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Background: While obesity is a risk factor for postoperative complications, its impact following sepsis is unclear. The primary objective of this study was to evaluate the association between obesity and mortality following admission to the surgical intensive care unit (SICU) with sepsis., Methods: We conducted a single center retrospective review of SICU patients grouped into obese (n = 766, body mass index ≥30 kg/m 2 ) and nonobese (n = 574; body mass index, 18-29.9 kg/m 2 ) cohorts. Applying 1:1 propensity matching for age, sex, comorbidities, sequential organ failure assessment, and transfer status, demographic data, comorbidities, and sepsis presentation were compared between groups. Primary outcomes included in-hospital and 90-day mortality, ICU length of stay, need for mechanical ventilation (IMV) and renal replacement therapy (RRT). p < 0.05 was considered significant., Results: Obesity associates with higher median ICU length of stay (8.2 vs. 5.6, p < 0.001), need for IMV (76% vs. 67%, p = 0.001), ventilator days (5 vs. 4, p < 0.004), and RRT (23% vs. 12%, p < 0.001). In-hospital (29% vs. 18%, p < 0.0001) and 90-day mortality (34% vs. 24%, p = 0.0006) was higher for obese compared with nonobese groups. Obesity independently predicted need for IMV (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.1), RRT (OR, 2.2; 95% CI, 1.5-3.1), in-hospital (OR, 2.1; 95% CI, 1.5-2.8), and 90-day mortality (HR, 1.4; 95% CI, 1.1-1.8), after adjusting for sequential organ failure assessment, age, sex, and comorbidities. Comparative survival analyses demonstrate a paradoxical early survival benefit for obese patients followed by a rapid decline after 7 days (logrank p = 0.0009)., Conclusion: Obesity is an independent risk factor for 90-day mortality for surgical patients with sepsis, but its impact appeared later in hospitalization. Understanding differences in systemic responses between these cohorts may be important for optimizing critical care management., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer., (© 2024. The Author(s).)

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity., Competing Interests: WH advises for Novo Nordisk and Intercept Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Blaszczak, Jalilvand and Hsueh.)

Obesity is associated with a state of chronic low-grade inflammation both systemically and within specific tissues, including adipose tissue (AT). In murine models of obesity, there is a shift in the inflammatory profile of the AT immune cells, with an accumulation of proinflammatory M1 macrophages that surround the expanding adipocyte. However, much less is known about the immune cell composition and how to best define AT macrophages in humans. Objective . The goals of the current study were to determine the contribution of macrophages to the stromal vascular fraction (SVF) in lean versus obese human visceral AT (VAT); examine the expression of common M1, M2, and pan macrophage markers; and determine the association of specific macrophage types with known biomarkers of obesity-related cardiometabolic disease. Research Design and Methods . VAT biopsies were obtained from obese ( n = 50) and lean ( n = 8) patients during elective surgery. Adipocytes and SVF were isolated, and the SVF was subjected to flow cytometry analyses. Results . Our results indicate that VAT macrophages are increased in obesity and associate with biomarkers of CVD but that many macrophages do not fall into currently defined M1/M2 classification system based on CD206 receptor expression levels. Conclusions . VAT macrophages are increased in obese subjects, but the current markers used to define macrophage populations are inadequate to distinguish differences in human obesity. Further studies are needed to delineate the function of AT macrophages in the maintenance and progression of human AT inflammation in obesity.

Deiodinase type II (D2), encoded by DIO2 , catalyzes the conversion of T4 to bioactive T3. T3 not only stimulates adaptive thermogenesis but also affects adipose tissue (AT) lipid accumulation, mitochondrial function, inflammation, and potentially systemic metabolism. Although better defined in brown AT, the precise role of DIO2 expression in white AT remains largely unknown, with data derived only from whole fat. Therefore, the purpose of this study was to determine whether subcutaneous (SAT) and visceral (VAT) adipocyte-specific gene expression of DIO2 differs between obese and lean patients and whether these differences relate to alterations in mitochondrial function, fatty acid flux, inflammatory cytokines/adipokines, and ultimately insulin sensitivity. Accordingly, adipocytes of 73 obese and 21 lean subjects were isolated and subjected to gene expression analyses. Our results demonstrate that obese compared to lean human individuals have increased adipocyte-specific DIO2 expression in both SAT and VAT. Although higher DIO2 was strongly related to reduced fatty acid synthesis/oxidation and mitochondrial function, we found no relationship to proinflammatory cytokines or insulin resistance and no difference based on diabetic status. Our results suggest that adipocyte-derived DIO2 may play a role in weight maintenance but is likely not a major contributor to obesity-related insulin resistance.

•Extreme obesity may preclude patients from primary surgical management of endometrial cancer.•Bariatric surgery is a safe and effective method of rapid weight loss in patients with extreme obesity.•Delayed hysterectomy, after weight loss from bariatric surgery, is an option in select patients with endometrial cancer.

Decreased adipose tissue regulatory T cells contribute to insulin resistance in obese mice, however, little is known about the mechanisms regulating adipose tissue regulatory T cells numbers in humans. Here we obtain adipose tissue from obese and lean volunteers. Regulatory T cell abundance is lower in obese vs. lean visceral and subcutaneous adipose tissue and associates with reduced insulin sensitivity and altered adipocyte metabolic gene expression. Regulatory T cells numbers decline following high-fat diet induction in lean volunteers. We see alteration in major histocompatibility complex II pathway in adipocytes from obese patients and after high fat ingestion, which increases T helper 1 cell numbers and decreases regulatory T cell differentiation. We also observe increased expression of inhibitory co-receptors including programmed cell death protein 1 and OX40 in visceral adipose tissue regulatory T cells from patients with obesity. In human obesity, these global effects of interferon gamma to reduce regulatory T cells and diminish their function appear to instigate adipose inflammation and suppress adipocyte metabolism, leading to insulin resistance. Murine models of obesity suggest that decreases in the adipose tissue regulatory T cell compartment may contribute to insulin resistance, but how this corresponds in the human clinical context is less well understood. Here the authors propose a role for interferon gamma in shrinking the adipose tissue regulatory T cell compartment seen in human obesity and assess the alterations seen during induction of dietary changes. [ABSTRACT FROM AUTHOR]

Background: The impact of obesity on the pathogenesis and prognosis of necrotizing soft tissue infections (NSTIs) is unclear. The goal of this study was to characterize differences in NSTI presentation and outcomes by obesity status. Patients and Methods: A retrospective analysis of institutional data for patients diagnosed with NSTIs were identified (n = 619; 2011-2020). Patients were divided based on obesity (body mass index [BMI] ≥ 30 kg/m2) and non-obese (BMI <30 kg/m2). Primary outcomes included NSTI location, micro-organisms, and index hospitalization data. Multiple logistic regression was used to model predictors of in-hospital and 90-day mortality. Results: The obese cohort (n = 390; 63%) had higher rates of congestive heart failure and type 2 diabetes mellitus. There were no differences in length of stay, mortality, or discharge disposition between groups. A higher rate of respiratory failure was observed in the obese versus non-obese group (36.7% vs. 20.9%; p < 0.0005). The obese cohort was associated with perineal (40.8% vs. 27.0%) and torso NSTIs (20.9% vs. 15.8%; p < 0.005) but reduced staphylococcal (19.2% vs. 27.4%; p = 0.02) and group A streptococcal (2.6% vs. 6.5%; p = 0.03) infections, and increased polymicrobial infections. Class 2 obesity was a negative predictor for in-hospital mortality (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.03-0.5) and 90-day mortality (OR, 0.3; 95% CI, 0.1-0.8), when adjusting for demographic data, type of infection, and baseline comorbidities. Conclusions: Necrotizing soft tissue infections in obesity may present with unique distributions and microbial characteristics. Class 2 obesity may exhibit a survival benefit compared with non-obese patients, suggestive of an obesity paradox. [ABSTRACT FROM AUTHOR]