Charité Clinical Journal Club (English) by Fred Luft - 01.05.2019

The N Engl J Med image of the week concerns a 37-year-old man who presented with a 4-year history of excessive sweating, headaches, and joint pain. His wife had also noticed increasing skin folds on his scalp. What is the most likely diagnosis? You are offered acromegaly, amyloidosis, systemic sclerosis, hypogonadism, and sarcoidosis. We review the diagnosis. Angiotensin-receptor blockers (ARBs) are one of four drug classes recommended for the initial treatment of hypertension (Ger. Sartane). In Germany there are 20 million persons with hypertension; many ingest ARBs (sartans). On January 25, 2019, Food and Drug Administration (FDA) Commissioner, Scott Gottlieb, and Director of the FDA Center for Drug Evaluation and Research Janet Woodcock released a statement updating the public on large-scale voluntary recalls of various products containing ARBs. Two probable carcinogens had been identified in active pharmaceutical ingredients used by some manufacturers (in China and India) of valsartan, irbesartan, and losartan. The same was the case in Europe. “The ARB recalls provide an opportunity for the FDA, pharmacies, and health systems to evaluate all aspects of the response, from timely identification of potential impurities, to removal of recalled lots, to helping patients navigate the complexities of prescription changes, to monitoring them for adverse events after these changes are made”; so state the authors. The fact that Big-Pharma unloads these compounds on third-world manufacturers after the profits decline was not discussed by the authors. Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection that is caused by the JC virus and is typically fatal unless immune function can be restored. HIV patients, immunosuppressed cancer patients, and multiple-sclerosis patients receiving natalizumab are at risk for developing PML. Programmed cell death protein 1 (PD-1) is a negative regulator of the immune response that may contribute to impaired viral clearance. Whether or not PD-1 blockade with pembrolizumab could reinvigorate anti–JC virus immune activity in patients with PML is unknown. Investigators administered pembrolizumab at a dose of 2 mg per kilogram of body weight every 4 to 6 weeks to eight adults with PML, each with a different underlying predisposing condition. Each patient received at least one dose but no more than three doses. Of 8 patients, 5 seemed to improve. Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection. Investigators conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir–velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The HCV-infected organs did even better than organs without HCV. Patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. We inspect a longer-term followup corroborating the earlier findings. Diphtheria toxin is an exotoxin from Corynebacteria that is incorporated into cells and binds to the elongation factor-2 (EF-2), blocking translation and driving cells into apoptosis...