Spinal epidural lipomatosis (SEL) is a disorder characterized by excessive accumulation of epidural adipose tissue, resulting in spinal canal stenosis and neurological symptoms. In recent years, obesity-related SEL has been increasingly recognized as a manifestation of ectopic fat deposition associated with metabolic dysfunction and has been re-evaluated as a potentially reversible condition following weight reduction. However, reports describing radiological and clinical improvement of SEL after metabolic and bariatric surgery (MBS) remain limited, and this disease concept and therapeutic strategy have not yet gained sufficient attention in Japan. Herein, we report a case of SEL that improved following MBS. A 49-year-old man with severe obesity (body weight 160 kg; BMI 48.3 kg/m2) presented with several obesity-related diseases. MRI revealed spinal canal stenosis due to SEL with accompanying neurological symptoms, which did not improve despite medical weight-loss therapy. Laparoscopic sleeve gastrectomy was performed as MBS. At 1 year postoperatively, body weight had decreased to 122.4 kg (BMI 36.9 kg/m2), corresponding to 23.5% total weight loss and 43.2% excess weight loss. The cross-sectional area of epidural fat (EF) decreased from 4.22 cm2 preoperatively to 2.25 cm2 postoperatively, while the dural sac (DS) area increased from 0.61 to 2.32 cm2. Accordingly, the EF-to-DS (EF/DS) ratio decreased from 6.92 to 0.97, and the Borré classification improved from Grade III to Grade I. Neurological symptoms were alleviated, and no spinal decompression surgery was required. MBS led to meaningful improvement in patient-oriented outcomes accompanied by radiological resolution of SEL. Obesity-related SEL may represent a reversible condition driven by ectopic fat accumulation, and MBS may serve as a therapeutic option in carefully selected patients.
Maintaining fat-free mass (FFM) during weight loss is important to maintain a healthy body composition. This review examined changes in FFM during weight loss induced by diet and exercise interventions, incretin-based therapies, and bariatric surgery, and assessed whether the relative loss of FFM differs by weight-loss modality. A systematic search of PubMed, Cochrane Library, and Embase was conducted for randomised controlled trials published from 2015 to October 21st, 2025. Eligible studies included adults with overweight or obesity (with or without type 2 diabetes), achieving ≥ 10% weight loss of total body weight through diet and exercise, incretin-based, or surgical interventions. The studies were required to report measurements of either FFM using dual-energy X-ray absorptiometry or muscle mass using computed tomography or magnetic resonance imaging. Twelve diet and exercise, five incretin-based therapy, and four bariatric surgical studies (1334 participants) were included. The pooled changes in FFM were -1.8 kg (95% CI: -2.6, -1.0) for diet and exercise interventions, -4.8 kg (95% CI: -5.6, -3.9) for incretin-based therapies versus placebo, and -9.1 kg (95% CI: -12.3, -6.0) for bariatric surgery. The proportion of total weight loss attributable to FFM was 14.9% for diet with/without exercise interventions (22.3% for diet without exercise and 7.7% for diet with exercise), 33.3% for incretin-based therapies, and 34.2% for surgical interventions. Among the included studies with ≥ 10% weight loss in individuals with overweight or obesity, diet and exercise interventions were associated with the smallest reductions in FFM, whereas incretin-based therapies and bariatric surgery showed substantially greater losses. Given the importance of FFM, strategies to preserve FFM, particularly exercise, should be included in all weight-loss approaches.
Obesity is one of the world's leading health burdens. The prevalence of overweight and obesity continues to rise globally, creating significant healthcare and socioeconomic challenges. Effective strategies are essential to address this crisis. To thematically map global obesity management strategies and policies, focusing on policy- and system-level features relevant to national implementation, to inform context-sensitive policy considerations in Thailand and similar health systems. A scoping review was conducted to map global obesity management policies and identify key themes, challenges, success factors, and future directions. Electronic databases, including PubMed, EMBASE, and Scopus, were searched for relevant documents published between January 1, 2004, and June 30, 2024. The gray literature was also reviewed to assess the reimbursement status of obesity medications. The analysis identified three main policy domains: public policy, food security and healthy environments, and healthcare system support. Through the scoping review and thematic synthesis, 19 distinct policy themes were identified. High-income countries generally demonstrated more comprehensive and integrated strategies compared to middle-income countries. Regarding medical reimbursement for obesity treatment, coverage for bariatric surgery was more commonly available across settings, whereas reimbursement for anti-obesity medications remained limited. For example, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were reimbursed for obesity indications in selected high-income countries, including Denmark and the United Kingdom. In contrast, in countries such as the United States, China, and Thailand (restricted to the Civil Servant Medical Benefit Scheme), these agents were reimbursed primarily for type 2 diabetes rather than for weight management. Integrated strategies that combine prevention and treatment, supported by interagency collaboration, are critical for effective obesity management. Additionally, designing policies that align with the social, cultural, and economic context of each country is crucial for achieving sustainable obesity management.
Plasma 4β-hydroxycholesterol (4β-OHC) normalized for the levels of its parent cholesterol (4β-OHC/C) is an endogenous biomarker for hepatic CYP3A4. This study evaluated CYP3A4 activity longitudinally in individuals while their obesity status was changing. 4β-OHC/C was measured pre-surgery (n = 54) and 2 years after Roux-en-Y gastric bypass (n = 30) and used as an input for creating virtual twins of each patient within physiologically-based pharmacokinetic (VT-PBPK) models, alongside other available data (e.g., demographics). Additionally, individual CYP3A4 abundance quantified from liver biopsies during surgery was available. Predicted CYP3A4 abundance using 4β-OHC/C was within twofold of the measured abundance in 85% of the individuals (n = 54). Pre-surgery VT-PBPK models informed by biomarker data predicted area under curve after intravenous midazolam (AUCinf,iv) within twofold of observed values in 85% of individuals (geometric mean fold error (GMFE) = 1.58). VT-PBPK models using CYP3A4 protein measurements showed similar performance (83% within twofold, GMFE = 1.66), verifying the biomarker approach. The post-surgery VT-PBPK models were revised to reflect surgery-related alterations and changes in obesity status. Hepatic CYP3A4 activity at 2 years was predicted from 4β-OHC/C measured in the same individuals. Biomarker-informed models predicted midazolam AUCinf,iv within twofold for 87% of individuals (GMFE = 1.48; n = 30). ~60% of observed oral midazolam PK parameters were predicted within twofold, improving to 70% when the surgery model assumed full intestinal CYP3A4/5 recovery. This study highlights the utility of 4β-OHC/C for continuous monitoring of CYP3A4 activity and possibility to use biomarker-informed VT-PBPK models for individual dose requirements of intravenously administered CYP3A substrates in individuals with obesity over the course of weight loss treatment.
Obesity is a chronic, relapsing disease that increasingly spans generations within households, yet contemporary metabolic and bariatric surgery (MBS) models remain oriented toward individuals or single-generation patients. A growing body of evidence demonstrates that obesity risk, behaviors, and treatment responses cluster within family systems, and that MBS produces measurable metabolic and behavioral effects among untreated spouses, partners, and children. Concurrently, decades of pediatric research confirm that caregiver engagement and integration is one of the strongest determinants of successful obesity treatment. Together, these observations support a paradigm shift toward an intergenerational, family-centered model of MBS, in which the household becomes the unit of care. This perspective synthesizes evidence supporting the biological, behavioral, and environmental interdependence of obesity within families and outlines a comprehensive framework for implementing household-level bariatric care. Core components include integrated pediatric-adult clinical infrastructure; combined multidisciplinary teams trained across the age spectrum; harmonized protocols for evaluation, education, and follow-up; coordinated scheduling and workflow alignment; and family-based behavioral strategies that promote shared goals, consistent routines, and mutual accountability. Operational and policy innovations, such as cross-departmental agreements, unified electronic health records, and coordinated billing can facilitate sustainable implementation. We further identify research priorities, including quantifying metabolic ripple effects among untreated family members, evaluating bundled household-level interventions, and developing validated metrics to assess changes in the home environment. Treating the household as the patient offers a promising strategy to enhance medical obesity treatment, surgical durability, improve adherence, and disrupt intergenerational transmission of obesity. As obesity increasingly presents as a family condition, an intergenerational MBS model may help realign treatment with the realities of lived experience and improve outcomes across generations.
With the global prevalence of obesity, researches on metabolic bariatric surgery for patients with obesity and end-stage liver disease that require liver transplantation has gained increasing attention. This study aimed to perform a bibliometric analysis of metabolic bariatric surgery for patients with obesity and end-stage liver disease that require liver transplantation from 1900 to 2025 to identify major contributors and current research status, and to look forward to the research trends and future development prospects in this field. A total of 121 relevant articles from 1 January 1900 to 5 February 2025 were obtained from the Web of Science Core Collection database. VOS viewer and Cite Space were utilized as bibliometric tools to analyze and visualize knowledge mapping. A total of 121 publications were identified, 24 nations/regions participated in this field, with 695 scholars from 91 institutions. Mayo Clinic (USA) dominates with 13 publications and 516 citations; UC San Francisco (6 pubs, 416 cites) and the University of Toronto (2 pubs, 205 cites, over 100 cites per pub) excel in quality. The top 10 features 7 US institutions, plus ones from Canada, Europe, and South America, forming the field's high-impact core cluster. Our study analyzes 121 publications (1997-2025) on liver transplantation and metabolic bariatric surgery. The field is dominated by U.S. institutions, particularly the Mayo Clinic. Researches mainly focus on following areas: surgical timing (before, during, or after transplantation), management of post-transplant obesity, liver status, donor applications, and obesity-related liver diseases. Current evidence mainly limited to retrospective studies and case reports with small sample sizes. Future work requires prospective, multi-center trials and an international registry to establish standardized guidelines for this evolving field.
Rotator cuff tears (RCTs) are a common cause of shoulder pain and can severely affect patients' ability to perform daily activities. Comorbidities, such as obesity, are known to influence the outcomes of RCT repair, particularly in the context of arthroscopic surgery. However, the effect of obesity on postoperative outcomes following RCT repair has not been sufficiently explored, especially in patients undergoing minimally invasive procedures. This study aims to evaluate the impact of obesity on postoperative pain, range of motion, and functional recovery after arthroscopic rotator cuff repair. This retrospective cohort study included 50 patients who underwent arthroscopic RCT repair between January 1, 2022, and January 1, 2025. All patients were followed for a minimum of two years postoperatively. Data collected included factors such as fatty infiltration (Goutallier grade), tendon retraction (Patte grade), obesity (BMI ≥ 30), education level, and smoking status. The primary outcomes assessed were postoperative pain (Visual Analog Scale, VAS), range of motion (active forward flexion and external rotation), UCLA Shoulder Score, and ASES Score. The average age of the study participants was 59.9 ± 7.4 years, with 28% of patients being female. A total of 42 patients (84%) had a full-thickness rotator cuff tear. The median time from diagnosis to surgery was 22.5 months (IQR: 17.3-29.8 months), with a median follow-up duration of 30.2 months (IQR: 26.3-34.1 months). Eighteen patients (36%) were classified as obese (BMI ≥ 30). Obese patients demonstrated a trend toward higher postoperative pain (VAS: 4.8 ± 2.8 vs. 4.0 ± 3.2, p = 0.076), and showed significantly reduced active forward flexion (130.5° ± 48.4° vs. 137.6° ± 52.7°, p = 0.035) and external rotation (40.3° ± 17.4° vs. 48.4° ± 19.5°, p = 0.024) compared to non-obese patients. BMI was negatively correlated with improvements in both forward flexion and abduction following surgery. This study found that obesity was significantly associated with reduced active forward flexion (p = 0.035) and external rotation (p = 0.024) following arthroscopic rotator cuff repair, and demonstrated a trend toward higher postoperative pain levels (p = 0.076) that did not reach conventional statistical significance. Functional recovery, as assessed by UCLA and ASES scores, showed a consistent directional trend toward poorer outcomes in obese patients; however, these differences were not statistically significant (p = 0.196 and p = 0.322, respectively), and should be interpreted with caution given the limited sample size. These findings highlight obesity as a potential risk factor for reduced range of motion recovery following rotator cuff repair, while acknowledging that its impact on broader functional outcomes remains to be confirmed in larger prospective studies. Tailored perioperative and rehabilitation strategies targeting obese patients may help optimize postoperative recovery, though further evidence is needed to guide specific clinical recommendations.
Obesity increases the risk of common diseases and mortality, placing a significant burden on our aging society. Bariatric surgery results in significant weight loss; however, the amount of associated health gain is currently less studied, particularly in the first two years. We modelled mortality-associated biological age according to established blood markers in a prospective cohort of 505 patients that underwent bariatric surgery. The difference between biological age and chronological age (age acceleration) as a molecular marker of health gain was evaluated at different time points with mixed effects models. At baseline, biological age acceleration was positively correlated to higher smoking exposure as well as increased body mass, particularly in males. Twelve months after surgery, patients were on average 5.55 years younger (slope and 95% confidence intervals (95% CI): -5.55 [-6.12; -4.97]) which remained stable until 24 months. When adjusted for changes in body mass index over time, the effect seizes decreased to 3.32 years younger age at 12 months post-surgery (slope and 95% CI: -3.32 [-4.26; -2.37]), indicating an age-rejuvenating effect - more pronounced in men - beyond weight loss. Individual markers such as glucose and C-reactive protein levels as well as blood cell counts contributing to biological age computation showed a generally more favorable change after surgery. In conclusion, biological age was markedly reduced in patients undergoing bariatric surgery resulting in a 40-50% reduction in expected mortality after two years, particularly in men. Our findings support the use of biological age as a clinically meaningful, patient-centered marker of treatment success after bariatric surgery.
Patients with severe obesity and BMI ≥ 50 kg/m² represent a high-risk group for metabolic bariatric surgery (MBS), and long-term outcome data in this population remain limited. This study aimed to evaluate the safety and long-term efficacy of MBS in patients with BMI ≥ 50 kg/m². A retrospective multicenter observational study including patients who underwent MBS between 2007 and 2014 and completed at least 10 years of follow-up. Patients were stratified into two groups based on preoperative BMI (< 50 vs. ≥50 kg/m²). Outcomes included long-term weight loss (%TWL, %EWL), remission of type 2 diabetes mellitus (T2DM), hypertension (HT), obstructive sleep apnea (OSA), and gastroesophageal disease (GERD); perioperative complications, and revisional procedures. Eighty-nine patients had baseline BMI ≥ 50 kg/m². Mean follow-up was 11.10 years. Patients with BMI ≥ 50 kg/m² more frequently reached ≥ 20% TWL (77.53 vs. 53.15%, p < 0.001). The proportion of patients achieving ≥ 50% EWL in group with ≥ 50 BMI was 58.43% and results were comparable between groups. Median final BMI remained higher in the BMI ≥ 50 kg/m² group (36.33 vs. 32.27 kg/m², p < 0.001). Remission rates in the BMI ≥ 50 kg/m² group were 59.1% for T2DM, 61.5% for HT, 57.1% for OSA, and 75.0% for GERD, with no significant differences between groups. 30-day postoperative complications occurred in 7.86% of patients with BMI ≥ 50 kg/m²; this value was not significantly different from the lower-BMI group. Revisional surgery was required more frequently in patients with BMI ≥ 50 kg/m² (43.82 vs. 19.90%, p < 0.001), predominantly due to weight regain. MBS in patients with BMI ≥ 50 kg/m² results in durable weight loss and significant improvement of obesity-associated diseases. However, patients with obesity class IV and higher remain at a elevated risk of revisional surgery.
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To determine whether CT-derived body composition and kidney function better predict cefazolin concentrations at the surgical site than body weight alone in patients with obesity undergoing colorectal surgery. Current cefazolin prophylaxis guidelines recommend dose escalation from 2 g to 3 g in patients weighing ≥120 kg. However, body weight inconsistently reflects antibiotic distribution at the surgical site. We conducted a prospective study of adults with obesity undergoing elective colorectal surgery who received cefazolin prophylaxis and had preoperative CT imaging. Cefazolin concentrations were measured in plasma, subcutaneous adipose tissue, and colorectal tissue during surgery. CT-derived body composition metrics were quantified using analytic morphomics. Modeling and simulations were used to identify predictors of target attainment in subcutaneous tissue. Agreement between revised physiologic dosing criteria and current weight-based guidance was assessed in both a derivation cohort and an independent external cohort. Among 153 patients, 58 were included in model development and 95 in prospective evaluation. Weight and BMI did not improve model performance. Subcutaneous fat area (SFA) predicted tissue exposure, while creatinine clearance (CLcr) predicted elimination. Current weight-based dosing achieved 78%-84% target attainment. A revised framework of SFA ≥500 cm2 or ≥300 cm2 with CLcr ≥90 mL/min identified an additional 10%-14% of patients for dose adjustment, improving identification of underdosing-related SSI risk without unnecessary antibiotic use. Cefazolin exposure is better explained by local adiposity and kidney function than by the current ≥120 kg weight-based dosing threshold.
Obesity increases the risk of breast cancer (BC), and bariatric surgery may lower overall cancer risk. However, the impact of sleeve gastrectomy (SG) timing on cancer outcomes remains unclear. Using the TriNetX global health research network, we identified 4,439,072 women diagnosed with severe obesity (BMI >35 kg/m2) between 2010 and 2019. Patients were grouped into SG and nonsurgical controls, with SG patients further stratified by surgery timing: early (≤6 months), intermediate (6-12 months), and delayed (1-3 years) post-diagnosis. Propensity score matching adjusted for demographics, comorbidities, BMI, and HbA1c. Outcomes included 5-year incidences of mortality, cancer, and metastasis. SG was associated with lower 5-year all-cause mortality across all timing groups compared to the control group. Early SG was significantly associated with a reduced 5-year incidence of BC (risk ratio [RR]: 0.799; 95% CI: 0.647 to 0.987; P = .037), gynecologic cancer (RR: 0.490; 95% CI: 0.378 to 0.635; P < .001), and metastasis (RR: 0.306; 95% CI: 0.230 to 0.408; P < .001). By contrast, delayed SG was associated with an increased risk of BC (RR: 1.404; 95% CI: 1.107 to 1.781; P = .005). Age-stratified analyses indicated that the association between SG timing and outcomes appeared more pronounced in patients aged ≥45 years. Our findings highlight the importance of timely bariatric surgery in optimizing both metabolic and oncologic outcomes, particularly in older women with obesity.
This sub-analysis of the ACTION APAC study aimed to identify perceptions, attitudes and behaviors related to obesity and its management among people with obesity (PwO) and healthcare providers (HCPs) in the Philippines, identifying barriers to effective care and contributing to management strategies. ACTION APAC was a cross-sectional, non-interventional, descriptive survey conducted from April 14 to May 23, 2022 across nine countries, involving 1,000 PwO and 201 HCPs. Most participants agreed that obesity is an illness but 91% of PwO felt losing weight was entirely their responsibility. Both groups identified similar motivators and barriers to weight loss. Weight stigma significantly impacted PwO but fewer than half discussed weight with their HCPs. Many PwO were happy with their weight and did not consider themselves as having obesity. Lifestyle modifications were preferred for weight management by both groups, while HCPs were reluctant to prescribe pharmacotherapy or recommend bariatric surgery due to lack of knowledge and cost, respectively. The study revealed a discrepancy between recognizing obesity as an illness and attitudes towards its treatment, highlighting a need for better education and tailored management strategies that consider cultural factors in the Philippines.
Patients with obesity hospitalized for acute medical illness are at increased venous thromboembolism (VTE) risk, but evidence on predictors of VTE and major bleeding (MB) to optimize individual risk stratification and thromboprophylaxis remains limited, in particular for patients with extreme obesity. This study assessed pharmacologic regimen, event rates, and predictors for VTE and MB among hospitalized medical patients with obesity receiving thromboprophylaxis using enoxaparin. Patients with body mass index (BMI) of ≥30 kg/m2 hospitalized for acute medical illness who received thromboprophylaxis with enoxaparin were selected from the Optum database. Event rates over a 90-day follow-up after enoxaparin initiation were estimated via the Kaplan-Meier method. Factors associated with outcome events were identified via Cox proportional hazard models. Among 58,186 eligible patients, 17,398 (30%) had a BMI of >40 kg/m2; 56.9% received high-dose enoxaparin (>40 mg), and 42.8% received the standard dose (≤40 mg). The median duration of enoxaparin prophylaxis (3 days) was shorter than the length of the hospitalization (4 days). The 90-days cumulative incidence was 3.2% (95% CI, 3.1-3.4) for VTE and 1.8% (95% CI, 1.7-1.9) for MB. The highest VTE rates were observed in patients with cancer-related hospitalizations (7.8%). A history of VTE and MB were the strongest predictors of VTE (HR, 4.1; 95% CI, 3.6-4.7) and MB (HR, 2.8; 95% CI, 2.0-3.7), respectively. Acutely ill patients with obesity received enoxaparin for shorter duration than their hospitalization, with over half receiving a high-dose adjustment by weight. The VTE rates were nonnegligible in this population and exceed MB rates across illness subgroups, suggesting a need for individualized risk stratification to optimize thromboprophylaxis.
Bariatric surgery might impact the thyroid function test and, in hypothyroid patients, the dose of levothyroxine (LT4), but data are not univocal. We evaluated changes in thyroid function during the first year following bariatric surgery in patients without pre-existing thyroid disease, as well as adjustments in LT4 dosage in those with thyroid disorders, comparing the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). A retrospective observational study including 69 patients on LT4 therapy (Tr) and 85 patients with normal thyroid function (Nt) at pre-surgical work-up and at regular follow-up at 45 days, 3-6 months and 1-year visits after surgery. The mean body weight reduction for the entire cohort was in 31.4 ± 0.7% 1 year after surgery. In the two Nt groups, TSH levels remained stable throughout the observation period, without differences for type of surgery and without relationship with body weight. After bariatric surgery, the patients treated with LT4, belonging to both Tr-RYGB and Tr-SG, needed to increase the dosage per kg body weight to achieve stable TSH. At 1 year, the increase of LT4/kg/die was higher in the Tr-RYGB group than Tr-SG group (0.44 vs 0.30 mcg/kg/die, p = 0.032). In patients with severe obesity and normal thyroid function, TSH levels are not related with body weight change. Patients treated with LT4, after bariatric surgery need to in-crease the dosage per kg of body weight of the LT4 especially after surgery with malabsorptive component (RYGB) compared to restrictive surgery (SG).
Obesity is a chronic, relapsing, and multifactorial disease that poses a significant public health challenge in Switzerland, where approximately 43% of adults are overweight or obese. This new clinical practice guidance establishes a structured, multidisciplinary framework for healthcare professionals, emphasising that assessment, treatment and care should focus on improving overall health metrics, resolving comorbidities and achieving functional gains, rather than solely on numerical weight loss. Crucially, the guidance mandates a non-stigmatising, empathetic approach to combat weight bias, reduce internalised stigma and build therapeutic trust. Accurate diagnosis and risk stratification begin with measuring body mass index (BMI), using adjusted cutoffs for specific ethnic populations. However, since BMI alone may not fully capture cardiometabolic risk, we recommend integrating waist circumference and body composition analyses. Physicians must conduct a comprehensive assessment to identify mechanical and metabolic comorbidities - spanning cardiometabolic, respiratory, gastrointestinal, musculoskeletal and mental health domains, among others - and systematically evaluate the patient's daily functioning and health-related quality of life. Care is organised across a tiered system. Primary care physicians play a central role in screening, initial management, and long-term monitoring. Patients with a BMI of 35 kg/m² or higher, or those with severe obesity-related complications, should be referred to specialised medical obesity services. The foundation of all weight management is a multimodal lifestyle intervention. This intervention includes medical nutrition therapy favouring minimally processed, nutrient-dense diets, such as the Mediterranean pattern; individualised physical activity plans targeting 150-300 minutes of moderate aerobic exercise per week alongside resistance training; and behavioural strategies, such as cognitive behavioural therapy, to address emotional eating and enhance self-efficacy. When lifestyle modifications are insufficient, adjunctive therapies are indicated. The pharmacological landscape has been revolutionised by incretin-based therapies, notably GLP-1 and dual GIP/GLP-1 receptor agonists (e.g. semaglutide and tirzepatide). These medications produce substantial weight reduction and cardiovascular benefits, although clinicians must carefully navigate current reimbursement criteria. For patients with severe or treatment-resistant obesity, bariatric/metabolic surgery, such as Roux-en-Y gastric bypass and sleeve gastrectomy, offers highly effective, durable outcomes but necessitates lifelong interdisciplinary follow-up. Finally, the guidance highlights the necessity of individualised care for special populations, including tailored strategies for children, reproductive-age women and older adults, for whom preserving muscle mass and bone health is prioritised over absolute weight loss.
Food-derived bioactive compounds offer an attractive and sustainable approach to metabolic disease prevention, yet mechanistic evidence supporting their efficacy in pediatric obesity remains limited. This study investigates the thermogenic potential of ferulic acid (FA), a plant-derived phenolic compound, when delivered via a dendrimer-based nanocarrier. Using an integrative strategy combining network pharmacology, molecular docking, cellular assays, animal models, and clinical biomarker analysis, we demonstrate that FA-loaded generation 3 PAMAM nanoparticles (FA-PG3) effectively activate adipose tissue thermogenesis. Computational analyses identified UCP1 as a central molecular target of FA, with PPARγ and PRDM16 acting as critical upstream regulators. FA-PG3 nanoparticles exhibited optimized nanoscale properties and sustained FA release. In vitro, FA-PG3 promoted beige adipocyte differentiation, enhanced mitochondrial respiration, and increased thermogenic gene expression. In vivo, FA-PG3 improved energy expenditure, insulin sensitivity, and adipose browning in obese mice, while UCP1 silencing largely abolished these metabolic benefits. Notably, children with severe obesity exhibited significantly lower circulating levels of browning-associated adipokines, supporting the clinical relevance of targeting thermogenic pathways. Our findings highlight a previously underappreciated food-derived, nano-enabled strategy for metabolic reprogramming and position FA-PG3 as a promising translational candidate for addressing pediatric obesity through adipose tissue thermogenesis.
This study aimed to describe epidemiology and management of severe surgical site infections (SSIs) following cochlear implantation (CI) and to identify risk factors. A retrospective monocentric study of all CI procedures was performed at our tertiary referral centre between January 2018 and December 2023. Data on patient demographics, clinical features and postoperative infections were collected. Severe SSIs were defined as abscess, skin flap necrosis or device extrusion requiring hospitalisation and/or IV antibiotics. Univariate and multivariate analyses were performed to identify risk factors. Of the 383 CIs, 3.6% (n = 14) developed severe SSIs. A salvage surgery was attempted in 85.7% of cases and the device explantation rate was of 71.4%. Staphylococcus aureus and Pseudomonas aeruginosa were the most identified pathogens. Chronic otorrhea was identified as a statistically significant risk factor for severe SSI (p < 0.001). No significant associations were found with obesity, tobacco use, diabetes, bilateral implantation or implantation renewal. Severe SSIs following CI are rare but challenging to treat, with a poor outcome. Chronic otorrhea appears to be a significant risk factor. Early intervention with IV antibiotics followed by salvage surgery may help avoid explantation.
Functional bradycardia, characterized by a heart rate below the normal range due to dysregulation of the autonomic nervous system (ANS), poses a clinical challenge with limited treatment options. Symptomatic sinus bradycardia is an uncommon but potentially significant complication following bariatric surgery. Cardioneuroablation (CNA) has emerged as a novel therapeutic intervention targeting the cardiac ANS to modulate heart rate. This case series describes two patients, with the aim of providing a simplified but successful approach with targeted partial CNA for sinus bradycardia complicating bariatric surgery.
The impact of preoperative weight loss and body composition changes on surgical and patient-reported outcomes remains unclear in gastrointestinal cancer patients. Prehabilitation programmes integrating exercise, nutrition and psychological support can improve surgical readiness and recovery but the role of body mass and composition changes within such services is not well understood. This study aims to investigate the associations between preoperative changes in body mass and composition and surgical, physical fitness, nutritional and quality of life outcomes among people with obesity undergoing surgery for upper gastrointestinal or colorectal cancer within the context of a cancer prehabilitation service (Active Together). This prospective observational study will recruit 100 adults (≥18 years; body mass index ≥30 kg/m²) scheduled for curative upper gastrointestinal or colorectal cancer surgery and enrolled in the Active Together prehabilitation service. Participants will attend two study visits: one as soon as possible after diagnosis and one within 2 weeks before surgery. Participants will undergo body mass, composition and size measurements and complete questionnaires on their nutritional status and quality of life. Routinely collected surgical outcomes (complications, operative approach and duration, length of hospital stay, readmissions, 1-year survival) and Active Together assessment data (physical fitness, psychological well-being, nutritional status) will also be collected. Correlation analyses and regression models will be used to explore the associations between preoperative changes in body mass and composition and surgical, physical fitness, nutritional status and quality of life outcomes. Ethical approval has been obtained from the Health Research Authority (Integrated Research Application System project ID 361634; Research Ethics Comittee reference 26/YH/0019). Written informed consent will be obtained from all participants. Data will be processed in accordance with General Data Protection Regulations and the Data Protection Act 2018. Findings will be disseminated via peer-reviewed publications, conference presentations and patient and public involvement activities.