Adaptive infusion of a glucagon-like peptide-1/glucagon receptor co-agonist G3215, in adults with overweight or obesity: Results from a phase 1 randomized clinical trial.

AIMS: To determine whether a continuous infusion of a glucagon-like peptide receptor (GLP-1R)/glucagon receptor (GCGR) co-agonist, G3215 is safe and well tolerated in adults with overweight or obesity. METHODS: A phase 1 randomized, double blind, placebo-controlled trial of G3215 in overweight or obese participants, with or without type 2 diabetes. RESULTS: Twenty-six participants were recruited and randomized with 23 completing a 14-day subcutaneous infusion of G3215 or placebo. The most common adverse events were nausea or vomiting, which were mild in most cases and mitigated by real-time adjustment of drug infusion. There were no cardiovascular concerns with G3215 infusion. The pharmacokinetic characteristics were in keeping with a continuous infusion over 14 days. A least-squares mean body weight loss of 2.39 kg was achieved with a 14-day infusion of G3215, compared with 0.84 kg with placebo infusion (p < .05). A reduction in food consumption was also observed in participants receiving G3215 and there was no deterioration in glycaemia. An improved lipid profile was seen in G3215-treated participants and consistent with GCGR activation, a broad reduction in circulating amino acids was seen during the infusion period. CONCLUSION: An adaptive continuous infusion of the GLP-1/GCGR co-agonist, G3215, is safe and well tolerated offering a unique strategy to control drug exposure. By allowing rapid, response-directed titration, this strategy may allow for mitigation of adverse effects and afford significant weight loss within shorter time horizons than is presently possible with weekly GLP-1R and multi-agonists. These results support ongoing development of G3215 for the treatment of obesity and metabolic disease.

Dual-modality emergency management of a rare cause of an aorto-oesophageal fistula: a case report.

Aorto-oesophageal fistula (AOF) is a life-threatening condition that usually presents with upper gastro-intestinal haemorrhage. This case report details the emergency presentation and management of a 51-year-old male who presented with hematemesis secondary to an impacted denture (ingested two years previously) in the oesophagus that had led to an AOF. This necessitated urgent thoracic endovascular aortic repair followed by thoracotomy, oesophagotomy, T-tube insertion and oesophagostomy. This is the first documentation in the literature of the dual-modality management for this rare cause of AOF and demonstrates the multidisciplinary approach to successful management of this complex yet rare presentation.

The role of colonoscopy and CT colonography in patients presenting with symptoms of constipation.

OBJECTIVE: There is controversy whether constipation as a primary presenting complaint is an indication for diagnostic colonoscopy. CT colonography (CTC) is a less invasive and more acceptable alternative. We compared the completion and sensitivity of colonoscopy with CTC in patients who presented with the primary symptom of constipation. METHODS: A retrospective study was conducted which examined the first 100 colonoscopies and 100 CTCs carried out for the primary symptom of constipation from June 2012 to December 2013. The primary outcome measure was failure rate of the investigations. Secondary outcomes included reasons for failure and comparison of cost effectiveness between the two modalities. RESULTS: A total of 200 patients were included in this study. Of these, the first consecutive 100 colonoscopies and 100 CTCs were included. One colonic cancer was detected in each of the CTC and the colonoscopy arm, respectively. 37 (37%) attempted colonoscopies were incomplete examinations. The most common reasons were discomfort (51.4%) and poor bowel preparation (27%). There was no failure of CTC. For 100 patients, CTC as a primary investigation was a more cost-effective investigation (p ≤ 0.01) costing £55,016 as compared with colonoscopy costing £73,666. CONCLUSION: There is an unacceptably high failure rate of colonoscopy in patients who presented with the primary symptom of constipation. Hence, we propose that CTC may be an acceptable first-line investigation with a further colonoscopy/flexible sigmoidoscopy if lesions are detected. Advances in knowledge: First study to examine the use of CTC in patients with constipation.

A rare case of a chest wall abscess caused by a migrating oesophageal stent. An iatrogenic gastrocutaneous fistula.

We report the case of a 65-year-old male, who presented with septicaemia and a chest wall mass on a background of oesophageal carcinoma. This chest wall mass measured 10 cm by 10 cm, was fluctuant, and was situated on the anterior chest wall. Owing to local erythema and surgical emphysema, necrotising fasciitis was suspected and thus intravenous antibiotic and fluid therapy were instituted. Following a chest radiograph, which confirmed the presence of subcutaneous gas, the patient underwent thoraco-abdomino-pelvic CT, which demonstrated oesophageal stent migration through the gastric fundus to the chest wall, between the 10th and 11th left ribs. Through this migration tract, the chest wall was contaminated with gastric contents, accounting for the mass and sepsis. The patient underwent endoscopic stent removal, and incision and drainage to create a gastrocutaneous fistula. Additionally, a nasojejunal tube and intravenous line were sited for jejunal and total parenteral nutrition, respectively, in order to promote healing of the fistula.

Systemic heparinisation in laparoscopic live donor nephrectomy.

Introduction. Systemic heparinisation is advocated during laparoscopic live donor nephrectomy (LDN) as a preventative measure against renal vascular thrombosis during the warm ischaemic interval. This study compares the outcome with and without the administration of systemic heparinisation. Methods. A retrospective analysis was performed on 186 consecutive LDN patients between April 2008 and November 2012. Systemic heparin (2000-3000 IU) was administered intravenously to donors (hep n = 109). From January 2010, heparin was not used systemically in this group of LDN (no hep n = 77). Outcome measures included donor and recipient complications, initial graft function, and 12 month graft survival. Results. The demographics of both heparinised and non-heparinised donors were similar. The warm ischaemic time (WIT) was comparable in both groups (WIT; hep 5 ± 3 versus no hep 5 ± 3 minutes; P = 1.000). There was no difference in complication rates, no episodes of graft thrombosis, and no incidences of primary nonfunction in either group. Delayed graft function occurred in 4/109 and 1/77 (3.6% versus 1.2%; P = 0.405) and there was no significant difference in graft survival (P = 0.650). Conclusion. Omitting systemic heparinisation during laparoscopic donor nephrectomy is a feasible and safe approach that does not compromise donor or recipient outcome.