Charité Clinical Journal Club by Fred Luft - 24.05.2017

The N Engl J Med image of the week shows a bone marrow aspiration smear. You are offered acute promyelocytic leukemia, chronic lymphocytic leukemia, multiple myeloma, acute lymphocytic leukemia, and chronic myeloid leukemia. The diagnosis is made on the appearance of cytoplasmic red elongated rod-like inclusion bodies. Mast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. Investigators conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma. Imatinib emerges as an asthma treatment. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) is an eosinophilic vasculitis. Mepolizumab, an anti–interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis. In a multicenter, double-blind, parallel-group, phase 3 trial, investigators randomly assigned participants with relapsing or refractory eosinophilic granulomatosis with polyangiitis who had received treatment for at least 4 weeks and were taking a stable prednisolone or prednisone dose to receive 300 mg of mepolizumab or placebo, administered subcutaneously every 4 weeks, plus standard care, for 52 weeks. Remission was achieved but only in about half the patients receiving mepolizumab. The cholesteryl ester transfer protein (CETP) inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. Eli Lilly and Co. sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, investigators enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. As in the earlier trials of CETP inhibition, the laboratory values improved but cardiovascular events did not. In patients with acute heart failure, early intervention with an intravenous natriuretic peptide vasodilator (ularitide) has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients’ long-term prognosis. In a double-blind trial, cardiologists randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. In an intention-to-treat analysis, the drug did not reduce myocardial injury (as indicated by cardiac troponin T levels), did not affect a clinical composite end point, and did not influence disease progression, as shown by the lack of effect on cardiovascular mortality. Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia. In a clinical trial involving 160 obese older adults, life-style enthusiasts evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss. Participants were randomly assigned to a weight-management program plus one of three exercise programs — aerobic training, resistance training, or combined aerobic and resistance training — or to a control group (no weight-management or exercise program). The primary outcome was the change in Physical Performance Test score from baseline to 6 months (scores range from 0 to 36 points; higher scores indicate better performance). Both aerobic and resistance training appeared to be effective. The review is on the physiological effects of chronic hypoxia. The author is John West, an 89 year-old physician-physiologist friend of mine. The N Engl J Med case involves a young woman with world-wide travels. She develops granulomatous skin lesions and chronic inflammation. After multiple visits to physicians, someone tries to measure blood pressure in both arms and discovers major discrepancies. In the Lancet, the global burden of disease folks now tackle patterns of global health financing in two difficult papers. The poor countries do worse than the rich countries. High doses of corticosteroids are considered the standard treatment for pemphigus.