A 43-year-old woman presented to the emergency room for a 3-day history of oppressive chest pain and dyspnoea. Her past medical history was unremarkable. On admission, she had a temperature of 37.7°C, blood pressure 120/80 mmHg, and heart rate 79 b.p.m. Physical exam revealed decreased breath sounds at lung bases with ronchi. Because of oxygen desaturation (Sp_O2 89%), continuous positive airway pressure (CPAP) was positioned.

Microbes hijack prostate cancer therapy: Androgens such as testosterone and dihydrotestosterone are essential for male reproduction and sexual function. Androgens can also influence the growth of prostate tumor cells, and androgen deprivation therapy (ADT) either by surgical means (castration) or pharmacological approaches (hormone suppression), is the cornerstone of current prostate cancer treatments. Pernigoni et al . found that when the body was deprived of androgens during ADT, the gut microbiome could produce androgens from androgen precursors (see the Perspective by McCulloch and Trinchieri). Gut commensal microbiota in ADT-treated patients or castrated mice produced androgens that were absorbed into the systemic circulation. These microbe-derived androgens appeared to favor the growth of prostate cancer and helped to facilitate development into a castration- or endocrine therapy–resistant state. —PNK

Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-associated HCC involves both viral and host factors. The latter include a functionally inefficient CD8⁺T-cell response that fails to clear the infection from the liver but sustains a chronic necroinflammatory process that contributes to the development of HCC. According to this scenario, amelioration of immune-mediated chronic liver injury may prevent HCC. Because platelets facilitate immune-mediated liver injury by promoting the hepatic accumulation of virus-specific CD8⁺T cells, we evaluated the long-term consequences of antiplatelet therapy in an HBV transgenic mouse model of chronic immune-mediated necroinflammatory liver disease that progresses to HCC. Treatment with aspirin and clopidogrel during the chronic phase of the disease diminished the number of intrahepatic HBV-specific CD8⁺T cells and HBV-nonspecific inflammatory cells, the severity of liver fibrosis, and the development of HCC. Antiplatelet therapy improved overall survival without causing significant side effects. In contrast, the same antiplatelet regimen had no antitumor effect when HCC was induced nonimmunologically by chronic exposure to a hepatotoxic chemical. The unprecedented observation that antiplatelet therapy inhibits or delays immune-mediated hepatocarcinogenesis suggests that platelets may be key players in the pathogenesis of HBV-associated liver cancer and supports the notion that immune-mediated necroinflammatory reactions are an important cause of hepatocellular transformation during chronic hepatitis.

OBJECTIVE—Fatty liver may be involved in the pathogenesis of type 2 diabetes. Physical exercise is a tool to improve insulin sensitivity, but little is known about its effect on intrahepatic fat (IHF) content. The purpose of this study was to examine the association of habitual physical activity, insulin resistance, and adiponectin with IHF content. RESEARCH DESIGN AND METHODS—Participants were 191 (77 female and 114 male) apparently healthy, nonalcoholic individuals (aged 19–62 years; BMI 17.0–35.5 kg/m2). IHF content was assessed in a quantitative fashion and noninvasively as a continuous variable by means of 1H magnetic resonance spectroscopy (MRS), and habitual physical activity was assessed by means of a questionnaire. Fatty liver was defined as IHF content of >5% wet weight, and insulin sensitivity was estimated using the computer homeostasis model assessment (HOMA)-2 indexes. RESULTS—A reduced prevalence of fatty liver in the quartile of the most physically active individuals (25, 11, 25, and 2% in quartile 1, 2, 3, and 4, respectively; χ2 = 15.63; P = 0.001) was found along with an inverse correlation between the physical activity index and the IHF content when plotted as continuous variables (Pearson’s r = −0.27; P < 0.000). This association was not attenuated when adjusted for age, sex, BMI, HOMA-2, and adiponectin (partial correlation r = −0.25; P < 0.001). CONCLUSIONS—This study demonstrated that a higher level of habitual physical activity is associated with a lower IHF content and suggested that this relationship may be due to the effect of exercise per se.

Aims The addition of trimetazidine to standard treatment has been shown to improve left ventricular (LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo³¹P-magnetic resonance spectroscopy (³¹P-MRS), the effects of trimetazidine on LV cardiac phosphocreatine and adenosine triphosphate (PCr/ATP) ratio in patients with heart failure. Methods and results Twelve heart failure patients were randomized in a double-blind, cross-over study to placebo or trimetazidine (20 mg t.i.d.) for two periods of 90 days. At the end of each period, all patients underwent exercise testing, 2D echocardiography, and MRS. New York Heart Association (NYHA) class, ejection fraction (EF), maximal rate–pressure product, and metabolic equivalent system (METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac ³¹P-MRS. On trimetazidine, NYHA class decreased from 3.04±0.26 to 2.45±0.52 (P=0.005), whereas EF (34±10 vs. 39±10%, P=0.03) and METS (from 7.44±1.84 to 8.78±2.72, P=0.03) increased. The mean cardiac PCr/ATP ratio was 1.35±0.33 with placebo, but was increased by 33% to 1.80±0.50 (P=0.03) with trimetazidine. Conclusion Trimetazidine improves functional class and LV function in patients with heart failure. These effects are associated to the observed trimetazidine-induced increase in the PCr/ATP ratio, indicating preservation of the myocardial high-energy phosphate levels.