A Prospective Observational Cohort of Clinical Outcomes in Medical Inpatients prescribed Pharmacological Thromboprophylaxis Using Different Clinical Risk Assessment Models(COMPT RAMs).

The Caprini and Padua venous thromboembolism (VTE) risk assessment models (RAMs) are used to assess VTE risk in surgical and in medical patients respectively. This study aims to compare the proportion of medical inpatients eligible for VTE prophylaxis using the hospital Caprini-based RAM to using the Caprini and Padua RAMs and to assess the associated clinical outcomes. In a prospective observational study, we assessed 297 adult medical inpatients for whom VTE thromboprophylaxis was initiated according to the hospital Caprini-based RAM, referred to as the Lebanese American University Medical Center RAM (LAUMC-RAM). The Padua, Caprini and IMPROVE bleeding risk scores were also assessed for all patients. Bleeding and thromboembolism were evaluated at 14 and 30 days post VTE risk assessment. Pharmacologic thromboprophylaxis was warranted in 97.6%, 99.7%, and 52.9% of patients using the Caprini-based, Caprini, and Padua RAMs respectively. The Caprini-based and Caprini RAMs were highly correlated (r = 0.873 p < 0.001) and were significantly less correlated with the Padua RAM. Major and overall bleeding occurred in 1.4% and 9.2% respectively. VTE was reported in 0.4% with no VTE related mortality. In hospitalized medical patients, the Caprini-based RAM can accurately distinguish low and high VTE risk without resulting in increased risk of bleeding.

Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-ß.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a complex disease for which the pathogenesis is poorly understood. In this study, we identified lactic acid as a metabolite that is elevated in the lung tissue of patients with IPF. OBJECTIVES: This study examines the effect of lactic acid on myofibroblast differentiation and pulmonary fibrosis. METHODS: We used metabolomic analysis to examine cellular metabolism in lung tissue from patients with IPF and determined the effects of lactic acid and lactate dehydrogenase-5 (LDH5) overexpression on myofibroblast differentiation and transforming growth factor (TGF)-ß activation in vitro. MEASUREMENTS AND MAIN RESULTS: Lactic acid concentrations from healthy and IPF lung tissue were determined by nuclear magnetic resonance spectroscopy; α-smooth muscle actin, calponin, and LDH5 expression were assessed by Western blot of cell culture lysates. Lactic acid and LDH5 were significantly elevated in IPF lung tissue compared with controls. Physiologic concentrations of lactic acid induced myofibroblast differentiation via activation of TGF-ß. TGF-ß induced expression of LDH5 via hypoxia-inducible factor 1α (HIF1α). Importantly, overexpression of both HIF1α and LDH5 in human lung fibroblasts induced myofibroblast differentiation and synergized with low-dose TGF-ß to induce differentiation. Furthermore, inhibition of both HIF1α and LDH5 inhibited TGF-ß-induced myofibroblast differentiation. CONCLUSIONS: We have identified the metabolite lactic acid as an important mediator of myofibroblast differentiation via a pH-dependent activation of TGF-ß. We propose that the metabolic milieu of the lung, and potentially other tissues, is an important driving force behind myofibroblast differentiation and potentially the initiation and progression of fibrotic disorders.