Background The COVID-19 pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well-described. Methods We performed a multi-center cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. Results Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (IQR 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [aOR 3.0, 95%CI 1.7-5.5, p<0.001], congestive heart failure [aOR 3.2, 95%CI 1.4-7.0, p=0.004], chronic lung disease [aOR 2.5, 95%CI 1.2-5.2, p=0.018], obesity [aOR 1.9, 95% CI 1.0-3.4, p=0.039]) and presenting findings (lymphopenia [aOR 1.9, 95%CI 1.1-3.5, p=0.033], abnormal chest imaging [aOR 2.9, 95%CI 1.1-7.5, p=0.027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. Conclusions Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.
Background: Few studies have explored dialysis patients’ perspectives on dialysis decision-making and end-of-life-care (EoLC) preferences. We surveyed a racially diverse cohort of maintenance dialysis patients in the Cleveland, OH, USA, metropolitan area. Materials and methods: In this cross-sectional study, we administered a 41-item questionnaire to 450 adult chronic dialysis patients. Items assessed patients’ knowledge of their kidney disease as well as their attitudes toward chronic kidney disease (CKD) treatment issues and EoLC issues. Results: The cohort included 67% Blacks, 27% Caucasians, 2.8% Hispanics, and 2.4% others. The response rate was 94% (423/450). Most patients considered it essential to obtain detailed information about their medical condition (80.6%) and prognosis (78.3%). Nearly 19% of respondents regretted their decision to start dialysis. 41% of patients would prefer treatment(s) aimed at relieving pain rather than prolonging life (30.5%), but a majority would want to be resuscitated (55.3%). Only 8.4% reported having a designated healthcare proxy, and 35.7% reported completing a living will. A significant percentage of patients wished to discuss their quality of life (71%), psychosocial and spiritual concerns (50.4%), and end-of-life issues (38%) with their nephrologist. Conclusion: Most dialysis patients wish to have more frequent discussions about their disease, prognosis, and EoLC planning. Findings from this study can inform the design of future interventions.
Chimeric antigen receptor T cells (CAR‐T) are genetically modified T cells with a chimeric antigen receptor directed against a specific tumor‐associated antigen like CD19 in lymphoma. CAR‐T cells have shown encouraging activity against recurrent and refractory diffuse large B cell lymphomas (DLBCL). However concurrent use of immunosuppressive agents was prohibited in most CAR‐T trials effectively excluding patients with prior solid organ transplantation (SOT) and posttransplant lymphoproliferative disorders (PTLD). We report the outcomes for three patients with PTLD refractory to immunochemotherapy 10‐20 years after SOT who received CAR‐T therapy between January 2018 and December 2019. One patient had an orthotopic heart transplant, the second had a deceased donor kidney transplant, and the third had a pancreas after kidney transplant (PAK). All patients developed complications of CAR‐T therapy such as cytokine release syndrome, immune effector cell‐associated neurotoxicity syndrome, and acute kidney injury requiring renal replacement therapy in the two out of three patients. All patients expired after withdrawal of care due to lack of response to CAR‐T therapy. In addition, the PAK patient developed acute pancreatitis after CAR‐T therapy. This case series identifies the challenges of using CAR‐T therapy to manage refractory PTLD in SOT recipients and its possible complications.
Background. Antibody-mediated rejection (AMR) continues to have a deleterious impact on kidney allograft survival. Recent evidence supports use of tocilizumab for treatment of chronic active AMR, but it has not been assessed for treatment of acute active AMR. Methods. We performed a single-center, observational study of kidney transplant recipients who received at least 1 dose of tocilizumab in addition to conventional therapies for acute active AMR between October 2016 and October 2018 with follow-up through August 2019. Results. Seven patients were included. All 7 patients received tocilizumab 8 mg/kg (max dose, 800 mg) monthly. We noted a 50% or greater reduction in immunodominant donor-specific antibodies in 4 of 6 patients. Renal function improved or stabilized in all patients throughout the duration of therapy. One patient developed cytomegalovirus esophagitis and 1 had a potential hypersensitivity reaction. In the extended follow-up, 1 patient had mixed rejection and 2 patients had T-cell–mediated rejection, which occurred 6 to 24 mo after completion of therapy. Conclusions. Tocilizumab may be considered as an addition to conventional therapies for treatment of acute active AMR. More studies are needed to determine which patients may benefit from therapy and to examine the appropriate duration of treatment.
IMPORTANCE Increased levels of ambient fine particulate matter (PM 2.5 ) air pollution are associated with increased risks for detrimental health outcomes, but risks for patients with kidney transplants (KTs) remain unknown. OBJECTIVE To investigate the association of PM 2.5 exposure with KT outcomes. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study was conducted using data on patients who received KTs from 2004 to 2016 who were identified in the national US transplant registry and followed up through March 2021. Multiple databases were linked to obtain data on PM 2.5 concentration, KT outcomes, and patient clinical, transplant, and contextual factors. Data were analyzed from April 2020 through July 2021.EXPOSURES Exposures included post-KT time-dependent annual mean PM 2.5 level (in 10 μg/m 3 ) and mean PM 2.5 level in the year before KT (ie, baseline levels) in quartiles, as well as baseline annual mean PM 2.5 level (in 10 μg/m 3 ). MAIN OUTCOMES AND MEASURESAcute kidney rejection (ie, rejection within 1 year after KT), time to death-censored graft failure, and time to all-cause death. Multivariable logistic regression for kidney rejection and Cox analyses with nonlinear assessment of exposure-response for deathcensored graft failure and all-cause death were performed. The national burden of graft failure associated with PM 2.5 levels greater than the Environmental Protection Agency recommended level of 12 μg/m 3 was estimated. RESULTS Among 112 098 patients with KTs, 70 522 individuals (62.9%) were older than age 50 years at the time of KT, 68 117 (60.8%) were men, and the median (IQR) follow-up was 6.0 (3.9-8.9) years. There were 37 265 Black patients (33.2%), 17 047 Hispanic patients (15.2%), 48 581 White patients [43.3%]), and 9205 patients (8.2%) of other race or ethnicity. The median (IQR) baseline PM 2.5 level was 9.8 (8.3-11.9) μg/m 3 . Increased baseline PM 2.5 level, compared with quartile 1 baseline PM 2.5 level, was not associated with higher odds of acute kidney rejection for quartile 2 (adjusted odds ratio [aOR], 0.99; 95% CI, 0.92-1.06) but was associated with increased odds for quartile 3 (aOR, 1.11; 95% CI, 1.04-1.20) and quartile 4 (aOR, 1.13; 95% CI, 1.05-1.23). Nonlinear assessment of exposure-response for graft failure and death showed no evidence for nonlinearity. Increased PM 2.5 levels were associated with increased risk of death-censored graft failure (adjusted hazard ratio[aHR] per 10 μg/m 3 increase, 1.17; 95% CI, 1.09-1.25) and all-cause death (aHR per 10 μg/m 3 increase, 1.21; 95% CI, 1.14-1.28). The national burden of death-censored graft failure associated with PM 2.5 above 12 μg/m 3 was 57 failures (95% uncertainty interval, 48-67 failures) per year among patients with KTs.
The emergence of SARS-CoV-2 and the clinical syndrome of COVID-19 resulted in a major decrease in transplant volumes during the first months of the pandemic followed by a change in practice, with strict screening and SARS-CoV-2 PCR testing prior to transplant. Protocols required a negative SARS-CoV-2 PCR prior to proceeding with transplantation. Many transplants were delayed nationwide due to persistent positive PCRs in asymptomatic patients, sometimes for months. 1Currently the Centers for Disease Control and Prevention does not routinely recommend a test of cure to determine when isolation for COVID-19 can be discontinued. 2 For patients with mild to moderate COVID-19, replication-competent virus has not been recovered after 10 days following symptoms. 3,4 Recovery of replication-competent
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