Pembrolizumab-induced severe rejection and graft intolerance syndrome resulting in renal allograft nephrectomy.

INTRODUCTION: Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection. CASE REPORT: We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome.Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy. DISCUSSION: As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.

Correction: The Impact of Clostridium Difficile Infections on In-Hospital Outcomes of Venous Thromboembolism (Deep Vein Thrombosis or Pulmonary Embolism) Hospitalizations.

[This corrects the article DOI: 10.7759/cureus.9195.].

Hydralazine-Induced Dual Antineutrophil Cytoplasmic Antibody Positive Vasculitis and Nephritis.

Drug-induced autoimmunity occurs when exposure to a causative agent leads to serologic or clinical autoimmune responses. Syndromes that may be associated with drug-induced autoimmunity include antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) and drug-induced lupus (DIL). When drug-induced autoimmunity involves the kidney, histological patterns of injury include pauci-immune glomerulonephritis (GN), which occurs with AAV, and immune complex-mediated GN, which is associated with DIL. We present a case of hydralazine-induced dual ANCA-positive vasculitis and nephritis.

The Impact of Clostridium Difficile Infections on In-Hospital Outcomes of Venous Thromboembolism (Deep Vein Thrombosis or Pulmonary Embolism) Hospitalizations.

Background Clostridium difficile infection (CDI) is associated with high mortality. Studies have shown an increased rate of venous thromboembolism (VTE) in patients with CDI. However, literature regarding the impact of CDI on outcomes of VTE-related hospitalizations is scarce. Our study aimed to assess the impact of CDI on in-hospital outcomes among VTE hospitalizations. Methods The 2016 National Inpatient Sample (NIS) was used to identify all adult hospitalizations in the United States with a primary discharge diagnosis of acute VTE. Hospitalizations with deep vein thrombosis (DVT) or pulmonary embolism (PE) were included under VTE. The sample was stratified based on the presence or absence of active CDI. Chi-square test and weighted Student's t-test were used to analyze categorical and continuous variables, respectively. The adjusted odds ratio (OR) for clinical outcomes were calculated using multivariate logistic regression analysis. Subgroup analyses for DVT and PE hospitalizations were performed. All analyses were completed in SAS (SAS Institute Inc., Cary, NC), and a p-value of <0.05 was considered statistically significant. Results We identified 382,585 weighted hospitalizations for VTE. Among them, 0.8% had concomitant CDI. The presence of CDI was associated with a statistically significant increase in in-hospital mortality (6% vs. 3%), hospitalization cost ($147,356.5 vs. $55,193), and length of stay (13.7 vs. 5.4 days). There were more incidents of bleeding and acute respiratory failure requiring prolonged ventilation in patients with CDI. The odds of stroke were significantly higher in patients with CDI and DVT. Conclusion CDI independently increased in-hospital mortality in VTE. Preventing CDI in the VTE population may mitigate complications, improve in-hospital outcomes, and reduce treatment costs.

Calciphylaxis in the Setting of Hemodialysis, Liver Cirrhosis, and Warfarin Therapy for Atrial Fibrillation: An Argument for Alternative Anti-Embolic Therapy.

Calciphylaxis, also referred to as calcific uremic arteriolopathy, is a rare, life-threatening cutaneous systemic disease that typically occurs in the setting of end-stage renal disease (ESRD). ESRD is the most recognized risk factor for calciphylaxis but it is not the sole risk factor. Calciphylaxis has also been associated with liver cirrhosis with or without concurrent renal disease. The current case describes a patient who developed calciphylaxis in the setting of hemodialysis, liver cirrhosis, and atrial fibrillation managed with warfarin therapy, all risk factors for calciphylaxis. The need for alternatives to warfarin therapy, specifically in patients with atrial fibrillation on hemodialysis for ESRD who are at increased risk for calciphylaxis, is discussed. Specifically, the left atrial appendage occluder device is described and the need for interdisciplinary management of these patients is stressed.

A Pain in the Neck - A Case of Intramedullary Spinal Ependymoma.

Spinal cord tumors are sporadic and account for around 2%-4% of central nervous system neoplasms. Ependymoma is one of the most common spinal cord neoplasms and can present with different neurological signs and symptoms. They commonly present with neck or back pain and associated neurological involvement, with sensory symptoms usually antedating the motor symptoms. We now present a rare case of spinal ependymoma in a 26-year-old female who presented with isolated neck pain and the absence of other neurological symptoms. Attention to peculiar characteristics like isolated neck pain might be an essential key to early diagnosis and better prognosis.