Enantioselective Phase-Transfer-Catalyzed Synthesis of Spirocyclic Azetidine Oxindoles.

Spiro-3,2'-azetidine oxindoles combine two independently important pharmacophores in an understudied spirocyclic motif that is attractive for medicinal chemistry. Here, the enantioselective synthesis of these structures is achieved in up to 2:98 er through intramolecular C-C bond formation, involving activation of the substrate with a novel SF-containing chiral cation phase-transfer (PT) catalyst. The products are readily elaborated/deprotected to afford medicinally relevant enantioenriched compounds.

Acid-Mediated Ring Expansion of 2,2-Disubstituted Azetidine Carbamates to 6,6-Disubstituted 1,3-Oxazinan-2-ones.

The ring expansion of 2-ester-2-arylazetidine carbamates can be achieved using Brønsted acids to form 6,6-disubstituted 1,3-oxazinan-2-ones. The reaction is rapid at room temperature with Boc or Cbz derivatives and proceeds with excellent yield (up to 96%) and broad substrate scope. Derivatives of drug compounds and natural products are incorporated.

Rapid Assembly of Saturated Nitrogen Heterocycles in One-Pot: Diazo-Heterocycle "Stitching" by N-H Insertion and Cyclization.

Methods that provide rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. Here, a strategy is described for the preparation of 2,2-disubstituted azetidines, pyrrolidines, piperidines, and azepanes bearing ester and diverse aryl substituents. A one-pot rhodium catalyzed N-H insertion and cyclization sequence uses diazo compounds to stitch together linear 1,m-haloamines (m=2-5) to rapidly assemble 4 -, 5 -, 6 -, and 7 -membered saturated nitrogen heterocycles in excellent yields.

Development and Validation of a Disease-Specific Instrument to Measure Diet-Targeted Quality of Life for Postoperative Patients with Esophagogastric Cancer.

Background: Patients who have undergone esophagectomy or gastrectomy have certain dietary limitations because of changes to the alimentary tract. This study attempted to develop a psychometric scale, named "Esophago-Gastric surgery and Quality of Dietary life (EGQ-D)," for assessment of impact of upper gastrointestinal surgery on diet-targeted quality of life.

Methods: Using qualitative methods, the study team interviewed both patients and surgeons involved in esophagogastric cancer surgery, and we prepared an item pool and a draft scale.

A placebo-controlled, double-blind, randomized, multicenter study to assess the effects of dronedarone 400 mg twice daily for 12 weeks on atrial fibrillation burden in subjects with permanent pacemakers.

Purpose: Dronedarone is a benzofuran derivative with a pharmacological profile similar to amiodarone but has a more rapid onset of action and a much shorter half-life (13-19 h). Our goal was to evaluate the efficacy of dronedarone in atrial fibrillation (AF) patients using dual-chamber pacemakers capable of quantifying atrial fibrillation burden.

Methods: Pacemakers were adjusted to optimize AF detection.

Development and validation of a symptom scale to evaluate postoperative patients with esophagogastric cancer.

Background: Postgastrectomy or esophagectomy symptoms can be a significant burden for patients. However, no standard scale for evaluating these symptoms has been established. We recently developed a postoperative symptom-specific scale.

A comparative study of survival after minimally invasive and open oesophagectomy.

Background: Oesophageal cancer is increasing in incidence worldwide. Minimally invasive techniques have been used to perform oesophagectomy, but concerns regarding these techniques remain. Since its description by Cuschieri in 1992, the use of minimally invasive oesophagectomy (MIO) has increased, but still only used in a minority of resections in the UK in 2009.

The effect of centralisation on the outcomes of oesophagogastric surgery--a fifteen year audit.

Introduction: Centralisation of oesophagogastric (OG) resectional services has been proposed to improve patient outcomes in terms of perioperative mortality and long-term survival. Centralisation of services occurred in Gloucester 5 years ago. The aim of this paper is to assess if local patient outcomes have benefited from centralisation.

The effect of intraperitoneal local anesthesia in laparoscopic cholecystectomy: a systematic review and meta-analysis.

Intraperitoneal administration of local anesthesia is often used to improve pain relief after laparoscopic cholecystectomy. We have conducted a meta-analysis to establish the efficacy of this technique in reducing early postoperative abdominal pain. A systematic literature search revealed 24 randomized, controlled trials assessing intraperitoneal local anesthetic use in laparoscopic cholecystectomy that met inclusion criteria.

Leukocyte count as an independent predictor of recurrent ischemic events.

Background And Purpose: Inflammatory markers predict first-time ischemic events. We investigated whether leukocyte and differential counts predict recurrent events and ischemic events in high-risk populations, and whether such events are preceded by acutely exacerbated inflammation.

Methods: We studied 18 558 patients with ischemic stroke, myocardial infarction, or peripheral arterial disease who participated in the trial of Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE), a study that compared the occurrence of ischemic stroke, myocardial infarction, or vascular death under randomized treatment with aspirin or clopidogrel.