaxis. In multivariate analysis, only allograft type predicted transmission risk (HR [CI] lung 1.609 [1.159, 2.234] and liver 1.644 [1.209, 2.234] vs kidney). For 53 D+ donating to >1 R- with adequate follow-up, 43 transmitted to all, three transmitted to none, and seven transmitted inconsistently with lungs and livers always transmitting but donor-matched heart, kidney or kidney-pancreas allografts sometimes not. Kidney pairs transmitted concordantly. CMV transmission risk is allograft-specific and unchanged despite antiviral prophylaxis. Tracking transmission and defining donor factors associated with transmission escape may provide novel opportunities for more targeted CMV prevention and improve outcome analysis in antiviral and vaccine trials. 相似文献
Universal prophylaxis for cytomegalovirus (CMV) prevention is viable but, compared with a preemptive strategy, leads to higher incidence of late‐onset disease (LOD) associated with poor patient and graft survival. The purpose of this study was to compare LOD with early onset disease (EOD), with a focus on the highest risk kidney transplant recipients (KTRs): CMV seronegative recipients transplanted from seropositive donors (D+R?). Since CMV control depends on both antiviral treatment and specific immune response, we also compared Vδ2‐negative (Vδ2neg) γδ T cell expansion involved in CMV infection resolution. EOD was defined as occurring <3 mo and LOD as occurring >3 mo after transplantation. Depending on the period, universal prophylaxis or preemptive treatment was used. Overall, 168 D+R? KTRs were included between 2003 and 2011. LOD was associated with a lower peak DNAemia (p = 0.04), fewer recurrences (odds ratio 0.16; 95% confidence interval 0.05–0.55; p = 0.01) and shorter anti‐CMV curative treatment (40 vs. 60 days, p < 0.0001). As a corollary, we found that Vδ2neg γδ T cell expansion was faster in LOD than in EOD (31 vs. 168 days after the beginning of CMV disease, p < 0.0001). In D+R? KTRs, universal prophylaxis is associated with more LOD, which had better infection management and a faster immune response. These results support the use of universal prophylaxis over a preemptive strategy and reappraise outcomes of LOD. 相似文献
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