A tutorial for model-based evaluation and translation of cardiovascular safety in preclinical trials.

Assessment of drug-induced effects on the cardiovascular (CV) system remains a critical component of the drug discovery process enabling refinement of the therapeutic index. Predicting potential drug-related unintended CV effects in the preclinical stage is necessary for first-in-human dose selection and preclusion of adverse CV effects in the clinical stage. According to the current guidelines for small molecules, nonclinical CV safety assessment conducted via telemetry analyses should be included in the safety pharmacology core battery studies.

Long-term safety and efficacy of olokizumab in patients with rheumatoid arthritis and inadequate response to tumor necrosis factor inhibitor therapy in phase II studies.

Objective: This study aimed to evaluate the long-term safety and efficacy of olokizumab (OKZ), an anti-interleukin (IL)-6 monoclonal antibody, in patients with rheumatoid arthritis (RA) and inadequate response to tumor necrosis factor-alpha inhibitors.

Methods: Eligible patients completed study RA0056, which tested several doses of OKZ, placebo (PBO), and tocilizumab (TCZ) plus methotrexate (MTX) in Western countries, and RA0083 included several doses of OKZ and PBO plus MTX in Asian countries. Both studies were followed by open-label extension (OLE) studies with OKZ 120 mg every 2 weeks, RA0057 and RA0089, respectively.

Frontiers in urethra regeneration: current state and future perspective.

Despite the positive achievements attained, the treatment of male urethral strictures and hypospadiases still remains a challenge, particularly in cases of severe urethral defects. Complications and the need for additional interventions in such cases are common. Also, shortage of autologous tissue for graft harvesting and significant morbidity in the location of harvesting present problems and often lead to staged treatment.

Bladder Organoids and Spheroids: Potential Tools for Normal and Diseased Tissue Modelling.

Bladder-related diseases are among the most common and costly to the healthcare system, and therefore require new approaches to treatment. Organoids and spheroids are 3D cultures that mimic organ features ex vivo and offer novel approaches for diagnostic and therapeutic assessment. The aim of this article was to provide a systematic review of the literature related to bladder organoids and spheroids, applied to disease diagnosis, characterization, and treatment.

Risk factors for urethral stricture and/or bladder neck contracture after monopolar transurethral resection of the prostate for benign prostatic hyperplasia.

Objective:: To identify risk factors for urethral stricture and/or bladder neck contracture after transurethral resection of benign prostatic hyperplasia.

Materials And Methods:: We performed a retrospective analysis of 402 patients, which underwent a monopolar transurethral resection of the prostate in the urology clinic of Sechenov First Moscow State Medical University for prostatic hyperplasia during the period 2011-2014. Urethral stricture and (or) bladder neck contracture in the postoperative period were diagnosed in 61 (15.

Efficacy and Safety of Ixabepilone and Capecitabine in Patients With Advanced Triple-negative Breast Cancer: a Pooled Analysis From Two Large Phase III, Randomized Clinical Trials.

Introduction: The purpose of this study was to evaluate the safety and efficacy of ixabepilone plus capecitabine in patients with metastatic or locally advanced triple-negative breast cancer (TNBC).

Patients And Methods: We conducted a pooled analysis of patients with TNBC enrolled in 2 phase III trials (NCT00080301 and NCT00082433), pretreated or resistant to an anthracycline and a taxane. In each study, patients were randomized to receive ixabepilone 40 mg/m (3-hour intravenous infusion, day 1), plus oral capecitabine 1000 mg/m twice daily (days 1-14), or capecitabine alone 1250 mg/m twice daily (days 1-14), every 3 weeks.