Contemporary Use of Venoarterial Extracorporeal Membrane Oxygenation: Insights from the Multicenter RESCUE Registry

BackgroundVenoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a life-saving therapy for patients with cardiovascular collapse, but identifying patients unlikely to benefit remains a challenge.Methods and ResultsWe created the RESCUE registry, a retrospective, observational registry of adult patients treated with VA-ECMO between January 2007 and June 2017 at 3 high-volume centers (Columbia University, Duke University, and Washington University) to describe short-term patient outcomes. In 723 patients treated with VA-ECMO, the most common indications for deployment were postcardiotomy shock (31%), cardiomyopathy (including acute heart failure) (26%), and myocardial infarction (17%). Patients frequently suffered in-hospital complications, including acute renal dysfunction (45%), major bleeding (41%), and infection (33%). Only 40% of patients (n = 290) survived to discharge, with a minority receiving durable cardiac support (left ventricular assist device [n = 48] or heart transplantation [n = 7]). Multivariable regression analysis identified risk factors for mortality on ECMO as older age (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.12–1.42) and female sex (OR, 1.44; 95% CI, 1.02–2.02) and risk factors for mortality after decannulation as higher body mass index (OR 1.17; 95% CI, 1.01-1.35) and major bleeding while on ECMO support (OR, 1.92; 95% CI, 1.23–2.99).ConclusionsDespite contemporary care at high-volume centers, patients treated with VA-ECMO continue to have significant in-hospital morbidity and mortality. The optimization of outcomes will require refinements in patient selection and improvement of care delivery.     

Osteoblast-specific overexpression of amphiregulin leads to transient increase in femoral cancellous bone mass in mice

The epidermal growth factor receptor ligand amphiregulin (AREG) has been implicated in bone physiology and in bone anabolism mediated by intermittent parathyroid hormone treatment. However, the functions of AREG in bone have been only incipiently evaluated in vivo. Here, we generated transgenic mice overexpressing AREG specifically in osteoblasts (Col1-Areg). pQCT analysis of the femoral metaphysis revealed increased trabecular bone mass at 4, 8, and 10 weeks of age in Col1-Areg mice compared to control littermates. However, the high bone mass phenotype was transient and disappeared in older animals. Micro-CT analysis of the secondary spongiosa confirmed increased trabecular bone volume and trabecular number in the distal femur of 4-week-old AREG-tg mice compared to control littermates. Furthermore, μ-CT analysis of the primary spongiosa revealed unaltered production of new bone trabeculae in distal femora of Col1-Areg mice. Histomorphometric analysis revealed a reduced number of osteoclasts in 4-week-old Col1-Areg mice, but not at later time points. Cancellous bone formation rate remained unchanged in Col1-Areg mice at all time points. In addition, bone mass and bone turnover in lumbar vertebral bodies were similar in Col1-Areg and control mice at all ages examined. Proliferation and differentiation of osteoblasts isolated from neonatal calvariae did not differ between Col1-Areg and control mice. Taken together, these data suggest that AREG overexpression in osteoblasts induces a transient high bone mass phenotype in the trabecular compartment of the appendicular skeleton by a growth-related, non-cell autonomous mechanism, leading to a positive bone balance with unchanged bone formation and lowered bone resorption.     

Bone Metabolism Discrepancy in Type 2 Diabetes Mellitus Patients With and Without Non-Alcoholic Fatty Liver Disease

To explore the distribution of several bone metabolic indicators in type 2 diabetes patients (T2DM) with and without non-alcoholic fatty liver disease (NAFLD) and to preliminarily evaluate the relationship of bone metabolism with NAFLD in patients with T2DM. The hospitalized patients with T2DM were divided into the group of T2DM complicated with NAFLD and the group of T2DM alone according to the results of ultrasonic diagnosis. The general information and laboratory test data such as bone metabolism indexes of these patients were collected and the differences of the indexes between the 2 groups were compared. Furthermore, the independent influencing factors of NAFLD in patients with T2DM were analyzed. A total of 186 patients were included in the study. Compared with patients with T2DM only, patients with T2DM combined with NAFLD were characterized with younger age (p < 0.001), higher BMI (p = 0.016), ALT (p = 0.001), TG (p = 0.005), HOMA-IR (p = 0.005), and lower HDL-C (p = 0.031). Significant discrepancy of age (OR 1.052, p = 0.001), ALT (OR 0.964, p = 0.047), HOMA-IR (OR 0.801, p = 0.005), and T-PINP (OR 1.022, p = 0.008) was found using multivariate logistic regression model. Significant discrepancy of T-PINP was found in T2DM patients with and without NAFLD. Further studies are needed to explore whether T-PINP could be used as a predictor of fatty liver disease, osteoporosis, and other related complications in patients with T2DM.