Relationship between Volitional and Non-Volitional Quadriceps Muscle Endurance in Patients with Chronic Obstructive Pulmonary Disease.

Volitional assessment of quadriceps muscle endurance is clinically relevant in patients with chronic obstructive pulmonary disease (COPD). However, studies that determine the construct validity of volitional tests by comparing them to non-volitional measures are lacking. Therefore, the aim of the current study is to evaluate the correlation between volitional and non-volitional quadriceps muscle endurance in patients with COPD.

High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

Background: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations.

Methods: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery.

Pharmacokinetics and Macrophage Inhibitory Cytokine-1 Pharmacodynamics of the Murine Double Minute 2 Inhibitor, Navtemadlin (KRT-232) in Fed and Fasted Healthy Subjects.

This single 60-mg dose, 4-period crossover study assessed the effect of food and formulation change on navtemadlin (KRT-232) pharmacokinetics (PK) and macrophage inhibitory cytokine-1 (MIC-1) pharmacodynamics. Healthy subjects (N = 30) were randomized to 3 treatment sequences, A: new tablet, fasted (reference, dosed twice); B: new tablet, 30 minutes after a high-fat meal (test 1); C: old tablet, fasted (test 2). PK/pharmacodynamic parameters were measured over 0 to 96 hours.

Relationship Between Hepatic Gene Expression, Intestinal Microbiota, and Inferred Functional Metagenomic Analysis in NAFLD.

Introduction: We previously reported a lower fecal abundance of Ruminococcus spp., Faecalibacterium prausnitzii , and Coprococcus spp. in nonalcoholic fatty liver disease (NAFLD).

Optimal patient selection for successful two-stage hepatectomy of bilateral colorectal liver metastases.

Two-stage hepatectomy (TSH) is one of the specific surgical techniques that can expand the pool of resectable patients with initially unresectable colorectal liver metastases (CRLM). The indication of TSH for CRLM is only bilateral, multinodular disease, which cannot be resected by a single hepatectomy. TSH is nowadays considered an effective treatment for selected patients, with acceptable morbidity/mortality rates and promising long-term outcomes.

Donor HLA Class 1 Evolutionary Divergence Is a Major Predictor of Liver Allograft Rejection : A Retrospective Cohort Study.

Background: The HLA evolutionary divergence (HED), a continuous metric quantifying the peptidic differences between 2 homologous HLA alleles, reflects the breadth of the immunopeptidome presented to T lymphocytes.

Objective: To assess the potential effect of donor or recipient HED on liver transplant rejection.

Design: Retrospective cohort study.

Phase 1 Concentration-QTc and Cardiac Safety Analysis of the MDM2 Antagonist KRT-232 in Patients With Advanced Solid Tumors, Multiple Myeloma, or Acute Myeloid Leukemia.

Cardiac safety and plasma concentration-QTc interval analyses were completed using data from 2 phase 1 studies of the selective mouse double minute chromosome 2 antagonist, KRT-232, in patients with solid tumors or multiple myeloma and acute myeloid leukemia (AML) who received KRT-232 doses of 15 to 480 mg once daily (QD; N = 130). A linear mixed-effects model related change from baseline Fridericia-corrected QT interval (ΔQTcF) to KRT-232 plasma concentrations. The final model included parameters for the intercept (with between-subject variability), KRT-232 concentration-ΔQTcF slope, and baseline QTcF effect on the intercept.

Is there an Exposure-Response Relationship for Nivolumab in Real-World NSCLC Patients?

Pharmacokinetic/pharmacodynamic data from real-world cohort are sparse in non small-cell lung cancer (NSCLC) patients treated with nivolumab. The aim of this prospective observational study was to explore the exposure-response relationship for effectiveness and toxicity of nivolumab in 81 outpatients with metastatic lung cancer. Nivolumab plasma trough concentrations (Cmin) were assayed at days 14, 28, and 42.