Transcriptional and epigenetic changes after dietary and surgical weight loss interventions in an animal model of obesity.

BACKGROUND: Identifying determinants that can predict response to weight loss interventions is imperative for optimizing therapeutic benefit. We aimed to identify changes in DNA methylation and mRNA expression of a subset of target genes following dietary and surgical interventions in high-fat-diet (HFD)-induced obese rats. METHODS: Forty-two adult Wistar Han male rats were divided into two groups: control rats (n = 7) and obese rats (n = 28), fed a HFD for 10 weeks (t10). Obese rats were randomly subdivided into five intervention groups (seven animals per group): (i) HFD; (ii) very-low-calorie diet (VLCD); (iii) sham surgery, and (iv) sleeve gastrectomy (SG). At week sixteen (t16), animals were sacrificed and tissue samples were collected to analyze changes in DNA methylation and mRNA expression of the selected genes. RESULTS: By type of intervention, the surgical procedures led to the greatest weight loss. Changes in methylation and/or expression of candidate genes occurred proportionally to the effectiveness of the weight loss interventions. Leptin expression, increased sixfold in the visceral fat of the obese rats, was partially normalized after all interventions. The expression of fatty acid synthase (FASN) and monocyte chemoattractant protein 1 (MCP-1) genes, which was reduced 0.5- and 0.15-fold, respectively, in the liver tissue of obese rats, were completely normalized after weight loss interventions, particularly after surgical interventions. The upregulation of FASN and MCP-1 gene expression was accompanied by a significant reduction in promoter methylation, up to 0.5-fold decrease in the case of the FASN (all intervention groups) and a 0.8-fold decrease in the case of the MCP-1 (SG group). CONCLUSIONS: Changes in tissue expression of specific genes involved in the pathophysiological mechanisms of obesity can be significantly attenuated following weight loss interventions, particularly surgery. Some of these genes are regulated by epigenetic mechanisms.

Recommendations on the management of severe obesity in patients with inflammatory bowel disease of the Spanish Group on Crohn's Disease and Ulcerative Colitis (GETECCU), Spanish Society of Obesity (SEEDO), Spanish Association of Surgery (AEC) and Spanish Society of Digestive Endoscopy (SEED). / Recomendaciones sobre el manejo de la obesidad grave en pacientes con enfermedad inflamatoria intestinal del Grupo Español de Trabajo en Enfermedad Inflamatoria Intestinal (GETECCU), Sociedad Española de Obesidad (SEEDO), Asociación Española de Cirugía (AEC) y Sociedad Española de Endoscopia Digestiva (SEED).

Obesity is a multifactorial, chronic, progressive and recurrent disease considered a public health issue worldwide and an important determinant of disability and death. In Spain, its current prevalence in the adult population is about 24% and an estimated prevalence in 2035 of 37%. Obesity increases the probability of several diseases linked to higher mortality such as diabetes, cardiovascular disease, hyperlipidemia, arterial hypertension, non-alcoholic fatty liver disease, several types of cancer, or obstructive sleep apnea. On the other hand, although the incidence of inflammatory bowel disease (IBD) is stabilizing in Western countries, its prevalence already exceeds 0.3%. Paralleling to general population, the current prevalence of obesity in adult patients with IBD is estimated at 15-40%. Obesity in patients with IBD could entail, in addition to its already known impact on disability and mortality, a worse evolution of the IBD itself and a worse response to treatments. The aim of this document, performed in collaboration by four scientific societies involved in the clinical care of severe obesity and IBD, is to establish clear and concise recommendations on the therapeutic possibilities of severe or typeIII obesity in patients with IBD. The document establishes general recommendations on dietary, pharmacological, endoscopic, and surgical treatment of severe obesity in patients with IBD, as well as pre- and post-treatment evaluation.

Preoperative triage to detect SARS-CoV-2 infection in surgical patients: lessons learned for resuming surgery.

PURPOSE: To define the impact of the COVID-19 outbreak on hospital surgical activity and assess the incidence of perioperative COVID-19 within two protocolized screening pathways for elective and non-elective surgery. METHODS: We conducted a prospective cohort study of adults undergoing surgery during the COVID-19 outbreak. The elective pathway included telephone surveys and a quantitative polymerase-chain-reaction test (RT-PCR) only for patients who were asymptomatic and at low risk of infection. Only patients with negative screening underwent surgery. In the non-elective pathway, preoperative screening was performed during the hospital admission. RESULTS: Among 835 patients considered for the elective pathway, 725 had negative RT-PCR results and underwent surgery. This reflects an 83% reduction in surgical activity from 2019. Moreover, 596 patients underwent non-elective surgery, representing a 28% reduction. Preoperatively, 39 patients (6.5%) tested positive for SARS-CoV-2 and underwent surgery through the non-elective pathway, vs. none in the elective pathway (p < 0.001). Postoperatively, 1.4% of elective surgery patients and 2.2% of non-elective surgery patients tested positive (p > 0.05). Mortality was higher in non-elective surgery (0.6% vs. 2.9%, p < 0.001) and in patients with COVID-19 (0% vs. 14%, p < 0.001). CONCLUSIONS: The low incidence of COVID-19 in elective surgeries during the outbreak demonstrates the importance and effectiveness of preoperative screening, combining surveys and RT-PCR.

Weight-loss thresholds after bariatric surgery and cardiovascular outcomes: more is better.

BACKGROUND/OBJECTIVES: Whether the extent of weight loss (WL) modulates bariatric surgery (BS) cardiovascular benefits has scarcely been assessed. Several WL thresholds have been commonly used to classify BS patients as good or poor responders without a proven clinical relevance. We examined the relationship between the magnitude of WL after BS and post-surgery major adverse cardiovascular-event (MACE) incidence. We also compared the performance of three different insufficient weight-loss (IWL) criteria for their association with MACE. SUBJECTS AND METHODS: All individuals who underwent a primary Roux-en Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in our institution at least six years before data analysis (12/2020) were included in the study. Data on MACE were available in 1638 of 1700 participants (96.4%). Proportional-hazard Cox analyses were performed to ascertain the association between MACE, WL, and the three IWL criteria. IWL was defined as: <50% excess weight loss (<50% EWL), <20% total body-weight loss (<20% TBWL), and -1 standard deviation of alterable weight-loss percentage (<1 SD% AWL). RESULTS: During a mean follow-up of 10.2 ± 2.8 years, 86 participants experienced a first post-surgery MACE. Higher WL at one year (HR: 0.77 (95% CI: 0.61-0.98)) and 5 years (HR: 0.63 (95% CI: 0.42-0.92)) was related to a lower incidence of MACE. All short-term criteria for defining IWL were similarly associated with MACE, yet <1 SD% AWL identified more at-risk subjects. Five-year TBWL < 20% and 5-year <1 SD-AWL% were significantly associated with a higher risk for CV events. TBWL < 20% identified more subjects at risk. CONCLUSIONS: The extent of WL is closely related to long-term MACE incidence. Patients who lost -1SD% AWL at one year or <20% TBWL at five years may be considered poor responders.

Biological Determinants of Metabolic Syndrome in Visceral and Subcutaneous Adipose Tissue from Severely Obese Women.

The metabolic syndrome (MetS) is a cluster of the most dangerous heart attack risk factors: diabetes or raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. The goal of this study is to compare the state of the main features of obesity-associated white adipose tissue (WAT) dysfunction in 66 women with severe obesity without (MetS-) or with MetS (MetS+). Fat cell area, adipocyte size distribution and histological fibrosis were analysed in visceral (VAT) and abdominal subcutaneous WAT (SAT) in 33 age- and BMI-matched pairs of MetS- and MetS+ subjects. The mRNA expression of 93 genes implicated in obesity-associated WAT dysfunction was analysed by RT-qPCR in both fat depots. MetS+ females showed higher adipocyte hypertrophy in both fat depots and increased fibrosis and expression of macrophage and hypoxia markers in SAT. Transcriptional data suggest increased fatty acid oxidation in SAT and impaired thermogenesis and extracellular matrix remodelling in VAT from MetS+ subjects. A sPLS-DA model, including SAT expression of PPARA and LEPR genes identified MetS with an AUC = 0.87. Despite equal age, BMI and body composition, MetS+ females display morphological and transcriptional differences in both WAT depots, especially in SAT. These factors may contribute to the transition to MetS.

Antibiotic-resistant microorganisms in patients with bloodstream infection of intraabdominal origin: risk factors and impact on mortality.

BACKGROUND: Knowledge of resistance patterns is essential to choose empirical treatment. We aimed to determine the risk factors for antibiotic-resistant microorganisms (ARM) in intraabdominal infections (IAI) and their impact on mortality. METHODS: Retrospective cohort study of patients with bacteremia from IAI origin in a single hospital between January 2006 and July 2017. RESULTS: A total of 1485 episodes were recorded, including 381 (25.6%) due to ARM. Independent predictors of ARM were cirrhosis (OR 2; [95% CI 1.15-3.48]), immunosuppression (OR 1.49; 1.12-1.97), prior ceftazidime exposure (OR 3.7; 1.14-11.9), number of prior antibiotics (OR 2.33; 1.61-3.35 for 1 antibiotic), biliary manipulation (OR 1.53; 1.02-2.96), hospital-acquisition (OR 2.77; 1.89-4) and shock (OR 1.48; 1.07-2). Mortality rate of the whole cohort was 11.1%. Age (OR 1.03; 1.01-1.04), cirrhosis (OR 2.32; 1.07-4.38), urinary catheter (OR 1.99; 1.17-3.38), ultimately (OR 2.28; 1.47-3.51) or rapidly (OR 13.3; 7.12-24.9) fatal underlying disease, nosocomial infection (OR 2.76; 1.6-4.75), peritonitis (OR 1.95, 1.1-3.45), absence of fever (OR 2.17; 1.25-3.77), shock (OR 5.96; 3.89-9.13), and an ARM in non-biliary infections (OR 2.14; 1.19-3.83) were independent predictors of 30-day mortality. Source control (OR 0.24; 0.13-0.44) and 2015-2017 period (OR 0.29; 0.14-0.6) were protective. CONCLUSION: Biliary manipulation and septic shock are predictors of ARM. The presence of an ARM from a non-biliary focus is a poor-prognosis indicator. Source control continues to be of paramount importance.

Exposure to virtual reality as a tool to reduce peri-operative anxiety in patients undergoing colorectal cancer surgery: a single-center prospective randomized clinical trial.

BACKGROUND: More than 60% of patients who undergo surgery for colorectal cancer experience anxiety at some point during the perioperative period. In addition to the obvious impact on the experience of the therapeutic process, the presence of anxiety has also been associated with the appearance of complications. Virtual reality could reduce it by simulating the controlled exposure of the patient to the conscious part of the surgical process. METHODS: Single-center randomized clinical trial (NCT04058600) in which patients who were to undergo surgery for colorectal cancer and who had not previously undergone surgery as adults were exposed, prior to hospital admission, to virtual reality software in which all perioperative phases in which the patient is awake, from admission to discharge, were recreated. The main objective was to determine the presence of pre- and post-exposure anxiety using the validated State-Trait Anxiety Inventory Scale (STAI-S) and Hospital Anxiety and Depression Scale (HADS). RESULTS: A total of 126 patients were recruited (58 exposed, 68 unexposed). There were no differences between the groups in terms of age, gender, anesthetic risk, type of surgery. or levels of preoperative anxiety or depression. After exposure, all anxiety/depression rating scales decreased significantly. CONCLUSIONS: The use of simulation using virtual reality can reduce perioperative anxiety in patients undergoing surgery for colorectal cancer.

Management of the staple line in laparoscopic sleeve gastrectomy: comparison of three different reinforcement techniques.

BACKGROUND: Nowadays, laparoscopic sleeve gastrectomy (LSG) is one of the most widely performed bariatric procedures. Different techniques have been described to reduce the rate of complications associated with the staple line, but no consensus has been reached. The aim of this study was to determine the incidence of surgical complications after LSG with three different approaches to the staple line. PATIENTS AND METHODS: A retrospective matched analysis was performed, comparing three groups of 100 patients each: partial oversewing of the staple line (PO group), complete oversewing of the staple line (CO group), and reinforcement with buttress material (BM group). Operative time, early surgical complications (superficial surgical site infection, leakage and hemorrhage), length of stay, weight evolution, and revisional surgery rates were analyzed. RESULTS: All three groups were comparable at baseline. All surgeries were performed laparoscopically. Operative time was significantly longer in the CO group (PO: 84.2 ± 22; CO: 104.7 ± 17; BM: 82.3 ± 22; PO vs CO, p = 0.021; BM vs CO, p = 0.011). There were no differences in length of stay, early surgical complications, and weight outcomes at 36 months between the groups. The need for a revisional surgery was significantly higher in the CO group compared to the PO group (PO: 3%; CO: 14%; BM: 9%; PO vs CO, p = 0.005). CONCLUSION: The CO group required a longer operative time. There were no differences in early surgical complications between the groups. The CO group had a higher need for revisional surgery than the PO group.

The first modified Delphi consensus statement on sleeve gastrectomy.

INTRODUCTION: Sleeve gastrectomy (SG) is the commonest bariatric procedure worldwide. Yet there is significant variation in practice concerning its various aspects. This paper report results from the first modified Delphi consensus-building exercise on SG. METHODS: We established a committee of 54 globally recognized opinion makers in this field. The committee agreed to vote on several statements concerning SG. An agreement or disagreement amongst ≥ 70.0% experts was construed as a consensus. RESULTS: The committee achieved a consensus of agreement (n = 71) or disagreement (n = 7) for 78 out of 97 proposed statements after two rounds of voting. The committee agreed with 96.3% consensus that the characterization of SG as a purely restrictive procedure was inaccurate and there was 88.7% consensus that SG was not a suitable standalone, primary, surgical weight loss option for patients with Barrett's esophagus (BE) without dysplasia. There was an overwhelming consensus of 92.5% that the sleeve should be fashioned over an orogastric tube of 36-40 Fr and a 90.7% consensus that surgeons should stay at least 1 cm away from the angle of His. Remarkably, the committee agreed with 81.1% consensus that SG patients should undergo a screening endoscopy every 5 years after surgery to screen for BE. CONCLUSION: A multinational team of experts achieved consensus on several aspects of SG. The findings of this exercise should help improve the outcomes of SG, the commonest bariatric procedure worldwide, and guide future research on this topic.

Protective effects of 17-ß-oestradiol and phytoestrogen on age-induced oxidative stress and inhibition of surfactant synthesis in rat type II pneumocytes.

Epidemiological data suggest protective effects of oestrogen and phytoestrogen on lung tissue. This study aimed to elucidate the role of 17-ß-oestradiol and phytoestrogen in age-related inhibition of surfactant synthesis and oxidative stress in rat type II pneumocytes. Forty male and 66 female Wistar rats were used. Female rats were randomly kept intact or ovariectomized at age 12 months. At age 22 months, ovariectomized rats received 17-ß-oestradiol, soy extract, or no treatment. Oxidative stress markers CO, NO, cGMP and lipid peroxide (LPO), antioxidant enzymes and phosphatidylcholine (PC) were measured in cultured type II pneumocytes isolated at ages 2, 14, 18, 22 and 24 months. Old, male and ovariectomized rats showed significantly higher CO, NO, cGMP and LPO and lower PC content and antioxidant enzymes. 17-ß-oestradiol and phytoestrogen significantly reversed these effects. In conclusion, aging and oestrogen deprivation decreased PC synthesis and altered the redox status in type II pneumocytes, which were partially restored by 17-ß-oestradiol or soy supplementation.

A Distinctive NAFLD Signature in Adipose Tissue from Women with Severe Obesity.

Development and severity of nonalcoholic fatty liver disease (NAFLD) have been linked to obesity and white adipose tissue (WAT) dysfunction plays a key role in this relation. We compared the main features of subcutaneous (SAT) and visceral WAT (VAT) tissue dysfunction in 48 obese women without (Ob) and with NAFLD (Ob-NAFLD) undergoing bariatric surgery and matched for age, BMI and T2D status. Fat cell area, adipocyte size distribution, the degree of histological fibrosis and the mRNA expression of adipokines and genes implicated in inflammation, adipogenesis, angiogenesis, metabolism and extracellular matrix remodeling were measured by RT-qPCR in both fat depots. Ob-NAFLD group showed higher TG and lower HDL circulating levels, increased VAT fat cell area and similar WAT fibrosis in comparison with Ob group. A sPLS-DA was performed in order to identify the set of genes that better characterize the presence of NAFLD. Finally, we build a multinomial logistic model including seven genes that explained 100% of the variance in NAFLD and correctly predicted 100% of cases. Our data support the existence of distinctive NAFLD signatures in WAT from women with severe obesity. A better understanding of these pathways may help in future strategies for the prevention and treatment of NAFLD.

[National survey on the treatment of acute appendicitis in Spain during the initial period of the COVID-19 pandemic]. / Encuesta nacional sobre el tratamiento de la apendicitis aguda en España durante la fase inicial de la pandemia por COVID-19.

INTRODUCTION: The COVID-19 pandemic has had a significant impact on Spanish hospitals, which have had to allocate all available resources to treat these patients, reducing the ability to attend other common pathologies. The aim of this study is to analyze how the treatment of acute appendicitis has been affected. METHODS: A national descriptive study was carried out by a online voluntary distribution of a specific questionnaire with Google Drive™ distributed by email by the Spanish Association of Surgeons (AEC) to all affiliated surgeons actually working in Spain (5203) opened from April 14th to April 24th. RESULTS: We received 337 responses from 170 centers. During the first month of the pandemic the incidence of acute appendicitis has decreased. Although conservative management has increased, surgical option has been the most used in both simple and complicated appendicitis. Despite the fact that the laparoscopic approach continues to be the most widely used in our services, the open approach has increased during this pandemic period. CONCLUSION: Highlight the contribution of this study in terms of knowledge of the status of the treatment of acute appendicitis during this first month of the pandemic, being able to serve for a better possible organization in future waves of the pandemic and a reorganization of current protocols and management of acute appendicitis in a pandemic situation.

[National survey on the treatment of cholelitiasis in Spain during the initial period of the COVID-19 pandemic]. / Encuesta nacional sobre el tratamiento de la colelitiasis en España durante la fase inicial de la pandemia por COVID-19.

Introduction: The extraordinary impact of COVID-19 pandemic on Spanish hospitals has led to a redistribution of resources for the treatment of these patients, with a decreased capacity of care for other common diseases. The aim of the present study is to analyse how this situation has affected the treatment of cholecystitis and cholelythiasis. Methods: It is a descriptive national study after online voluntary distribution of a specific questionnaire with Google Drive™ to members of the Spanish Association of Surgeons (AEC). Results: We received 153 answers (one per hospital). Elective cholecystectomies have been cancelled in 96.7% of centres. Conservative treatment for acute cholecystitis has been selected in 90% (previously 18%), and if operated, 95% have been performed laparoscopically. Globally, only 49% perform preoperative diagnostic tests for SARS-CoV-2, and 58.5% recognize there have been cases confirmed postoperatively after other surgeries, with worse surgical outcomes in 54%. Conclusions: This survey shows that most of the Spanish centers are following the surgical societies suggestions during the pandemic. However, some data requires to be taken into account for the next phase of the pandemic.

A Meta-analysis of Prophylaxis of Surgical Site Infections with Topical Application of Povidone Iodine Before Primary Closure.

BACKGROUND: Povidone iodine (PVI) is a widely used antiseptic solution among surgeons. A meta-analysis based on randomized controlled trials (RCTs) was conducted to establish whether application of PVI before wound closure could reduce surgical site infection (SSI) rates. METHODS: Systematic review of MEDLINE/PubMed, Scopus, CINAHL, and Web of Science databases from inception to September 2017, with no language restrictions. Only RCTs were retrieved. The primary outcome was the SSI rate. Meta-analysis was complemented with trial sequential analysis (TSA). RESULTS: A total of 7601 patients collected from 16 RCTs were analyzed. A reduction in overall SSI rate was found (RR 0.64, 95% CI 0.48-0.85, P = 0.002, I2 = 65%), which was attributed to patients undergoing elective operations (n = 2358) and mixed elective/urgent operations (n = 2019). When RCTs of uncertain quality (n = 9) were excluded, the use of PVI before wound closure (n = 4322 patients) was not associated with a significant reduction of SSI (RR 0.81, 95% CI 0.55-1.20, P = 0.29, I2 = 51%) and was only significant in clean wounds (RR 0.25, 95% CI 0.09-0.70, P = 0.008, I2 = 0%). For the primary outcome, the TSA calculation using a relative risk reduction of 19% and an 11% proportion of control event rate (CER) with 51% of I2, the accrued information size (n = 4322) was 32.8% of the estimated optimal information size (n = 13,148). CONCLUSIONS: There is no conclusive evidence for a strong recommendation of topical PVI before wound closure to prevent SSI.

Recommendations of «not-to-do¼: Proposals of the Spanish Association of Surgeons to the project «Commitment to quality of scientific societies¼. / Recomendaciones de «no hacer¼: propuestas de la Asociación Española de Cirujanos al proyecto de «Compromiso por la calidad de las sociedades científicas¼.

INTRODUCTION: The initiative of the Spanish Ministry of Health «Commitment to quality of scientific societies¼, aims to reduce unnecessary interventions of healthcare professionals. METHODS: The Spanish Association of Surgeons has selected 22 experts from the different sections that have participated in the identification of 26 proposals «do not do¼ to be ordered by the expected impact its implementation would have according to the GRADE methodology. From these proposals, the Delphi technique was used to select 5 recommendations presented in more detail in this article. RESULTS: The 5 selected recommendations are: Do not perform cholecystectomy in patients with asymptomatic cholelithiasis; do not keep bladder catheterization more than 48hours; do not extend antibiotic prophylaxis treatments more than 24hours after a surgical procedure; do not perform routine antibiotic prophylaxis for uncomplicated clean and no prosthetic surgery; and do not use antibiotics postoperatively after uncomplicated appendicitis. CONCLUSION: The Spanish Association of Surgeons's participation in this campaign has allowed a reflection on those activities that do not add value in the field of surgery and it is expected that the spread of this process serves to reduce its performance.

Can LigaSure™ be used to perform sleeve gastrectomy? - Tensile strength and histological changes.

INTRODUCTION: LigaSure™ was developed as an alternative to suture ligatures, hemoclips and staplers for ligating vessels and tissue bundles. The aim of the present study was to determine whether LigaSure can be used as a welding instrument in the performance of laparoscopic sleeve gastrectomy. MATERIAL AND METHODS: Gastric specimens were assigned into four groups. Group 1 - specimens remained with the staple line intact. Group 2 - the staple line was oversewn. Group 3 - the staple line was resected with LigaSure. Group 4 - staple line was resected with LigaSure and the seal was oversewn. In all specimens the pressure tolerance was assessed using a portable sensor. RESULTS: In group 1 the leak pressure was 34.7 ± 11.7 whereas in group 2 specimens the pressure increased three-fold (101.9 ± 21.4). The LigaSure seal alone (group 3) achieved a mean pressure of 13.7 mmHg. However, in group 4 there was an exponential increase on their burst strength up to 142 mmHg (p = 0.0005). CONCLUSION: According to our results, LigaSure could be used to perform laparoscopic sleeve gastrectomy with reduction of staple-line bleeding and, when reinforced with a running suture, it achieves a strength that approaches that of staples plus oversewing.

[Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?]. / Carcinoma broncogénico no microcítico resecado, estadio pIIIA-N2. ¿En qué pacientes la adyuvancia ofrece mayor beneficio?

BACKGROUND: Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. METHODS: A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. RESULTS: The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). CONCLUSIONS: Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma.

FABP4 Expression in Subcutaneous Adipose Tissue Is Independently Associated with Circulating Triglycerides in Obesity.

Hypertriglyceridemia (HTG) has been associated with an increased risk of pancreatitis and cardiovascular disease. Adipose tissue plays a major role in lipid metabolism, mobilization and distribution. We have compared the histological and transcriptomic profiles of the subcutaneous (SAT) and visceral (VAT) adipose tissues from subjects with severe obesity undergoing bariatric surgery with (Ob-HTG, n = 37) and without HTG (Ob-NTG, n = 67). Mean age and BMI were 51.87 ± 11.21 years, 45.78 ± 6.96 kg/m2 and 50.03 ± 10.17 years, 44.04 ± 4.69 kg/m2, respectively. The Ob-HTG group showed higher levels of glycosylated hemoglobin, fasting plasma glucose, high-sensitivity C-reactive protein and prevalence of hypertension. The degree of fibrosis was increased by 14% in SAT from the Ob-HTG group (p = 0.028), while adipocyte size distribution was comparable. Twenty genes were found differentially expressed in SAT and VAT between study groups. Among them, only SAT expression of FABP4 resulted significantly associated with circulating triglyceride levels after adjusting for other covariates and independently explained 5% of the variance in triglyceride levels in the combined model. This relationship was not found in the cohort of lean or overweight patients with normotriglyceridemia (non-Ob, n = 21). These results emphasize the contribution of SAT to triglyceride concentrations in obesity and indicate that FABP4 may be a potential drug target for the treatment of HTG.

Expression of Adipose Tissue Extracellular Matrix-Related Genes Predicts Weight Loss after Bariatric Surgery.

BACKGROUND: We evaluated the association between white adipose tissue parameters before bariatric surgery (BS) and post-surgical weight loss, with an especial focus on extracellular matrix (ECM) gene expression. METHODS: Paired samples from subcutaneous (SAT) and visceral adipose tissue (VAT) were obtained from 144 subjects undergoing BS. The association between total body weight loss (%TBWL) at 12 months after BS and the histological characteristics and gene expression of selected genes in SAT and VAT was analyzed. RESULTS: Fat cell area, size-frequency distribution, and fibrosis in SAT or VAT prior to surgery were not associated with %TBWL. On the contrary, the SAT expression of COL5A1 and COL6A3 was associated with %TBWL after BS (both p < 0.001), even after adjusting for age, gender, baseline BMI, and type 2 diabetes status (T2D). Furthermore, in logistic regression analyses, the expression of these genes was significantly associated with insufficient WL (IWL = TBWL < 20%) after BS (respectively, p = 0.030 and p = 0.031). Indeed, in ROC analysis, the prediction of IWL based on sex, age, BMI, T2D, and the type of surgery (AUC = 0.71) was significantly improved with the addition of SAT-COL5A1 gene expression (AUC = 0.88, Z = 2.13, p = 0.032). CONCLUSIONS: Our data suggest that the expression of SAT ECM-related genes may help explain the variability in TBWL following BS.