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In the Semaglutide Treatment Effect in People with obesity and HFpEF (STEP-HFpEF) program, semaglutide improved heart failure (HF)-related symptoms, physical limitations, and exercise function, and reduced bodyweight in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Whether semaglutide improves functional status, as assessed by NYHA functional class, is unknown. The goal of this study was to examine the effects of semaglutide on change in NYHA functional class over time. We also investigated the effects of semaglutide on HF-related symptoms, physical limitations, and bodyweight and other trial endpoints across baseline NYHA functional class categories. This was a prespecified analysis of pooled data from 2 international, double-blind, randomized trials (STEP-HFpEF and STEP-HFpEF type 2 diabetes [STEP-HFpEF DM], comprising the STEP-HFpEF program), which collectively randomized 1,145 participants with obesity-related HFpEF to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. The outcome of interest for this analysis was the change in NYHA functional class (baseline to 52 weeks). We also investigated the effects of semaglutide on the dual primary, confirmatory secondary, and selected exploratory endpoints according to baseline NYHA functional class. More semaglutide-treated than placebo-treated patients had an improvement in NYHA functional class (32.6% vs 21.5%, respectively; OR: 2.20 [95% CI: 1.62-2.99; P < 0.001]) and fewer semaglutide-treated patients experienced deterioration in NYHA functional class (2.09% vs 5.24%, respectively; OR: 0.36 [95% CI: 0.19-0.70; P = 0.003]) at 52 weeks. Semaglutide (vs placebo) improved the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CCS) across NYHA functional class categories; this was especially pronounced in those in NYHA functional classes III/IV (10.5 points [95% CI: 6.6-14.4 points]) vs NYHA functional class II (6.0 points [95% CI: 3.4-8.6 points]) (P interaction = 0.06). By contrast, the degree of reduction in bodyweight was similar with semaglutide vs placebo regardless of baseline NYHA functional class category (NYHA functional class II, −8.4% [95% CI: −9.4% to −7.3%]; NYHA functional classes III/IV, −8.3% [95% CI: −9.9% to −6.8%]; P interaction = 0.96). Semaglutide consistently improved 6-minute walking distance (6MWD), the hierarchical composite endpoint (death, HF events, differences in KCCQ-CSS, and 6MWD changes), and reduced C-reactive protein and N-terminal prohormone of brain natriuretic peptide across NYHA functional class categories (all P interactions = NS). In patients with obesity-related HFpEF, fewer semaglutide-treated than placebo-treated patients had a deterioration, and more had an improvement, in NYHA functional class at 52 weeks. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced bodyweight and biomarkers of inflammation and congestion in all NYHA functional class categories. Semaglutide-mediated improvements in health status were especially large in patients with NYHA functional classes III/IV. (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure and Obesity; NCT04788511) (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes; NCT04916470) [ABSTRACT FROM AUTHOR]

Aim: The aim was to investigate factors influencing obesity among stroke survivors based on demographics and lifestyle behaviors. Background: Stroke survivors are more likely to experience stroke recurrence within a few years. As obesity is a traditional risk factor for stroke, obesity should be managed in stroke survivors to prevent stroke recurrence. Methods: A cross-sectional secondary data analysis analyzed data from the 2017 United States Behavioral Risk Factor Surveillance System (BRFSS) survey. Demographics, frequency of vegetable and fruit intake, smoking, alcohol use, physical activity, and sleep were examined. Results: Among 1032 stroke survivors, 57.8% were obese. Advanced age, female sex, veteran status, at least once-daily fruit intake, current smoking, and lack of physical activity were associated with obesity. Conclusion: Stroke survivors should be encouraged to pursue healthy behaviors to manage obesity. Appropriate transitional care, including diet education and tailored exercise, can be an effective strategy. [ABSTRACT FROM AUTHOR]

Summary: Adipose tissue is the first and primary target organ of obesity and the main source of circulating miRNAs in patients with obesity. This systematic review aimed to analyze and summarize the generation and mechanisms of adipose‐derived miRNAs and their role as early predictors of various obesity‐related complications. Literature searches in the PubMed and Web of Science databases using terms related to miRNAs, obesity, and adipose tissue. Pre‐miRNAs from the Human MicroRNA Disease Database, known to regulate obesity‐related metabolic disorders, were combined for intersection processing. Validated miRNA targets were sorted through literature review, and enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes via the KOBAS online tool, disease analysis, and miRNA transcription factor prediction using the TransmiR v. 2.0 database were also performed. Thirty miRNAs were identified using both obesity and adipose secretion as criteria. Seventy‐nine functionally validated targets associated with 30 comorbidities of these miRNAs were identified, implicating pathways such as autophagy, p53 pathways, and inflammation. The miRNA precursors were analyzed to predict their transcription factors and explore their biosynthesis mechanisms. Our findings offer potential insights into the epigenetic changes related to adipose‐driven obesity‐related comorbidities. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine the association between different metabolic obesity phenotypes and the non-alcoholic fatty liver disease (NAFLD). Methods: This cross-sectional analysis utilized data from the baseline phase of the Ravansar non-communicable diseases (RaNCD) cohort study, which involved 8,360 adults. Participants with a Fatty Liver Index (FLI) score of ≥ 60 was classified as having NAFLD. The FLI score was calculated using liver non-invasive markers and anthropometric measurements. Participants were categorized into four phenotypes based on the presence or absence of metabolic syndrome and obesity. Logistic regression analysis was used to evaluate the association of NAFLD and obesity phenotypes. Results: According to the FLI index, the prevalence of NAFLD was 39.56%. Participants with FLI scores of ≥ 60 had higher energy intake compared to those in the FLI < 60 group (P = 0.033). In subjects with metabolically unhealthy phenotypes, the level of physical activity was lower compared to those with metabolically healthy phenotypes. The risk of NAFLD in males with the metabolically healthy-obese phenotype increased by 8.92 times (95% CI: 2.20, 15.30), those with the metabolically unhealthy-non-obese phenotype increased by 7.23 times (95% CI: 5.82, 8.99), and those with the metabolically unhealthy-obese phenotype increased by 32.97 times (95% CI: 15.70, 69.22) compared to the metabolically healthy-non-obese phenotype. Similarly, these results were observed in females. Conclusion: This study demonstrated that the risk of NAFLD is higher in individuals with metabolically healthy/obese, metabolically unhealthy/non-obese, and metabolically unhealthy/obese phenotypes compared to those with non-obese/metabolically healthy phenotypes. [ABSTRACT FROM AUTHOR]

Background: Obesity and central obesity are multifactorial conditions with genetic and non-genetic (lifestyle and environmental) contributions. There is incomplete understanding of whether lifestyle modifies the translation from respective genetic risks into phenotypic obesity and central obesity, and to what extent genetic predisposition to obesity and central obesity is mediated via lifestyle factors. Methods: This is a cross-sectional study of 201,466 (out of approximately 502,000) European participants from UK Biobank and tested for interactions and mediation role of lifestyle factors (diet quality; physical activity levels; total energy intake; sleep duration, and smoking and alcohol intake) between genetic risk for obesity and central obesity. BMI-PRS and WHR-PRS are exposures and obesity and central obesity are outcomes. Results: Overall, 42.8% of the association between genetic predisposition to obesity and phenotypic obesity was explained by lifestyle: 0.9% by mediation and 41.9% by effect modification. A significant difference between men and women was found in central obesity; the figures were 42.1% (association explained by lifestyle), 1.4% (by mediation), and 40.7% (by modification) in women and 69.6% (association explained by lifestyle), 3.0% (by mediation), and 66.6% (by modification) in men. Conclusions: A substantial proportion of the association between genetic predisposition to obesity/central obesity and phenotypic obesity/central obesity was explained by lifestyles. Future studies with repeated measures of obesity and lifestyle would be needed to clarify causation. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use. Methods: We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses. Results: Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs. Conclusion: Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients' quality of life. [ABSTRACT FROM AUTHOR]

Aims: The aims of this study were to update risk estimates of obesity related co-morbidities and to provide evidence of the importance of obesity prevention to decision makers. Methods: The study included 25- to 74-year-old participants (N =22,977) of the National FINRISK Studies in 1997, 2002 and 2007. Body mass index was calculated from measured weight and height at baseline. Data on morbidity were ascertained via linkage to the National Hospital Discharge Register, the Cancer Register and the records of the Social Insurance Institution of Finland until the end of year 2018. The Cox proportional hazards model was used to estimate associations between weight status and the risk of the end-point diseases during follow-up, with adjustment for age and smoking. Results: At baseline, 31% of participants had at least one of the investigated diseases. Overweight, obesity and severe obesity were associated with type 2 diabetes, gout, gallbladder diseases and knee and hip osteoarthritis during the follow-up in both men and women. The risk of coronary heart disease was increased in men who were overweight, obese and severely obese and in women who were obese and severely obese. Risk of asthma was increased only among women who were obese and severely obese. No associations were found between obesity and breast, prostate or colorectal cancer. Conclusions: The study showed a strong relationship between excess body weight and the prevalence and incidence of several diseases. Obesity prevention is essential to reduce disease burden in the future. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is the standard of care for patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC); however, NAC can be associated with significant side effects and morbidity in some patients. NAC may contribute to sarcopenia, obesity, and the combination of the two. Our study examined the effects of NAC on body composition and the association between body composition and adverse events. METHODS: We created a retrospective database of patients with non-metastatic MIBC receiving NAC prior to RC. The change in skeletal muscle index (SMI) and fat mass index (FMI) was calculated using computed tomography (CT) scans done within three months prior to NAC and after the first two cycles. The association between body composition (sarcopenia, obesity, and sarcopenic obesity) and preoperative adverse events was investigated using a multivariable logistic regression. Changes in body composition were calculated using a paired Student's t-test. RESULTS: A total of 70 patients were included in our study. There was a mean decrease in SMI of 2.2±3.2 cm2/m2. Adiposity and FMI were unchanged by NAC. Sarcopenic obesity was found to be associated with adverse events among patients receiving NAC in the multivariable analysis. There was a total of 637 preoperative complications with grades 1-2 and 33 complications with grades 3-5. CONCLUSIONS: Based on our retrospective cohort study, NAC did not affect obesity and FMI, but there was a significant decrease in SMI. Sarcopenic obesity was associated with increased severity of NAC adverse events. As such, the presence of this factor may help predict tolerance of NAC. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease worldwide. Obesity has been proven to increase the susceptibility of an individual to infections, but the relationship between obesity and COVID-19 is still unclear. This study aimed to conduct a systematic review and meta-analysis of the prevalence of obesity and its effects in patients with COVID-19. Methods: Web of Science, PubMed and Embase were searched for English language studies up to May 22, 2020. We used a random or fixed-effects model to calculate pooled prevalence rates and odds ratio (OR) with 95% confidence intervals (CI). Results: Twelve studies with a total of 14 364 patients met the inclusion criteria. The pooled prevalence of obesity in patients with COVID-19 was 32.0% (95% CI, 26%-38%, P <.001). The prevalence of obesity in ICU COVID-19 patients were 37.0% (95% CI, 29%-46%, P <.001). Comparing between obese and non-obese patients, the meta-analysis showed that obesity was an important risk factor associated with COVID-19 patients needed for ICU care (OR: 1.36, 95% CI 1.22-1.52, P <.001). Conclusion: Obesity was highly prevalent (32.0%) in patients with COVID-19, especially in ICU patients (37.0%), and was an important risk factor for COVID-19 patients needed for ICU care. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses articles in the issue on topics including "the effects of weight neutral approaches on clinical outcomes and digital interventions in the preconception period", and "active weight loss interventions to study the behaviour change process".

Aims: This work aims to investigate the association between obesity and risk of delayed discharge and unplanned readmission in day surgery patients. Background: Day surgeries are well received and developing rapidly. Associations between obesity and delayed discharge and unplanned readmission, which are clinically relevant outcomes in day surgeries, are complex. Design: A systematic review and meta‐analysis was conducted. Data Sources: The PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, VIP, and Wan Fang databases were comprehensively searched from inception until January 2021. Review Methods: Two independent reviewers assessed the studies and extracted data. Pooled estimates were obtained using a random‐effects model. Results: Eleven articles published between 2007 and 2020 were finally included. Obesity appeared not to increase the risk of delayed discharge. However, morbid obesity seemed to be associated with a higher risk of delayed discharge. The meta‐analysis revealed no relationship between higher body mass index (BMI) and unplanned readmission for day surgery patients. Conclusions: Obesity appeared not to increase the risk of delayed discharge except in patients with morbid obesity. Additionally, a higher BMI was not associated with increased risk of unplanned readmission after day surgery. Future studies are required to address this issue further in different types of surgery and areas. Summary statement: What is already known about this topic? The complexity and flexibility of day surgeries have gradually broadened, but selecting the most suitable patients for day surgery is important for safety.Controversies exist on the association between obesity and risk of delayed discharge and unplanned readmission in day surgery patients. What this paper adds? This systematic review and meta‐analysis suggests that obesity did not significantly increase the risk of delayed discharge except in patients with morbid obesity.A higher BMI was not associated with increased risk of unplanned readmission after day surgery. The implications of this paper: Obesity should not be regarded as a contraindication to day surgery although patients with morbid obesity should be scheduled with caution and evaluated on a case‐by‐case basis. Future studies are required to address this issue further in more types of surgery and in different areas. [ABSTRACT FROM AUTHOR]

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥30 kg/m2 , or with a BMI of 27.0–29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence revealed the role of adipokines in carbohydrates and fat metabolism. The present study was designed to evaluate the adiponectin, leptin, and resistin levels in prediabetes subjects and evaluate the relationship between these adipokines and insulin resistance. Methods: A hospital-based descriptive study was conducted for one year. 200 individuals who met the inclusion criteria were enrolled in the study. Based on the oral glucose tolerance test, the study subjects were grouped into healthy controls (n = 100), prediabetic non-obese (n = 61), and prediabetic obese (n = 39). Blood glucose estimation was done by the glucose oxidase peroxidase method. Chemiluminescent immunoassay was used for the measurement of insulin level and homeostasis model assessment-estimated insulin resistance was used for the assessment of insulin resistance. Serum adipokines levels were determined by ELISA. Statistical analysis was performed by using SPSS Software. Results: Serum adiponectin levels decreased significantly in obese prediabetes (7.21 ± 2.15 µg/ml) when compared to non-obese prediabetes (7.28 ± 2.41 µg/ml) and healthy control subjects (13.64 ± 2.88 µg/ml, p < 0.001). Serum leptin levels increased significantly in obese prediabetes (13.59 ± 2.59 ng/ml) when compared to non-obese prediabetes (9.84 ± 2.66 ng/ml) and healthy control subjects (12.28 ± 2.65 ng/ml, p < 0.001). Serum resistin levels increased significantly in obese prediabetes (17.67 ± 3.60 ng/ml) when compared to non-obese prediabetes (17.2 ± 3.93 ng/ml) and healthy control subjects (14.46 ± 4.16 ng/ml, p < 0.001). Adiponectin-leptin ratio decreased significantly in obese prediabetes (0.56 ± 0.22) when compared to non-obese prediabetes (0.79 ± 0.4) and healthy control subjects (1.15 ± 0.37; p < 0.001). Fasting insulin resistance was statistically significant (p < 0.001) in all groups. Conclusion: The present study strongly suggests that the adipokine profile is an ideal diagnostic tool to predict prediabetes and metabolic syndrome, especially among those with insulin resistance. [ABSTRACT FROM AUTHOR]

Objectives: Stillbirth is an important health problem, and in Mexico, only half of the stillbirths have an explainable cause. The aim of this study was to implement a multidisciplinary workup to identify the etiology and potential risk factors for stillbirth at the Hospital Universitario "Dr. José Eleuterio González". Methods: This is a prospective, descriptive, observational study that included stillbirths from the Obstetrics Service from October 1st, 2019 to May 25, 2020. Evaluation strategies included a complete maternal medical history, physical examination of the fetus, and a photographic medical record. For every stillbirth either a prenatal ultrasound, a postnatal x-ray, or a fetal autopsy, were needed. Multiplex Ligation Probe Amplification (MLPA) was performed with an umbilical cord sample. Results: Thirty-three stillbirths were reported; 21 were included in the analysis. Eleven women (52.3%) had known risk factors for stillbirth, mainly elevated body mass index and diabetes. On physical examination, external birth defects were found in 8 fetuses (38%). X-ray was performed in 14 cases (66%), alterations were detected as a probable etiologic cause just in one. All cases underwent MLPA, which were reported negative. Three cases had criteria for autopsy. Findings were inconclusive to determine etiology. Conclusions: The best tools for evaluation of stillbirth were the elaboration of clinical history, physical examination, and prenatal ultrasound. Diabetes and obesity were the most frequent risk factors found in our population. These factors are preventable by implementing strategies that lead to better prenatal care. Significance: Stillbirth is a health problem whose causes are rarely evaluated and explained to the families that go through this situation. To completely explain the causes of stillbirth a complete workup should be performed, where a multidisciplinary participation is needed. Mainly these workups have been performed retrospectively, however we introduce a complete evaluation of stillbirth since the moment of arrival to obstetrics department and performing evaluations for fetal, maternal or combined causes, including genetic testing; detecting key health issues in our population, that can be prevented with an adequate prenatal care. [ABSTRACT FROM AUTHOR]

Aims. The prevalence of obesity is rapidly increasing during the past decades. While previous research has focused on the early outcome after cardiac surgery or specific complications, the current study covers the whole burden of obesity in the field of cardiac surgery over short term and long term. Endpoints of the study were all-cause mortality, perioperative outcome, and wound-healing disorders (WHDs). Methods. 14.754 consecutive patients who underwent cardiac surgery over a 14 years' time period were analyzed. BMI classifications were used according to the WHO definition. Results. Mean survival was 11.95 years ± 0.1; CI 95% [12.04–12.14]. After adjustment for clinical baseline characteristics, obesity classes' I–III (obesity) did not affect 30-day mortality or all-cause mortality during the whole observational period. After adjustment for known risk factors, the risk for WHDs doubled at least in obesity patients as follows: obesity I (OR = 2.06; CI 95% [1.7–2.5]; p < 0.0001), obesity II (OR = 2.5; CI 95% [1.83–3.41]; p < 0.0001), and obesity III (OR = 4.12; CI 95% [2.52–6.74]; p < 0.0001). The same applies to the risk for sternal reconstruction that is substantially elevated in obesity I (OR = 2.23; CI 95% [1.75–2.83]; p < 0.0001), obesity II (OR = 2.81; CI 95% [1.91–4.13]; p < 0.0001), and obesity III (OR = 2.31; CI 95% [1.08–4.97]; p = 0.03). No significant correlation could be found between obesity and major adverse events in the perioperative course like renal failure, ventilation >24 h, re-exploration, or cerebrovascular events. Conclusions. Cardiac surgery is safe in obesity as short- and long-term mortality are not increased, and major adverse events during the perioperative course are similar to control patients. The burden of obesity lies in substantially increased rates of wound-healing disorders and sternal reconstructions. [ABSTRACT FROM AUTHOR]

Arthritis is the leading cause of disability in Ireland with knee osteoarthritis the most common presentation. One in five women and one in 10 men over the age of 60 in Ireland are diagnosed with osteoarthritis. The causative factors are multifactorial, but the increasing incidence of obesity is contributing greatly to the occurrence of osteoarthritis of the weight-bearing joints. The rheumatology advanced nurse practitioner is an autonomous clinical practitioner and potential solution to the growing numbers of people needing interventions for osteoarthritis, due to their ability to assess, diagnose, treat, and discharge these patients who ordinarily would be assessed from a medical waiting list. As obesity is becoming increasingly prevalent, it is important to address this with the patient cohort to try to reduce the burden of disease and treat not only the symptomatic knee osteoarthritis but the causative factors and provide patient-centred care. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the associations of obesity and clinical characteristics including interleukin-6 (IL-6) with hospital length of stay (LOS) in coronavirus disease-2019 (COVID-19) patients in Korea. Methods: A retrospective descriptive study design was employed to analyze medical data from a government-designated hospital in a city of Korea. Clinical data were collected from 256 patients with COVID-19 in negative-pressure isolation wards in 2021. The following parameters were analyzed: body mass index (BMI), IL-6 levels, age, sex, comorbidities, healthy habitsat the time ofadmission, and LOS. The statistical package SPSS 26.0 was used for descriptive statistics, the independent t-test, the chi-square test, and partial correlation coefficients. Results: The age of COVID-19 patients was positively correlated with BMI (r = -.16, p = .012), IL-6 levels (r = .14, p = .022) and LOS (r = .26, p < .001). Obesity, non-drinking, hypertension, and older age were associated with longer LOS. Conclusion: These results suggest that age, obesity, and hypertension in COVID-19 patients are related to LOS. Studies investigating other factors that can affect long-term hospitalization in COVID-19 patients are suggested. [ABSTRACT FROM AUTHOR]

This article presents a study that explores the relationship between operative time and obesity-related outcomes in total knee arthroplasty (TKA). The study reveals that longer operative times are associated with higher odds of readmission, reoperation, and postoperative complications. However, the interaction between obesity and operative time is more complex, with different outcomes depending on the length of the procedure. The article emphasizes the need to consider multiple patient characteristics when assessing operative times and suggests alternative data sources for more representative samples. It also highlights the importance of making decisions about TKA based on individual patient needs rather than solely relying on weight or comorbidities. [Extracted from the article]

Background Obesity-based cutoffs in TKA are premised on higher rates of postoperative complications. However, operative time may be associated with postoperative complications, leading to an unnecessary restriction of TKA in patients with obesity. If operative time is associated with these obesity-related outcomes, it should be accounted for in order to ensure all measurable factors associated with negative outcomes are examined for patients with obesity after TKA. Questions/purposes We asked: (1) Is operative time, controlling for BMI class, associated with readmission, reoperation, and postoperative major and minor complications? (2) Is operative time associated with a difference in the direction or strength of obesity-related adverse outcomes? Methods In this comparative study, we extracted all records on elective, unilateral TKA between January 2014 and December 2020 in the American College of Surgeons National Surgical Quality Improvement Program database, resulting in an initial sample of 394,381 TKAs. Patients with emergency procedures (0.1% [270]) and simultaneous bilateral TKAs (2% [8736]), missing or null data (1% [4834]), and those with operative times less than 25 minutes (0.1% [548]) were excluded, leaving 96% (379,993) of our original sample size. The National Surgical Quality Improvement Program database was selected because of its inclusion of operative time, which is not found in any other national database. BMI was subdivided into underweight (BMI < 18.5 kg/m², < 1% [719]), normal weight (BMI 18.5 to 24.9 kg/m², 9% [34,513]), overweight (BMI 25.0 to 29.9 kg/m², 27% [101,538]), Class I obesity (BMI 30.0 to 34.9 kg/m², 29% [111,712]), Class II obesity (BMI 35.0 to 39.9 kg/m², 20% [76,605]), and Class III obesity (BMI ≥ 40.0 kg/m², 14% [54,906]). The mean operative time was 91 ± 36 minutes, 61% of patients were women (233,062 of 379,993), and the mean age was 67 ± 9 years. Patients with obesity tended to be younger and more likely to have preoperative comorbidities and longer operative times than patients with normal weight. Multivariable logistic regression models examined the main effects of operative time with respect to 30-day readmission, reoperation, and major and minor medical complications, while adjusting for BMI class and other covariates including age, sex, race, smoking status, and number of preoperative comorbidities. We then evaluated the potential interaction effect of BMI class and operative time. This interaction term helps determine whether the association of BMI with postoperative outcomes changes based on the duration of the surgery, and vice versa. If the interaction term is statistically significant, it implies the association of BMI with adverse postoperative outcomes is inconsistent across all patients. Instead, it varies with the operative time. Adjusted odds ratios and 95% confidence intervals were calculated, and interaction effects were plotted. Results After controlling for obesity, longer procedure duration was independently associated with higher odds of all outcomes (30-minute estimates; adjusted ORs are per minute), including readmission (9% per half-hour of surgical duration; adjusted OR 1.003 [95% CI 1.003 to 1.004]; p < 0.001), reoperation (15% per half-hour of surgical duration; adjusted OR 1.005 [95% CI 1.004 to 1.005]; p < 0.001), postoperative major complications (9% per half-hour of surgical duration; adjusted OR 1.003 [95% CI 1.003 to 1.004]; p < 0.001), and postoperative minor complications (18% per half-hour of surgical duration; adjusted OR 1.006 [95% CI 1.006 to 1.007]; p < 0.001). The interaction effect indicates that patients with obesity had lower odds of reoperation than patients with normal weight when operative times were shorter, but higher odds of reoperation with a longer operative duration. Conclusion We found that operative time, a proxy for surgical complexity, had a moderate, differential association with obesity over a 30-minute period. Perioperative modification of surgical complexity such as surgical techniques, training, and team dynamics may make safe TKA possible for certain patients who might have otherwise been denied surgery. Decisions to refuse TKA to patients with obesity should be based on a holistic assessment of a patient's operative complexity, rather than strictly assessing a patient's weight or their ability to lose weight. Future studies should assess patient-specific characteristics that are associated with operative time, which can further push the development of techniques and strategies that reduce surgical complexity and improve TKA outcomes. Level of Evidence Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Objective The objective of this study is to examine the relationship between body mass index (BMI) and complications for patients undergoing postpartum permanent contraception. Study Design Retrospective cohort study of patients aged 18 or older who had a vaginal delivery at an academic hospital between 2011 and 2016 and underwent a postpartum tubal ligation during the delivery admission. There were three comparative groups: nonobese (BMI ≤ 29 kg/m 2), obese (BMI 30–39 kg/m 2), and morbidly obese BMI (≥40 kg/m 2). The outcome of interest was composite operative complications which included any occurrence of an intraoperative, postoperative, or anesthesia complication. Results A total of 921 patients were included for analysis. Average operative time was statistically longer for patients in the morbidly obese group (33 minutes) vs. the nonobese (25 minutes) and obese (29 minutes) groups (p < 0.0001). Composite complications were greater for the obese groups, but not statistically significant (5.1 vs. 6 vs. 16%, p = 0.06). Wound complications were significantly greater for the obese groups (0.8 vs. 1.5 vs. 5.5%, p = 0.01). A logistic regression model demonstrated that only operative time was predictive of operative complications. Conclusion Overall complications of postpartum tubal complications are low; however, our study did demonstrate significantly longer operative time and wound complications for patients with obesity. The findings of our study indicate that postpartum permanent contraception can remain as an option for these patients. Further studies may help identify the best practices to decrease operative time and subsequent wound complications. This study contributes to the limited data regarding obesity and postpartum permanent contraception. We found increased operative time and wound complications for obese patients. Additional studies may identity best practices to decrease these complications. Given our findings of overall low operative complications, postpartum permanent contraception can remain an option for obese patients. [ABSTRACT FROM AUTHOR]

Objectives: This study examined the mechanism of fat mass and obesity‐related gene (FTO)‐mediated heme oxygenase‐1 (HO‐1) m6A modification facilitating neurological recovery in spinal cord injury (SCI) mice. FTO/HO‐1 was identified as a key regulator of SCI as well as a potential target for treatment of SCI. Methods: An SCI mouse was treated with pcDNA3.1‐FTO/pcDNA3.1‐NC/Dac51. An oxygen/glucose deprivation (OGD) cell model simulated SCI, with cells treated with pcDNA3.1‐FTO/si‐HO‐1/Dac51. Motor function and neurobehavioral evaluation were assessed using the Basso, Beattie, and Bresnahan (BBB) scale and modified neurological severity score (mNSS). Spinal cord pathology and neuronal apoptosis were assessed. Further, FTO/HO‐1 mRNA and protein levels, HO‐1 mRNA stability, the interaction of YTHDF2 with HO‐1 mRNA, neuronal viability/apoptosis, and HO‐1 m6A modification were evaluated. Results: Spinal cord injury mice exhibited reduced BBB, elevated mNSS scores, disorganized spinal cord cells, scattered nuclei, and severe nucleus pyknosis. pcDNA3.1‐FTO elevated FTO mRNA, protein expression, and BBB score; reduced the mNSS score of SCI mice; decreased neuronal apoptosis; improved the cell arrangement; and improved nucleus pyknosis in spinal cord tissues. OGD decreased FTO expression. FTO upregulation ameliorated OGD‐induced neuronal apoptosis. pcDNA3.1‐FTO reduced HO‐1 mRNA and protein and HO‐1 m6A modification, while increasing HO‐1 mRNA stability and FTO in OGD‐treated cells. FTO upregulated HO‐1 by modulating m6A modification. HO‐1 downregulation attenuated the effect of FTO. pcDNA3.1‐FTO/Dac51 increased the HO‐1 m6A level in mouse spinal cord tissue homogenate, reduced BBB, boosted mNSS scores of SCI mice, aggravated nucleus pyknosis, and increased neuronal apoptosis in spinal cord tissues, confirming that FTO mediated HO‐1 m6A modification facilitated neurological recovery in SCI mice. Conclusion: The fat mass and obesity‐related gene modulates HO‐1 mRNA stability by regulating m6A modification levels, thereby influencing HO‐1 expression and promoting neurological recovery in SCI mice. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is associated with a worse prognosis in COVID-19 patients with acute respiratory distress syndrome (ARDS). Veno-venous (V-V) Extracorporeal Membrane Oxygenation (ECMO) can be a rescue option, however, the direct impact of morbid obesity in this select group of patients remains unclear. Methods: This is an observational study of critically ill adults with COVID-19 and ARDS supported by V-V ECMO. Data are from 82 institutions participating in the COVID-19 Critical Care Consortium international registry. Patients were admitted between 12 January 2020 to 27 April 2021. They were stratified based on Body Mass Index (BMI) at 40 kg/m2. The endpoint was survival to hospital discharge. Results: Complete data available on 354 of 401 patients supported on V-V ECMO. The characteristics of the high BMI (>40 kg/m2) and lower BMI (≤40 kg/m2) groups were statistically similar. However, the 'high BMI' group were comparatively younger and had a lower APACHE II score. Using survival analysis, older age (Hazard Ratio, HR 1.49 per-10-years, CI 1.25–1.79) and higher BMI (HR 1.15 per-5 kg/m2 increase, CI 1.03 – 1.28) were associated with a decreased patient survival. A safe BMI threshold above which V-V ECMO would be prohibitive was not apparent and instead, the risk of an adverse outcome increased linearly with BMI. Conclusion : In COVID-19 patients with severe ARDS who require V-V ECMO, there is an increased risk of death associated with age and BMI. The risk is linear and there is no BMI threshold beyond which the risk for death greatly increases. [ABSTRACT FROM AUTHOR]

The interactive effects of obesity and physical inactivity on lipid metabolism and prevalent dyslipidemia are scarcely reported in rural regions. 39029 subjects were obtained from the Henan Rural Cohort, and their metabolic equivalents (METs) of physical activity (PA) were computed. Independent associations of the obesity indices and PA with either lipid indices or prevalent dyslipidemia were analyzed by generalized linear models, and additive effects of obesity and PA on prevalent dyslipidemia were further quantified. Each obesity index was positively associated with total cholesterol, triglyceride, low-density lipoprotein or prevalent dyslipidemia but negatively associated with high-density lipoprotein, whereas the opposite association of PA with either each lipid index or prevalent dyslipidemia was observed. Joint association of PA and each obesity index with each lipid index and prevalent dyslipidemia was observed. Furthermore, the association of each obesity index in association with each lipid index was attenuated by increased PA levels. [ABSTRACT FROM AUTHOR]

Low fitness and obesity at midlife are individually associated with later‐life decline in cognition and health. However, the relationship between profiles of midlife fitness and obesity with midlife cognition is unclear and was examined by this study. Participants from the third follow‐up of the Childhood Determinants of Adult Health study (2014–2019; aged 36–49 years) were assessed for obesity (body mass index [BMI]), cardiorespiratory (physical work capacity) and muscular fitness (isometric grip and leg strength), and these factors were entered into a latent profile analysis. Psychomotor‐attention, learning–working memory and global cognition composites were derived from z‐scores of individual CogState battery tests. Linear regression analyses examined associations between profiles of fitness and obesity with cognition, adjusting for age, sex, education, alcohol and smoking. Using data from 617 participants [44.4 ± 2.6 (mean ± SD) years, 52% female], we identified 5 mutually exclusive profiles of obesity and fitness. Relative to those with the lowest fitness and highest BMI (5% of sample), those with a profile of (1) highest muscular fitness and average BMI (9%), (2) average muscular fitness and BMI (61%) and (3) highest cardiorespiratory fitness (CRF) and below average BMI (7%) all exhibited better global cognition [at least 0.44 (0.12, 0.77) SD, 95% CI] and psychomotor‐attention performance [at least 0.59 (0.27, 0.91) SD, 95% CI]. Compared with low fitness and unhealthy BMI levels, possessing average or high muscular and CRF and a healthy BMI in midlife was associated with better cognitive performance. Enhancing fitness and reducing obesity in midlife could contribute to improved cognitive performance in middle age. Highlights: Profiles containing adults with a combination of low levels of cardiorespiratory and muscular fitness and higher levels of obesity were associated with lower psychomotor‐attention and global cognition at midlife.Possessing average or higher levels of fitness, and lower obesity at midlife, was associated with better cognitive performance at midlife compared to those with lower fitness and unhealthy BMIs.Maintaining fitness and reducing obesity at midlife may contribute to greater cognitive performance at midlife and beyond and reduce the risk of cognitive decline. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare the results of cementless bilateral total knee arthroplasty (TKA) between individuals in different obesity groups. Materials and methods: This was a retrospective cohort study. Patients with a body mass index (BMI) greater than 25 who underwent bilateral TKA for gonarthrosis between 2014 and 2020 and completed a minimum follow-up of 24 months were included. Age, sex, height, weight, BMI, operation time, length of stay, patient satisfaction, knee scores and complications were compared. Patients with missing data, who were followed for less than 24 months or had postoperative fractures around the knee were excluded. Results: There was a significant difference between the groups in terms of operation time (Class III > overweight > Class II > Class I p < 0.001). There was a significant difference in complications between the groups (Class III > Class I > Class II > overweight p = 0.010). According to our pairwise comparison, complications were more common in the class III group than in the overweight group. Knee score (KS) and function score (FS) increased significantly after surgery in all groups (p < 0.001), with no difference in FS (p = 0.448). Knee score changes were greater in the overweight and class I groups (p < 0.001). There was a significant interaction between both KS and FS and person satisfaction (p < 0.001). Conclusion: Cementless TKA improved KS and FS in all obesity groups, yielded high patient satisfaction. Although the incidence of complications was higher in the morbidly obese patients than in the overweight patients, the difference was not significant. Patients with morbid obesity should be informed about related risks before planning cementless TKA. [ABSTRACT FROM AUTHOR]

Background: Stoma prolapse (SP) is a common stoma-related complication, particularly in loop colostomies. This study aimed to investigate potential risk factors for SP development after laparoscopic loop colostomy. Methods: In total, data from 140 patients who underwent laparoscopic loop colostomy were analyzed between September 2016 and March 2022. Risk factors for SP were investigated retrospectively. Results: The median follow-up duration after colostomy was 12.5 months, and SP occurred in 33 (23.6%) patients. Multivariate analysis showed that being overweight (body mass index ≥ 25; odds ratio [OR], 8.69; 95% confidential interval [CI], 1.61–46.72; p = 0.012) and having a thin rectus abdominis penetration of the stoma (< 8.9 mm; OR, 8.22; 95% CI, 2.50–27.05; p < 0.001) were independent risk factors for SP. Other patient characteristics and surgical factors associated with stoma construction were unrelated to SP development. Conclusions: Being overweight and the route penetrating the thinner rectus abdominis during stoma construction was associated with a significantly higher incidence of SP after laparoscopic loop colostomy. Selecting a construction site that penetrates the thicker rectus abdominis muscle may be crucial for preventing SP. [ABSTRACT FROM AUTHOR]

Simple Summary: This systematic review explores the relationship between obesity and renal-cell carcinoma (RCC), focusing on how different types of fat measurements influence the behavior and prognosis of the disease. Despite some studies suggesting a protective role of certain fat deposits, particularly visceral adipose tissue (VAT), conflicting findings exist across different adipose metrics and RCC subtypes. Methodological variations and limitations, such as retrospective designs and sample size constraints, pose challenges to standardization and generalizability. Further research efforts are needed to understand these associations better and establish standardized approaches for adiposity assessment in RCC patients, which could inform clinical practice and therapeutic decision-making. (1) Background: Renal-cell carcinoma (RCC) incidence has been steadily rising, with obesity identified as a potential risk factor. However, the relationship between obesity and RCC prognosis remains unclear. This systematic review aims to investigate the impact of different adipose tissue measurements on RCC behavior and prognosis. (2) Methods: A search of MEDLINE databases identified 20 eligible studies focusing on various fat measurements, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PRAT), and the Mayo adhesive probability (MAP) score. (3) Results: The review revealed conflicting findings regarding the association between adipose tissue measurements and RCC outcomes. While some studies suggested a protective role of certain fat deposits, particularly VAT, against disease progression and mortality, others reported contradictory results across different adipose metrics and RCC subtypes. (4) Conclusions: Methodological variations and limitations, such as retrospective designs and sample size constraints, pose challenges to standardization and generalizability. Further research is needed to understand these associations better and establish standardized approaches for adiposity assessment in RCC patients, which could inform clinical practice and therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal adenoma formation has multiple contributing factors and how these risk factors interact is not precise. Past studies have demonstrated that increased weight is one of the risk factors of colorectal adenoma formation, but does not mean participants with normal body weight are not concerned about colorectal adenoma formation. We aimed to explore the specific risk factors for colorectal adenomas in individuals with normal body weight, who are often overlooked, and the interaction between these risk factors. Background: We aimed to evaluate the interaction between colorectal adenoma risks among asymptomatic individuals in terms of metabolic health status and obesity, and examine the normal waist-to-hip ratio (WHR) in adults with colorectal adenoma risk. Methods: A cross-sectional, retrospective study was conducted at MacKay Memorial Hospital involving 16,996 participants who underwent bidirectional gastrointestinal endoscopy between 2013 and 2023. The study recorded important clinicopathological characteristics, including age, body mass index and WHR, Framingham Risk Score (FRS), blood glucose level, and Helicobacter pylori (H. pylori) infection status. Results: Multivariate logistic regression analysis demonstrated that elevated hemoglobin A1C (HbA1c), increased FRS, positive H. pylori infection, and WHR ≥ 0.9 are independent risk factors for colorectal adenoma. In examining the interaction between FRS and WHR using multivariate logistic regression to evaluate adenoma risk, the OR for the interaction term was 0.95, indicating a decline in adenoma risk when considering the interaction between these two factors. Incorporating HbA1c into the analysis, evaluating the interaction between FRS and WHR still demonstrated a statistically significant impact on adenoma risk (OR 0.96, p < 0.001). Participants with WHR < 0.9, elevated FRS, positive H. pylori infection, and increased HbA1c levels were associated with a higher risk of colorectal adenoma formation. Remarkably, the increased risk of adenoma due to rising HbA1c levels was statistically significant only for those with a WHR < 0.9. Conclusions: An increase in FRS and HbA1c or a positive H. pylori infection still warrants vigilance for colorectal adenoma risk when WHR is 0.9. These factors interacted with each other and were found to have a minimal decline in adenoma risk when considering the interaction between WHR and FRS. [ABSTRACT FROM AUTHOR]

In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II–IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A 1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA 1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 −8·4% [−9·2 to −7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. Novo Nordisk. [ABSTRACT FROM AUTHOR]

The "missing" heritability of complex traits may be partly explained by genetic variants interacting with other genes or environments that are difficult to specify, observe, and detect. We propose a new kernel-based method called Latent Interaction Testing (LIT) to screen for genetic interactions that leverages pleiotropy from multiple related traits without requiring the interacting variable to be specified or observed. Using simulated data, we demonstrate that LIT increases power to detect latent genetic interactions compared to univariate methods. We then apply LIT to obesity-related traits in the UK Biobank and detect variants with interactive effects near known obesity-related genes (URL: https://CRAN.R-project.org/package=lit). [ABSTRACT FROM AUTHOR]

Objective In the setting of a growing obese obstetric population, we sought to determine whether differences in body mass index (BMI) and obesity class influenced both serum magnesium levels and the likelihood of achieving therapeutic levels for eclampsia prophylaxis after standard boluses of magnesium sulfate. Study Design This is a retrospective cohort study of patients treated with magnesium sulfate in the setting of either preeclampsia with severe features or preterm labor between 2010 and 2016. Subjects were categorized by BMI: Normal (BMI < 30 kg/m 2), Class 1 (BMI 30–34.9 kg/m 2), Class 2 (BMI 35–39.9 kg/m 2), and Class 3 (BMI ≥ 40 kg/m 2). Study participants' demographics, intrapartum characteristics, and adverse reactions were compared among the groups. Logistic regression models were used to calculate unadjusted and adjusted odds ratios comparing the likelihood of each BMI class reaching therapeutic eclamptic prophylactic levels. Linear regression models were also evaluated to determine the relationship between BMI and post-bolus serum magnesium levels. Results Of the 760 people who met the inclusion criteria, 313 (41.1%) had normal BMI, 190 (25.0%) had Class 1 obesity, 135 (17.8%) had Class 2 obesity, and 122 (16.1%) had Class 3 obesity. When adjusted for confounders, those with Class 1 obesity were 54% less likely to achieve serum levels deemed therapeutic for seizure prophylaxis compared with normal BMI counterparts. Meanwhile, those with Class 2 or 3 obesity were 90% less likely. Linear regression models also demonstrated an inverse association between BMI and post-bolus serum magnesium levels. Conclusion Increasing BMI has a significant effect on post-bolus serum magnesium levels regardless of standard loading dose used. Immediately after bolus administration, obese gravidas are significantly less likely to reach levels effective for eclamptic seizure prophylaxis. When considering which bolus to administer in an obese gravida, it may be more beneficial to choose a 6 g load. Key Points BMI has an inverse relationship with post-bolus serum magnesium levels. Obese gravidas were less likely to reach eclampsia prophylaxis levels regardless of bolus type. Obesity class, not just the presence or absence of obesity, plays a role in serum magnesium levels. [ABSTRACT FROM AUTHOR]

Simple Summary: Epidemiologic evidence and previous research have established obesity, diabetes and the metabolic syndrome as risk factors for pancreatic cancer in humans, while the precise mechanisms remain incompletely characterized. The concept that these metabolic diseases may be driven by diet implies that many cancers could be prevented or delayed through lifestyle modifications. By design, genetically engineered mouse models expressing oncogenic mutants of KRAS protein within the epithelial cells of the pancreas closely recapitulate the human disease. Research on diet-induced obesity in such mice implies the involvement of diverse factors including elevated insulin/insulin-like growth factors, inflammation, and genetic/epigenetic alterations and has revealed dramatic acceleration of cancer incidence that was more marked in males than females. The present research uses proteomic and phosphoproteomic analysis as a foundation to assess differentially expressed proteins and associated signal transduction pathways, yielding further novel mechanistic insights into the influence of tumor microenvironment on diet-induced obesity-associated pancreatic cancer. Diet-induced obesity (DIO) promotes pancreatic ductal adenocarcinoma (PDAC) in mice expressing KRasG12D in the pancreas (KC mice), but the precise mechanisms remain unclear. Here, we performed multiplex quantitative proteomic and phosphoproteomic analysis by liquid chromatography–tandem mass spectrometry and further bioinformatic and spatial analysis of pancreas tissues from control-fed versus DIO KC mice after 3, 6, and 9 months. Normal pancreatic parenchyma and associated proteins were steadily eliminated and the novel proteins, phosphoproteins, and signaling pathways associated with PDAC tumorigenesis increased until 6 months, when most males exhibited cancer, but females did not. Differentially expressed proteins and phosphoproteins induced by DIO revealed the crucial functional role of matrisomal proteins, which implies the roles of upstream regulation by TGFβ, extracellular matrix-receptor signaling to downstream PI3K-Akt-mTOR-, MAPK-, and Yap/Taz activation, and crucial effects in the tumor microenvironment such as metabolic alterations and signaling crosstalk between immune cells, cancer-associated fibroblasts (CAFs), and tumor cells. Staining tissues from KC mice localized the expression of several prognostic PDAC biomarkers and elucidated tumorigenic features, such as robust macrophage infiltration, acinar–ductal metaplasia, mucinous PanIN, distinct nonmucinous atypical flat lesions (AFLs) surrounded by smooth muscle actin-positive CAFs, invasive tumors with epithelial–mesenchymal transition arising close to AFLs, and expanding deserted areas by 9 months. We next used Nanostring GeoMX to characterize the early spatial distribution of specific immune cell subtypes in distinct normal, stromal, and PanIN areas. Taken together, these data richly contextualize DIO promotion of Kras-driven PDAC tumorigenesis and provide many novel insights into the signaling pathways and processes involved. [ABSTRACT FROM AUTHOR]

Purpose: Osteoporosis is a metabolic bone disease characterized by decreased bone strength and mass, which predisposes patients to fractures and is associated with high morbidity and mortality. Like osteoporosis, obesity and diabetes are systemic metabolic diseases associated with modifiable risk factors and lifestyle, and their prevalence is increasing. They are related to decreased quality of life, functional loss and increased mortality, generating high costs for health systems and representing a worldwide public health problem. Growing evidence reinforces the role of bone marrow adipose tissue (BMAT) as an influential factor in the bone microenvironment and systemic metabolism. Given the impact of obesity and diabetes on metabolism and their possible effect on the bone microenvironment, changes in BMAT behavior may explain the risk of developing osteoporosis in the presence of these comorbidities. Methods: This study reviewed the scientific literature on the behavior of BMAT in pathological metabolic conditions, such as obesity and diabetes, and its potential involvement in the pathogenesis of bone fragility. Results: Published data strongly suggest a relationship between increased BMAT adiposity and the risk of bone fragility in the context of obesity and diabetes. Conclusion: By secreting a broad range of factors, BMAT modulates the bone microenvironment and metabolism, ultimately affecting skeletal health. A better understanding of the relationship between BMAT expansion and metabolic disturbances observed in diabetic and obese patients will help to identify regulatory pathways and new targets for the treatment of bone-related diseases, with BMAT as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Objective Obesity conveys a risk for RA development, while paradoxically, associating with less radiographic progression after RA diagnosis. Using MRI we can study this surprising association in detail from MRI-detected synovitis and osteitis to MRI-detected erosive progression, which precedes radiographic progression. Previous research suggested obesity associates with less osteitis and synovitis. We therefore aimed to (i) validate the previously suggested association between BMI and MRI-detected osteitis/synovitis; (ii) study whether this is specific for ACPA-positive or ACPA-negative RA or also present in other arthritides; (iii) study whether MRI-detected osteitis associates with MRI-detected erosive progression; and (iv) study whether obesity associates with MRI-detected erosive progression. Methods We studied 1029 early arthritis patients (454 RA, 575 other arthritides), consecutively included in Leiden Early Arthritis Clinic. At baseline patients underwent hand-and-foot MRI that were RAMRIS-scored, and 149 RA patients underwent follow-up MRIs. We studied associations between baseline BMI and MRI-detected osteitis/synovitis (using linear regression), and erosive progression (using Poisson mixed models). Results In RA, higher BMI associated with less osteitis at disease onset (β = 0.94; 95% CI: 0.93, 0.96) but not with synovitis. Higher BMI associated with less osteitis in ACPA-positive RA (β = 0.95; 95% CI: 0.93, 0.97), ACPA-negative RA (β = 0.97; 95% CI: 0.95, 0.99) and other arthritides (β = 0.98; 95% CI: 0.96, 0.99). Over 2 years, overweight and obesity associated with less MRI-detected erosive progression (P  = 0.02 and 0.03, respectively). Osteitis also associated with erosive progression over 2 years (P  < 0.001). Conclusions High BMI relates to less osteitis at disease onset, which is not confined to RA. Within RA, high BMI and less osteitis associated with less MRI-detected erosive progression. This suggests that the protective effect of obesity on radiographic progression is exerted via a path of less osteitis and subsequently fewer MRI-detected erosions. [ABSTRACT FROM AUTHOR]

Aim: The combination of dynapenia (age-related muscle weakness) and obesity is referred to as dynapenic obesity. We examined the associations between dynapenic obesity and cortical bone thickness and trabecular bone density. Methods: The participants were 797 community-dwelling postmenopausal women (with an average age of 62.5 years) who were stratified into normopenia without obesity, dynapenia without obesity (dynapenia), normopenia with obesity (obesity) and dynapenia with obesity (dynapenia obesity) groups based on their grip strength and body fat percentage. Cortical bone thickness and trabecular bone density were measured using ultrasonic bone densitometry. The participants were further divided into those with low cortical bone thickness and low trabecular bone density. Logistic regression analysis was used to identify associated factors. Results: Individuals with dynapenia (odds ratio [OR] 1.77, 95% confidence interval [CI] 1.16-2.68), obesity (OR 2.46, 95% CI 1.62-3.75) and dynapenic obesity (OR 4.07, 95% CI 2.44-6.79) all significantly increased the odds of low cortical bone thickness. Conversely, the odds of low trabecular bone density were significantly lower in the obesity group (OR 0.65, 95% CI 0.43-0.99) and dynapenic obesity group (OR 0.60, 95% CI 0.37-0.97). Conclusions: Dynapenic obesity was found to be associated with cortical bone thinning that might compromise bone health. Postmenopausal women with dynapenic obesity might need to be closely monitored for preserving bone health. [ABSTRACT FROM AUTHOR]

Obesity is highly prevalent in breast cancer (BC) survivors. Adipose tissue promotes inflammation, affecting recurrence, morbidity, and quality of life. This study aimed to determine the relationship of body composition parameters with the levels of C-reactive protein (CRP) and interleukin 6 (IL-6) in female BC survivors. Additionally, we evaluated the association of log-transformed serum concentrations of CRP and IL-6 with the appendicular skeletal lean mass index (ASMI). The results showed that CRP was positively associated with body fat percentage (BFP; β adjusted =.08, 95% CI:.02–.14) in all participants, and with fat mass index (FMI; β =.24, 95% CI:.08–.40) only in premenopausal women. IL-6 was positively associated with FMI (β adjusted =.16, 95% CI:.03–.29), while ASMI decreased as CRP levels increased (β adjusted = −.30, 95% CI: −.53 to −.06). Interventions to improve body composition in BC survivors should also consider the role of inflammatory markers in changes in body composition to avoid sarcopenic obesity (SO) and the risk of BC recurrence. [ABSTRACT FROM AUTHOR]

Purpose: Obesity is a strong risk factor for many diseases, with controversy regarding the cause(s) of tuberculosis (TB) reflected by contradictory findings. Therefore, a larger sample population is required to determine the relationship between obesity and TB, which may further inform treatment. Methods: Obesity-related indicators and TB mutation data were obtained from a genome-wide association study database, while representative instrumental variables (IVs) were obtained by screening and merging. Causal relationships between exposure factors and outcomes were determined using two-sample Mendelian randomization (MR) analysis. Three tests were used to determine the representativeness and stability of the IVs, supported by sensitivity analysis. Results: Initially, 191 single nucleotide polymorphisms were designated as IVs by screening, followed by two-sample MR analysis, which revealed the causal relationship between waist circumference [odds ratio (OR): 2.13 (95% confidence interval (CI): 1.19–3.80); p = 0.011] and TB. Sensitivity analysis verified the credibility of the IVs, none of which were heterogeneous or horizontally pleiotropic. Conclusion: The present study determined the causal effect between waist circumference and TB by two-sample MR analysis and found both to be likely to be potential risk factors. [ABSTRACT FROM AUTHOR]

Background: The incidence of endometrial cancer is globally increasing. Aotearoa New Zealand is no exception with a 59% increase in cases over that last ten years. Aims: We report a sub‐set of themes which pertain to provider reflections of rising endometrioid‐type endometrial cancer incidence in individuals with high weight. Materials and Methods: Fifteen semi‐structured interviews with healthcare professionals experienced in providing care to women with endometrial cancer were audio‐recorded and transcribed. Interviews were analysed using reflexive thematic analysis. Results: Two main themes emerged: (1) concerns for the future; and (2) impact on fertility and treatment options. Healthcare professionals discussed rising incidence in younger people and a need for increased awareness about the association of excess weight as a risk factor for developing the disease. The concern extended to workforce and equipment shortfalls of meeting the needs of individuals with higher weight, which subsequently influenced treatment options, health outcomes and survivorship. Conclusions: Rising incidence of endometrial cancer in individuals with high weight presents multiple chances for inequitable access and health outcomes over the care continuum for endometrial cancer. Action is required to address incidence, awareness, access to equitable and inclusive treatment, and survivorship. [ABSTRACT FROM AUTHOR]

Aim: To assess the impact of adult body mass index (BMI) trajectories on the risk of obesity‐related noncommunicable diseases (NCDs) in the U.S. adults after adjustment for sociodemographic and lifestyle factors. Methods: Data were extracted from the National Health and Nutrition Examination Survey conducted from 2007 to 2018, including male and female participants aged 29–59 years. Rao‐Scott adjusted chi‐square was employed to detect associations between categorical variables in descriptive analyses. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for NCDs and BMI trajectories, adjusted for sociodemographic and lifestyle factors. Kaplan–Meier curves illustrated the cumulative incidence over time. Results: Analyses were carried out on 15 721 participants and revealing significant differences among BMI trajectories in terms of demographic, lifestyle, and health characteristics. The overall prevalence of NCDs was 28.0% (95%CI:26.6–28.9). The cumulative incidence over time was higher in the high increase, moderate increase, and mixed trajectory groups, with a correspondingly higher cumulative risk (p < 0.001). Non‐overweight trajectory was considered reference category in Cox models. The BMI trajectories were independently associated with an increased risk of NCDs, even after adjusting for potential confounders (HR: 1.7; 95%CI: 1.4–1.9 for moderate increase; HR: 3.6; 95%CI: 3.2–4.1 for high increase; and HR: 2.4; 95%CI: 2.1–2.7, for mixed). Furthermore, differences between males and females were also observed. Conclusion: The transition to and persistence of obesity into adulthood increases the risk of NCDs. The implementation of targeted interventions with long‐term monitoring of BMI may be beneficial in the prevention of future obesity‐related NCDs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adolescents with overweight or obesity are at greater risk of having physical and psychosocial consequences. With increased disparities and inadequate literature on prevalence of adolescent weight status in rural Appalachia, there is potential for further complications. Unfortunately, adolescent obesity treatment options are often limited, especially in medically underserved regions. METHODS: This cross‐sectional study of adolescents at eight rural Appalachian schools examined weight status among and associations between body mass index percentile (BMIp) categories and health‐related perceptions and weight‐control intentions. Previously validated instruments were utilized. Analyses included independent samples t‐tests, ANOVA tests, and chi‐squared tests. RESULTS: Of 814 adolescents (ages 11‐13; 55.0% girls), BMIp revealed 20.8% overweight, 22.7% obese, and 10.6% severely obese. Adolescents with higher BMIp categories reported poorer self‐rated health, inaccurate weight perceptions, and greater weight loss intentions (all p <.05). CONCLUSIONS: Findings, including high prevalence of adolescents with overweight and obesity, emphasize the need for more obesity prevention and treatment options. Schools may be an ideal setting to reach at‐risk adolescents and provide obesity prevention and treatment options, especially in medically underserved regions such as rural Appalachia. Opportunities and challenges to apply findings, including school‐based obesity programs, are discussed. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa (AN) and atypical AN are conceptualized as distinct illnesses, despite similar characteristics and sequelae. Whereas DSM‐5 differentiates youth with AN and atypical AN by the presence of clinical 'underweight' (i.e., 5th BMI percentile for age‐and‐sex (BMI%)), we hypothesized that using this weight cut‐off to discern diagnoses creates a skewed distribution for premorbid weight. Method: Participants included hospitalized youth with AN (n = 165, 43.1%) and atypical AN (n = 218, 56.9%). Frequency analyses and chi‐square tests assessed the distribution of premorbid BMI z‐scores (BMIz) for diagnosis. Non‐parametric Spearman correlations and Stepwise Linear regressions examined relationships between premorbid BMIz, admission BMIz, and weight loss in kg. Results: Premorbid BMIz distributions differed significantly for diagnosis (p <.001), with an underrepresentation of 'overweight/obesity' (i.e., BMI% ≥ 85th) in AN. Despite commensurate weight loss in AN and atypical AN, patients with premorbid 'overweight/obesity' were 8.31 times more likely to have atypical AN than patients with premorbid BMI% < 85th. Premorbid BMIz explained 57% and 39% of the variance in admission BMIz and weight loss, respectively. Discussion: Findings support a homogenous model of AN and atypical AN, with weight loss predicted by premorbid BMI in both illnesses. Accordingly, premorbid BMI and weight loss (versus presenting BMI) may better denote the presence of an AN‐like phenotype across the weight spectrum. Findings also suggest that differentiating diagnoses with BMI% < 5th requires that youth with higher BMIs lose disproportionately more weight for an AN diagnosis. This is problematic given unique treatment barriers experienced in atypical AN. Public significance: Anorexia nervosa (AN) and atypical AN are considered distinct conditions in youth, with differential diagnosis hinging upon a presenting weight status of 'underweight' (i.e., BMI percentile for age‐and‐sex (BMI%) < 5th). In our study, youth with premorbid 'overweight/obesity' (BMI% ≥ 85th) disproportionately remained above this threshold, despite similar weight loss. Coupled with prior evidence for commensurate characteristics and sequelae in both diagnoses, we propose that DSM‐5 differentiation of AN and atypical AN inadvertently reinforces weight stigma and may contribute to treatment disparities in atypical AN. [ABSTRACT FROM AUTHOR]

Objective To examine the association of CRF and adiposity with cardiometabolic risk factors and metabolic syndrome among emerging adults. Participants: 5681 (60.1% Men; 21 ± 1years) college students from a large university located in the northeast of the United States. Methods: Participants completed an objective health assessment that involved the assessment cardiometabolic risk factors, CRF, and adiposity. Data of 5681 students' (60.1% Men; 21 ± 1years) who had CRF, adiposity, all risk factors necessary to determine metabolic syndrome evaluated were analyzed using logistic regression analyses. Results: Poor CRF and elevated adiposity were associated with cardiometabolic risk factors and metabolic syndrome regardless of sex, with the association between adiposity and risk factors found to be stronger compared to CRF. Conclusions: Targeted and tailored screening and interventions are urgently needed to reduce adiposity and increase CRF to avoid serious short and long-term negative health outcomes in this population. [ABSTRACT FROM AUTHOR]

We estimated the prevalence and time trends of the double burden of malnutrition (DBM) in Guatemala and explored its occurrence based on socio-demographic factors. This was a secondary data analysis using information from four Demographic and Health Surveys covering the period 1998–2015. The unit of analysis was the household within which information was gathered from women 18–49 years and their children, 6–59 months. The main outcome was the prevalence of any DBM in the household (co-existence of undernutrition and overnutrition in a woman, her children or both). We estimated the prevalence of any DBM by survey and analysed time trends. Stepwise logistic regression was used to explore the occurrence of DBM and socio-demographic factors. We analysed 39,749 households across all surveys. The prevalence of any DBM was 25.3% (95%CI: 22.1–28.7) in 1998–99, 23.8% (22.0–25.8) in 2002, 25.9% (24.3–27.5) in 2008–09 and 24.2% (22.9–25.5) in 2014–15, with no significant change over time (P = 0.782). Characteristics associated with lower odds of any DBM were rural residence, female-headed household, wealth and women's secondary education. Higher odds were seen for households with electricity, women >25y, indigenous and with >2 children. Our findings revealed that a quarter of Guatemala's households suffer from DBM, which has remained unchanged for 17 years. Interventions should prioritise urban areas, households of lower socio-economic status and those less educated. To increase awareness of policymakers of this pressing public health concern, further research on DBM could be strengthened by prospective study designs, integrating all household members and expanding the types of malnutrition. [ABSTRACT FROM AUTHOR]

Purpose: The coronavirus disease 2019 (COVID‐19) generates long‐term sequelae, but studies investigating patients with chronic pain syndrome (CPS) are limited. This study aimed to establish the etiological factors of CPS in patients with post‐COVID‐19 conditions. Methods: This was a case–control retrospective study. The predictor variables were sex, diabetes mellitus, obesity (predisposing factors), unfavorable socioeconomic conditions, impaired rehabilitation (disabling factors), repeated exposure to COVID‐19 (precipitating factor), home isolation, stress overload, fear of dying, admission to intensive care unit, prone positioning, and use of medications (reinforcing factors). The outcome variable was the presence of CPS. Findings: This study included 120 individuals. Prolonged days of isolation (p = 0.005), fear (p < 0.001), stress overload (p < 0.001), and impaired rehabilitation (p = 0.003) were significantly associated with CPS. Conclusions: A significant relationship was found between prolonged days of isolation, fear, stress overload, impaired rehabilitation, and CPS. Implications for nursing practice: The study findings can assist nurses by promoting their knowledge of the causes of CPS and supporting the care planning needs of patients with post‐COVID‐19 conditions, in addition to promoting the use of the NANDA‐International taxonomy. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of colorectal cancer (CRC) in the United States (US) has decreased significantly over the last several decades, but primarily in those 65 years of age and older. However, there has been a dramatic global increase in the incidence of colorectal cancer in patients younger than 50 years old. This cohort is known as early-onset colorectal cancer (EOCRC) and is projected to rise in incidence. This epidemiologic change is poorly understood, but the sharp increase in the incidence of obesity and metabolic dysfunction have been linked to this phenomenon. The aim of our study is to examine the complex inflammatory mechanisms affecting EOCRC, including obesity, hormonal effects, inflammatory processes, and the tumor environment. With an improved understanding of these interactions, new methods to prevent and treat EOCRC could reduce its incidence and prolong survival in affected patients. Metabolic dysfunction associated with obesity leads to a chronic pro-inflammatory state with systemic effects, including the alteration of macrophage metabolism. Tumor-associated macrophages have been linked to the formation of cancer through the production of metabolites such as itaconate. Itaconate downregulates peroxisome proliferator-activated receptor gamma as a tumor-suppressing factor and upregulates anti-inflammatory cytokines in M2-like macrophages. Similarly, leptin and adiponectin also influence macrophage cytokine expression and contribute to the progression of colorectal cancer via changes in gene expression within the PI3K/AKT pathway. This pathway influences cell proliferation, differentiation, and tumorigenesis. This work provides a review of obesity-related hormones and inflammatory mechanisms leading to the development and progression of early-onset colorectal cancer (EOCRC). A literature search was performed using the PubMed and Cochrane databases to identify studies related to obesity and EOCRC, with keywords including 'EOCRC', 'obesity', 'obesity-related hormones', 'itaconate', 'adiponectin', 'leptin', 'M2a macrophage', and 'microbiome'. With this concept of pro-inflammatory markers contributing to EOCRC, increased use of chemo-preventative agents such as aspirin may have a protective effect. Elucidating this association between obesity-related, hormone/cytokine-driven inflammatory effects with EOCRC may help lead to new therapeutic targets in preventing and treating EOCRC. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a serious health condition affecting women of reproductive age. High prevalence of PCOS and associated metabolic complications needs effective treatment and management. This study evaluated the efficacy of optimal nutraceutical combinations in improving PCOS characteristics using system biology-based mathematical modelling and simulation. Methods: A shortlisting of eight potent nutraceuticals was carried out with literature search. Menstrual cycle model was used to perform simulations on an in-silico population of 2000 individuals to test individual and combined effects of shortlisted nutraceuticals on five PCOS characteristics [oligomenorrhea, anovulation, hirsutism, infertility, and polycystic ovarian morphology (PCOM)] for a duration of 6 months. Efficacy was tested across lean and obese phenotypes and age groups. Results: Individual assessment of nutraceuticals revealed seven most potent compounds. Myo-inositol among them was observed to be the most effective in alleviating the PCOS characteristics. The in-silico population analysis showed that the combination of melatonin and ALA along with myo-inositol was efficacious in restoring the hormonal balance across age-groups and Body Mass Index (BMI) categories. Conclusion: Supplementation with the combination of myo-inositol, melatonin, and ALA demonstrated potential in managing PCOS symptoms in our in-silico analysis of a heterogeneous population, including lean and obese phenotypes across various severities and age groups, over a 6-month period. Future clinical studies are recommended to validate these findings. [ABSTRACT FROM AUTHOR]

Introduction. Oncologic mastectomy in the setting of obesity poses challenges in achieving a flat closure that includes the lateral adiposity. The angel wing (AW) technique was developed to address this issue. We aim to demonstrate the safety of AW by evaluating incidence of arm lymphedema (AL) and decreased range of motion (dROM) in patients postmastectomy with and without the AW closure. Methods. We performed a single-center retrospective cohort study at an academic referral center of patients who underwent mastectomy with and without the AW technique from May 2014 to October 2022. Those who received breast reconstruction (immediate or delayed), partial mastectomy, and male patients were excluded. The presence of postoperative AL and dROM was evaluated. Subgroup analysis was performed for patient factors including BMI, extent of axillary surgery, PMRT, and pathologic stage. Results. A total of 390 patients met inclusion criteria. Of those, 173 (44.4%) underwent AW and 217 (55.6%) had non-AW mastectomy. Expectedly, the average BMI was significantly higher in the AW cohort (p < 0.0001). The overall rate of AL was 51/390 (13.1%), seen in 27 (15.6%) undergoing AW and 24 (11.1%) non-AW (p value = 0.18). While the rate of dROM within the cohort was 52/390 (13.1%), 27 (15.6%) underwent AW vs. 24 (11.1%) non-AW (p value = 0.22), resulting in no statistical significance between AW and non-AW mastectomy upon subsequent development of AL or dROM. Conclusion. Our study demonstrates the AW technique does not convey an increased risk of overall AL or dROM, even when considering known risk factors such as obesity, PMRT, and extent of axillary surgery. As we strive to provide our patients with improved surgical techniques for oncologic resection, we submit that this technique is a viable and safe option for achieving the goals of cosmesis with oncologic safety. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer (EC), a common and fatal disease, includes two histological subtypes; esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (ECA). To aid policymakers in the allocation of resources for the prevention and treatment of EC, updated data on EC deaths and disability‐adjusted life years (DALYs) attributable to high body mass index (BMI) are necessary. The objective of this study was to identify trends in EC associated with high BMI between 1990 and 2019 using 2019 Global Burden of Disease data. Methods: In this observational population‐based study, epidemiological data on the association between high BMI and EC were obtained from GBD 2019. The age‐standardized mortality rate (ASMRs) and disability‐adjusted life year rate (ASDRs) attributable to high BMI‐related EC were stratified by year, age, country, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of the ASMRs and ASDRs between 1990 and 2019. Results: In 2019, the proportion of EC deaths and DALYs attributed to high BMI was 18.1% and 18.9%, respectively, resulting in 89 904 (95% confidence interval [CI]: 27 879–171 255) deaths and 2 202 314 (95% CI: 681 901–4 173 080) DALYs. High BMI‐related deaths and DALYs showed a strong upward trend, increasing by more than two‐fold since 1990. East Asia and Western Europe showed the highest risk of EC mortality and DALYs attributable to high BMI; China and the USA bear the greatest burden. The ASMR and ASDR increased in five SDI regions. Conclusions: The incidence of EC is increasing, particularly in developing nations, which may be attributed to the prevalence of high BMI. To mitigate the impact of high BMI on the incidence of EC, it is important to increase awareness of its deleterious effects, which may alleviate the burden of this disease. [ABSTRACT FROM AUTHOR]

Objective: To provide an assessment of the cost burden of obesity across a spectrum of obesity-related comorbidities (ORCs) for four countries in South-Eastern Europe (SEE). Methods: A micro-costing analysis from the public payer perspective was conducted to estimate direct healthcare costs associated with ten obesity-related comorbidities (ORCs) in Czech Republic, Greece, Hungary, and Romania. A survey was administered to obtain healthcare resource use and unit cost data. Cost estimates were validated by local steering committees which comprised at least one public sector clinician and a panel of independent industry experts. Results: Chronic kidney disease and cardiovascular diseases were the costliest ORCs across all 4 countries, where annual cost burden per ORC exceeded 1,500 USD per patient per year. In general, costs were driven by the tertiary care resources allocated to address treatment-related adverse events, disease complications, and associated inpatient procedures. Conclusions: Our findings confirm that the high prevalence of obesity and its comorbidities result in substantial financial burden to all 4 SEE public payers. By quantifying the burden of obesity from a public healthcare perspective, our study aims to support policy efforts that promote health education and promotion in combating obesity in the region. [ABSTRACT FROM AUTHOR]