Activin Type II Receptor Blockade for Treatment of Muscle Depletion in Chronic Obstructive Pulmonary Disease. A Randomized Trial.

Rationale: Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators.

Objectives: To assess the effects of bimagrumab on skeletal muscle mass and function in patients with chronic obstructive pulmonary disease (COPD) and reduced skeletal muscle mass.

Methods: Sixty-seven patients with COPD (mean FEV, 1.

Goal-directed perfusion to reduce acute kidney injury: A randomized trial.

Objective: To determine whether a goal-directed perfusion (GDP) strategy aimed at maintaining oxygen delivery (DO) at ≥280 mL·min·m reduces the incidence of acute kidney injury (AKI).

Methods: This multicenter randomized trial enrolled a total of 350 patients undergoing cardiac surgery in 9 institutions. Patients were randomized to receive either GDP or conventional perfusion.

Adequacy of Intraoperative Nodal Staging during Surgical Resection of NSCLC: Influencing Factors and Its Relationship to Survival.

Introduction: Adequate intraoperative lymph node sampling is a fundamental part of lung cancer surgery, but adherence to standards is not well known. This study sought to measure the adequacy of intraoperative lymph node sampling at a regional Thoracic Surgery Centre and a tertiary lung cancer center in the United Kingdom.

Methods: This retrospective study analyzed the pathological reports from NSCLC resections over the 4-year period 2011-2014.

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci).

Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer.

Purpose: The monocarboxylate transporter 1 (MCT1) inhibitor, AZD3965, is undergoing phase I evaluation in the United Kingdom. AZD3965 is proposed, via lactate transport modulation, to kill tumor cells reliant on glycolysis. We investigated the therapeutic potential of AZD3965 in small cell lung cancer (SCLC) seeking rationale for clinical testing in this disease and putative predictive biomarkers for trial use.

Pharmacodynamics of liposomal amphotericin B and flucytosine for cryptococcal meningoencephalitis: safe and effective regimens for immunocompromised patients.

Background: Cryptococcal meningoencephalitis is a lethal infection with relatively few therapeutic options. The optimal dosage of liposomal amphotericin B (LAmB) alone or in combination with flucytosine is not known.

Methods: A murine model of cryptococcal meningoencephalitis was used.

Software for dosage individualization of voriconazole for immunocompromised patients.

The efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated.

Population pharmacokinetics of conventional and intermittent dosing of liposomal amphotericin B in adults: a first critical step for rational design of innovative regimens.

There is increased interest in intermittent regimen of liposomal amphotericin B, which may facilitate use in ambulatory settings. Little is known, however, about the most appropriate dosage and schedule of administration. Plasma pharmacokinetic data were acquired from 30 patients receiving liposomal amphotericin B for empirical treatment of suspected invasive fungal infection.

Combination of voriconazole and anidulafungin for treatment of triazole-resistant aspergillus fumigatus in an in vitro model of invasive pulmonary aspergillosis.

Voriconazole is a first-line agent for the treatment of invasive pulmonary aspergillosis. Isolates with elevated voriconazole MICs are increasingly being seen, and the optimal treatment regimen is not defined. We investigated whether the combination of voriconazole with anidulafungin may be beneficial for the treatment of A.

Pharmacodynamics of voriconazole in a dynamic in vitro model of invasive pulmonary aspergillosis: implications for in vitro susceptibility breakpoints.

Background: Voriconazole is a first-line agent for the treatment of invasive pulmonary aspergillosis (IPA). There are increasing reports of Aspergillus fumigatus isolates with reduced susceptibility to voriconazole.

Methods: An in vitro dynamic model of IPA was developed that enabled simulation of human-like voriconazole pharmacokinetics.

Pharmacodynamics of itraconazole against Aspergillus fumigatus in an in vitro model of the human alveolus: perspectives on the treatment of triazole-resistant infection and utility of airway administration.

Itraconazole is used for the prevention and treatment of infections caused by Aspergillus fumigatus. An understanding of the pharmacodynamics of itraconazole against wild-type and triazole-resistant strains provides a basis for innovative therapeutic strategies for treatment of infections. An in vitro model of the human alveolus was used to define the pharmacodynamics of itraconazole.

Pharmacokinetics and pharmacodynamics of posaconazole for invasive pulmonary aspergillosis: clinical implications for antifungal therapy.

Background: Posaconazole is a triazole with anti-Aspergillus activity. However, little is known about the utility of posaconazole as primary therapy for invasive pulmonary aspergillosis.

Methods: An in vitro model of the human alveolus was used to study the impact of minimum inhibitory concentrations (MIC) on exposure-response relationships.

Effect of addition of salmeterol versus doubling the dose of fluticasone propionate on specific airway resistance in children with asthma.

Based primarily on extrapolation from adult studies, current pediatric asthma guidelines advise the addition of long-acting beta₂-agonists for children symptomatic on low/moderate-dose inhaled corticosteroids before increasing the corticosteroid dose. This study was designed to compare the effect of combination salmeterol/fluticasone propionate (SFC) with doubling the dose of fluticasone propionate (FP) on specific airway resistance (sR(aw)) in moderate/severe persistent asthmatic children. A double-blind, randomized, controlled study was performed; children with asthma (4-11 years old; sR(aw) > 1.

Prevention of allergic sensitization by environmental control.

For about 20 years, investigators have been attempting to design studies to reduce exposure to allergens in order to prevent the development of allergic sensitization and thus prevent the onset of allergic disease, particularly asthma. Seven such studies-environmental control studies-have attempted to accomplish this by changing the domestic environment into which a high-risk child is born. Some of these studies also included a dietary intervention aimed at reducing the risk of development of sensitization to food allergens.