Synergistic Effects of Weight Loss and Catheter Ablation: Can microRNAs Serve as Predictive Biomarkers for the Prevention of Atrial Fibrillation Recurrence?

In atrial fibrillation (AF), multifactorial pathologic atrial alterations are manifested by structural and electrophysiological changes known as atrial remodeling. AF frequently develops in the context of underlying cardiac abnormalities. A critical mechanistic role played by atrial stretch is played by abnormal substrates in a number of conditions that predispose to AF, including obesity, heart failure, hypertension, and sleep apnea. The significant role of overweight and obesity in the development of AF is known; however, the differential effect of overweight, obesity, cardiovascular comorbidities, lifestyle, and other modifiable risk factors on the occurrence and recurrence of AF remains to be determined. Reverse remodeling of the atrial substrate and subsequent reduction in the AF burden by conversion into a typical sinus rhythm has been associated with weight loss through lifestyle changes or surgery. This makes it an essential pillar in the management of AF in obese patients. According to recently published research, microRNAs (miRs) may function as post-transcriptional regulators of genes involved in atrial remodeling, potentially contributing to the pathophysiology of AF. The focus of this review is on their modulation by both weight loss and catheter ablation interventions to counteract atrial remodeling in AF. Our analysis outlines the experimental and clinical evidence supporting the synergistic effects of weight loss and catheter ablation (CA) in reversing atrial electrical and structural remodeling in AF onset and in recurrent post-ablation AF by attenuating pro-thrombotic, pro-inflammatory, pro-fibrotic, arrhythmogenic, and male-sex-associated hypertrophic remodeling pathways. Furthermore, we discuss the promising role of miRs with prognostic potential as predictive biomarkers in guiding approaches to AF recurrence prevention.

Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals. / Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso.

BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

Minimally invasive transperitoneal partial versus radical nephrectomy in obese patients: perioperative and long-term functional outcomes from a large perspective contemporary series (RECORd2 project).

BACKGROUND: The aim of this study is to evaluate the perioperative and long-term functional outcomes of laparoscopic (LPN) and robot-assisted partial nephrectomy (RAPN) in comparison to laparoscopic radical nephrectomy (LRN) in obese patients diagnosed with renal cell carcinoma. METHODS: Clinical data of 4325 consecutive patients from The Italian REgistry of COnservative and Radical Surgery for cortical renal tumor Disease (RECORD 2 Project) were gathered. Only patients treated with transperitoneal LPN, RAPN, or LRN with Body Mass Index (BMI) ≥30 kg/m2, clinical T1 renal tumor and preoperative estimated glomerular filtration rate (eGFR) ≥60 mL/min, were included. Perioperative, and long-term functional outcomes were examined. RESULTS: Overall, 388 patients were included, of these 123 (31.7%), 120 (30.9%) and 145 (37.4%) patients were treated with LRN, LPN, and RAPN, respectively. No significant difference was observed in preoperative characteristics. Overall, intra and postoperative complication rates were comparable among the groups. The LRN group had a significantly increased occurrence of acute kidney injury (AKI) compared to LPN and RAPN (40.6% vs. 15.3% vs. 7.6%, P=0.001). Laparoscopic RN showed a statistically significant higher renal function decline at 60-month follow-up assessment compared to LPN and RAPN. A significant renal function loss was recorded in 30.1% of patients treated with LRN compared to 16.7% and 10.3% of patients treated with LPN and RAPN (P=0.01). CONCLUSIONS: In obese patients, both LPN and RAPN showcased comparable complication rates and higher renal function preservation than LRN. These findings highlighted the potential benefits of minimally invasive PN over radical surgery in the context of obese individuals.

Iron Deficiency Related to Obesity.

There is a direct correlation between being overweight and iron deficiency. Physiological changes occur in obese adipose cells that contribute to the development of iron deficiency (ID) and iron deficiency anemia (IDA). These changes disrupt the normal iron metabolic checks and balances. Furthermore, bariatric surgery can lead to long-term ID and IDA. Oral iron supplementation may not be effective for many of these patients. Intravenous iron infusions can significantly increase the quality of life for individuals experiencing this condition but are also associated with potentially serious complications. Adequate knowledge about intravenous (IV) iron administration can greatly increase the safety of this beneficial therapy. This review article explains the relationship between obesity, ID/IDA, bariatric surgery and the safe administration of IV iron.

Impact of body mass index at diagnosis on outcomes of pediatric acute leukemia: A systematic review and meta-analysis.

BACKGROUND: The incidence of childhood malnutrition i.e., both obesity and undernutrition, is on a rise. While there is extensive evidence of the influence of body mass index (BMI) on the survival and other important outcomes of adult cancers, the impact of childhood BMI on one of the common pediatric cancers i.e., leukemia is not well studied. METHODS: Systematic search of PubMed, Scopus, and Google Scholar databases was done to identify studies that were conducted among pediatric patients with leukemia and had examined outcomes of interest based on BMI at the time of diagnosis. RESULTS: Effect sizes were reported as pooled hazards ratio (HR) along with 95% confidence intervals (CI). A total of 17 studies were included. Compared to pediatric leukemia patients with normal BMI, underweight (HR 1.07, 95% CI: 1.04, 1.11) and obese (HR 1.42, 95% CI: 1.18, 1.71) children with leukemia had higher risks of overall mortality. Underweight (HR 1.10, 95% CI: 1.02, 1.19) and obese (HR 1.34, 95% CI: 1.15, 1.55) pediatric leukemia patients had a tendency to lower event-free survival compared to children with normal BMI. The risk of relapse was not significant for underweight, overweight, and obese children. CONCLUSIONS: Both underweight and obese status at the time of diagnosis were associated with poor survival outcomes in pediatric patients with leukemia.

Association of lncRNA MEG3 rs941576 polymorphism, expression profile, and its related targets with the risk of obesity-related colorectal cancer: potential clinical insights.

The identification of novel screening tools is imperative to empower the early detection of colorectal cancer (CRC). The influence of the long non-coding RNA maternally expressed gene 3 (MEG3) rs941576 single nucleotide polymorphism on CRC susceptibility remains uninvestigated. This research appraised MEG3 rs941576 association with the risk and clinical features of CRC and obesity-related CRC and its impact on serum MEG3 expression and its targets miR-27a/insulin-like growth factor 1 (IGF1)/IGF binding protein 3 (IGFBP3) and miR-181a/sirtuin 1 (SIRT1), along with the potential of these markers in obesity-related CRC diagnosis. 130 CRC patients (60 non-obese and 70 obese) and 120 cancer-free controls (64 non-obese and 56 obese) were enrolled. MEG3 targets were selected using bioinformatics analysis. MEG3 rs941576 was associated with magnified CRC risk in overall (OR (95% CI) 4.69(1.51-14.57), P = 0.0018) and stratified age and gender groups, but not with obesity-related CRC risk or MEG3/downstream targets' expression. Escalated miR-27a and IGFBP3 and reduced IGF1 serum levels were concomitant with MEG3 downregulation in overall CRC patients versus controls and obese versus non-obese CRC patients. Serum miR-181a and SIRT1 were upregulated in CRC patients versus controls but weren't altered in the obese versus non-obese comparison. Serum miR-181a and miR-27a were superior in overall and obesity-related CRC diagnosis, respectively; meanwhile, IGF1 was superior in distinguishing obese from non-obese CRC patients. Only serum miR-27a was associated with obesity-related CRC risk in multivariate logistic analysis. Among overall CRC patients, MEG3 rs941576 was associated with lymph node (LN) metastasis and tumor stage, serum MEG3 was negatively correlated with tumor stage, while SIRT1 was correlated with the anatomical site. Significant correlations were recorded between MEG3 and anatomical site, SIRT1 and tumor stage, and miR-27a/IGFBP3 and LN metastasis among obese CRC patients, while IGF1 was correlated with tumor stage and LN metastasis among non-obese CRC patients. Conclusively, this study advocates MEG3 rs941576 as a novel genetic marker of CRC susceptibility and prognosis. Our findings accentuate circulating MEG3/miR-27a/IGF1/IGFBP3, especially miR-27a as valuable markers for the early detection of obesity-related CRC. This axis along with SIRT1 could benefit obesity-related CRC prognosis.

Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry.

BACKGROUND: The proportion of heart failure patients with preserved ejection fraction has been rising over the past decades and has coincided with increases in the prevalence of obesity and metabolic syndrome. The relationship between these interconnected comorbidities and heart failure with preserved ejection fraction (HFpEF) is still poorly understood. This study characterized obesity and metabolic syndrome among real-world patients with HFpEF. METHODS: We identified adults with heart failure in the Veradigm Cardiology Registry, previously the PINNACLE Registry, with a left ventricular ejection fraction measurement ≥ 50% between 01/01/2016 and 12/31/2019. Patients were stratified by obesity diagnosis and presence of metabolic syndrome (≥ 3 of the following: diabetes, hypertension, hyperlipidemia, and obesity). We captured baseline demographic and clinical characteristics and used multivariable logistic regression to examine the odds of having cardiac (atrial fibrillation, coronary artery disease, coronary artery bypass surgery, myocardial infarction, and stroke/transient ischemic attack) and non-cardiac (chronic kidney disease, chronic liver disease, and peripheral artery disease) comorbidities of interest. The models adjusted for age and sex, and the main covariates of interest were obesity and metabolic burden score (0-3 based on the presence of diabetes, hypertension, and hyperlipidemia). The models were run with and without an obesity*metabolic burden score interaction term. RESULTS: This study included 264,571 patients with HFpEF, of whom 55.7% had obesity, 52.5% had metabolic syndrome, 42.5% had both, and 34.3% had neither. After adjusting for age, sex, and burden of other metabolic syndrome-associated diagnoses, patients with HFpEF with obesity had lower odds of a diagnosis of other evaluated comorbidities relative to patients without obesity. The presence of metabolic syndrome in HFpEF appears to increase comorbidity burden as each additional metabolic syndrome-associated diagnosis was associated with higher odds of assessed comorbidities except atrial fibrillation. CONCLUSION: Obesity was common among patients with HFpEF and not always co-occurring with metabolic syndrome. Multivariable analysis suggested that patients with obesity may develop HFpEF in the absence of other driving factors such as cardiovascular disease or metabolic syndrome.

Weight Loss Surgery Increases Kidney Transplant Rates in Patients With Renal Failure and Obesity.

OBJECTIVE: To describe the outcomes of kidney transplant (KT) candidates with obesity undergoing sleeve gastrectomy (SG) to meet the criteria for KT. METHODS: Retrospective analysis was conducted of electronic medical records of KT candidates with obesity (body mass index >35 kg/m2) who underwent SG in our institution. Weight loss, adverse health events, and the listing and transplant rates were abstracted and compared with the nonsurgical cohort. RESULTS: The SG was performed in 54 patients; 50 patients did not have surgery. Baseline demographic characteristics were comparable at the time of evaluation. Mean body mass index ± SD of the SG group was 41.7±3.6 kg/m2 at baseline (vs 41.5±4.3 kg/m2 for nonsurgical controls); at 2 and 12 months after SG, it was 36.4±4.1 kg/m2 and 32.6±4.0 kg/m2 (P<.01 for both). In the median follow-up time of 15.5 months (interquartile range, 6.4 to 23.9 months), SG was followed by active listing (37/54 people), and 20 of 54 received KT during a median follow-up time of 20.9 months (interquartile range, 14.7 to 28.3 months) after SG. In contrast, 14 of 50 patients in the nonsurgical cohort were listed, and 5 received a KT (P<.01). Three patients (5.6%) experienced surgical complications. There was no difference in overall hospitalization rates and adverse health outcomes, but the SG cohort experienced a higher risk of clinically significant functional decline. CONCLUSION: In KT candidates with obesity, SG appears to be effective, with 37% of patients undergoing KT during the next 18 months (P<.01). Further research is needed to confirm and to improve the safety and efficacy of SG for patients with obesity seeking a KT.

Risk factors of bleeding during rectal cancer surgery in obese patients in Japan.

BACKGROUND: According to several clinical trials for patients with rectal cancer, laparoscopic surgery significantly reduces intraoperative complications and bleeding compared with laparotomy and demonstrated comparable long-term results. However, obesity is considered one of the risk factors for increased surgical difficulty, including complication rate, prolonged operation time, and bleeding. METHODS: Patients with clinical pathological stage II/III rectal cancer and a body mass index of ≥25 kg/m2 who underwent laparotomy or laparoscopic surgery between January 2009 and December 2013 at 51 institutions participating in the Japan Society of Laparoscopic Colorectal Surgery were included. These patients were divided into major bleeding (>500 mL) group and minor bleeding (≤500 mL) group. The risk factors of major bleeding were evaluated by univariate and multivariate analyses. RESULTS: This study included 517 patients, of which 74 (19.9%) experienced major bleeding. Patient characteristics did not significantly differ between the two groups. The major bleeding group had a longer operative time (p < 0.001) and a larger tumor size than the minor bleeding group (p = 0.011). In the univariate analysis, age >65 years, laparotomy, operative time >300 min, and multivisceral resection were significantly associated with intraoperative massive bleeding. In the multivariate analysis, age >65 years (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.13-4.82), laparotomy (OR, 20.82; 95% CI, 11.56-39.75), operative time >300 min (OR, 5.39; 95% CI, 1.67-132), and multivisceral resection (OR, 10.72; 95% CI, 2.47-64.0) showed to be risk factors for massive bleeding. CONCLUSION: Age >65 years, laparotomy, operative time >300 min, and multivisceral resection were risk factors for massive bleeding during rectal cancer surgery in patients with obesity.

Triglyceride to HDL Cholesterol Ratio for the Identification of MASLD in Obesity: A Liver Biopsy-Based Case-Control Study.

Associations between dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Previous studies have shown that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio may be a surrogate marker of MASLD, assessed by liver ultrasound. However, no studies have evaluated the utility of this ratio according to biopsy-proven MASLD and its stages. Therefore, our aim was to evaluate if the TG/HDL-C ratio allows for the identification of biopsy-proven MASLD in patients with obesity. We conducted a case-control study in 153 patients with obesity who underwent metabolic surgery and had a concomitant liver biopsy. Fifty-three patients were classified as no MASLD, 45 patients as metabolic dysfunction-associated steatotic liver-MASL, and 55 patients as metabolic dysfunction-associated steatohepatitis-MASH. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the TG/HDL-C ratio to detect MASLD. We also compared the area under the curve (AUC) of the TG/HDL-C ratio, serum TG, and HDL-C. A higher TG/HDL-C ratio was observed among patients with MASLD, compared with patients without MASLD. No differences in the TG/HDL-C ratio were found between participants with MASL and MASH. The greatest AUC was observed for the TG/HDL-C ratio (AUC 0.747, p < 0.001) with a cut-off point of 3.7 for detecting MASLD (sensitivity = 70%; specificity = 74.5%). However, no statistically significant differences between the AUC of the TG/HDL-C ratio and TG or HDL-C were observed to detect MASLD. In conclusion, although an elevated TG/HDL-C ratio can be found in patients with MASLD, this marker did not improve the detection of MASLD in our study population, compared with either serum TG or HDL-C.

Impact of obesity on sentinel lymph node biopsy outcomes and survival in breast cancer patients: A single-center retrospective study.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a common choice for axillary surgery in patients with early-stage breast cancer (BC) who have clinically negative lymph nodes. Most research indicates that obesity is a prognostic factor for BC patients, but studies assessing its association with the rate of positive sentinel lymph nodes (SLN) and the prognosis of patients with early BC undergoing SLNB are limited. METHODS: Between 2013 and 2016, 7062 early-stage BC patients from the Shanghai Cancer Center of Fudan University were included. Based on the Chinese Body Mass Index (BMI) classification standards, the patients were divided into three groups as follows: normal weight, overweight, and obese. Propensity score matching analysis was used to balance the baseline characteristics of the participants. Logistic regression analysis was used to determine the association between obesity and positive SLN rate. Cox regression analysis was used to investigate whether obesity was an independent prognostic factor for early-stage BC patients who had undergone SLNB. RESULTS: No significant association was observed between obesity and positive SLN rate in early-stage BC patients who had undergone SLNB. However, multivariate analysis revealed that compared to patients with normal BMI, the overall survival (hazard ratio (HR) 2.240, 95% confidence interval (CI) 1.27-3.95, p = 0.005) and disease-free survival (HR 1.750, 95% CI 1.16-2.62, p = 0.007) were poorer in patients with high BMI. CONCLUSION: Obesity is an independent prognostic factor for early-stage BC patients who undergo SLNB; however, it does not affect the positive SLN rate.

Investigating a novel surrogate indicator of adipose accumulation in relation to erectile dysfunction.

INTRODUCTION: Although previous studies have linked obesity and erectile dysfunction, the novel surrogate indicators of adipose accumulation are more essential and dependable factors to consider. Therefore, the primary objective of the current investigation was to examine and clarify the association between metabolic score for visceral fat (METS-VF) and erectile dysfunction. METHODS: Firstly, multivariate logistic regression analysis, smoothed curve fitting, and threshold effect analysis were employed to investigate the association between METS-VF and erectile dysfunction. Mediation analysis was also performed to evaluate the mediating role of homocysteine and inflammation. After that, subgroup analysis was carried out to examine the stability of the correlation of METS-VF with erectile dysfunction in various population settings. Furthermore, the area under the receiver operating characteristic (ROC) curve and eXtreme Gradient Boosting (XGBoost) algorithm were utilized to assess the capability of identifying METS-VF in comparison to the other four obesity-related indicators in identifying erectile dysfunction. RESULTS: After adjusting for all confounding factors, METS-VF was strongly and favourablely correlated with erectile dysfunction. With each additional unit rise in METS-VF, the prevalence of erectile dysfunction increased by 141%. A J-shaped relationship between METS-VF and erectile dysfunction was discovered through smoothed curve fitting. Marital status, physical activity, and smoking status can potentially modify this association. This finding of the ROC curve suggests that METS-VF had a powerful identifying capacity for erectile dysfunction (AUC = 0.7351). Homocysteine and inflammation mediated 4.24% and 2.81%, respectively. CONCLUSION: The findings of the current investigation suggest that METS-VF can be considered a dependable identifying indicator of erectile dysfunction.

[Impact of obesity on the incidence of postoperative pulmonary complications following laparoscopic colorectal surgery].

Objective: To evaluate the effects of obesity on the incidence of postoperative pulmonary complications (PPCs) following laparoscopic colorectal surgery. Methods: A total of 150 patients with pathological diagnosis of colorectal cancer who accepted laparoscopic colorectal excision from January to May 2023 were retrospectively recruited. All the patients scored 26 points or more in the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) model, making them all in intermediate to high risks of PPCs. Patients were divided into obesity group and non-obesity group depending on whether they were obese or not. Propensity score matching (1∶1) was performed to achieve the balance of clinicopathological characteristics with the matching factors of age, sex, respiratory complications and ARISCAT score. A total of 96 patients were eventually enrolled, with 48 patients in obesity group and 48 patients in non-obesity group. Besides, the patients were divided into 25°-30° Trendelenburg subgroup and ±10°-15° Trendelenburg subgroup according to surgical sites for further analysis. The incidence of PPCs, the intraoperative airway pressure and blood biomarker expression of lung injury, including soluble receptor for advanced glycation end products (sRAGE) and angiopoietin-2 (ANG2) at postoperative day (POD) 1 and POD3 between the two groups were compared. The relationship between obesity and incidence of PPCs within 30 postoperative days were analyzed with unifactorial Cox proportional hazard model. Results: The obesity group was comprised of 35 males and 13 females with a median age of 60 (49, 69) years, and the non-obesity group was comprised of 35 males and 13 females with a median age of 60 (52, 67) years. The incidence of PPCs was 50.0% (24/48) in the obesity group, which was higher than 20.8% (10/48) in the non-obesity group and the incidence of grade Ⅰ PPCs and microatelectasis were 31.3% (15/48) and 33.3% (16/48), higher than the 12.5% (6/48) and 12.5% (6/48) of the non-obesity group (all P<0.05). The peak airway pressure (Ppeak) and plateau airway pressure (Pplat) of patients in obesity group were 34.0(31.5, 36.5) and 30.0(27.0, 32.0) cmH2O(1 cmH2O=0.098 kPa), which were significantly higher than the 26.0 (24.0, 29.5) and 22.0 (21.0, 26.5) cmH2O of the non-obesity group (all P<0.001). The ANG2 level of the obesity group at POD3 was 11.9 (8.4, 16.5) µg/L, which was higher than 9.2 (6.0, 12.3) µg/L of the non-obesity group (P=0.045). In 25°-30°Trendelenburg subgroup, the incidence of PPCs in obese patients were significantly higher than that of non-obese patients [41.4% (12/29) vs 11.4% (4/35), P=0.005]. In ±10°-15°Trendelenburg subgroup, no significant difference was found in PPCs incidence between obese and non-obese patients [63.2% (12/19) vs 46.2% (6/13), P=0.215]. The unifactorial Cox proportional hazard model analysis showed that obesity was a risk factor of PPCs in 30 postoperative days (HR=3.015, 95%CI: 1.438-6.321, P=0.001). Conclusion: In patients undergoing laparoscopic colorectal surgery with intermediate to high risk of PPCs, obesity raises intraoperative airway pressure and aggravates intraoperative lung endothelial injury. Obesity is a risk factor of PPCs in 30 postoperative days.

Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction.

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular populations in the cortex and hippocampus, as well as in VAT, during the chronic phase after combined TBI-HFD showed amplification of central and peripheral microglia/macrophage responses, including superadditive changes in selected gene expression signatures and pathways. Furthermore, combined TBI and HFD caused additive dysfunction in Y-Maze, Novel Object Recognition (NOR), and Morris water maze (MWM) cognitive function tests. These novel data suggest that HFD-induced obesity and TBI can independently prime and support the development of altered states in brain microglia and VAT, including the disease-associated microglia/macrophage (DAM) phenotype observed in neurodegenerative disorders. The interaction between HFD and TBI promotes a shift toward chronic reactive microglia/macrophage transcriptomic signatures and associated pro-inflammatory disease-altered states that may, in part, underlie the exacerbation of cognitive deficits. Thus, targeting of HFD-induced reactive cellular phenotypes, including in peripheral adipose tissue immune cell populations, may serve to reduce microglial maladaptive states after TBI, attenuating post-traumatic neurodegeneration and neurological dysfunction.

High Variability of Body Mass Index Is Independently Associated With Incident Heart Failure.

BACKGROUND: Heart failure (HF) is a serious condition with increasing prevalence, high morbidity, and increased mortality. Obesity is an established risk factor for HF. Fluctuation in body mass index (BMI) has shown a higher risk of cardiovascular outcomes. We investigated the association between BMI variability and incident HF. METHODS AND RESULTS: In the UK Biobank, we established a prospective cohort after excluding participants with prevalent HF or cancer at enrollment. A total of 99 368 White participants with ≥3 BMI measures during >2 years preceding enrollment were included, with a median follow-up of 12.5 years. The within-participant variability of BMI was evaluated using standardized SD and coefficient of variation. The association of BMI variability with incident HF was assessed using Fine and Gray's competing risk model, adjusting for confounding factors and participant-specific rate of BMI change. Higher BMI variability measured in both SD and coefficient of variation was significantly associated with higher risk in HF incidence (SD: hazard ratio [HR], 1.05 [95% CI, 1.03-1.08], P<0.0001; coefficient of variation: HR, 1.07 [95% CI, 1.04-1.10], P<0.0001). CONCLUSIONS: Longitudinal health records capture BMI fluctuation, which independently predicts HF incidence.

Association of lipid profile and obesity in patients with polycystic ovary syndrome.

Objective. Abnormal lipid profile and obesity increase the risk of polycystic ovary syndrome (PCOS). PCOS patients may have a greater risk of infertility, metabolic syndrome (MetS) and cardiovascular disease (CVD) due to abnormal lipid profile and obesity. The aim of the study was to find the association between abnormal lipid profile and obesity in patients with PCOS. Methods. In this case-control study, a total of 102 female subjects (51 diagnosed PCOS and 51 age-matched healthy controls) were enrolled, aged between 20-40 years. Biochemical parameters such as total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), very low-density lipoprotein-cholesterol (VLDL-C), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were estimated. Anthropometric parameters such as body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were recorded. A p<0.05 was considered statistically significant. Results. Mean of BMI, WC, WHR, LH, FSH, TC, TG, LDL-C, and VLDL-C was found significantly elevated in patients with PCOS as compared to controls (p<0.01). However, the mean of HDL-C was found significantly reduced in patients with PCOS as compared to controls (p<0.01). BMI has shown a significant positive correlation with WC (r=0.562, p<0.01) and WHR (r=0.580, p<0.01) among PCOS patients. LH has shown a significant positive correlation with FSH (r=0.572, p<0.01) among PCOS patients. TC has shown a significant positive correlation with TG (r=0.687, p<0.01), LDL-C (r=0.917, p<0.01), and VLDL-C (r=0.726, p<0.01) among PCOS patients. Conclusion. The results showed that abnormal lipid profile and obesity have a significant association with PCOS patients. Regular monitoring and treatment of PCOS patients are required to reduce the risk of infertility, MetS, and CVD.

Celastrol alleviates airway hyperresponsiveness and inflammation in obese asthma through mediation of alveolar macrophage polarization.

Obese asthma is a unique asthma phenotype that decreases sensitivity to inhaled corticosteroids, and currently lacks efficient therapeutic medication. Celastrol, a powerful bioactive substance obtained naturally from the roots of Tripterygium wilfordii, has been reported to possess the potential effect of weight loss in obese individuals. However, its role in the treatment of obese asthma is not fully elucidated. In the present study, diet-induced obesity (DIO) mice were used with or without ovalbumin (OVA) sensitization, the therapeutic effects of celastrol on airway hyperresponsiveness (AHR) and airway inflammation were examined. We found celastrol significantly decreased methacholine-induced AHR in obese asthma, as well as reducing the infiltration of inflammatory cells and goblet cell hyperplasia in the airways. This effect was likely due to the inhibition of M1-type alveolar macrophages (AMs) polarization and the promotion of M2-type macrophage polarization. In vitro, celastrol yielded equivalent outcomes in Lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells, featuring a reduction in the expression of M1 macrophage makers (iNOS, IL-1ß, TNF-α) and heightened M2 macrophage makers (Arg-1, IL-10). Mechanistically, the PI3K/AKT signaling pathway has been implicated in these processes. In conclusion, we demonstrated that celastrol assisted in mitigating various parameters of obese asthma by regulating the balance of M1/M2 AMs polarization.

Causal relationships of Helicobacter pylori and related gastrointestinal diseases on Type 2 diabetes: Univariable and Multivariable Mendelian randomization.

BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. RESULTS: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. CONCLUSION: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM.

Mitochondrial Ca2+ signaling is a hallmark of specific adipose tissue-cancer crosstalk.

Obesity is associated with increased risk and worse prognosis of many tumours including those of the breast and of the esophagus. Adipokines released from the peritumoural adipose tissue promote the metastatic potential of cancer cells, suggesting the existence of a crosstalk between the adipose tissue and the surrounding tumour. Mitochondrial Ca2+ signaling contributes to the progression of carcinoma of different origins. However, whether adipocyte-derived factors modulate mitochondrial Ca2+ signaling in tumours is unknown. Here, we show that conditioned media derived from adipose tissue cultures (ADCM) enriched in precursor cells impinge on mitochondrial Ca2+ homeostasis of target cells. Moreover, in modulating mitochondrial Ca2+ responses, a univocal crosstalk exists between visceral adipose tissue-derived preadipocytes and esophageal cancer cells, and between subcutaneous adipose tissue-derived preadipocytes and triple-negative breast cancer cells. An unbiased metabolomic analysis of ADCM identified creatine and creatinine for their ability to modulate mitochondrial Ca2+ uptake, migration and proliferation of esophageal and breast tumour cells, respectively.