Classification of death causes after transplantation (CLASS):Evaluation of methodology and initial results

Correct classification of death causes is an important component of transplant trials.We aimed to develop and validate a system to classify causes of death in hematopoietic stem cell (HSCT) and solid organ (SOT) transplant recipients.Case record forms (CRF) of fatal cases were completed, including investigator-designated cause of death. Deaths occurring in 2010 to 2013 were used for derivation; and were validated by deaths occurring in 2013 to 2015. Underlying cause of death (referred to as recorded underlying cause) was determined through a central adjudication process involving 2 external reviewers, and subsequently compared with the Danish National Death Cause Registry.Three hundred eighty-eight recipients died 2010 to 2015 (196 [51%] SOT and 192 [49%] HSCT). The main recorded underlying causes of death among SOT and HSCT were classified as cancer (20%, 48%), graft rejection/failure/graft-versus-host-disease (35%, 28%), and infections (20%, 11%). Kappa between the investigator-designated and the recorded underlying cause of death was 0.74 (95% CI 0.69-0.80) in derivation and comparable in the validation cohort. Death causes were concordant with the Danish National Death Cause Registry in 37.2% (95% CI 31.5-42.9) and 38.4% (95% CI 28.8-48.0) in the derivation and validation cohorts, respectively.We developed and validated a method to systematically and reliably classify the underlying cause of death among transplant recipients. There was a high degree of discordance between this classification and that in the Danish National Death Cause Registry

Enterococcal Infections the First Year after Liver Transplantation—A Prospective Cohort Study

This study aimed to investigate the incidence of enterococcal infections and determine risk factors associated with enterococcal bloodstream infection (BSI) within the first year post-liver transplantation (LTx). We included 321 adult liver transplant recipients transplanted from 2011 to 2019 in a prospective cohort study. Cumulative incidence of enterococcal infections and risk factors associated with BSI were investigated in a competing risk model and time-updated Cox models, respectively. A total of 223 enterococcal infections were identified in 89 recipients. The cumulative incidences of first enterococcal infection and first enterococcal BSI were 28% (95% CI (23–33)) and 11% (CI (7–14)), respectively. Risk factors associated with enterococcal BSI were previous infections in the biliary tract (HR, 33; CI (15–74); p < 0.001), peritoneum (HR, 8.1; CI (3–23); p < 0.001) or surgical site (HR, 5.5; CI (1.4–22); p = 0.02), recipient age (HR per 10 years increase, 1.2; CI (1.03–1.6); p = 0.03), and cold ischemia time (HR per one hour increase, 1.2; CI (1.1–1.3); p < 0.01). Enterococcal infections are highly prevalent the first year post-LTx, and recipients with enterococcal infections in the biliary tract, peritoneum, or surgical site are at increased risk of BSI. These findings may have implications for the choice of empiric antibiotics early post-LTx

Outbreak of Pneumocystis Pneumonia in Renal and Liver Transplant Patients Caused by Genotypically Distinct Strains of Pneumocystis jirovecii

BACKGROUND: An outbreak of 29 cases of Pneumocystis jirovecii pneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used. METHODS: P. jirovecii isolates from 22 transplant-cases, 2 colonized RTRs and 19 Pneumocystis-control samples were genotyped by restriction fragment length polymorphism and multi-locus sequence typing analysis. Contact tracing were used to investigate transmission. Potential risk factors were compared between PCP cases and matched non-PCP transplant patients. RESULTS: Three unique Pneumocystis genotypes were shared among 19 of the RTRs, LTRs and a colonized RTR in 3 distinct clusters, two of which overlapped temporally. In contrast, Pneumocystis-control samples harbored a wide range of genotypes. Evidence of possible nosocomial transmission was observed. Among several potential risk factors, only CMV viremia was consistently associated with PCP (P = 0.03; P = 0.009). Mycophenolate mofetile was associated with PCP risk only in the RTR population (P = 0.04). CONCLUSION: We identified three large groups infected with unique strains of Pneumocystis and provide evidence of an outbreak profile and nosocomial transmission. LTRs may be infected in PCP outbreaks simultaneously with RTRs and by the same strains, most likely by inter-human transmission. Patients are at risk several years after transplantation, but the risk is highest during the first 6 months post-transplantation. Since patients at risk cannot be identified clinically and outbreaks cannot be predicted, six months of PCP chemoprophylaxis should be considered for all renal and liver transplant recipients