Dual glucagon-like peptide-1 and glucagon receptor agonism reduces energy intake in type 2 diabetes with obesity.

AIMS: To establish which components of energy balance mediate the clinically significant weight loss demonstrated with use of cotadutide, a glucagon-like peptide-1 (GLP-1)/glucagon receptor dual agonist, in early-phase studies. MATERIALS AND METHODS: We conducted a phase 2a, single-centre, randomized, placebo-controlled trial in overweight and obese adults with type 2 diabetes. Following a 16-day single-blind placebo run-in, participants were randomized 2:1 to double-blind 42-day subcutaneous treatment with cotadutide (100-300 µg daily) or placebo. The primary outcome was percentage weight change. Secondary outcomes included change in energy intake (EI) and energy expenditure (EE). RESULTS: A total of 12 participants (63%) in the cotadutide group and seven (78%) in the placebo group completed the study. The mean (90% confidence interval [CI]) weight change was -4.0% (-4.9%, -3.1%) and -1.4% (-2.7%, -0.1%) for the cotadutide and placebo groups, respectively (p = 0.011). EI was lower with cotadutide versus placebo (-41.3% [-66.7, -15.9]; p = 0.011). Difference in EE (per kJ/kg lean body mass) for cotadutide versus placebo was 1.0% (90% CI -8.4, 10.4; p = 0.784), assessed by doubly labelled water, and -6.5% (90% CI -9.3, -3.7; p < 0.001), assessed by indirect calorimetry. CONCLUSION: Weight loss with cotadutide is primarily driven by reduced EI, with relatively small compensatory changes in EE.

Patients Engaged in Losing Weight Preoperatively Experience Improved Outcomes After Hiatal Hernia Repair.

BACKGROUND: Adherence to preoperative weight loss recommendations may serve as a surrogate for the level of engagement in hiatal hernia (HH) patients. This study aims to evaluate the relationship between achieving preoperative weight loss goals and outcomes after HH repair. METHODS: A retrospective review of 235 patients undergoing laparoscopic HH repair at a single institution was performed. Patients were grouped based on the percentage of weight loss goal achieved. Low achievement was defined as the bottom quartile of goal achievement (≤75%); high achievement was defined as the top quartile (≥140%). Baseline characteristics, clinical outcomes, and patient reported outcomes (PROMs) were compared between groups. RESULTS: 131/235 (55.7%) achieved their weight loss goal. No differences in baseline characteristics or clinical outcomes were observed between the low and high achievement groups. While both groups experienced improvements in PROMs postoperatively, patients in the high achievement group demonstrated significantly lower symptom burden at one-month postoperatively. Further, high-achievement patients were more likely to experience complete resolution of common HH symptoms at one-month postoperatively, including no difficulty swallowing food, no breathing difficulties or choking episodes, no choking when eating food, no choking when drinking liquid, and no regurgitation of food or liquid. CONCLUSIONS: In patients undergoing laparoscopic HH repair, patients achieving their preoperative weight loss goals experienced less overall symptom burden and lower prevalence of common symptoms one-month postoperatively than those with low levels of goal achievement. These results demonstrate that patients can take an active role in improving their own surgical outcomes and health status.

Metachronous Gastrointestinal Stromal Tumors of Different Histologies: An Unusual Case.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors accounting for only a small fraction of all primary malignant tumors of the gastrointestinal tract. Histologically, GISTs are classified as epithelioid, spindle type, or mixed. We present a case of a 66-year-old male incidentally noted to have a pedunculated gastric mass along the lesser curvature of the stomach during a laparoscopic Nissen fundoplication and hiatal hernia repair. A wedge resection was performed and the pathology demonstrated a 3.7 cm GIST of epithelioid type. Four years after the initial surgery, a jejunal mass was identified via CT enterography as part of a workup for ongoing iron deficiency anemia. A laparoscopic small bowel resection was performed, and the pathology revealed a new primary 3.2 cm GIST of the spindle cell subtype. Three years after surgery, surveillance imaging is negative for any recurrence. This appears to be the first report of the occurrence of metachronous primary GISTs of different histologic subtypes, separated by location.

Enigmatic fossil plants with three-dimensional, arborescent-growth architecture from the earliest Carboniferous of New Brunswick, Canada.

The evolution of arborescence in Devonian plants, followed by their architectural radiation in the Carboniferous, is a transition fundamental to Earth-system processes and ecological development. However, this evolutionary transition in trees is based on preserved trunks, of which only a few known specimens possess crowns. We describe Mississippian-aged (Tournaisian) trees with a unique three-dimensional crown morphology from New Brunswick, Canada. The trees were preserved by earthquake-induced, catastrophic burial of lake-margin vegetation. The tree architecture consists of an unbranched, 16-cm-diameter trunk with compound leaves arranged in spirals of ∼13 and compressed into ∼14 cm of vertical trunk length. Compound leaves in the upper ∼0.75 m of the trunk measure >1.75 m in length and preserve alternately arranged secondary laterals beginning at 0.5 m from the trunk; the area below the trunk bears only persistent leaf bases. The principal specimen lacks either apical or basal sections, although an apex is preserved in another. Apically, the leaves become less relaxed toward horizontal and are borne straight at an acute angle at the crown. The compact leaf organization and leaf length created a crown volume of >20-30 m3. This growth strategy likely maximized light interception and reduced resource competition from groundcover. From their growth morphology, canopy size, and volume, we propose that these fossils represent the earliest evidence of arborescent subcanopy-tiering. Moreover, although systematically unresolved, this specimen shows that Early Carboniferous vegetation was more complex than realized, signaling that it was a time of experimental, possibly transitional and varied, growth architectures.