Recreational drug toxicity with severe hyperthermia: Rapid onsite treatment and clinical course.

Electronic dance music festivals have gained notoriety in the critical care and emergency medicine fields due to an alarming incidence of hospitalizations and deaths related to the high prevalence of recreational drug use. Recreational drug use toxicity, in part related to sympathomimetic toxidromes, may cause hyponatremia, seizures, rhabdomyolysis, hyperkalemia, acidosis, coagulopathy, circulatory shock, multi-organ failure, and even death. This wide-ranging syndrome has been referred to as psychostimulant drug-induced toxicity. Rapid onsite diagnosis and treatment, with attention to the A-B-C's of clinical emergencies, is essential to preserve life. We describe a patient presenting with the highest recorded core temperature in a survivor of psychostimulant drug-induced toxicity, and emphasize management principles of this life-threatening and increasingly prevalent condition.

Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations.

Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early-phase studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) in 2014. The number of FDA-approved agents of this class is rapidly enlarging with indications for treatment spanning across a spectrum of malignancies. The purpose of this review is to highlight the clinical development of PD-1 and PD-L1 inhibitors in cancer therapy to date. In particular, we focus on detailing the registration trials that have led to FDA-approved indications of anti-PD-1 and anti-PD-L1 therapies in cancer. As the number of PD-1/PD-L1 inhibitors continues to grow, predictive biomarkers, mechanisms of resistance, hyperprogressors, treatment duration and treatment beyond progression, immune-related toxicities, and clinical trial design are key concepts in need of further consideration to optimize the anticancer potential of this class of immunotherapy.