Could Glucagon-Like Peptide-1 (GLP-1) receptor antagonists be used to treat obstructive sleep apnoea in children and adolescents with obesity?

Although semaglutide 2.4 mg has demonstrated significant weight loss efficacy in clinical trials, real-world data, particularly with regard to clinically complex and underrepresented populations, remain limited. The study aims to assess the real-world effectiveness and patient-reported outcomes associated with the use of semaglutide 2.4 mg in individuals with severe and complex obesity. The study also intends to characterize weight loss response in pre-defined subgroups of patients and to identify predictors of weight loss using machine learning. SEMASEARCH is a retrospective multicentric observational cohort embedded within the French early-access program for semaglutide 2.4 mg. A total of 1100 patients with severe obesity (BMI ≥ 40 kg/m2 with at least one treated obesity-related complication) were retrospectively included from 11 expert obesity centers, based on prospectively collected data at baseline, 6 months, and 12 months. Subgroups include patients with a history of bariatric surgery, binge eating disorder, hypothalamic obesity, age ≥ 60 years or altered body composition, BMI ≥ 60 kg/m2, and those receiving psychotropic medications. Assessments include clinical, biological, and body composition data, as well as standardized questionnaires evaluating eating behaviour, physical activity, sleep, quality of life, digestive symptoms, and mental health. Body weight change since treatment initiation, with assessment at 6 and 12 months. Clinically meaningful weight loss (≥ 10%) at 12 months, metabolic improvements, patient-reported outcomes, body composition changes, and tolerance. SEMASEARCH will provide real-world evidence on Semaglutide 2.4 mg use in patients living with severe and complex obesity. It will also address major knowledge gaps in specific populations underrepresented in clinical trials and generate predictive models of weight loss response.

The Growing Impact of Severe Obesity on 90-Day Outcomes After Elective Primary Total Hip Arthroplasty: A National Propensity-Matched Study.

Severe obesity and in-hospital outcomes in acute myocardial infarction: Insights into the role of systemic inflammation.

Severe obesity is associated with impaired respiratory and lung mechanics, including increased airway resistance. This study aimed to evaluate changes in respiratory system impedance and airway mechanics after bariatric surgery in adults with severe obesity. Adults with severe obesity (n = 12) were evaluated before and after bariatric surgery using impulse oscillometry. Anthropometric measures and respiratory system impedance parameters, including airway resistance (R5 and R20), reactance (X5), and resonant frequency (Fres), were assessed and compared between time points. Weight loss after bariatric surgery was associated with significant reductions in airway resistance (R5 and R20) and Fres, indicating improvements in respiratory system mechanics. Bariatric surgery improved respiratory system impedance and airway mechanics in adults with severe obesity. Impulse oscillometry detected respiratory mechanical improvements after weight loss and may represent a sensitive tool for evaluating changes in lung mechanics in this population.

Left ventricular hypertrophy (LVH) is prevalent in obesity. Cardiotrophin-1 (CT-1), an interleukin-6 family cytokine implicated in myocardial remodeling, has an unclear role in obesity-associated LVH. This study examined whether CT-1 mediates the association between systolic blood pressure (BP) and left ventricular (LV) mass index in obesity. Seventy-three adults with body mass index (BMI) ≥35 kg/m 2 underwent clinical evaluation, echocardiography, and serum CT-1 measurement. Mediation analysis was performed using SPSS PROCESS macro (Model 4), with systolic BP as the independent variable, CT-1 as the mediator, and LV mass index as the dependent variable, adjusting for age, sex, and BMI. Mean BMI, systolic BP, LV mass index, and CT-1 level were 42.4 ± 5.7 kg/m 2 , 146 ± 15 mmHg, 50.7 ± 11.8 g/m 2.7 , and 283.07 ± 632.94 pg/ml, respectively. LV mass index correlated with BMI ( r = 0.533, P < 0.001) and systolic BP ( r = 0.267, P = 0.022). CT-1 correlated with systolic BP ( r = 0.300, P = 0.010) and LV mass index ( r = 0.325, P = 0.005), but not BMI. Mediation analysis showed CT-1 fully mediated the systolic BP-LV mass index association, with a significant indirect effect ( B = 0.070, 95% CI [0.007, 0.168]) and a non-significant direct effect ( B = -0.042, P = 0.600, 95% CI [-0.201, 0.117]). CT-1 mediates the effect of BP on LV mass in severe obesity, suggesting that CT-1 may be a biomarker or therapeutic target in obesity-associated LVH.

How to build an adolescent bariatric surgery program.

Fibronectin type III domain-containing 4 (FNDC4) protein regulates hepatocyte insulin sensitivity, mitochondrial homeostasis, and inflammation. We investigated in vitro and ex vivo whether hepatocyte-derived FNDC4 limits transforming growth factor-β1 (TGF-β1)-driven hepatic stellate cell (HSC) activation and fibrogenesis, contributing to attenuate liver fibrosis in obesity-associated metabolic dysfunction-associated steatotic liver disease (MASLD). Plasma (n=200) and hepatic expression (n=75) of FNDC4 together with liver fibrosis were determined in participants with severe obesity and available liver pathology analysis. The effects of FNDC4 on HSC activation, fibrogenesis, and migration triggered by TGF-β1 were examined in vitro using human LX-2 HSCs. Circulating and hepatic expression levels of FNDC4 were inversely correlated with liver fibrosis severity. FNDC4 was predominantly expressed in hepatocytes, not in HSCs, and localized to regions adjacent to fibrosis. In HSCs, FNDC4 treatment enhanced basal transdifferentiation into myoblast-like cells, increasing mitochondrial activity and glycolysis, key features of HSC activation. Mechanistically, AMPKα played a crucial role in FNDC4-induced elevation of mitochondrial DNA and mitochondrial network-regulating genes. Under TGF-β1 stimulation, FNDC4 selectively attenuated HSC collagen type I expression, apoptosis and ROS production, while concurrently increasing MMP-1, a key collagen-degrading enzyme, and GATA4, a transcription factor linked to cell deactivation. FNDC4 also inhibited TGF-β1-induced HSC migration by suppressing YAP expression and activation, a downstream target of AMPK. Hepatocyte-derived FNDC4 functions as an anti-fibrogenic factor by modulating HSC activation and suppressing TGF-β1-driven fibrogenesis and migration via the AMPK/YAP pathway. Reduced hepatic FNDC4 may contribute to persistent liver fibrosis in obesity-related MASLD.

The rising global prevalence of obesity has established bariatric surgery as a key therapeutic option; however, postoperative pain management remains a challenge. This study investigated the influence of body mass index (BMI) stratification on acute postoperative pain in patients undergoing bariatric surgery. Fifty-five patients aged 18-65years with BMI ≥ 30kg/m2 scheduled for laparoscopic sleeve gastrectomy were categorized into the obesity group (O group; 30kg/m2 ≤ BMI < 40kg/m2) and the severe obesity group (SO group; BMI ≥ 40kg/m2). Preoperative pain threshold and pain tolerance threshold, perioperative inflammatory cytokines, Brief Pain Inventory (BPI) scores, Quality of Recovery-15 (QoR-15) scores, postoperative resting and movement numeric rating scale (NRS) scores, patient-controlled analgesia (PCA) pump usage, cumulative analgesic consumption, and analgesic satisfaction were assessed. Compared with the O group, the SO group demonstrated a significantly higher pain tolerance threshold (4.1 ± 0.8 vs. 3.5 ± 1.0, P < 0.01), along with lower demand for PCA and reduced consumption of cumulative morphine milligram equivalents and flurbiprofen (P < 0.05). Notably, the primary outcome, the 24-h BPI score, showed no significant difference between the two groups. On postoperative days 1 and 3, tumor necrosis factor-α (TNF-α) levels were significantly lower in the O group, whereas no significant intergroup differences were observed in other inflammatory cytokines. No significant differences were observed in NRS or QoR-15 scores between the two groups. BMI may be considered as a factor for stratifying postoperative analgesia, favoring multimodal, opioid-sparing strategies in patients with severe obesity who demonstrate higher pain tolerance and lower analgesic requirements. Chinese Clinical Trial Registry, ChiCTR2400095080.

Bariatric surgery effectively treats severe obesity. However, long-term data on weight maintenance and patient well-being remain scarce. This study assessed patients' perspectives on their bariatric trajectory and outcomes of their historical and current status across multiple domains, irrespective of surgical procedure. A retrospective cohort study was conducted among patients who were referred to the Department of Medical Psychology for bariatric screening between 1998 and 2004. Of the 547 referred patients, eligible participants received a survey after informed consent addressing weight outcomes, current eating patterns, dietary guidelines adherence, expectation fulfillment, satisfaction, and peer advice. Sixty-two participants completed survey. Mean postoperative time since the initial surgery was 19 years (range 6-27). Mean preoperative weight decreased 33%, from 144.2 to 97.5kg. Preoperative Body Mass Index decreased from 50.3 to 34.0kg/m2. Healthy postoperative behaviors included regular meals, portion control and control regarding snacking between meals. Unhealthy behaviors included evening snacking, alcohol consumption and binge eating. One third reported using vitamins never or sometimes. Participants reported diverse encountered barriers regarding eating, drinking, physical and psychological health and social functioning. Most would choose surgery again except those with expectation-outcome discrepancies or ongoing weight instability. Peer advice emphasized comprehensive preoperative education on all potential postoperative consequences from multiple sources. After 19 years, weight loss, healthy eating and adherence to advice varied, yet most participants were satisfied regardless of weight loss or reoperation. We plea for lifelong follow-up care to optimize bariatric results regardless type of surgery.

The disproportionate burden of severe obesity in youth with special needs and the role of metabolic and bariatric surgery.

Seminars in pediatric sugery pediatric metabolic and bariatric surgery.

Sugar addiction at the crossroads of reward, metabolism, and culture.

Laparoscopic sleeve gastrectomy (LSG) is widely performed for severe obesity but is associated with postoperative gastroesophageal reflux disease (GERD) and esophageal motility disorders. Gastropexy has been proposed to preserve gastric anatomy and reduce complications. To evaluate the effect of gastropexy on esophageal manometric values following LSG. A randomized controlled study was conducted on 40 patients undergoing LSG at our Hospital, (20 with gastropexy, 20 without). Esophageal manometry was performed preoperatively and 6 months postoperatively. Postoperative symptoms, complications, and percentage of total body weight loss (%TBWL) were assessed. In the non-gastropexy group, there was a significant decrease in lower esophageal sphincter (LES) resting pressure and distal contractile integral (DCI) postoperatively (p = 0.002 and p = 0.01, respectively). The gastropexy group showed preserved LES pressure and DCI. Postoperative GERD symptoms, vomiting, and food intolerance were significantly less in the gastropexy group (p < 0.05). There was no significant difference in %TBWL between groups (p = 0.86). Operative time was longer in the gastropexy group (p < 0.001). Gastropexy step during LSG may play a role in preservation of the esophageal manometric values and reduces postoperative GERD and vomiting, although it increases operative time. Larger long-term trials are needed for confirmation.

Severe obesity (body mass index ≥ 40kg/m2 or ≥ 35kg/m2 with obesity-related comorbidities) is increasingly prevalent and independently associated with elevated perioperative morbidity and inferior oncologic outcomes in patients with colorectal cancer (CRC). Despite these risks, intentional preoperative weight optimization is not routinely incorporated into CRC management, owing to concerns regarding treatment delay, absence of guideline endorsement, and limited supporting evidence. A literature review was conducted using PubMed and Embase to evaluate the impact of severe obesity on morbidity, mortality, and oncologic outcomes in CRC. Peer-reviewed English-language studies involving adult human subjects were included, while conference abstracts, non-English publications, and studies unrelated to obesity and CRC were excluded. In the absence of published reports describing synchronized weight loss and CRC management in patients with severe obesity, three novel retrospective case examples were included to demonstrate feasibility during neoadjuvant treatment, with institutional review board approval obtained for all cases. Severe obesity complicates CRC staging due to limitations in cross-sectional imaging and anatomic delineation. Furthermore, severe and particularly visceral obesity is associated with increased rates of anastomotic leak, surgical site infection, and conversion to open surgery. Current CRC guidelines do not incorporate structured weight-loss strategies into standard treatment algorithms. Metabolic bariatric procedures, such as sleeve gastrectomy, achieve rapid and clinically meaningful weight reduction, often resulting in improved operative exposure and technical conditions for subsequent resection. Pharmacologic therapies, while more broadly accessible and less invasive, typically yield more modest reductions in visceral adiposity. Task force members report early experience across three distinct cases of locally advanced CRC in patients with severe obesity, demonstrating successful preoperative visceral fat reduction through multidisciplinary coordination incorporating metabolic bariatric surgery or pharmacologic therapy during neoadjuvant windows, followed by definitive oncologic resection. Severe obesity adversely influences CRC staging, operative complexity, and perioperative outcomes. Intentional metabolic optimization-through bariatric surgery or pharmacologic therapy-may represent a viable adjunct within multidisciplinary, patient-centered CRC care pathways. However, the absence of prospective short- and long-term outcome data underscores the need for systematic investigation to define optimal timing, safety parameters, and oncologic efficacy of weight-loss interventions in this high-risk population.

Severe obesity among adolescents in the United States is a major public health concern. While metabolic and bariatric surgery (MBS) is safe and effective for adolescents with severe obesity, no standardized lifestyle interventions are available to support MBS outcomes. TeenLyft, a 6-month behavioral support intervention adapted from the Diabetes prevention program, was provided to teens for peri-operative MBS care beginning four weeks before surgery. This study evaluated TeenLyft's efficacy on improving weight-related behaviors using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. Adolescents aged 13-18years were recruited from a single tertiary care center MBS program. Participants enrolled in TeenLyft received online educational videos. The five RE-AIM dimensions were assessed independently using a mixed-methods approach. Data sources included baseline (pre-surgery), 3- and 6-month post-MBS follow-up data on anthropometric measures and cardiometabolic biomarkers, interviews, and electronic health records. Quantitative data provided descriptive statistics, and paired t-tests assessed within-subject changes over time to evaluate effectiveness. Qualitative data were thematically analyzed. For Reach, 76 adolescents enrolled in TeenLyft, 47 of whom did not complete MBS, and 29 (38.1%) completed MBS, with participants indicating the program structure and suitability were reasons for enrollment. In terms of effectiveness (N = 29), older age was significantly associated with greater excess weight loss (EWL > 50%: 16.8 ± 0.7 vs. 15.3 ± 1.1years, p = 0.0083), as was female sex (p = 0.0062). As expected, weight and body mass index significantly decreased from pre-surgery to six months post-MBS (136.1kg to 95.7kg, p = 0.0001; BMI 48.3 to 33.3kg/m2, p = 0.0001). Adolescents reported that the program supported their physical and emotional health and wanted more mental health-related content. Adoption was influenced by clinical staff involvement in recruitment, content development, and content alignment with adolescent needs. Implementation followed the outlined protocols with some additional adaptations to boost engagement via additional social media platforms. Maintenance showed most adolescents attended follow-up clinic visits at 6- and 12-month (83% and 67% respectively). Adolescents emphasized that the program provided education and skills to support post-operative weight management. The RE-AIM framework suggested that TeenLyft was a successful approach for providing behavioral support pre-and post-MBS. Additional benefits could be bolstered with support for mental health management.Trial Registration: NCT05393570.

Elastography is central to fibrosis risk stratification in metabolic dysfunction-associated steatotic liver disease (MASLD). While vibration-controlled transient elastography (VCTE) is most widely used, magnetic resonance elastography (MRE) is more accurate. A discordance between them has been reported, and body mass index (BMI) has been proposed as a determinant. We investigated the impact of BMI on VCTE-MRE discordance in a real-world cohort. This retrospective study included 268 adults with MASLD who underwent VCTE and MRE within 30 days. The primary endpoint was high-grade cross-threshold discordance, defined as VCTE ≥ F3 with MRE < F2 or MRE ≥ F3 with VCTE < F2. Secondary endpoints included discordance at ≥F2,≥F3, and ≥ 2-stage disagreement. Predictors of high-grade discordance were evaluated using logistic regression adjusted for age, sex, and diabetes. BMI-stratified calibration models were developed to harmonize TE values into MRE-equivalent scores. VCTE and MRE showed moderate correlation (Spearman ρ = 0.54; log-Pearson r = 0.70) and moderate staged agreement (κ = 0.50). High-grade discordance occurred in 19.0% overall and increased sharply with BMI: 7.7% (< 25), 10.3% (25-29.9), 21.4% (30-34.9), and 64.7% (≥ 35). Discordance was predominantly TE-high/MRE-low. Multivariable analysis showed that every 5kg/m2 increase in BMI nearly tripled the odds of high-grade discordance (OR 2.70; 95% CI 1.93-3.93). Calibration modelling revealed that advanced VCTE values in patients with BMI ≥ 35 corresponded to MRE values well below the threshold for advanced fibrosis. In MASLD, VCTE-MRE discordance is strongly BMI-dependent and clinically consequential in severe obesity, supporting BMI-aware fibrosis triage and modality harmonization.

During periodontitis, pathogenic oral bacteria like Porphyromonas gingivalis may exert systemic effects directly by translocating into the bloodstream and indirectly by deregulating the gut microbiota, aggravating obesity-related complications. This study aimed to evaluate the links between the periodontal infection, the oral and gut microbiota composition, and the inflammatory and metabolic profile during obesity. Thirty-nine patients suffering from severe obesity, with (n = 23) or without (n = 16) periodontitis, were enrolled. We examined the subgingival microbiota composition, periodontal status and salivary inflammatory response. The fecal microbiota composition was assessed by metagenomic analysis. Inflammatory and metabolic markers were measured in the plasma and epiploon visceral adipose tissue collected during bariatric surgery. Results show that patients with periodontitis exhibited an oral microbiota dysbiosis characterized by an increased abundance of bacteria from the red and orange complexes, worsened periodontal parameters (plaque index, bleeding index, gingival recession, probing depth and clinical attachment level), and higher IL-6 salivary levels. In fecal samples of patients with periodontitis, a higher proportion of the Proteobacteria phylum and changes in functional profile of bacteria were detected. Periodontitis was also linked to higher circulating concentrations of anti-P. gingivalis IgG, total cholesterol and lipoprotein (a). Moreover, periodontitis was associated with an enhanced production of TLR2, MyD88 and TGFβ, as well as higher activities of SOD and catalase antioxidant enzymes in the adipose tissue. Overall, these findings demonstrate that during obesity, the periodontal infection correlates with deregulated oral and gut microbiota composition, higher levels of pro-inflammatory mediators, and altered markers of oxidative stress and lipid metabolism.

Current guidelines recommend overnight admission for children with severe obstructive sleep apnea (OSA) and obesity undergoing tonsillectomy, although most have uneventful postoperative courses. We aimed to identify low-risk subgroups within this high-risk population who may be candidates for same-day discharge. Retrospective cohort study of children aged 2-18 years with obesity (≥ 95th BMI percentile) and severe OSA (AHI ≥ 10 events/h and/or SpO2 nadir < 80%) undergoing tonsillectomy at a tertiary children's hospital (2021-2024). The primary outcome was a severe perioperative event: ICU admission, prolonged hospitalization (> 48 h), or need for advanced respiratory support. Bayesian logistic regression using informative priors identified predictors. Model-based risk stratification and simplified clinical rules were evaluated using sensitivity, specificity, and negative predictive value. Among 304 children, 36 (11.8%) experienced a severe event. SpO2 nadir was the strongest predictor (β = -0.668, 95% CrI [-1.164, -0.172], directional probability 99.6%), followed by Class III obesity (97.0%) and AHI (95.0%). Model-derived stratification identified 33% of patients with < 5% predicted probability of severe events. A clinical rule combining AHI < 25 events/h and SpO2 nadir > 85% showed sensitivity 85.7% and negative predictive value 99.5%, corresponding to an observed event rate < 5%. Most obese children with severe OSA do not experience severe perioperative events. Simple polysomnographic criteria can identify very low-risk patients who may be candidates for same-day discharge planning. These findings support a more individualized approach to postoperative admission; prospective validation is needed before implementation.

Type 2 diabetes mellitus (T2DM) and prediabetes are common complications of severe obesity. Although the Finnish Diabetes Risk Score (FINDRISC) is a widely used tool for diabetes risk assessment, its performance has not been specifically evaluated in populations with severe obesity. In this cross-sectional study, 632 adults with severe obesity (median BMI 46.2kg/m²) underwent oral glucose tolerance testing (OGTT) and HbA1c assessment. FINDRISC was calculated for each participant. The primary endpoint was the ability of FINDRISC to identify previously undiagnosed T2DM. Secondary endpoints included the prevalence of glycemic categories and the associations between FINDRISC and circulating adipokines. Normoglycemia, prediabetes, and previously undiagnosed T2DM were identified in 44%, 46%, and 10% of participants, respectively. FINDRISC values increased progressively with worsening glucose tolerance (p < 0.001). The area under the ROC curve for detection of undiagnosed T2DM was 0.72 (95% CI 0.65-0.78). A FINDRISC cut-off of 13 showed high sensitivity (95.1%) and negative predictive value (98.2%), allowing 26% of individuals to be spared additional blood testing. Adiponectin and leptin levels were significantly lower in participants with diabetes compared with those with normoglycemia or prediabetes. Approximately one in ten persons with severe obesity had previously undiagnosed T2DM. In this population, FINDRISC demonstrated good performance as a rule-out screening tool, supporting its use to reduce unnecessary diagnostic testing and to guide targeted diabetes screening in severe obesity.