Donor-Derived Metastatic Melanoma and Checkpoint Inhibition.

Donor-derived malignancy, particularly melanoma, is a rare but known complication of organ transplantation. Here we describe a case of metastatic melanoma in a deceased-donor kidney transplant recipient. After diagnosis, the patient was successfully treated with cessation of immunosuppression, explantation of the renal allograft, and novel melanoma therapies, including the mutation-targeted agents dabrafenib and trametinib and the immune checkpoint inhibitor nivolumab. These 2 new classes of melanoma therapy have revolutionized the course of metastatic melanoma, altering it from one of nearly certain mortality to one of potential cure. This case reviews the mechanisms of action of these therapies and reports our experience with them in the rare setting of donor-derived melanoma in a dialysis-dependent patient.

Identification of Risk Factors Associated With Clostridium difficile Infection in Liver Transplantation Recipients: A Single-Center Analysis.

Clostridium difficile remains the leading cause of health care-associated infectious diarrhea, and its incidence and severity are increasing in liver transplant recipients. Several known risk factors for C difficile infection (CDI) are inherently associated with liver transplantation, such as severe underlying illness, immunosuppression, abdominal surgery, and broad-spectrum antibiotic use. We conducted a single-center retrospective case control study to characterize risk factors for CDI among patients who received a liver transplant from January 2008 to December 2012. We also examined the associations of post-transplantation CDI with transplant outcomes. Cases were defined as having diarrhea with a positive test for C difficile by either toxin A/B enzyme immunoassay (EIA) or glutamate dehydrogenase EIA and polymerase chain reaction within 1 year after transplantation. Sixty-five consecutive patients were evaluated, of which 15 (23%) developed CDI. The median time from transplantation to CDI diagnosis was 65 days (interquartile range [IQR] 13-208) and more than one-half (53%) had severe infection. Risk factors that were associated with CDI among liver transplant recipients included: (1) previous history of CDI (20% vs 0%; P = .001); (2) exposure to proton-pump inhibitor therapy (93% vs 60%; P = .015); (3) antimicrobial therapy before transplantation (47% vs 18%; P = .039); (4) a prolonged length of stay before transplantation (1 day [IQR, 1-19] vs 1 day [IQR, 0-1]; P = .028); and (5) chronic kidney disease (53% vs 20%; P = .011). There was no significant differences in patient survivals at 6 months (93% vs 96%; P = .67) and 12 months (87% vs 94%; P = .35) among CDI case and control subjects, respectively.

Serum creatinine elevation after switch to dolutegravir in a human immunodeficiency virus-positive kidney transplant recipient.

Dolutegravir is a preferred antiretroviral drug for human immunodeficiency virus (HIV)-infected patients following solid organ transplantation. It has potent antiretroviral activity and does not interact with calcineurin inhibitors. We describe a case of an HIV-infected kidney transplant patient, who was noted to have a rising serum creatinine following initiation of dolutegravir. At first, an acute rejection episode was suspected, but this finding was later attributed to inhibition of creatinine secretion by dolutegravir. We suggest that an awareness of this potential effect of dolutegravir is important for providers who take care of HIV-positive kidney transplant recipients, in order to prevent potentially unnecessary testing.

Low rates of vaccination in listed kidney transplant candidates.

Despite clear consensus and strong recommendations, vaccination rates of kidney transplant (KT) recipients have remained below targets. As vaccination is most effective if it is given prior to transplantation and the initiation of immunosuppression, patients should ideally have their vaccination status assessed and optimized in the pre-transplant period. We performed a retrospective chart review to characterize vaccination rates and factors associated with gaps in vaccination in a single-center population of waitlisted patients being evaluated for kidney transplantation. We evaluated 362 KT patients. Three-quarters were receiving dialysis at the time of evaluation. Immunization rates were low with 35.9% of patients having completed vaccination for Pneumococcus, 55% for influenza, 6.9% for zoster, and 2.5% for tetanus. On multivariable analysis, patients who received other vaccines, including influenza, tetanus, or zoster vaccine (odds ratio [OR] 10.55, 95% confidence interval [CI] 5.65-19.71) were more likely to receive pneumococcal vaccine. Blacks (OR 0.24, 95% CI 0.12-0.47) were less likely to receive pneumococcal vaccine compared to whites. Patients on dialysis, and those active on the waiting list were more likely to receive pneumococcal vaccine than other groups (OR 2.81, 95% CI 1.44-5.51, and OR 1.84, 95% CI 1.08-3.14, respectively). We found that the overall immunization rate against common vaccine-preventable infections was low among patients evaluated for kidney transplantation. A significant gap remains between recommendations and vaccine uptake in clinical practice among this high-risk population.

Trends and Patterns in Reporting of Patient Safety Situations in Transplantation.

Analysis and dissemination of transplant patient safety data are essential to understanding key issues facing the transplant community and fostering a "culture of safety." The Organ Procurement and Transplantation Network's (OPTN) Operations and Safety Committee de-identified safety situations reported through several mechanisms, including the OPTN's online patient safety portal, through which the number of reported cases has risen sharply. From 2012 to 2013, 438 events were received through either the online portal or other reporting pathways, and about half were self-reports. Communication breakdowns (22.8%) and testing issues (16.0%) were the most common types. Events included preventable errors that led to organ discard as well as near misses. Among events reported by Organ Procurement Organization (OPOs), half came from just 10 of the 58 institutions, while half of events reported by transplant centers came from just 21 of 250 institutions. Thirteen (23%) OPOs and 155 (62%) transplant centers reported no events, suggesting substantial underreporting of safety-related errors to the national database. This is the first comprehensive, published report of the OPTN's safety efforts. Our goals are to raise awareness of safety data recently reported to the OPTN, encourage additional reporting, and spur systems improvements to mitigate future risk.

Successful treatment of acute severe graft-versus-host-disease in a pancreas-after-kidney transplant recipient: case report.

The development of acute graft-versus-host-disease (GVHD) in recipients of pancreas transplants is a rare and quite often a fatal post-transplantation complication. We present a 38-year-old male with a longstanding history of type 1 diabetes mellitus and end-stage kidney disease, with a living unrelated kidney transplant from his wife for 3 years, who received an enteric-drained 5-antigen HLA-mismatched deceased-donor pancreas. Five weeks after transplantation, he presented with spiking fevers, severe skin rash, diarrhea, pancytopenia, and increasingly abnormal liver function tests. Skin biopsies were consistent with grade 3 acute GVHD. The patient was treated for GVHD with escalated doses of tacrolimus, pulse doses of steroids, and basiliximab. He was discharged after a 4-week hospital stay with complete resolution of his rash, fever, abnormal liver enzymes, and leukopenia. He remained in good health with excellent kidney and pancreas allograft function 3 years later.

Kidney disease after heart and lung transplantation.

Kidney disease is a commonly recognized complication of heart and lung transplantation and is associated with increased morbidity and mortality. While the spectrum of kidney disease in this population is wide-ranging, studies indicate that between 3% and 10% of these patients will ultimately develop end-stage renal disease (ESRD). This review examines the risk factors for both acute and chronic kidney injury, with a particular emphasis on the role of calcineurin inhibitor-mediated nephrotoxicity in both these settings. Against the background of current National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, we have further considered and recommended appropriate strategies for long-term management of kidney disease-related manifestations in heart and lung transplant recipients. Specific aspects addressed include retarding progressive renal injury and minimizing nephrotoxicity, as well as treatment of hypertension, hyperlipidemia and anemia. Finally, for patients in this population with advanced kidney disease, renal replacement therapy options are discussed. Based on the impact of chronic kidney disease on outcomes in both heart and lung recipients, we advocate early referral to a nephrologist for patients displaying evidence of significant renal dysfunction.

Induction of cytotoxic T lymphocyte antigen 4 (CTLA-4) restricts clonal expansion of helper T cells.

Cytotoxic T lymphocyte antigen (CTLA)-4 plays an essential role in immunologic homeostasis. How this negative regulator of T cell activation executes its functions has remained controversial. We now provide evidence that CTLA-4 mediates a cell-intrinsic counterbalance to restrict the clonal expansion of proliferating CD4(+) T cells. The regulation of CTLA-4 expression and function ensures that, after approximately 3 cell divisions of expansion, most progeny will succumb to either proliferative arrest or death over the ensuing three cell divisions. The quantitative precision of the counterbalance hinges on the graded, time-independent induction of CTLA-4 expression during the first three cell divisions. In contrast to the limits imposed on unpolarized cells, T helper type 1 (Th1) and Th2 effector progeny may be rescued from proliferative arrest by interleukin (IL)-12 and IL-4 signaling, respectively, allowing appropriately stimulated progeny to proceed to the stage of tissue homing. These results suggest that the cell-autonomous regulation of CTLA-4 induction may be a central checkpoint of clonal expansion of CD4(+) T cells, allowing temporally and spatially restricted growth of progeny to be dictated by the nature of the threat posed to the host.

Factors associated with self-disclosure of HIV serostatus to significant others.

OBJECTIVES: To examine rates and patterns of self-disclosure of HIV serostatus amongst individuals attending an out-patient HIV clinic in East London. DESIGN: A cross-sectional survey design was used. METHODS: A volunteer sample of 95 out-patient HIV clinic attendees completed a self-report questionnaire examining patterns of disclosure to self-identified significant others, reasons for disclosure and non-disclosure, satisfaction with social support (SSQ6), quality of life (MOS-30) and anxiety and depression (HADS). Self-disclosure was examined in relation to cultural background, gender, satisfaction with social support, and medical and psychological variables. RESULTS: Seventy-nine men and 16 women reported a mean disclosure rate of 68% to self-identified significant others. Five individuals had not disclosed their HIV status to anyone; 91% of individuals had informed their partner. Friends were more frequently informed (79%) than family (53%). Ethnicity (p <.001) and length of time since testing HIV seropositive (p <.05) emerged as significant predictors of disclosure. Global satisfaction with social support was negatively correlated with depression but was not associated with the total rate of HIV disclosure. Frequently reported reasons for non-disclosure included wanting to protect others from distress and fear of discrimination. CONCLUSIONS: Self-disclosure of HIV serostatus rates was highest for partners, followed by friends, and lowest for family members. Patterns of disclosure of HIV serostatus varied in relation to ethnicity. Fifteen years into the HIV epidemic, social stigma continues to contribute towards non-disclosure of diagnosis.