Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial.

BACKGROUND: Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial. METHODS: We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25-70 years with obesity (BMI 30-55 kg/m2), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at ClinicalTrials.gov, NCT03524365. FINDINGS: Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants with biopsy-proven NASH to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]), or sleeve gastrectomy (n=96 [33%]). In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with lifestyle modification (15 [16%]; p<0·0001). The calculated probability of NASH resolution was 3·60 times greater (95% CI 2·19-5·92; p<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (2·23-6·02; p<0·0001) in the sleeve gastrectomy group compared with in the lifestyle modification group. In the per protocol analysis (236 [82%] participants who completed the trial), the primary endpoint was met in 54 (70%) of 77 participants in the Roux-en-Y gastric bypass group and 55 (70%) of 79 participants in the sleeve gastrectomy group, compared with 15 (19%) of 80 in the lifestyle modification group (p<0·0001). No deaths or life-threatening complications were reported in this study. Severe adverse events occurred in ten (6%) participants who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management. INTERPRETATION: Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH. FUNDING: Fondazione Policlinico Universitario A Gemelli, Policlinico Universitario Umberto I and S Camillo Hospital, Rome, Italy.

Accurate liquid biopsy for the diagnosis of non-alcoholic steatohepatitis and liver fibrosis.

OBJECTIVE: Clinical diagnosis and approval of new medications for non-alcoholic steatohepatitis (NASH) require invasive liver biopsies. The aim of our study was to identify non-invasive biomarkers of NASH and/or liver fibrosis. DESIGN: This multicentre study includes 250 patients (discovery cohort, n=100 subjects (Bariatric Surgery Versus Non-alcoholic Steato-hepatitis - BRAVES trial); validation cohort, n=150 (Liquid Biopsy for NASH and Liver Fibrosis - LIBRA trial)) with histologically proven non-alcoholic fatty liver (NAFL) or NASH with or without fibrosis. Proteomics was performed in monocytes and hepatic stellate cells (HSCs) with iTRAQ-nano- Liquid Chromatography - Mass Spectrometry/Mass Spectrometry (LC-MS/MS), while flow cytometry measured perilipin-2 (PLIN2) and RAB14 in peripheral blood CD14+CD16- monocytes. Neural network classifiers were used to predict presence/absence of NASH and NASH stages. Logistic bootstrap-based regression was used to measure the accuracy of predicting liver fibrosis. RESULTS: The algorithm for NASH using PLIN2 mean florescence intensity (MFI) combined with waist circumference, triglyceride, alanine aminotransferase (ALT) and presence/absence of diabetes as covariates had an accuracy of 93% in the discovery cohort and of 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery cohort and 88% and 100% in the validation cohort, respectively.The area under the receiver operating characteristic (AUROC) for NAS level prediction ranged from 83.7% (CI 75.6% to 91.8%) in the discovery cohort to 97.8% (CI 95.8% to 99.8%) in the validation cohort.The algorithm including RAB14 MFI, age, waist circumference, high-density lipoprotein cholesterol, plasma glucose and ALT levels as covariates to predict the presence of liver fibrosis yielded an AUROC of 95.9% (CI 87.9% to 100%) in the discovery cohort and 99.3% (CI 98.1% to 100%) in the validation cohort, respectively. Accuracy was 99.25%, sensitivity 100% and specificity 95.8% in the discovery cohort and 97.6%, 99% and 89.6% in the validation cohort. This novel biomarker was superior to currently used FIB4, non-alcoholic fatty liver disease fibrosis score and aspartate aminotransferase (AST)-to-platelet ratio and was comparable to ultrasound two-dimensional shear wave elastography. CONCLUSIONS: The proposed novel liquid biopsy is accurate, sensitive and specific in diagnosing the presence and severity of NASH or liver fibrosis and is more reliable than currently used biomarkers. CLINICAL TRIALS: Discovery multicentre cohort: Bariatric Surgery versus Non-Alcoholic Steatohepatitis, BRAVES, ClinicalTrials.gov identifier: NCT03524365.Validation multicentre cohort: Liquid Biopsy for NASH and Fibrosis, LIBRA, ClinicalTrials.gov identifier: NCT04677101.

Y Not Roux-en-Y?: Resolution of Barrett's Esophagus After Surgical Conversion of Gastric Sleeve in Two Patients.

Esophageal lesions ranging from erosive esophagitis to Barrett's esophagus (BE) eventually develop months-years after sleeve gastrectomy (SG), representing a significant post-surgical issue in GI practice. Roux-en-Y gastric bypass (RYGB) conversion is a widespread and effective method of managing reflux and esophageal complications following SG. Although some studies using a limited sample size have demonstrated that RYGB performed as a primary procedure may regress BE presumably by reducing reflux, whether the same may apply to RYGB performed as revision surgery after SG has scarcely been addressed in the literature. Though histological regression of BE following primary RYGB occurs in 51.9% of patients, with regression of Barrett's dysplasia in 50% of cases, revisional RYGB yields a remission rate as high as 81.8% for Barrett's metaplasia and 100% for dysplastic lesions, although the number of subjects in the published studies are very small. We report two patients who developed GERD and BE following SG with complete regression 12 months after conversion to RYGB in both subjects, confirming the substantially greater proportion of BE resolution in patients undergoing RYGB as revision surgery following SG.

Novel Modality of Endoluminal Anastomotic Integrity Assessment with Fluoroangiography After Left-sided Colorectal Resections.

BACKGROUND: Several methods have been described for the intraoperative evaluation of colorectal anastomotic integrity. Technological evolution has allowed to progress from basic mechanical methods to the use of more sophisticated techniques. This study describes a novel endoluminal modality of colorectal anastomotic assessment through the use of a Disposable Rigid Scope Introducer (DRSI) also allowing for intraoperative endoluminal perfusion evaluation by indocyanine green (ICG) fluoroangiography in patients undergoing left-sided colorectal resection. METHODS: The DRSI consists of an endoluminal introducer device made up of an insertion tube and port connected to an insufflation bulb to manually insufflate the sigmoid and rectum and is compatible with any laparoscopic camera, also allowing for ICG fluoroangiography for perfusion purposes. RESULTS: The DRSI was successfully used to assess anastomotic integrity after left-sided colorectal resections performed in 16 consecutive patients. The DRSI allowed to visualize by fluoroangiography the quality of tissue perfusion at the anastomotic site in all cases, contributing to the decision of avoiding loop ileostomies in low rectal resections. In 2 cases, the DRSI showed the presence of significant anastomotic bleeding which was successfully controlled by laparoscopic suture placement. No adverse event resulted from the use of this device. CONCLUSIONS: The DRSI combines direct endoluminal visualization of the anastomosis together with real-time evaluation of its blood flow. This device holds great potential for prompt intraoperative detection of anastomotic alterations, possibly reducing the risk of postoperative anastomotic bleeding or leaks related to mechanical construction/perfusion issues. Potential advantages of this device warrant larger cohort studies and prospective randomized trials.

Bariatric/Metabolic Surgery.

Bariatric surgery is a gastro-intestinal surgery aimed at obtaining weight loss in obesity. The rapid metabolic effects of this type of operations provided a rational to change its name to metabolic surgery, in fact often the improvement of metabolic diseases is observed before a meaningful weight reduction.In this review, we examine the effects of laparoscopic metabolic surgery on life expectancy, type 2 diabetes, hypertension, cardiovascular disease and cancer.Furthermore, we review the surgical endoscopy approaches to obesity including primary obesity procedures and revision procedures that address weight regain after bariatric surgery.Finally, as a bridge to the specific chapter, we summarize the effects on weight reduction of new anti-obesity medications.

Small intestinal metabolism is central to whole-body insulin resistance.

OBJECTIVE: To assess the role of jejunum in insulin resistance in humans and in experimental animals. DESIGN: Twenty-four subjects undergoing biliopancreatic diversion (BPD) or Roux-en-Y gastric bypass (RYGB) were enrolled. Insulin sensitivity was measured at baseline and at 1 week after surgery using oral glucose minimal model.We excluded the jejunum from intestinal continuity in pigs and created a jejunal loop with its vascular and nerve supply intact accessible from two cutaneous stomas, and reconnected the bowel with an end-to-end anastomosis. Glucose stable isotopes were given in the stomach or in the jejunal loop.In vitro studies using primary porcine and human hepatocytes or myoblasts tested the effects of plasma on gluconeogenesis or glucose uptake and insulin signalling. RESULTS: Whole-body insulin sensitivity (SI∙104: 0.54±0.12 before vs 0.82±0.11 after BPD, p=0.024 and 0.41±0.09 before vs 0.65±0.09/pM/min after RYGB, p=not significant) and Glucose Disposition Index increased only after BPD. In pigs, insulin sensitivity was significantly lower when glucose was administered in the jejunal loop than in the stomach (glucose rate of disappearance (Rd) area under the curve (AUC)/insulin AUC∙10: 1.82±0.31 vs 2.96±0.33 mmol/pM/min, p=0.0017).Metabolomics showed a similar pattern before surgery and during jejunal-loop stimulation, pointing to a higher expression of gluconeogenetic substrates, a metabolic signature of impaired insulin sensitivity.A greater hepatocyte phosphoenolpyruvate-carboxykinase and glucose-6-phosphatase gene expression was elicited with plasma from porcine jejunal loop or before surgery compared with plasma from jejunectomy in pigs or jejunal bypass in humans.Stimulation of myoblasts with plasma from porcine jejunal loop or before surgery reduced glucose uptake, Ser473-Akt phosphorylation and GLUT4 expression compared with plasma obtained during gastric glucose administration after jejunectomy in pigs or after jejunal bypass in humans. CONCLUSION: Proximal gut plays a crucial role in controlling insulin sensitivity through a distinctive metabolic signature involving hepatic gluconeogenesis and muscle insulin resistance. Bypassing the jejunum is beneficial in terms of insulin-mediated glucose disposal in obesity. TRIAL REGISTRATION NUMBER: NCT03111953.

GORD and Barrett's oesophagus after bariatric procedures: multicentre prospective study.

INTRODUCTION: Gastro-oesophageal reflux disease (GORD) after bariatric surgery is a debated topic. This study investigated the prevalence of GORD and associated oesophageal complications following bariatric procedures-namely, adjustable gastric banding (AGB), sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one-anastomosis gastric bypass (OAGB). METHODS: This was a prospective multicentre study designed to evaluate the long-term effects of bariatric surgery on GORD. Patients were studied at baseline, at >10 years following AGB, SG, and RYGB, and at >3 years following OAGB (due to the more recent recognition of OAGB as a standard bariatric procedure). Patients were assessed by endoscopy and GORD symptom evaluation. RESULTS: A total of 241 patients were enrolled. A minimum follow-up of 10 years was completed by 193 patients following AGB (57 patients), SG (95 patients), and RYGB (41 patients), and of >3 years by 48 subjects following OAGB. GORD symptoms increased following AGB and SG (from 14 to 31.6 per cent and from 26.3 to 58.9 per cent, respectively; P < 0.0001), improved following RYGB (from 36.6 to 14.6 per cent; P < 0.0001), and were unchanged following OAGB. The overall prevalence of erosive oesophagitis was greater in the SG group (74.7 per cent) than in the AGB (42.1 per cent), RYGB (22 per cent), and OAGB (22.9 per cent) groups (P < 0.0001). Barrett's oesophagus was found only in patients who had SG (16.8 per cent). Biliary-like gastric stagnation was found in a greater proportion of SG and OAGB patients (79.7 and 69.4 per cent, respectively) than in other treatment groups (P < 0.0001). The prevalence of biliary-type reflux into the oesophagus was higher in patients who underwent SG (74.7 per cent), compared with other treatment groups. CONCLUSION: Bariatric surgery leads to gastro-oesophageal complications of variable severity, particularly SG, which can result in a large proportion of patients developing Barrett's oesophagus.

Gastro-oesophageal reflux disease (GORD)-related oesophageal sequelae following bariatric surgery confirm the importance of postoperative endoscopic surveillance in early detection of such conditions. Sleeve gastrectomy was shown to be correlated with the highest prevalence of GORD, biliary-type gastric and oesophageal reflux, and erosive oesophagitis. This, in turn, appeared to be responsible for the high number of cases of Barrett's oesophagus found in this group of patients. Adjustable gastric banding displayed minimal effectiveness in terms of weight loss, along with a high number of reoperations, also due to band-related complications. The study showed one-anastomosis gastric bypass to be associated with a high percentage of subjects who developed often severe inflammation of the gastrojejunal anastomosis or of the gastric pouch, as a consequence of chronic biliary-type duodenogastric reflux. Finally, our results suggest that Roux-en-Y gastric bypass could represent the most 'reliable' bariatric procedure in terms of GORD resolution, and the only operation not requiring any reintervention in our cohort of patients. Each surgical procedure leads to gastro-oesophageal modifications of variable extent, which need to be taken into consideration when selecting the designated bariatric operation.

Duodenal-jejunal bypass improves nonalcoholic fatty liver disease independently of weight loss in rodents with diet-induced obesity.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver-related mortality. NAFLD is associated with obesity, hepatic fat accumulation, and insulin resistance, all of which contribute to its pathophysiology. Weight-loss is the main therapy for NAFLD, and metabolic surgery is the most effective treatment for morbid obesity and its metabolic comorbidities. Although has been reported that Roux-en-Y gastric bypass can reverse NAFLD, it is unclear whether such effects result from reduced weight, from a lower calorie-intake, or from the direct influence of surgery on mechanisms contributing to NAFLD. We aimed to investigate whether gastrointestinal (GI) bypass surgery could induce direct effects on hepatic fat accumulation and insulin resistance, independently of weight reduction. Twenty Wistar rats on a high-fat diet underwent duodenal-jejunal-bypass (DJB) or sham operation and were pair fed (PF) for 15 wk after surgery to obtain a matched weight. Outcome measures include ectopic fat deposition, expression of genes and proteins involved in fat metabolism, insulin-signaling, and gluconeogenesis in liver and muscle. Despite no differences in body weight and calorie intake, DJB showed lower ectopic fat accumulation, improved peripheral and hepatic insulin sensitivity, and enhanced lipid droplet degradation. In both tissues, DJB increased insulin signaling, whereas hepatic key enzymes involved in gluconeogenesis and de novo lipogenesis were decreased. These findings suggest that DJB can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of NAFLD that share a mutual pathway, in which perilipin-2 (PLIN2) seems to be the main player, supporting further investigation into strategies that target the gut to treat metabolic liver diseases.NEW & NOTEWORTHY Our findings suggest that duodenal-jejunal bypass can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of nonalcoholic fatty liver disease that share a mutual pathway, in which perilipin-2 seems to be the main player. Our study supports further investigation into the role of proximal small intestine exclusion in the pathophysiology of nonalcoholic fatty liver disease to uncover less invasive treatments that mimic the effects of metabolic surgery and aims to prevent and treat metabolic liver disease.

Lipidomic Changes in Skeletal Muscle in Patients after Biliopancreatic Diversion.

The mechanisms behind the fast improvements of insulin sensitivity and release of the diabetic metabolic state after bariatric surgery are still not completely understood. To further elucidate the effects on the individual cellular level, we applied mass spectrometry to investigate the changes in the lipidomic profile of skeletal muscle cells before and after biliopancreatic diversion in six patients. We found a decrease in lipid storage species, mainly triacylglycerides (e. g., TAG 52:2 from 19.84 to 13.26 mol%; p=0.028), and an increase in structural and signaling lipids, including phosphatidylcholines [PC 36:2 (18:1/18:1) from 0.12 to 0.65 mol%; p=0.046], phosphatidylinositols (PI 36:2 from 0.008 to 0.039 mol%; p=0.046), and cardiolipins (CL 72:8 from 0.16 to 1.22 mol%; p=0.043). The proportional increase in structural lipids was directly and the decrease in TAGs was inversely correlated to improved post-operative insulin sensitivity, measured by euglycemic hyperinsulinemic clamp. Thus, short-term recovery of insulin sensitivity after biliopancreatic diversion may, beside gut hormonal adaptation, mechanical factors, shifts in the gut microbiome, and changes in bile acid and phospholipid metabolism, additionally be attributed to a metabolic recovery of skeletal muscle cells, reflected by normalization of the cellular lipidomic profile. Further studies are needed to investigate whether improved insulin sensitivity of skeletal muscle might be directly associated with the degradation of ectopic triglycerides, thereby reducing the reservoir of lipotoxic intermediates, which might interfere with insulin signaling and hamper mitochondrial metabolism.

Massive pelvic recurrence of uterine leiomyomatosis with intracaval-intracardiac extension: video case report and literature review.

BACKGROUND: Uterine leiomyomas represent the gynecological neoplasm with the highest prevalence worldwide. This apparently benign pathological entity may permeate into the venous system causing the so-called intravenous leiomyomatosis of the uterus (IVL). IVL may seldom extend to large caliber veins and reach the right cardiac chambers or pulmonary arteries and cause signs of right sided congestive heart failure and sudden death. Due to its low incidence, however, IVL with intracardiac extension is often misdiagnosed resulting in deferred treatment. No consensus has been obtained regarding the standard surgical approach to be used for this rare condition. We describe the case of a massive pelvic recurrence of uterine leiomyomatosis with intracardiac extension and provide a review of the literature, analyzing management and surgical outcomes. CASE PRESENTATION: We present the case of a 46-year-old premenopausal woman presenting with lower-extremity edema, recurrent syncopes and a history of subtotal hysterectomy for multiple uterine fibroids. She was diagnosed with pelvic recurrence of uterine leiomyomatosis and IVL with cardiac involvement. A two-stage surgical excision of the intracardiac-intracaval mass and pelvic leiomyomatosis was performed. The patient had an uneventful recovery and no evidence of recurrence was observed on follow-up. CONCLUSIONS: By virtue of the rarity of the present pathology, awareness is widely scarce and diagnosis is often delayed. Early recognition is difficult due to initial aspecific and subtle clinical manifestations. Nevertheless, suspicion should be held high in premenopausal women with known history of uterine leiomyomata, presenting with cardiovascular symptoms and evidence of a free-floating mass within the right cardiac chambers. In-depth imaging is crucial for defining its anatomical origin and relations. Prompt surgical treatment with radical excision of pelvic and intravenous leiomyomatosis guarantees favorable outcomes and excellent prognosis with low rates of recurrence, whereas delayed diagnosis and treatment exposes to increased risk of congestive heart failure and sudden death.

How to Choose the Best Metabolic Procedure?

Bariatric/metabolic surgery has proven to be effective in inducing and maintaining diabetes remission-although with a percentage of patients undergoing hyperglycemia relapse-weight loss, and improvement of the cardiovascular risk. It is, however, associated with mortality, although low, and early and late complications. In particular, metabolic complications are related to vitamin deficiency due to the erratic absorption of the supplemented vitamins and to the unpredictable compliance of patients to vitamin and trace element supplementation. In addition, often, the general practitioners and even the specialists are unaware of the clinical effects of metabolic dysfunction following malabsorptive surgery. The choice of the surgical procedure should be the balance between benefits and risks. Our review addresses this important question trying to give some suggestions.

Spider surgical system versus multiport laparoscopic surgery: performance comparison on a surgical simulator.

BACKGROUND: The rising interest towards minimally invasive surgery has led to the introduction of laparo-endoscopic single site (LESS) surgery as the natural evolution of conventional multiport laparoscopy. However, this new surgical approach is hampered with peculiar technical difficulties. The SPIDER surgical system has been developed in the attempt to overcome some of these challenges. Our study aimed to compare standard laparoscopy and SPIDER technical performance on a surgical simulator, using standardized tasks from the Fundamentals of Laparoscopic Surgery (FLS). METHODS: Twenty participants were divided into two groups based on their surgical laparoscopic experience: 10 PGY1 residents were included in the inexperienced group and 10 laparoscopists in the experienced group. Participants performed the FLS pegboard transfers task and pattern cutting task on a laparoscopic box trainer. Objective task scores and subjective questionnaire rating scales were used to compare conventional laparoscopy and SPIDER surgical system. RESULTS: Both groups performed significantly better in the FLS scores on the standard laparoscopic simulator compared to the SPIDER. Inexperienced group: Task 1 scores (median 252.5 vs. 228.5; p = 0.007); Task 2 scores (median 270.5 vs. 219.0; p = 0.005). Experienced group: Task 1 scores (median 411.5 vs. 309.5; p = 0.005); Task 2 scores (median 418.0 vs. 331.5; p = 0.007). Same aspects were highlighted for the subjective evaluations, except for the inexperienced surgeons who found both devices equivalent in terms of ease of use only in the peg transfer task. CONCLUSIONS: Even though the SPIDER is an innovative and promising device, our study proved that it is more challenging than conventional laparoscopy in a population with different degrees of surgical experience. We presume that a possible way to overcome such challenges could be the development of tailored training programs through simulation methods. This may represent an effective way to deliver training, achieve mastery and skills and prepare surgeons for their future clinical experience.

Can liquid biopsies for MASH help increase the penetration of metabolic surgery? A narrative review.

This narrative review highlights current evidence on non-invasive tests to predict the presence or absence as well as the severity of metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition characterized by fat accumulation in the liver that affects 32 % of the world population. The most severe form of MASLD is MASH in which hepatocyte ballooning and inflammation are present together with steatosis; MASH is often associated with liver fibrosis. MASH diagnosis is determined by invasive liver biopsy. Hence, there is a critical need for non-invasive MASH tests. Plasma biomarkers for MASH diagnosis generally have low sensitivity (62-66 %), and specificity (78-82 %). Monocyte levels of Perilipin2 (PLIN2) predict MASH with an accuracy of 92-93 %, and sensitivity and specificity of 90-95 % and 88-100 %, respectively. This liquid biopsy test can facilitate the study of MASH prevalence in general populations and also monitor the effects of lifestyle, surgical, and pharmacological interventions. Without any FDA-approved MASH therapeutic, and with metabolic surgery markedly surpassing the efficacy of lifestyle modification, an accurate and reliable liquid biopsy could help more people choose surgery as a treatment for MASH.

Dicarboxylic acids counteract the metabolic effects of a Western diet by boosting energy expenditure.

Obesity has reached pandemic proportion not only in the West but also in other countries around the world; it is now one of the leading causes of death worldwide. A Western diet is rich in saturated fats and provides more calories than necessary, contributing to the rise of the obesity rate. It also promotes the development of liver steatosis, insulin resistance, hyperglycemia, and hyperlipidemia. In this issue of the JCI, Goetzman and colleagues describe the effects of consuming dicarboxylic acids (DAs) as an alternative source of dietary fat. The 12-carbon dicarboxylic acid (DC12) was administered to mice at 20% of their daily caloric intake for nine weeks in place of triglycerides. Notably, the change in diet increased the metabolic rate, reduced body fat, reduced liver fat, and improved glucose tolerance. These findings highlight DAs as useful energy nutrients for combatting obesity and treating various metabolic disorders.

Use of dicarboxylic acids in type 2 diabetes.

Even-number, medium-chain dicarboxylic acids (DAs), naturally occurring in higher plants, are a promising alternative energy substrate. Unlike the homologous fatty acids, DAs are soluble in water as salts. They are ß-oxidized, providing acetyl-CoA and succinyl-CoA, the latter being an intermediate of the tricarboxylic acid cycle. Sebacic acid and dodecanedioic acid, DAs with 10 and 12 carbon atoms respectively, provide 6.6 and 7.2 kcal g⁻¹ each; therefore, their energy density is intermediate between glucose and fatty acids. Dicarboxylic acids have been proved to be safe in both experimental animals and humans, and their use has recently been proposed in diabetes. Studies in animals and humans with type 2 diabetes showed that oral administration of sebacic acid improved glycaemic control, probably by enhancing insulin sensitivity, and reduced hepatic gluconeogenesis and glucose output. Moreover, dodecanedioic acid intake reduced muscle fatigue during exercise in subjects with type 2 diabetes, suggesting an improvement of energy utilization and 'metabolic flexibility'. In this article, we review the natural sources of DAs, their fate in animals and humans and their effect in improving glucose metabolism in type 2 diabetes.

Efficacy of Sleeve Gastrectomy with Concomitant Hiatal Hernia Repair versus Sleeve-Fundoplication on Gastroesophageal Reflux Disease Resolution: Systematic Review and Meta-Analysis.

(1) Background: There is still disagreement over how sleeve gastrectomy (SG) affects gastroesophageal reflux disease (GERD). The debate regarding the best option for patients undergoing bariatric surgery who are also affected by GERD and/or hiatal hernia continues to divide the community of bariatric surgeons. While concomitant hiatal hernia repair (SG + HHR) has been proposed as a means of reducing the risk of GERD following SG with varying degrees of success, the addition of a fundoplication (SG + FP) has been suggested in recent years as a way to improve the lower esophageal sphincter's competency. The aim of this study is to systematically review and meta-analyze the efficacy of SG + HHR versus SG + FP on GERD remission in patients with obesity. (2) Methods: A systematic review of the literature was conducted, and studies analyzing the effects of SG + HHR versus SG + FP on postoperative GERD were included. The methodological quality of included trials was evaluated. The primary outcome was postoperative GERD rate, erosive esophagitis, and 12-month weight loss. Secondary outcomes included postoperative complications and mortality. The PRISMA guidelines were used to carry out the present systematic review (PROSPERO Registration Number: CRD42023405600). (3) Results: Fifteen articles with a total of 1164 patients were included in the meta-analysis; 554 patients underwent SG + HHR while 610 underwent SG + FP. In the SG + HHR group, 58.5 ± 28.9% of subjects presented clinical GERD symptoms compared to 20.4 ± 17.5% postoperatively (p < 0.001). In the SG + FP group, 64.8 ± 39.4% were affected by GERD preoperatively compared to only 5 ± 8.1% postoperatively (p < 0.001). SG + FP patients had a significantly greater GERD remission compared to SG + HHR (p < 0.001). Weight loss was similar between groups (p = 0.125). The rate of leaks was 0.18% and 0.33% in the SG + HHR and SG + FP, respectively (p = 0.657), while perforations were significantly higher after SG + FP compared to the SG + HHR group (3.1% versus 0%, p = 0.002). The mortality rate was significantly greater in the SG + FP group (0.5% versus 0%, p = 0.002). (4) Conclusions: This study revealed that both SG with concomitant HHR and sleeve-fundoplication are effective in terms of reflux resolution and weight outcomes, with superiority of SG + FP in terms of GERD control, despite a greater overall complication rate. Both strategies can therefore be suggested as a suitable alternative variant to a conventional SG in subjects with obesity and concomitant hiatal hernia and/or GERD. Studies with extended follow-up and direct comparisons of these surgical approaches to conventional SG are warranted.

Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis.

Introduction: Over the past 20 years, the increasing use of combined therapy with immunosuppressants and biologic agents has markedly reduced the use of steroids in the management of inflammatory bowel diseases (IBD). However, medical therapy seems to promote, in the long run, carcinogenesis resulting in an increased risk of developing different types of malignancies, including lymphomas. The aim of this study was to systematically review the current incidence and prognosis of lymphoid neoplasms occurring in patients with IBD. Methods: Studies analyzing the incidence of lymphomas in subjects of age >18 years affected by IBD were included in this systematic review and meta-analysis. Studies focusing on pediatric populations, not reporting person-years of follow-up, or with a duration < 1 year were excluded. PubMed, Embase, Web of Science Core Collection, and Cochrane Central Register were searched from inception through January 2022. Publication bias within studies was assessed using Begg's and Egger's tests and random effects model. Quantitative results were synthesized using relative-risk meta-analysis. PRISMA guidelines were used to carry out this systematic review (PROSPERO Registration Number: CRD42023398348). Results: A total of 345 studies published between 1985 and 2022, with a total of 6,17,386 patients were included in the meta-analysis. Substantial heterogeneity between studies prevented the pooling of estimates (I2 = 97.19%). Evidence of publication bias was overall low (p = 0.1941). Patients affected by Crohn's disease (CD) were 1,86,074 (30.13%), while 2,78,876 (46.17%) were diagnosed with UC. The remaining 23.7% of cases were diagnosed with indeterminate colitis. Immunomodulators and biologic therapy were used in 24,520 (5.27%), and 17,972 (3.86%) patients, respectively. Reported incidence rates for lymphoma in IBD ranged from 0.0/100,000 person/years (py) (95% CI 0.0-3.7/100,000) to 89/100,000 py (95% CI 36-160/100,000). Reported incidence rates of lymphoma in CD ranged from 0.0/100,000 py (95% CI 0.0-3.7/100,000) to 91/100,000 py (95% CI 18-164/100,000). For UC, the incidence rate ranged from 0.0/100,000 py (95% CI 0.0-3.7/100,000) to 95/100,000 py (95% CI 0-226/100,000). Male-to-female ratio was ~4:1. Therapy with immunomodulators was directly associated with an increased incidence of lymphoma (p < 0.0001). Evidence of publication bias was overall low (p = 0 .1941). Conclusions: The evidence arising from this study highlights a correlation between the use of immunomodulators and subsequent lymphoma development. Combined multidisciplinary approach and long-term follow-up are warranted in order to decrease mortality deriving from the coexistence of both conditions. Systematic review registration: Identifier: CRD42023398348.

The Role of Antibiotic Prophylaxis in Anastomotic Leak Prevention during Elective Colorectal Surgery: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction: Despite several perioperative care advancements and innovations in surgical procedures and technologies, the incidence rate of anastomotic leaks (ALs) after colorectal surgery has not substantially decreased. Gut microbiota can play a critical role in the healing process of anastomotic tissue and alterations in its composition may be largely to blame for anastomotic insufficiency. The use of specific antibiotics for preoperative large bowel decontamination could significantly influence the rate of ALs. The aim of this study was to systematically assess the various antibiotic prophylactic regimen strategies for primary prevention of ALs during colorectal surgery, in view of the available evidence. Methods: A systematic review of the literature was conducted, and randomized clinical trials (RCTs) analyzing prophylactic antibiotic bowel preparation in colorectal surgery were included. PubMed, Embase, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched from inception through to 30 November 2022. The methodological quality of the included trials was evaluated. The primary outcome was AL rate; secondary outcomes were superficial/deep surgical site infections (SSIs). The PRISMA guidelines were used to carry out the present systematic review. Results: Thirteen RCTs published between 1977 and 2022, with a total of 4334 patients were included in the meta-analysis. Antibiotic prophylaxis was administered orally in 11/13 studies and intravenously in 2 studies. Patients randomly assigned to antibiotic prophylaxis, regardless of the regimen, had a reduced risk of ALs (p = 0.003) compared to mechanical bowel preparation (MBP) alone. The use of antibiotic prophylaxis was also more effective in significantly reducing SSIs (p < 0.001). Conclusions: The evidence points to an advantage of oral antibiotic prophylaxis in terms of AL rate, a significant contributor to perioperative morbidity, mortality, and rising healthcare expenditures. In light of such results, the use of antibiotic prophylaxis should be strongly encouraged prior to colorectal surgery.