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Background: Solid organ transplant (SOT) recipients are predicted to have worse COVID-19 outcomes due to their compromised immunity. However, this association remains uncertain because published studies have had small sample sizes and variability in chronic comorbidity adjustment. Methods: In this retrospective cohort study conducted at a multihospital health system, we compared COVID-19 outcomes and survival up to 60 days following hospital admission in SOT recipients taking baseline immunosuppressants versus hospitalized control patients. Results: The study included 4,562 patients who were hospitalized with COVID-19 (108 SOT recipients and 4,454 controls) from 03/2020 to 08/2020. Mortality at 60 days was higher for SOT recipients (17% SOT vs 10% control; unadjusted odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.04–2.91, P = 0.04). We then conducted a 1:5 propensity matched cohort analysis (100 SOT recipients; 500 controls) using age, sex, race, body mass index, hypertension, diabetes, chronic kidney disease, liver disease, admission month, and area deprivation index. Within 28 days of admission, SOT recipients had fewer hospital-free days (median; 17 SOT vs 21 control; OR = 0.64, 95%CI 0.46–0.90, P = 0.01) but had similar ICU-free days (OR = 1.20, 95%CI 0.72–2.00, P = 0.49) and ventilator-free days (OR = 0.91, 95%CI 0.53–1.57, P = 0.75). There was no statistically significant difference in 28-day mortality (9% SOT vs 12% control; OR = 0.76, 95%CI 0.36–1.57, P = 0.46) or 60-day mortality (16% SOT vs 14% control; OR = 1.15, 95%CI 0.64–2.08, P = 0.64). Conclusions: Hospitalized SOT recipients appear to need additional days of hospital care but can achieve short-term mortality outcomes from COVID-19 that are similar to non-SOT recipients in a propensity matched cohort study. [ABSTRACT FROM AUTHOR]

Response to two doses of a nucleoside‐modified messenger ribonucleic acid (mRNA) vaccine was evaluated in a large solid‐organ transplant program. mRNA COVID‐19 vaccine was administered to transplant candidates and recipients who met study inclusion criteria. Qualitative anti‐SARS‐CoV‐2 Spike Total Immunoglobulin (Ig) and IgG‐specific assays, and a semi‐quantitative test for anti‐SARS‐CoV‐2 Spike protein IgG were measured in 241 (17.2%) transplant candidates and 1163 (82.8%) transplant recipients; 55.2% of whom were non‐Hispanic White and 44.8% identified as another race. Transplant recipients were a median (IQR) of 3.2 (1.1, 6.8) years from transplantation. Response differed by transplant status: 96.0% versus 43.2% by the anti‐SARS‐CoV‐2 Total Ig (candidates vs. recipients, respectively), 93.5% versus 11.6% by the anti‐SARS‐CoV‐2 IgG assay, and 91.9% versus 30.1% by anti‐spike titers after two doses of vaccine. Multivariable analysis revealed candidates had higher likelihood of response versus recipients (odds ratio [OR], 14.6; 95 %CI 2.19, 98.11; P =.02). A slightly lower response was demonstrated in older patients (OR.96; 95 %CI.94,.99; P =.002), patients taking antimetabolites (OR,.21; 95% CI.08,.51; P =.001). Vaccination prior to transplantation should be encouraged. [ABSTRACT FROM AUTHOR]

Lymphocyte-depleting induction lowers acute rejection ( AR) rates among high-immunologic risk ( HIR) renal transplant recipients, including African Americans ( AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dn DSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin ( ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dn DSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor ( LD) recipients to 30% in younger AA deceased donor ( DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non- AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dn DSA among all HIR recipients. Development of both AR and dn DSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups. [ABSTRACT FROM AUTHOR]

Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by "indirect" viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovirresistant CMV disease. All patients initially developed "breakthrough" viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV. [ABSTRACT FROM AUTHOR]

Thepharmacokinetics of tacrolimus are influenced by many factors, including genetic variability, acute infections, liver dysfunction, and interacting medications, which can result in elevated concentrations.The most appropriate management of acute tacrolimus toxicity has not been defined though case reports exist describing the therapeutic use of enzyme inducers to increase tacrolimus metabolism and decrease concentrations. We are reporting on the utilization of phenytoin to assist in decreasing tacrolimus concentrations in a case series of four solid organ transplant recipients with acute, symptomatic tacrolimus toxicity presenting with elevated serum creatinine, potassium, and tacrolimus trough concentrations greater than 30 ng/mL. All four patients had the potential causative agents stopped or temporarily held and were given 300 to 400mg/day of phenytoin for two to three days.Within three days of beginning phenytoin, all four patients had a decrease in tacrolimus concentration to less than 15 ng/mL, a return to or near baseline creatinine concentration, and lack of phenytoin-related side effects.Therefore, phenytoin appears to be a safe and potentially beneficial treatment option in patients with symptomatic tacrolimus toxicity. [ABSTRACT FROM AUTHOR]

Gainer SM, Patel SJ, Seethamraju H, Moore LW, Knight RJ, Gaber AO. Increased mortality of solid organ transplant recipients with H1N1 infection: a single center experience. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01443.x. © 2011 John Wiley & Sons A/S. Abstract: Immunosuppressed solid organ transplant recipients are included in the cohort at increased risk for complications of viral infections such as the newly encountered H1N1. A retrospective review was performed to collect data on patients hospitalized during a recent H1N1 epidemic. H1N1 was suspected based on symptoms and real-time reverse-transcriptase-polymerase-chain-reaction assay confirmed the diagnosis. From August through October of 2009, 89 patients were admitted to The Methodist Hospital, Houston, Texas, with H1N1. Eighteen were solid organ transplant recipients with an age range of 34-69 yr. This group included nine kidney, five lung, one kidney-pancreas, one liver, and two heart recipients. Severe cardiac or pulmonary comorbidities existed in over half of non-transplant patients, while only eight of these non-transplant patients were otherwise healthy. Eighty-nine percent of transplant patients presented with fever or chills, 72% with cough, and 56% with gastrointestinal distress. Symptoms were similar to non-transplant patients. All transplant patients were treated with oseltamivir. Two non-transplant patients and three transplant patients died. Thirty-day survival was 97% in non-transplant and 83% in transplant patients (p = 0.02). In the context of an initial epidemic of H1N1, infection was associated with increased risk of complications and mortality in solid organ transplant recipients. [ABSTRACT FROM AUTHOR]

Knight RJ, Daly L. The impact of pancreas transplantation on patient employment opportunities. Clin Transplant 2004: 18: 49–52. © Blackwell Munksgaard, 2004 A questionnaire study was designed to determine whether the quality of life benefit provided by receiving a kidney–pancreas (KP) transplant increased the incentive to return to work, compared with patients receiving a kidney alone (KA) transplant. A confidential questionnaire was sent to 58 patients with insulin-dependent diabetes mellitus who had functioning grafts at least 6 months post-transplant. Thirty-eight patients had received a KP transplant and 20 patients, a KA transplant. Eighty-three percent of patients returned the questionnaire (87% of KP and 75% of KA patients [p: non-significant (ns)] . The pre-transplant demographic variables of age, gender, educational status, and need for dialysis, were equivalent between the KP and KA groups, respectively (p: ns). At the time of transplantation 39% of KP patients and 33% of KA patients were employed at least 20 h/wk (p: ns). However, post-transplant significantly more KP patients (73%) were working compared with KA patients (27%, p: 0.04). Additionally, pre-transplant employment was independently associated with post-transplant work status (p: 0.01). These data suggest that the improvement in quality of life associated with pancreas transplantation provide an added incentive for diabetics with renal insufficiency to seek employment. [ABSTRACT FROM AUTHOR]