Aruchuna Ruban

Context: The liver/foregut satiety hormone liver-expressed antimicrobial peptide 2 (LEAP2) is an inverse agonist at the acyl ghrelin receptor (GHSR), increasing after food intake and decreasing after bariatric surgery and short-term nonsurgical weight loss, but effects of long-term dietary weight loss are unknown. Objective: The objective of this study was to examine and compare the effects of these interventions on fasting and postprandial plasma LEAP2 and investigate potential metabolic mediators of changes in plasma LEAP2. Methods: Plasma LEAP2 was measured in a previously published 2-year trial comparing standard medical management (SMM) (including 600-kcal/day deficit) with duodenal-jejunal bypass liner (DJBL, Endobarrier) insertion (explanted after 1 year) in adults with obesity and inadequately controlled type 2 diabetes mellitus. Results: In the SMM group (n = 25-37), weight decreased by 4.3%, 8.1%, 7.8%, and 6.4% at 2, 26, 50, and 104 weeks and fasting plasma LEAP2 decreased from baseline mean ± SD 15.3 ± 0.9 ng/mL by 1.7, 3.8, 2.1, and 2.0 ng/mL, respectively. Absolute/decreases in fasting plasma LEAP2 positively correlated with absolute/decreases in body mass index, glycated hemoglobin A1c, fasting plasma glucose, serum insulin, homeostatic model assessment for insulin resistance, and serum triglycerides. Despite greater weight loss in the DJBL group (n = 23-30) at 26 to 50 weeks (10.4%-11.4%), the decrease in fasting plasma LEAP2 was delayed and attenuated (vs SMM), which may contribute to greater weight loss by attenuating GHSR signaling. Plasma LEAP2 did not increase with weight regain from 50 to 104 weeks after DJBL explant, suggesting a new set point with weight loss maintenance. Increases in plasma LEAP2 after a 600-kcal meal (10.8%-16.1% at 1-2 hours) were unaffected by weight loss, improved glucose metabolism, or DJBL insertion (n = 9-25), suggesting liver rather than duodenum/jejunum may be the primary source of postprandial LEAP2 secretion. Conclusion: These findings add to our understanding of the regulation and potential physiological role of plasma LEAP2.

Small intestinal bacterial overgrowth is a small bowel disorder characterised by excessive amounts of bacteria populating the small intestine leading to symptoms of abdominal pain, bloating and change in bowel habit. This creates some degree of diagnostic uncertainty due to the overlap of these symptoms with numerous other gastrointestinal conditions. Quantitative culture of jejunal aspirates is the gold standard diagnostic test but has largely been replaced by glucose and lactulose breath tests due to their relative ease and accessibility. The approach to treatment centres around reducing bacterial numbers through antibiotic therapy and managing any predisposing factors. Further research is required in order to define the optimum antibiotic choice and duration of therapy as well as the potential diagnostic utility of home breath testing and capsule-based technology.

Bariatric surgery is an effective treatment for obesity and its metabolic related disorders. With the numbers of bariatric procedures being performed rising annually endoscopists are now more likely than ever to encounter this patient cohort on routine diagnostic lists. Endoscopy plays a vital role in both the pre and postoperative periods to diagnose and treat certain complications associated with bariatric surgery. Preoperative endoscopy may be useful in identifying pathologies that then influence the type of bariatric surgery being proposed. Postoperative endoscopy has an established role in identifying and managing complications such as anastomotic leaks and gastrointestinal bleeding. As endoscopic techniques develop, these complications may be managed without the need for surgical intervention or revision. Increased knowledge and awareness of the indications for endoscopy, together with the altered anatomy and common complications of bariatric surgery, is paramount in managing these patients effectively.

Efficacy and Mechanism Evaluation Volume: 7, Issue: 6, Published in November 2020

Gastroparesis is characterized by delayed gastric emptying, with symptoms such as nausea, vomiting and abdominal pain, in the absence of mechanical obstruction. In most cases, it is idiopathic although diabetes mellitus is another leading cause. The physiology of gastric emptying is a complex process which is influenced by various inputs including the central nervous system, enteric nervous system and gut hormones. Developments in our understanding of gastroparesis have now demonstrated dysfunction in these systems, thus disrupting normal gastric emptying. Once mechanical obstruction is excluded, gastric scintigraphy remains the gold standard for diagnosis although wireless motility capsule and breath testing are alternative methods for diagnosis. Treatment for gastroparesis is challenging, and widely available therapies are often limited either by their poor evidence for efficacy or concerns over their long-term safety profile. Novel prokinetic agents have shown initial promise in clinical trials, and new endoscopic techniques such as gastric per-oral endoscopic myotomy are emerging. These new treatment modalities may provide an option in refractory gastroparesis with the adage of reduced morbidity compared to surgical treatments.

Recruiting participants into clinical trials is notoriously difficult and poses the greatest challenge when planning any investigative study. Poor recruitment may not only have financial ramifications owing to increased time and resources being spent but could adversely influence the clinical impact of a study if it becomes underpowered. Herein, we present our own experience of recruiting into a nationally funded, multicentre, randomised controlled trial (RCT) of the Endobarrier versus standard medical therapy in obese patients with type 2diabetes. Despite these both being highly prevalent conditions, there were considerable barriers to the effectiveness of different recruitment strategies across each study site. Although recruitment from primary care proved extremely successful at one study site, this largely failed at another site prompting the implementation of multimodal recruitment strategies including a successful media campaign to ensure sufficient participants were enrolled and the study was adequately powered. From this experience, we propose where appropriate the early engagement and investment in media campaigns to enhance recruitment into clinical trials. Trial Registration: ISRCTN30845205 .

Purpose of Review Obesity is increasing at an alarming rate and now poses a global threat to humankind. In recent years, we have seen the emergence of medical devices to combat the obesity epidemic. These therapeutic strategies are discussed in this review dividing them into gastric and duodenal therapies. Recent Findings Traditionally, medical devices for obesity such as the intragastric balloon have focused on reducing gastric size, but more recently there has been a shift towards developing devices that modulate neural and hormonal responses to induce early satiety thus reducing oral intake. Summary Medical devices for obesity treatment may have a role in those patients who are struggling to control their weight despite significant lifestyle modifications such as diet and exercise and who decline or are unfit for bariatric surgery. For the wider adoption and integration of these devices in the obesity treatment paradigm, more long-term efficacy and safety data from randomised controlled trials are required.

Haemolytic uraemic syndrome is a rarely seen in adults often leading to critical illness. This case highlights how difficult it can be to establish a diagnosis and treat when a patient presents with bloody diarrhoea. A 17-year-old Iraqi man presented to the emergency department with abdominal pain and bloody diarrhoea. He was initially treated as acute appendicitis, undergoing an appendectomy but following a recurrence in his symptoms a colonoscopy was performed. A diagnosis of shiga toxin-producing Escherichia coli leading to HUS was suspected following histology obtained at colonoscopy and this was confirmed on antibody testing. Despite intravenous fluids and supportive therapy the patient’s symptoms and condition deteriorated. He developed seizures and acute renal failure requiring intubation and plasma exchange in the intensive care setting. He eventually required treatment with ecluzimab therapy; a monoclonal antibody and subsequently made a full recovery. Haemolytic uraemic syndrome is a triad of progressive renal failure, thrombocytopenia and haemolytic anaemia which is a condition rarely seen in adults. It is usually associated with an E. coli infection and supportive therapy remains the mainstay of treatment.

Obesity is a major health and economic crisis facing the modern world. It is associated with excess mortality and morbidity and is directly linked to common conditions such as type 2 diabetes mellitus, coronary heart disease and sleep apnoea. The management of obesity and its associated complications has evolved in recent years, with a shift towards more definitive strategies such as bariatric surgery. This review encompasses the dietary, pharmacological and surgical strategies currently available for the management of obesity.