Same-day discharge robot-assisted laparoscopic prostatectomy: feasibility, safety and patient experience.

Objectives: To report a single centre's experience of the feasibility, safety and patient acceptability of same-day discharge robot-assisted laparoscopic prostatectomy (RALP).

Subjects/patients And Methods: Between June 2015 and December 2021, a total of 180 pre-selected consecutive patients underwent RALP with the intention to discharge on the same day as surgery. Cases were performed by two surgeons.

Pharmacokinetics and Safety Study of HN0037, a Novel Anti-Human Herpes Simplex Virus Inhibitor, in Healthy Volunteers.

HN0037 is a helicase-primase inhibitor developed to treat herpes simplex virus (HSV) infection. This study evaluated the safety, tolerability, and pharmacokinetics of HN0037, following oral administration in healthy volunteers. This double-blind, placebo-controlled, phase 1 study comprised two parts.

Major Urological Cancer Surgery for Patients is Safe and Surgical Training Should Be Encouraged During the COVID-19 Pandemic: A Multicentre Analysis of 30-day Outcomes.

Unlabelled: COVID-19 has resulted in the deferral of major surgery for genitourinary (GU) cancers with the exception of cancers with a high risk of progression. We report outcomes for major GU cancer operations, namely radical prostatectomy (RP), radical cystectomy (RC), radical nephrectomy (RN), partial nephrectomy (PN), and nephroureterectomy performed at 13 major GU cancer centres across the UK between March 1 and May 5, 2020. A total of 598 such operations were performed.

Three wound-dressing strategies to reduce surgical site infection after abdominal surgery: the Bluebelle feasibility study and pilot RCT.

Background: Surgical site infection (SSI) affects up to 20% of people with a primary closed wound after surgery. Wound dressings may reduce SSI.

Objective: To assess the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of dressing types or no dressing to reduce SSI in primary surgical wounds.

Guidance for elective single-embryo transfer should be applied to frozen embryo transfer cycles.

Purpose: To provide clinicians with data showing the benefits of transferring a single blastocyst in frozen embryo transfer (FET) cycles so that they may counsel their patients accordingly.

Methods: This is a closed cohort study of 678 FET cycles occurring between January 2011 and December 2017 in a private IVF laboratory and associated physicians' practice. Patients included in the analysis were less than 38 years of age at oocyte collection, had at least two vitrified blastocysts, and were undergoing their first autologous FET cycle.

Ritonavir-boosted danoprevir plus peginterferon alfa-2a and ribavirin in Asian chronic hepatitis C patients with or without cirrhosis.

Background And Aim: Chronic hepatitis C is an important public health problem in Asia. We evaluated the safety, efficacy, and pharmacokinetics of fixed-dose ritonavir-boosted danoprevir plus peginterferon alfa-2a/ribavirin in treatment-naive Asian patients with chronic hepatitis C virus (HCV) genotype (G)1 infection.

Methods: Treatment-naive G1 patients in Taiwan, Thailand, and Korea with serum HCV-RNA level ≥ 10  IU/mL received ritonavir-boosted danoprevir 125/100 mg twice daily plus peginterferon alfa-2a/ribavirin for either 12 (noncirrhotic patients: Arm A, n = 34) or 24 weeks (cirrhotic patients: Arm B, n = 27) in this phase II open-label study.

Minority Underrepresentation in Academia: Factors Impacting Careers of Surgery Residents.

Background: Underrepresentation of minorities within academic surgery is an ever present problem with a profound impact on healthcare. The factors influencing surgery residents to pursue an academic career have yet to be formally investigated. We sought to elucidate these factors, with a focus on minority status.

Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor.

Epidermal growth factor receptor (EGFR) inhibitors have been used clinically in the treatment of non-small-cell lung cancer (NSCLC) patients harboring sensitizing (or activating) mutations for a number of years. Despite encouraging clinical efficacy with these agents, in many patients resistance develops leading to disease progression. In most cases, this resistance is in the form of the T790M mutation.

Sphygmomanometer cuffs: a potential source of infection!

We evaluated the potential pathogenic hazard of sphygmomanometer blood pressure cuffs (BPCs) in a hospital setting. Prospectively, the presence of bacterial organisms on 120 BPCs in 14 medical wards and outpatient clinics in a district general hospital in London was assessed. Swabs taken from the inner aspect of the cuffs were cultured using standard microbiological techniques.

Structure- and reactivity-based development of covalent inhibitors of the activating and gatekeeper mutant forms of the epidermal growth factor receptor (EGFR).

A novel series of small-molecule inhibitors has been developed to target the double mutant form of the epidermal growth factor receptor (EGFR) tyrosine kinase, which is resistant to treatment with gefitinib and erlotinib. Our reported compounds also show selectivity over wild-type EGFR. Guided by molecular modeling, this series was evolved to target a cysteine residue in the ATP binding site via covalent bond formation and demonstrates high levels of activity in cellular models of the double mutant form of EGFR.

Sub-Saharan African randomised clinical trials into male circumcision and HIV transmission: methodological, ethical and legal concerns.

In 2007, WHO/UNAIDS recommended male circumcision as an HIV-preventive measure based on three sub-Saharan African randomised clinical trials (RCTs) into female-to-male sexual transmission. A related RCT investigated male-to-female transmission. However, the trials were compromised by inadequate equipoise; selection bias; inadequate blinding; problematic randomisation; trials stopped early with exaggerated treatment effects; and not investigating non-sexual transmission.

Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients.

Introduction: Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin.

Material And Methods: Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa-2a (40KD) 180 or 90 µg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin.

Embryo disposition: choices made by patients and donor oocyte recipients.

Objective: To compare final embryo disposition between patients and donor oocyte recipients.

Design: Retrospective study.

Setting: Private infertility practice.

Physicochemical properties of the nucleoside prodrug R1626 leading to high oral bioavailability.

The nucleoside analog R1479 is a potent and highly selective inhibitor of NS5b-directed hepatitis C virus (HCV) RNA polymerase in vitro. Because of its limited permeability, lipophilic prodrugs of R1479 were screened. Selection of the prodrug involved optimization of solubility, permeability, and stability parameters.

R1626 plus peginterferon Alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin.

Unlabelled: R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time-dependent and dose-dependent reduction of HCV RNA levels in a previous study. The present study evaluated the efficacy and safety of R1626 administered for 4 weeks in combination with peginterferon alfa-2a +/- ribavirin in HCV genotype 1-infected treatment-naive patients. Patients were randomized to: DUAL 1500 (1500 mg R1626 twice daily [bid] + peginterferon alfa-2a; n = 21); DUAL 3000 (3000 mg R1626 bid + peginterferon alfa-2a; n = 32); TRIPLE 1500 (1500 mg R1626 bid + peginterferon alfa-2a + ribavirin; n = 31); or standard of care (SOC) (peginterferon alfa-2a + ribavirin; n = 20).

Robust antiviral activity of R1626, a novel nucleoside analog: a randomized, placebo-controlled study in patients with chronic hepatitis C.

Unlabelled: The nucleoside analog R1479 is a potent and highly selective inhibitor of nonstructural protein 5B-directed hepatitis C virus (HCV) replication in vitro. R1626, a tri-isobutyl ester prodrug of R1479, was developed to increase bioavailability and improve antiviral activity. A multicenter, observer-blinded, randomized, placebo-controlled, multiple ascending dose, phase 1b study was designed to evaluate the safety, pharmacokinetics, and antiviral activity and to potentially identify the maximum tolerated dose of R1626 in patients with chronic hepatitis C.

Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: selective inhibitors of Aurora B kinase with potent anti-tumor activity.

A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume.

Sterol 14alpha-demethylase as a potential target for antitrypanosomal therapy: enzyme inhibition and parasite cell growth.

Sterol 14alpha-demethylases (CYP51) serve as primary targets for antifungal drugs, and specific inhibition of CYP51s in protozoan parasites Trypanosoma brucei (TB) and Trypanosoma cruzi (TC) might provide an effective treatment strategy for human trypanosomiases. Primary inhibitor selection is based initially on the cytochrome P450 spectral response to ligand binding. Ligands that demonstrate strongest binding parameters were examined as inhibitors of reconstituted TB and TC CYP51 activity in vitro.

Description of live poultry markets in the United States and factors associated with repeated presence of H5/H7 low-pathogenicity avian influenza virus.

In 2005 the National Animal Health Monitoring System conducted a survey in 183 live poultry markets throughout the United States. The objectives of this study were to describe characteristics of live poultry markets in the United States and to identify potential risk factors for markets to be repeatedly positive for low-pathogenicity avian influenza virus (LPAIV) H5/H7. A questionnaire was administered to market operators that included questions regarding types of birds and other animals in the market, biosecurity, and cleaning and disinfecting practices.