Semaglutide as a potential treatment for obesity in Smith-Kingsmore syndrome (SKS) patients: A mosaic mutation case report.

We present for the first-time efficacy and tolerability of GLP-1-RA (Semaglutide) in Smith-Kingsmore syndrome (SKS). SKS is a rare genetic disorder characterized by intellectual disability, macrocephaly, seizures and distinctive facial features due to MTOR gene mutation. We present a 22-year-old woman with mosaic SKS and severe obesity (Body Mass Index ≥40 kg/m²), treated with semaglutide. She achieved a 9 kg (7.44%) weight loss over 12 months without adverse effects.This case highlights semaglutide's potential in managing obesity in SKS patients, emphasizing the need for further research in this rare genetic disorder.

Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery.

OBJECTIVE: This retrospective cohort study aimed to assess the effectiveness of semaglutide 2.4 mg in patients with severe obesity (BMI ≥ 40 kg/m2 ) who had previously undergone bariatric surgery (BS) but failed to achieve satisfactory weight loss or experienced weight regain compared with patients without a history of BS with similar BMI. METHODS: The authors analyzed data from 129 patients with a BMI ≥ 40 kg/m2 , including 39 with (BS+) and 90 without (BS-) a history of BS. The patients received semaglutide treatment for 24 weeks starting at 0.25 mg/wk and gradually increasing to reach a final dose of 2.4 mg/wk. The treatment outcomes were assessed based on the percentage of weight loss, changes in BMI, and waist circumference. RESULTS: Semaglutide treatment resulted in significant 9.1% weight loss in the BS+ group, with no significant difference in weight loss between the BS+ and BS- groups. CONCLUSIONS: This study is the first, to the authors' knowledge, to compare the effectiveness of semaglutide treatment in patients with versus those without a history of BS, providing valuable evidence of its efficacy. By focusing on individuals with severe obesity (BMI > 40 kg/m2 and associated comorbidities), it fills a gap in the current literature and highlights the potential of semaglutide 2.4 mg as a treatment option for this specific population.

Factors associated with meropenem pharmacokinetic/pharmacodynamic target attainment in septic critically ill patients treated with extended intermittent infusion or continuous infusion.

OBJECTIVES: The use of extended intermittent infusion (EII) or continuous infusion (CI) of meropenem is recommended in intensive care unit (ICU) patients, but few data comparing these two options are available. This retrospective cohort study was conducted between 1 January 2019 and 31 March 2020 in a teaching hospital ICU. It aimed to determine the meropenem plasma concentrations achieved with CI and EII. METHODS: The study included septic patients treated with meropenem who had one or more meropenem plasma trough (Cmin) or steady-state concentration (Css) measurement(s), as appropriate. It then assessed the factors independently associated with attainment of the target concentration (Cmin or Css ≥ 10 mg/L) and the toxicity threshold (Cmin or Css ≥ 50 mg/L) using logistic regression models. RESULTS: Among the 70 patients analysed, the characteristics of those treated with EII (n = 33) and CI (n = 37) were balanced with the exception of estimates glomerular filtration rate (eGFR): median 30 mL/min/m2 (IQR 30, 84) vs. 79 mL/min/m2 (IQR 30, 124). Of the patients treated with EII, 21 (64%) achieved the target concentration, whereas 31 (97%) of those treated with CI achieved it (P < 0.001). Factors associated with target attainment were: CI (OR 16.28, 95% CI 2.05-407.5), daily dose ≥ 40 mg/kg (OR 12.23, 95% CI 1.76-197.0; P = 0.03) and eGFR (OR 0.98, 95% CI 0.97-0.99; P = 0.02). Attainment of toxicity threshold was associated with daily dose > 70 mg/kg (OR 35.5, 95% CI 5.61-410.3; P < 0.001). CONCLUSION: The results suggest the use of meropenem CI at 40-70 mg/kg/day, particularly in septic ICU patients with normal or augmented renal clearance.