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Abstract Introduction Most gastric tumors are adenocarcinomas. Primary gastric adenosquamous carcinoma is a rare malignancy, mostly associated with Asian populations. It constitutes less than one percent of all gastric carcinomas and its clinical presentation is the same as adenocarcinoma. It occurs more frequently in the proximal stomach, usually presents with muscular layer invasion and tends to be found in advanced stages at diagnosis, with a worse prognosis than adenocarcinoma. Case presentation We report the case of an 84-year-old Caucasian woman with an adenosquamous carcinoma extending to her serosa with lymphatic and venous invasion (T3N1M1). Nodal and hepatic metastasis presented with both cellular types, with dominance of the squamous component. Conclusions Adenosquamous gastric cancer is a rare diagnosis in western populations. We present the case of a woman with a very aggressive adenosquamous carcinoma with a preponderance of squamous cell component in the metastasis. Several origins have been proposed for this kind of carcinoma; either evolution from adenocarcinoma de-differentiation or stem cell origin might be possible. The hypothesis that a particular histological type of gastric cancer may arise from stem cells might be a field of research in oncological disease of the stomach.

Introduction: Patients with body mass index (BMI) ≥ 50 kg/m 2 , classified with obesity class IV/V, require complex treatments. Intragastric balloon (IGB) is a possible treatment before metabolic bariatric surgery (MBS) that may reduce peri-operative complications. This study evaluates IGB outcomes and complications before MBS in patients with Obesity IV/V, and subsequent MBS results, regarding weight loss and comorbidity resolution., Methods: Retrospective cohort study of all patients with BMI above 50 kg/m 2 submitted to IGB before MBS between 2009 and 2023 in a high-volume center. Variables analyzed included weight loss after IGB and MBS, IGB complications, and comorbidity resolution. Suboptimal clinical responses were defined as %TWL < 5% for IGB, %TWL < 20% for MBS, and %TWL < 25% or BMI ≥ 35 kg/m 2 for IGB + MBS., Results: Seventy-four patients (mean BMI 58.8 ± 8 kg/m 2 ) were included. After IGB, the mean %TWL was 14.2 ± 8.5%, with a 21.6% complication rate, predominantly nausea and vomiting, and one death. Suboptimal clinical response of IGB affected 13.5% of patients, and 5.4% required early removal. Two years after MBS, the mean %TWL was 38.2 ± 11.6%, mainly due to MBS, yet approximately one-third of %TWL was attributed to IGB. No correlation was found between IGB and MBS outcomes. At 2-year follow-up, 45.1% patients had %TWL ≥ 25 and BMI < 35 kg/m 2 ., Conclusion: The IGB is a treatment option before MBS in patients with Obesity Class IV/V, with acceptable weight loss outcomes but not infrequent complications. A multidisciplinary approach is mandatory, and all treatments must be considered in this difficult subset of patients., (© 2024. The Author(s).)

Introduction: The Single Anastomosis Sleeve Ileal (SASI) bypass is a new bariatric surgery corresponding to an adaptation of the Santoro approach, consisting of a sleeve gastrectomy (SG) followed by loop gastroileostomy. Therefore, we aimed to systematically assess all the current literature on SASI bypass in terms of safety, weight loss, improvement in associated comorbidities, and complications., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) recommendations, we conducted a systematic review and meta-analysis by searching three databases (PubMed, Scopus, and Web of Science). We performed a meta-analysis of risk ratios and mean differences to compare surgical approaches for excessive weight loss, improvement/remission in type 2 diabetes mellitus (T2DM), hypertension (HT), dyslipidemia (DL), obstructive sleep apnea (OSA), and complications. Heterogeneity was assessed using the I 2 statistic., Results: Eighteen studies were included in the qualitative analysis and four in the quantitative analysis, comparing SASI bypass with SG and One-Anastomosis Gastric Bypass (OAGB). A comparison between Roux-en-Y Gastric Bypass (RYGB) and SASI bypass could not be performed. Compared to SG, the SASI bypass was associated with improved weight loss (MD = 11.32; 95% confidence interval (95%CI) [7.89;14.76]; p < 0.0001), and improvement or remission in T2DM (RR = 1.35; 95%CI [1.07;1.69]; p = 0.011), DL (RR = 1.41; 95%CI [1.00;1.99]; p = 0.048) and OSA (RR = 1.50; 95%CI [1.01;2.22]; p = 0.042). No statistically significant differences in any of the assessed outcomes were observed when compared with OAGB. When compared to both SG and OAGB, the complication rate of SASI was similar., Conclusion: Although studies with longer follow-up periods are needed, this systematic review and meta-analysis showed that SASI bypass has a significant effect on weight loss and metabolic variables. Variations in outcomes between studies reinforce the need for standardization., (© 2024. The Author(s).)

(1) Background: Portomesenteric Venous Thrombosis (PMVT) is a rare but serious complication of Metabolic Bariatric Surgery (MBS). Although more frequently reported after laparoscopic sleeve gastrectomy (LSG), the risk factors for PMVT remain unclear. This study aims to compare the incidence and determinants of PMVT between LSG and laparoscopic Roux-en-Y gastric bypass (LRYGB). (2) Methods: A retrospective analysis of 5235 MBSs conducted at our institution between 2015 and 2023 identified five cases of PMVT. Additionally, a systematic review in March 2023, covering PubMed, Web of Science and Scopus, was performed. Several data were analyzed regarding risk factors. (3) Results: In our case series, the incidence of PMVT was 0.1%. The five cases described involved four females with a BMI between 39.7 and 56.0 kg/m 2 . Their comorbidities were associated with metabolic syndrome, all women used oral contraceptive and two patients were diagnosed with thrombophilia or pulmonary embolism. Per protocol, thromboprophylaxis was administered to all patients. Diagnosis was made at a median of 16 days post-surgery, with abdominal pain being the main presenting symptom. Acute cases were managed with enoxaparin, unfractionated heparin and fibrinolysis. One patient required surgery. Ten studies were included in the systematic review and 205 patients with PMVT were identified: 193 (94.1%) post-LSG and 12 post-LRYGB. The most common comorbidities were dyslipidemia, hypertension, diabetes, sleep apnea and liver disorders; (4) Conclusions: PMVT is a potentially life-threatening complication after MBS, requiring preventive measures, timely diagnosis and several treatments. Our findings suggest a higher occurrence in women with an elevated BMI and post-LSG. Tailored thromboprophylaxis for MBS patients at risk of PMVT may be warranted.

Background: Metabolic surgery is the foremost treatment for obesity and its associated medical conditions. Nonetheless, post-bariatric hypoglycemia (PBH) emerges as a prevalent complication. PBH pathophysiology implicates heightened insulin and glucagon-like peptide 1 (GLP-1) levels, with bile acids (BA) contributing to GLP-1 release. A plausible association exists between cholecystectomy and PBH, which is attributed to alterations in BA metabolism and ensuing hormonal responses. The objective of this retrospective cohort study was to evaluate the impact of cholecystectomy on PBH pharmacological treatment, diagnostic timelines and metabolic parameters., Materials and Methods: Patients diagnosed with PBH after bariatric surgery were evaluated based on their history of cholecystectomy. Demographic, anthropometric and clinical data were collected. Mixed meal tolerance tests (MMTT) results were compiled to assess metabolic responses., Results: Of the 131 patients with PBH included in the study, 29 had prior cholecystectomy. The time to PBH diagnosis was similar across groups. Patients with prior cholecystectomy required higher doses of acarbose (p = 0.046), compared to those without prior cholecystectomy. Additionally, MMTT revealed higher insulin (t = 60 min: p = 0.010 and t = 90 min: p = 0.034) and c-peptide levels (t = 60 min: p = 0.008) and greater glycemic variability in patients with prior cholecystectomy (p = 0.049), highlighting the impact of cholecystectomy on glucose metabolism., Conclusion: Our study offers novel insights into PBH pharmacotherapy, indicating that PBH patients with a history of cholecystectomy require elevated doses of acarbose for symptom control than PBH patients without such surgical history. Furthermore, our findings underscore the pivotal role of hyperinsulinism in PBH aetiology, emphasizing the significance of the BA-GLP-1-insulin axis., (© 2024. The Author(s).)

Obesity is a worldwide epidemic, and bariatric surgery is considered the primary treatment for long-term weight loss and managing obesity-related health issues. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most performed procedures. Nutritional deficiencies are a significant concern following bariatric surgery and can have serious consequences. This study aims to compare the incidence of nutritional deficiencies in patients undergoing RYGB and SG. A retrospective analysis was conducted on the nutritional status of 505 consecutive patients who underwent either RYGB or SG between January and December 2019. Data were collected regarding vitamin B12, folic acid, vitamin D, calcium, PTH, magnesium, hemoglobin, iron, ferritin, and transferrin at preoperative, 6-month, and 12-month intervals post-surgery. The RYGB group showed significantly higher excess weight loss. Vitamin B12, hemoglobin, and ferritin levels were consistently higher in the SG group throughout the study. Vitamin D deficiency was prevalent, with no significant difference between the groups. Vitamin B12 deficiency was significantly more common in the RYGB group (6 months: 17.46% vs. 4.69%, p < 0.001; 12 months: 16.74% vs. 0.93%, p < 0.001). Despite differences in their mechanisms, bariatric surgeries were associated with nutritional deficiencies. It is crucial to efficiently assess, prevent, and manage these deficiencies tailored to each surgical procedure.

Purpose: Although bariatric surgery is an effective intervention for obesity, it comes with risks such as early postoperative bleeding (EPB). Identifying preoperative risk factors for this complication can help patients' risk stratification and optimization. We performed a systematic review and meta-analysis to find predictors for early postoperative bleeding after Roux-en-Y gastric bypass (RYGB)., Methods: We conducted a systematic review, searching PubMed, Cochrane Library, and Web of Science until November 2023. We performed a random-effects meta-analysis to explore preoperative risk factors associated with early postoperative bleeding after RYGB. Sources of heterogeneity were explored by leave-one-out analyses., Results: 23 studies were included, comprising 232,488 patients. Male gender (meta-analytical RR = 1.42, 95%CI = 1.21-1.66, I 2  = 18%, Q Cochran test p-value = 0.29) and revisional surgery (meta-analytical RR = 1.35, 95%CI = 1.12-1.62, I 2  = 22%, Q Cochran test p = 0.21) were associated with higher risk of EPB. On average, patients with EPB were older than the remainder (MD for the mean age = 2.82 years, 95%CI = 0.97-4.67, I 2  = 0.00%, Q Cochran test p = 0.46). Except for hypertension (meta-analytical RR = 1.33, 95%CI = 1.02-1.73, I 2  = 66%, Q Cochran test p < 0.0001), comorbidities were not associated with a higher risk of EPB., Conclusion: Preoperative risk factors, including age, gender, hypertension, and revisional bariatric surgery, are associated with early postoperative bleeding after RYGB. Further primary studies, with higher methodological quality, are required to detail more risk factors., (© 2024. The Author(s).)

Purpose: This study examined the benefits of an 11-months multicomponent exercise program (MEP) on muscular strength (MS) after bariatric surgery., Methods: Of the 84 randomized patients, 41 participants from the exercise group (EG) and 20 participants from the control group (CG) were included in the analysis. The EG received supervised MEP for 11 months, starting 1-month post-bariatric surgery (BS) in addition to standard medical care, while the CG received medical care recommendations only. Knee and trunk MS was assessed by isokinetic dynamometry pre-surgery, 1-, 6-, and 12-month post-surgery, while body composition was assessed by dual-energy X-ray absorptiometry., Results: The MEP did not significantly impact absolute MS in the dominant knee and trunk regions at 6- and 12-month post-BS. However, relative MS showed significant improvements. At 6-month post-BS, knee flexion at 60°/s relative to body weight (BW) increased significantly (p = 0.047), as did knee extension at 180°/s relative to BW (p = 0.009), and knee extension at 60°/s relative to total lean mass (p=0.040). At 12-month post-BS, knee flexion at 60°/s relative to BW also significantly improved (p=0.038)., Conclusion: While absolute MS was not significantly improved with MEP, this study found significant enhancements in relative MS, particularly in dominant knee flexion post-MEP participation. Further research should explore different exercise intensities and frequencies to optimize postoperative MS recovery post-BS., Clinical Trial Registration: ClinicalTrials.gov (NCT02843048)., (© 2024. The Author(s).)

The mitochondrial voltage-dependent anion channel 1 (VDAC1) plays a central role in metabolism and apoptosis, which makes it a promising therapeutic target. Nevertheless, molecular mechanisms governing VDAC1 functioning remain unclear. Small-molecule ligands specifically interacting with the channel provide an attractive way of exploring its structure-function relationships and can possibly be used as founding stones for future drug-candidates. While around 30 VDAC1 ligands have been identified over the years, various techniques have been used by research teams, making a fair and direct comparison between compounds impossible. To tackle this issue, we performed ligand-binding assays on a representative set of seventeen known VDAC1 ligands using nano-differential scanning fluorimetry and microscale thermophoresis. While all the compounds have been confirmed as VDAC1 ligands by at least one method, combining both technologies lead to the selection of four molecules (cannabidiol, curcumin, DIDS and VBIT4) as chemical starting points for future design of VDAC1 selective ligands.

Introduction: The frequency of revisional bariatric surgery is increasing, but its effectiveness and safety are not yet fully established. The aim of our study was to compare short-term outcomes of primary (pRYGB and pSG) and revisional bariatric surgeries (rRYGB and rSG)., Methods: We performed a retrospective cohort study assessing all patients submitted to primary and revisional (after a failed AGB) RYGB and SG in 2019. Each patient was followed-up at 6 months and 12 months after surgery. We compared pRYGB vs. rRYGB, pSG vs. rSG and rRYGB vs. rSG on weight loss, surgical complications, and resolution of comorbidities., Results: We assessed 494 patients, of which 18.8% had undergone a revisional procedure. Higher weight loss at 6 and 12 months was observed in patients undergoing primary vs. revisional procedures. Patients submitted to rRYGB lost more weight than those with rSG (%EWL 12 months = 82.6% vs. 69.0%, p < 0.001). Regarding the resolution of obesity-related comorbidities, diabetes resolution was more frequent in pRYGB than rRYGB (54.2% vs. 25.0%; p = 0.038). Also, 41.7% of the patients who underwent rRYGB had dyslipidemia resolution vs. 0% from the rSG group (p = 0.035). Dyslipidemia resolution was also more common in pSG vs. rSG (68.6% vs. 0.0%; p = 0.001). No significant differences in surgical complications were found., Conclusion: Revisional bariatric surgery is effective and safe treating obesity and related comorbidities after AGB. Primary procedures appear to be associated with better weight loss outcomes. Further prospective studies are needed to better understand the role of revisional bariatric surgery., (© 2023. The Author(s).)

Objective: This study aimed to determine the effects of a multicomponent exercise intervention during the first year post-bariatric surgery (BS) on body composition, weight loss (WL), energy expenditure, and nutrient intake., Methods: A total of 84 patients were included in this study and were randomly assigned to either an exercise group (n = 41) or a control group (n = 20). The exercise group participated in a multicomponent exercise program that began 1-month post-BS, whereas the control group received only standard medical care post-BS. Body composition was assessed by dual-energy x-ray absorptiometry, and physical activity energy expenditure was assessed by accelerometers. Nutritional intake was assessed through a 4-day food diary., Results: A total of 6-months post-BS, exercise was found to be effective in mitigating the loss of lower-limb and appendicular lean mass (LM), as well as favoring trunk fat mass (FM) loss. Moreover, it further decreased percent FM and promoted additional excess WL. After 12 months, exercise not only reduced waist circumference but also helped to lessen the loss of total, trunk, and appendicular LM., Conclusions: Exercise further induced trunk fat mass, percent FM, excess WL, and waist circumference reductions. Moreover, exercise attenuated the loss of total and regional LM., (© 2023 The Obesity Society.)

Currently, there is no way to assess mechanical loading variables such as peak ground reaction forces (pGRF) and peak loading rate (pLR) in clinical settings. The purpose of this study was to develop accelerometry-based equations to predict both pGRF and pLR during walking and running. One hundred and thirty one subjects (79 females; 76.9 ± 19.6 kg) walked and ran at different speeds (2-14 km·h -1 ) on a force plate-instrumented treadmill while wearing accelerometers at their ankle, lower back and hip. Regression equations were developed to predict pGRF and pLR from accelerometry data. Leave-one-out cross-validation was used to calculate prediction accuracy and Bland-Altman plots. Our pGRF prediction equation was compared with a reference equation previously published. Body mass and peak acceleration were included for pGRF prediction and body mass and peak acceleration rate for pLR prediction. All pGRF equation coefficients of determination were above 0.96, and a good agreement between actual and predicted pGRF was observed, with a mean absolute percent error (MAPE) below 7.3%. Accuracy indices from our equations were better than previously developed equations. All pLR prediction equations presented a lower accuracy compared to those developed to predict pGRF. Walking and running pGRF can be predicted with high accuracy by accelerometry-based equations, representing an easy way to determine mechanical loading in free-living conditions. The pLR prediction equations yielded a somewhat lower prediction accuracy compared with the pGRF equations.

Introduction: In fragment-based drug design, fragment linking is a popular strategy where two fragments binding to different sub-pockets of a target are linked together. This attractive method remains challenging especially due to the design of ideal linkers., Areas Covered: The authors review the types of linkers and chemical reactions commonly used to the synthesis of linkers, including those utilized in protein-templated fragment self-assembly, where fragments are directly linked in the presence of the protein. Finally, they detail computational workflows and software including generative models that have been developed for fragment linking., Expert Opinion: The authors believe that fragment linking offers key advantages for compound design, particularly for the design of bivalent inhibitors linking two distinct pockets of the same or different subunits. On the other hand, more studies are needed to increase the potential of protein-templated approaches in FBDD. Important computational tools such as structure-based de novo software are emerging to select suitable linkers. Fragment linking will undoubtedly benefit from developments in computational approaches and machine learning models.

Background: Bariatric surgery is the most effective treatment for sustained weight reduction and obesity-related comorbidities. The development of gallstones as a result of rapid weight loss is a well-known consequence of bariatric procedures. It remains unclear, if there is an increased risk of these gallstones becoming symptomatic., Methods: A retrospective analysis of 505 consecutive patients submitted to either Roux-en-Y Gastric Bypass or Sleeve Gastrectomy between January and December 2019 was performed. The aim of our study was to determine the incidence of symptomatic cholelithiasis in asymptomatic patients with their gallbladder in situ after bariatric surgery and to identify potential risk factors for its development., Results: Of the 505 patients included, 79 (15.6%) underwent either previous cholecystectomy. (n = 67, 84.8%) or concomitant cholecystectomy during bariatric surgery (n = 12, 15.2%). Among the remaining 426 (84.4%) patients, only 8 (1.9%) became symptomatic during the 12-month follow-up period. When compared with patients who remained asymptomatic, they had a higher median preoperative BMI (47.0 vs. 42.8, p = 0.046) and prevalence of cholelithiasis on preoperative ultrasound (62.5% vs. 10.7%, p = 0.001). Multivariate analysis revealed preoperative BMI and cholelithiasis on preoperative ultrasound as independent risk factors for symptomatic biliary disease (OR 1.187, 95%CI 1.025-1.376, p = 0.022 and OR 10.720, 95%CI 1.613-71.246, p = 0.014, respectively)., Conclusion: Considering a low incidence of symptomatic gallstones after bariatric surgery, concomitant cholecystectomy should only be performed in symptomatic patients undergoing bariatric surgery. Preoperative factors, such as a higher BMI and positive ultrasound for cholelithiasis, may be related to the development of symptomatic gallstones., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The purpose of this study was to develop peak ground reaction force (pGRF) and peak loading rate (pLR) prediction equations for high-impact activities in adult subjects with a broad range of body masses, from normal weight to severe obesity. A total of 78 participants (27 males; 82.4 ± 20.6 kg) completed a series of trials involving jumps of different types and heights on force plates while wearing accelerometers at the ankle, lower back, and hip. Regression equations were developed to predict pGRF and pLR from accelerometry data. Leave-one-out cross-validation was used to calculate prediction accuracy and Bland-Altman plots. Body mass was a predictor in all models, along with peak acceleration in the pGRF models and peak acceleration rate in the pLR models. The equations to predict pGRF had a coefficient of determination (R 2 ) of at least 0.83, and a mean absolute percentage error (MAPE) below 14.5%, while the R 2 for the pLR prediction equations was at least 0.87 and the highest MAPE was 24.7%. Jumping pGRF can be accurately predicted through accelerometry data, enabling the continuous assessment of mechanical loading in clinical settings. The pLR prediction equations yielded a lower accuracy when compared to the pGRF equations.

Background: The frequency and management of gallstone disease (GD) in bariatric patients, including the role of routine prophylactic concomitant cholecystectomy (CCY), are still a matter of debate. This study aims to assess the risk of de novo GD in patients undergoing bariatric surgery (BS) and their predictive factors, as well as mortality and morbidity in prophylactic CCY compared to BS alone., Methods: We performed a systematic review, searching PubMed, EMBASE, and Web of Science until April 2021. We performed a Bayesian meta-analysis to estimate the risk of GD development after BS and the morbidity and mortality associated with BS alone versus BS + prophylactic CCY. Sources of heterogeneity were explored by meta-regression analysis., Results: The risk of de novo post bariatric GD was 20.7% (95% credible interval [95% CrI] = 13.0-29.7%; I 2  = 75.4%), and that of symptomatic GD was 8.2% ([95% CrI] = 5.9-11.1%; I 2  = 66.9%). Pre-operative average BMI (OR = 1.04; 95% CrI = 0.92-1.17) and female patients' proportion (OR = 1.00; 95% CrI = 0.98-1.04) were not associated with increased risk of symptomatic GD. BS + prophylactic CCY was associated with a 97% probability of a higher number of postoperative major complications compared to BS alone (OR = 1.74, 95% CrI = 0.97-3.55; I 2  = 56.5%). Mortality was not substantially different between the two approaches (OR = 0.79; 95% CrI = 0.03-3.02; I 2  = 20.7%)., Conclusion: The risk of de novo symptomatic GD after BS is not substantially high. Although mortality is similar between groups, odds of major postoperative complications were higher in patients submitted to BS + prophylactic CCY. It is still arguable if prophylactic CCY is a fitting approach for patients with a preoperative lithiasic gallbladder., (© 2023. The Author(s).)

Toll-like receptors (TLRs) represent attractive targets for developing modulators for the treatment of many pathologies, including inflammation, cancer, and autoimmune diseases. Here, we describe a protocol based on the DockBox package that enables to set up and perform structure-based virtual screening in order to increase the chance of identifying novel TLR ligands from chemical libraries., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Patients who undergo bariatric surgery (BS) have an increased risk of falls. Our aim was to determine if a multicomponent exercise intervention after BS improves balance. Eighty-four patients with obesity enrolled for BS were recruited and 1 month after BS randomly allocated to a control (CG; standard medical care) or exercise group (EG; exercise plus standard medical care) consisting of a supervised multicomponent training program (3d/week; 75 min/session; 5 months). Anthropometry, lower limb muscle strength (isokinetic dynamometer), vitamin D (ELISA) and balance in bipedal stance (force platform) were assessed pre-BS, 1 month and 6 months post-BS. One month post-BS, significant balance improvements were observed, namely in antero-posterior center of gravity (CoG) displacement and velocity, and medio-lateral and total CoG velocity. Between 1- and 6-months post-BS, improvements in balance were observed only in the EG, with a significant treatment effect on CoG displacement area and antero-posterior CoG displacement. No significant differences were observed between EG and CG over time in any of the anthropometric, muscle strength, and vitamin D variables assayed. In conclusion, a multicomponent exercise intervention program improves some balance parameters in patients with severe obesity following BS and therefore should be part of post-BS follow-up care as a potential strategy to reduce falls and associated injuries., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Bariatric surgery is the only proven treatment to significantly improve obesity and its associated comorbidities. The success of bariatric surgery goes beyond weight lost: quality of life (QoL) is acquiring relevance when evaluating outcomes after bariatric surgery but few studies evaluated factors influencing QoL at long term. The main objective of this study is to identify factors that could affect QoL more than 5 years after bariatric surgery., Methods: We performed an observational study in which we apply "Moorehead-Ardelt Quality of Life Questionnaire" to 94 patients that were submitted to bariatric surgery with more than 5years of follow-up. Patients questionnaire score was compared to several variables: age, sex, main surgical procedures, primary or revisional surgery, complications, weight loss, and improvement of comorbidities (diabetes, dyslipidemia, hypertension, musculoskeletal disorders, and psychiatry pathology)., Results: QoL was significantly influenced by weight loss outcomes (%excess weight loss, %total weight loss, and final body mass index). QoL was neither significantly influenced by sex or age, type of surgery nor previously failed bariatric surgeries or complications. Improvement of hypertension was related to increased QoL, but improvement of other associated comorbidities did not had significant impact on patient's QoL at long term., Conclusion: It appears that the main factors influencing long-term QoL after bariatric surgery are related to weight loss outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of PBJ-Associação Porto Biomedical/Porto Biomedical Society. All rights reserved.)

Purpose: Early postoperative bleeding is a common complication after laparoscopic Roux-en-Y gastric bypass (LRYGB) and is associated with significant morbidity. We aimed to identify predictors of early postoperative bleeding after LRYGB and characterize hemorrhagic events and 30-day postoperative outcomes., Material and Methods: We conducted a retrospective cohort study regarding all patients submitted to LRYGB in 2019 at a high-volume obesity center. Early postoperative bleeding was defined as any clinically significant evidence of hemorrhage in the early postoperative period. Demographic, preoperative, and intraoperative factors were evaluated for associations with postoperative bleeding. Postoperative outcomes were compared between patients with and without hemorrhage., Results: Of 340 patients submitted to LRYGB, 14 (4.1%) had early postoperative bleeding. Patients with bleeding had an increased preoperative left hepatic lobe diameter (8.4 vs. 7.3 cm, p = 0.048). Prior cholecystectomy (28.6 vs. 14.5%) and previous bariatric surgery (35.7 vs. 23.9%) tended to be more prevalent among these patients. Bleeding occurred at a median time of 31.2 [IQR 19.7-38.5] h. Thirteen patients presented with intraluminal bleeding and one with extraluminal bleeding. Melena was the most common symptom. All hemorrhages were clinically diagnosed, and 92.9% were managed conservatively. Postoperative bleeding was associated with longer hospital stay (3.5 vs. 2.0 days), higher reintervention (7.1 vs. 0%), and readmission (14.3 vs. 0%), all p < 0.05., Conclusions: Bleeding was the most frequent early complication after LRYGB. Patients with hepatomegaly and prior surgeries may have technically challenging LRYGB and should be carefully assessed. Perioperative strategies should be encouraged in high-risk patients to prevent bleeding., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A procedure is described of grafting the acrylic acid onto an oxygen/ozone-activated metallocene poly(ethylene-co-propylene). Consequently, the grafted copolymer is applied as a component in a metallocene polyolefin-based hot-melt adhesive composition with increased adhesion. The surface properties and adhesion strength of the prepared hot-melt adhesive (HMA) were determined and used to account for the effect of grafting. The application of grafted polyolefin as one of the components of the HMA mixture provides significant increase in adhesive strength, and it also results in increased compatibility and negligible effects on the technological parameters of the final composition. The obtained results may have significant impact for the practical application of prepared HMA for book bonding.

The extracellular matrix (ECM) plays an undisputable role in tissue homeostasis and its deregulation leads to altered mechanical and biochemical cues that impact cancer development and progression. Herein, we undertook a novel approach to address the role of gastric ECM in tumorigenesis, which remained largely unexplored. By combining decellularization techniques with a high-throughput quantitative proteomics approach, we have performed an extensive characterization of human gastric mucosa, uncovering its composition and distribution among tumor, normal adjacent and normal distant mucosa. Our results revealed a common ECM signature composed of 142 proteins and indicated that gastric carcinogenesis encompasses ECM remodeling through alterations in the abundance of 24 components, mainly basement membrane proteins. Indeed, we could only identify one de novo tumor-specific protein, the collagen alpha-1(X) chain (COL10A1). Functional analysis of the data demonstrated that gastric ECM remodeling favors tumor progression by activating ECM receptors and cellular processes involved in angiogenesis and cell-extrinsic metabolic regulation. By analyzing mRNA expression in an independent GC cohort available at the TGCA, we validated the expression profile of 12 differentially expressed ECM proteins. Importantly, the expression of COL1A2, LOX and LTBP2 significantly correlated with high tumor stage, with LOX and LTBP2 further impacting patient overall survival. These findings contribute for a better understanding of GC biology and highlight the role of core ECM components in gastric carcinogenesis and their clinical relevance as biomarkers of disease prognosis., Competing Interests: The 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 © 2022 Moreira, Ferreira, Carneiro, Figueiredo, Osório, Barbosa, Preto, Pinto-do-Ó, Carneiro and Seruca.)

Bariatric surgery, although an effective method, still has complications, like nutritional deficiencies. Our aim was to summarize the evidence on the frequency of complex B vitamin deficiencies in studies comparing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). We included 25 studies for qualitative synthesis and 21 studies for quantitative synthesis. Relevant data was extracted, including proportion of patients with deficiency and mean serum vitamin values in 3 different timeframes. B12 and folate were the most prevalent deficiencies. B12 deficiency was more common after RYGB and folate serum mean levels were higher after RYGB. SG causes less nutrient deficiency and is therefore a better technique from this point of view. More studies are needed on B2, B3, and B6 vitamins to draw better conclusions., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The voltage-dependent anion channel 1 (VDAC1) is a crucial mitochondrial transporter that controls the flow of ions and respiratory metabolites entering or exiting mitochondria. As a voltage-gated channel, VDAC1 can switch between a high-conducting "open" state and a low-conducting "closed" state emerging at high transmembrane (TM) potentials. Although cell homeostasis depends on channel gating to regulate the transport of ions and metabolites, structural hallmarks characterizing the closed states remain unknown. Here, we performed microsecond accelerated molecular dynamics to highlight a vast region of VDAC1 conformational landscape accessible at typical voltages known to promote closure. Conformers exhibiting durable subconducting properties inherent to closed states were identified. In all cases, the low conductance was due to the particular positioning of an unfolded part of the N-terminus, which obstructed the channel pore. While the N-terminal tail was found to be sensitive to voltage orientation, our models suggest that stable low-conducting states of VDAC1 predominantly take place from disordered events and do not result from the displacement of a voltage sensor or a significant change in the pore. In addition, our results were consistent with conductance jumps observed experimentally and corroborated a recent study describing entropy as a key factor for VDAC gating.

Purpose: In patients with type 2 diabetes mellitus (T2DM), bariatric surgery appears to be more effective than medical treatment (MT) at improving glycaemic control and decreasing cardiovascular risk. However, long-term effectiveness has not been systematically assessed using randomised controlled trials. In this study, we aimed to systematically assess randomised controlled trials, with at least 5 years of follow-up, on bariatric surgery in patients with T2DM and BMI ≥ 25 kg/m 2 , as well as to compare different bariatric procedures., Material and Methods: PubMed, SCOPUS and Web of Science were searched. We performed a network meta-analysis to evaluate the comparative effectiveness of the different procedures and MT in terms of full T2DM remission, weight loss, complications and cardiometabolic biomarkers. The quality of evidence was assessed using the Cochrane Risk of Bias Tool and CINeMA., Results: We included 11 primary studies. Laparoscopic one-anastomosis gastric bypass (LOAGB) was found to be one of the most effective treatments for full remission of T2DM (I 2  = 0, inconsistency p value = 0.9223). Biliopancreatic diversion without duodenal switch was found to be more effective than laparoscopic Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding regarding percent total cholesterol and low-density lipoprotein change. Regarding percent high-density lipoprotein and weight change, all analysed surgical treatments were shown to be more effective than MT. The confidence rating in our results was overall moderate, but most studies had high risk of performance and detection bias., Conclusion: Bariatric surgery seems to be effective for T2DM remission. LOAGB appears to be a good option in this context, and a possible alternative to laparoscopic duodenal switch, but the included primary studies in our review are not sufficiently powered to establish a more definitive conclusion. More studies with longer follow-up times are needed to comprehensively assess bariatric surgery in T2DM., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Mechanical unloading associated with weight loss might be one of the main causes for bariatric surgery (BS) induced bone loss. However, no study has tested this hypothesis through objectively measured accelerometry-derived gravitational loading. We aimed to assess how gravitational loading changes following BS and how this correlates with bone mass losses., Methods: Twenty-one patients submitted to gastric bypass were assessed before, 1, 6 and 12 months after BS for areal bone mineral density (BMD), calciotropic hormones, sclerostin, body composition and daily physical activity. Gravitational loading was determined as the sum of ground reaction forces assessed by accelerometer which considered the interaction between weight and daily ambulation., Results: Mechanical stimuli promoted through the significant increase in steps number counterbalanced the gravitational loading decreases derived from the significant weight loss after BS. Gravitational loading volume decreased between pre-BS and 1 month post-BS (-2215 kN·d -1 ; p = .023), but remained stable between 6 and 12 months post-BS, despite decreases on hip (-7.0%; p < .001), femoral neck (-8.8%; p < .001) and lumbar spine (-5.2%; p < .001) BMD. Serum sclerostin increased from pre-BS to 1 month post-BS (+0.118 ng·mL -1 ; p = .021), returning to pre-BS levels 6 months after surgery. Neither vitamin D nor parathyroid hormone were affected by BS. Weight variation was a predictor of BMD decreases at total hip (R 2  = 0.06; p = .026) and femoral neck (R 2  = 0.12; p = .022), whereas daily gravitational loading volume was not. Fat and lean mass changes were also predictors of BMD decrease at total hip (R 2  = 0.05; p = .031) and femoral neck (R 2  = 0.14; p = .010), respectively., Conclusion: Our findings suggest that gravitational loading only decreased during the first month after surgery remaining stable thereafter, and these changes do not seem to explain BS-induced bone loss. The association between weight and bone loss seems to result from other physiological aspects, fat and lean mass loss, rather than from gravitational loading decrease., (Copyright © 2021 Elsevier Inc. All rights reserved.)