TRPV4 Regulates the Macrophage Metabolic Response to Limit Sepsis-induced Lung Injury.

Sepsis is a systemic inflammatory response that requires effective macrophage metabolic functions to resolve ongoing inflammation. Previous work showed that the mechanosensitive cation channel, transient receptor potential vanilloid 4 (TRPV4), mediates macrophage phagocytosis and cytokine production in response to lung infection. Here, we show that TRPV4 regulates glycolysis in a stiffness-dependent manner by augmenting macrophage glucose uptake by GLUT1.

Effect of ethanol exposure on innate immune response in sepsis.

Alcohol use disorder, reported by 1 in 8 critically ill patients, is a risk factor for death in sepsis patients. Sepsis, the leading cause of death, kills over 270,000 patients in the United States alone and remains without targeted therapy. Immune response in sepsis transitions from an early hyperinflammation to persistent inflammation and immunosuppression and multiple organ dysfunction during late sepsis.

Perioperative Quality Initiative (POQI) consensus statement on perioperative assessment of right ventricular function.

Background: The right ventricle (RV) plays a central  role in the maintenance of effective cardiac pump function. Despite overwhelming evidence that perioperative RV dysfunction (RVD) and failure (RVF) are associated with poor clinical outcomes, there are very few published recommendations or guidelines for comprehensive, evidence-based RV assessment on the risk of developing either during the perioperative period.

Main Text: To address this gap, the Perioperative Quality Initiative-IX (POQI-IX) investigators group, comprised of clinical experts in anesthesiology, cardiovascular surgery, internal medicine, critical care medicine, and advanced practice nursing, has developed a consensus statement based on current literature, published society recommendations, and the clinical expertise of the group.

COVID-19 outcome is not affected by anti-CD20 or high-titer convalescent plasma in immunosuppressed patients.

The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma in the treatment of Coronavirus Disease 2019 (COVID-19) in immunosuppressed individuals remains controversial. We describe the course of COVID-19 in patients who had received anti-CD20 therapy within the 3 years prior to infection. We compared outcomes between those treated with and those not treated with high titer SARS-CoV2 convalescent plasma.

The role of everolimus in liver transplantation.

During the last 5 decades, liver transplantation has witnessed rapid development in terms of both technical and pharmacologic advances. Since their discovery, calcineurin inhibitors (CNIs) have remained the standard of care for immunosuppression therapy in liver transplantation, improving both patient and graft survival. However, adverse events, particularly posttransplant nephrotoxicity, associated with long-term CNI use have necessitated the development of alternate treatment approaches.

Application of the OMERACT filter to measures of core outcome domains in recent clinical studies of acute gout.

Objective: To determine the extent to which instruments that measure core outcome domains in acute gout fulfill the Outcome Measures in Rheumatology (OMERACT) filter requirements of truth, discrimination, and feasibility.

Methods: Patient-level data from 4 randomized controlled trials of agents designed to treat acute gout and 1 observational study of acute gout were analyzed. For each available measure, construct validity, test-retest reliability, within-group change using effect size, between-group change using the Kruskall-Wallis statistic, and repeated measures generalized estimating equations were assessed.

A varying-stage adaptive phase II/III clinical trial design.

Currently, adaptive phase II/III clinical trials are typically carried out with a strict two-stage design. The first stage is a learning stage called phase II, and the second stage is a confirmatory stage called phase III. Following phase II analysis, inefficacious or harmful dose arms are dropped, then one or two promising dose arms are selected for the second stage.

mTOR inhibition in liver transplantation: how to dose for effective/safe CNI reduction?

Everolimus (EVR) is a semi-synthetic mammalian target of rapamycin inhibitor currently under development for liver transplantation (LTx) in combination with reduced exposure tacrolimus (rTAC). The relative potency of EVR was assessed in order to generate evidence for concomitant EVR+rTAC exposure in LTx recipients (LTxR). Twelve month data from study H2304 (NCT00622869), a 24-month, randomized, multicenter study in 719 de novo LTxR comparing EVR+rTAC to standard TAC demonstrated superior renal function and comparable efficacy, including fewer and less severe biopsy proven acute rejections with EVR+rTAC.

A Bayesian-frequentist two-stage single-arm phase II clinical trial design.

It is well-known that both frequentist and Bayesian clinical trial designs have their own advantages and disadvantages. To have better properties inherited from these two types of designs, we developed a Bayesian-frequentist two-stage single-arm phase II clinical trial design. This design allows both early acceptance and rejection of the null hypothesis ( H(0) ).

The single dose pharmacokinetic profile of a novel oral human parathyroid hormone formulation in healthy postmenopausal women.

Parathyroid hormone (PTH), currently the only marketed anabolic treatment for osteoporosis, is available as the full-length hormone, human PTH1-84, or as the human PTH1-34 fragment (teriparatide). Both must be administered as a daily subcutaneous (sc) injection. A new oral formulation of human PTH1-34 (PTH134) is being developed as a more convenient option for patients.