Charité Clinical Journal Club (English) by Fred Luft - 19.12.2018

The N Engl J Med image involves an 18-year-old man, who presented to the emergency department with chest pain. What is the most likely childhood diagnosis associated with the findings of this coronary angiogram? You are offered: Kawasaki’s disease, Marfan’s syndrome, rheumatic heart disease, familial hypercholesterolemia, and Hodgkin’s lymphoma. One hundred years ago, 50 million persons on the planet diet because of H1N1 influenza. We commemorate that epidemic. In patients who have chronic heart failure with reduced left ventricular ejection fraction, severe secondary mitral-valve regurgitation is associated with a poor prognosis. Whether or not percutaneous mitral-valve repair (mitral valve clip procedure) improves clinical outcomes in this patient population is unknown. We inspect two trials, one from France (MITR-FR), and another from the US and elsewhere (COAPT). The primary efficacy outcome was a composite of death from any cause or unplanned hospitalization for heart failure at 12 months, for both. The European trial showed no benefits, while the US trial showed markedly positive benefits. We discuss possible reasons, including funding sources. Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term follow-up is sparse. Scandinavian investigators randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. We learn that in clinically detected prostate cancer, the benefit of radical prostatectomy in otherwise healthy men can be substantial, with a mean gain of almost 3 years of life after 23 years of follow-up. As consolidation therapy for acute myeloid leukemia (AML), allogeneic hematopoietic stem-cell transplantation provides a benefit in part by means of an immune-mediated graft-versus-leukemia effect. Investigators hypothesized that the immune-mediated selective pressure imposed by allogeneic transplantation may cause distinct patterns of tumor evolution in relapsed disease. They performed enhanced exome sequencing on paired samples obtained at initial presentation with AML and at relapse from 15 patients who had a relapse after hematopoietic stem-cell transplantation (with transplants from an HLA-matched sibling, HLA-matched unrelated donor, or HLA-mismatched unrelated donor) and from 20 patients who had a relapse after chemotherapy. They performed RNA sequencing and flow cytometry on a subgroup of these samples and on additional samples for validation. The study showed that AML cells that escaped the immune surveillance provided by allogeneic T cells after allogeneic hematopoietic stem-cell transplantation frequently had dysregulation of a number of pathways that regulate immune function. Epigenetic mechanisms are involved. Durvalumab is a selective, high-affinity, engineered, human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, allowing T cells to recognize and kill tumor cells. An earlier N Engl J Med report showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non–small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. In a followup evaluation, we find that overall survival was improved as well. We review substance-use disorders in later life. Alcohol remains on the top of the list. We then inspect a 54 year-old man with progressive heart failure and a diastolic decrescendo heart murmur. The blood pressure in his legs should have been measured! In the Lancet we learn that 258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. Investigators aimed to review and synthesize available mortality data on international migrants. The migrants received better healthcare in their new countries than those back home. Globally, a growing number of children and adolescents are left behind when parents migrate. Epidemiologists investigated the effect of parental migration on the health of left behind-children and adolescents in low-income and middle-income countries. To no great surprise, the children left behind do worse than control children...