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Vaccination before solid organ transplantation is recommended since post-transplantation immunosuppression is known to impair vaccine responses. However, little is known about post-transplantation seroprotection rates in organ transplant recipients vaccinated pre-transplantation. We aimed to investigate the proportion of transplant recipients vaccinated against hepatitis B virus (HBV) and invasive pneumococcal disease (IPD) pre-transplantation at the time of listing for transplantation with post-transplantation seroprotection. We included 136 solid organ transplant (SOT) recipients vaccinated at the time of listing for transplantation. We investigated post-transplantation antibody concentrations against HBV and IPD. Established antibody thresholds were used to define seroprotection. The proportions of SOT recipients with post-transplantation seroprotection were 27.9% ( n = 38) and 42.6% ( n = 58) against HBV and IPD, respectively. Compared to completing HBV vaccination pre-transplantation, completing post-transplantation vaccination (adjusted odds ratio (aOR): 7.8, 95% CI: 2.5-24.5, p < 0.001) and incomplete vaccination (aOR: 6.3, 95% CI: 1.2-32.6, p = 0.028) were associated with non-response against HBV, after adjustment for confounders. Importantly, patients with seroprotection at the time of listing had lower odds of non-response against HBV (aOR: 0.04, 95% CI: 0.0-0.1, p < 0.001) and IPD (aOR: 0.3, 95% CI: 0.1-0.7, p = 0.007) compared to those without seroprotection. SOT recipients vaccinated pre-transplantation had low post-transplantation seroprotection rates against HBV and IPD. However, SOT recipients with seroprotection at the time of listing had lower odds of non-response, suggesting early vaccination should be a priority.

Monitoring specific underlying causes of death in solid organ transplant (SOT) recipients is important in order to identify emerging trends and health challenges. This retrospective cohort study includes all SOT recipients transplanted at Rigshospitalet between January 1st, 2010 and December 31st, 2019. The underlying cause of death was determined using the newly developed Classification of Death Causes after Transplantation (CLASS) method. Cox regression analyses assessed risk factors for all-cause and cause-specific mortality. Of the 1774 SOT recipients included, 299 patients died during a total of 7511 person-years of follow-up (PYFU) with cancer (N = 57, 19%), graft rejection (N = 55, 18%) and infections (N = 52, 17%) being the most frequent causes of death. We observed a lower risk of all-cause death with increasing transplant calendar year (HR 0.91, 95% CI 0.86-0.96 per 1-year increase), alongside death from graft rejection (HR 0.84 per year, 95% CI 0.74-0.95) and death from infections (HR 0.86 per year, 95% CI 0.77-0.97). Further, there was a trend towards lower cumulative incidence of death from cardiovascular disease, graft failure and cancer in more recent years, while death from other organ specific and non-organ specific causes did not decrease. All-cause mortality among SOT recipients has decreased over the past decade, mainly due to a decrease in graft rejection- and infection-related deaths. Conversely, deaths from a broad range of other causes have remained unchanged, suggesting that cause of death among SOT recipients is increasingly diverse and warrants a multidisciplinary effort and attention in the future., Competing Interests: The authors have declared that no competing interests exist.

Post-transplant lymphoproliferative disease (PTLD) is a well-recognized complication after transplant. This study aimed to develop and validate a risk score to predict PTLD among solid organ transplant (SOT) recipients. Poisson regression identified predictors of PTLD with the best fitting model selected for the risk score. The derivation cohort consisted of 2546 SOT recipients transpanted at Rigshospitalet, Copenhagen between 2004 and 2019; 57 developed PTLD. Predictors of PTLD were high-risk pre-transplant Epstein-Barr Virus (EBV), IgG donor/recipient serostatus, and current positive plasma EBV DNA, abnormal hemoglobin and C-reactive protein levels. Individuals in the high-risk group had almost 7 times higher incidence of PTLD (incidence rate ratio (IRR) 6.75; 95% CI: 4.00-11.41) compared to the low-risk group. In the validation cohort of 1611 SOT recipients from the University Hospital of Zürich, 24 developed PTLD. A similar 7 times higher risk of PTLD was observed in the high-risk group compared to the low-risk group (IRR 7.17, 95% CI: 3.05-16.82). The discriminatory ability was also similar in derivation (Harrell's C-statistic of 0.82 95% CI (0.76-0.88) and validation (0.82, 95% CI:0.72-0.92) cohorts. The risk score had a good discriminatory ability in both cohorts and helped to identify patients with higher risk of developing PTLD.

Post-transplant diabetes mellitus (PTDM) is associated with a higher risk of adverse outcomes. We aimed to describe the proportion of patients with diabetes prior to solid organ transplantation (SOT) and post-transplant diabetes mellitus (PTDM) in three time periods (early-likely PTDM: 0-45 days; 46-365 days and >365 days) post-transplant and to estimate possible risk factors associated with PTDM in each time-period. Additionally, we compared the risk of death and causes of death in patients with diabetes prior to transplant, PTDM, and non-diabetes patients. A total of 959 SOT recipients (heart, lung, liver, and kidney) transplanted at University Hospital of Copenhagen between 2010 and 2015 were included. The highest PTDM incidence was observed at 46-365 days after transplant in all SOT recipients. Age and the Charlson Comorbidity Index (CCI Score) in all time periods were the two most important risk factors for PTDM. Compared to non-diabetes patients, SOT recipients with pre-transplant diabetes and PTDM patients had a higher risk of all-cause mortality death (aHR: 1.77, 95% CI: 1.16-2.69 and aHR: 1.89, 95% CI: 1.17-3.06 respectively). Pre-transplant diabetes and PTDM patients had a higher risk of death due to cardiovascular diseases and cancer, respectively, when compared to non-diabetes patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dos Santos, Hornum, Terrones-Campos, Crone, Wareham, Soeborg, Rasmussen, Gustafsson, Perch, Soerensen, Lundgren, Feldt-Rasmussen and Reekie.)

Background: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to investigate the incidence rate (IR) of PCP and the related hospitalization and mortality rates in liver transplant recipients in an era of routine prophylaxis., Methods: We included all adult liver transplant recipients transplanted at Rigshospitalet between January 1, 2011 and October 1, 2019. Microbiology data were obtained from the Danish Microbiology Database (MiBa), a national database containing all data from all Departments of Clinical Microbiology in Denmark receiving samples from both hospitals and general practices. According to local guidelines, PCP prophylaxis was initiated 1 week posttransplantation and discontinued after 6 months or sooner in patients experiencing side effects., Results: We included 343 liver transplant recipients with 1153 person-years of follow-up (PYFU), of which 269 (78%) received PCP prophylaxis during the first 6 months posttransplantation. Seven (2%) recipients were diagnosed with PCP during follow-up. In the first 6 months posttransplantation and in 269 transplant recipients who received prophylaxis there were zero PCP events while the IR was 32 (95% confidence interval [CI] 2.9-148) per 1000 PYFU in 74 recipient who did not receive prophylaxis. During 7th to 12th month posttransplantation the IR was 20 (95% CI: 5.5-53) per 1000 PYFU. All seven (100%) recipients diagnosed with PCP were hospitalized, however none died., Conclusions: PCP was not detected in liver transplant recipients while on prophylaxis. Though, it worth mentioning that two out of the seven PCP patients received high-dose prednisolone before the PCP event. All liver transplant recipients with PCP were hospitalized, but none died. Randomized clinical trials to determine the optimal duration of prophylaxis are warranted., (© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Bacterial and fungal bloodstream infections (BSI) are common after pediatric liver and kidney transplantations and associated with morbidity and mortality. However, knowledge about incidence rates, pathogen composition, and resistance patterns is limited. We aimed to describe the pattern of bacterial and fungal BSI in a cohort of pediatric liver and kidney transplant recipients., Methods: A prospective study of 85 pediatric liver and kidney transplant recipients transplanted from 2010 to 2017 with a total of 390 person-years of follow-up. Clinical characteristics and BSI were retrieved from national registries assuring nationwide follow-up for at least 1 year. BSI incidence rates and pathogen composition were investigated and stratified by the time post-transplantation and type of transplanted organ., Results: A total of 29 BSI were observed within the first 5 years post-transplantation with 16 different pathogens. The overall incidence rate of first BSI was 1.91 per 100 recipients per month (95% CI, 1.1-3.1) in the first year post-transplantation. The most common pathogens were Enterococcus faecium, Candida albicans, Escherichia coli, and Klebsiella pneumoniae. The pathogen composition depended on the transplanted organ with a higher proportion of BSI with Enterobacterales in kidney transplant recipients than in liver transplant recipients (67% vs. 20%, p = 0.03), while multiple pathogens were detected in the liver transplant recipients., Conclusions: BSI were common in pediatric liver and kidney transplant recipients and the pathogen composition differed between liver and kidney transplant recipients. Guidelines for empiric antibiotic therapy should consider the type of transplanted organ as well as the local resistance patterns.

We describe a 61-year-old man living with HIV on antiretroviral therapy (ART), who presented with headache, dizziness and blurred vision. Latest CD4 + cell count 3 months prior to admission was 570×10 6  cells/mL and HIV viral load <20 copies/mL. The patient was diagnosed with cerebrospinal fluid (CSF) lymphocytic pleocytosis, raised intracranial pressure and papilloedema. Neuroimaging showed normal ventricular volume and no mass lesions, suggesting (1) neuroinfection (2) idiopathic intracranial hypertension or (3) retroviral rebound syndrome (RRS) as possible causes. Neuroinfection was ruled out and idiopathic intracranial hypertension seemed unlikely. Elevated plasma HIV RNA level was detected consistent with reduced ART adherence prior to admission. RRS is a virological rebound after ART interruption, which can mimic the acute retroviral syndrome of acute primary infection. To the best of our knowledge, we describe the second case of RRS presenting as CSF lymphocytic pleocytosis and elevated intracranial pressure after low ART adherence., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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.