Development and Validation of a Score for Fibrotic Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: Noninvasive assessment of histological features of nonalcoholic fatty liver disease (NAFLD) has been an intensive research area over the last decade. Herein, we aimed to develop a simple noninvasive score using routine laboratory tests to identify, among individuals at high risk for NAFLD, those with fibrotic nonalcoholic steatohepatitis (NASH) defined as NASH, NAFLD activity score ≥4, and fibrosis stage ≥2. METHODS: The derivation cohort included 264 morbidly obese individuals undergoing intraoperative liver biopsy in Rome, Italy. The best predictive model was developed and internally validated using a bootstrapping stepwise logistic regression analysis (2000 bootstrap samples). Performance was estimated by the area under the receiver operating characteristic curve (AUROC). External validation was assessed in 3 independent European cohorts (Finland, n = 370; Italy, n = 947; England, n = 5368) of individuals at high risk for NAFLD. RESULTS: The final predictive model, designated as Fibrotic NASH Index (FNI), combined aspartate aminotransferase, high-density lipoprotein cholesterol, and hemoglobin A1c. The performance of FNI for fibrotic NASH was satisfactory in both derivation and external validation cohorts (AUROC = 0.78 and AUROC = 0.80-0.95, respectively). In the derivation cohort, rule-out and rule-in cutoffs were 0.10 for sensitivity ≥0.89 (negative predictive value, 0.93) and 0.33 for specificity ≥0.90 (positive predictive value, 0.57), respectively. In the external validation cohorts, sensitivity ranged from 0.87 to 1 (negative predictive value, 0.99-1) and specificity from 0.73 to 0.94 (positive predictive value, 0.12-0.49) for rule-out and rule-in cutoff, respectively. CONCLUSION: FNI is an accurate, simple, and affordable noninvasive score which can be used to screen for fibrotic NASH in individuals with dysmetabolism in primary health care.

Brain functional connectivity differences between responders and non-responders to sleeve gastrectomy.

PURPOSE: To compare resting-state functional connectivity (RSFC) of obese patients responders or non-responders to sleeve gastrectomy (SG) with a group of obese patients with no past medical history of metabolic or bariatric surgery. METHODS: MR images were acquired at 1.5 Tesla. Resting-state fMRI data were analyzed with statistical significance threshold set at p < 0.05, family-wise error (FWE) corrected. RESULTS: Sixty-two subjects were enrolled: 20 controls (age range 25-64; 14 females), 24 responders (excess weight loss > 50%; age range 23-68; 17 females), and 18 non-responders to sleeve gastrectomy (SG) (excess weight loss < 50%; age range 23-67; 13 females). About within-network RSFC, responders showed significantly lower RSFC with respect to both controls and non-responders in the default mode and frontoparietal networks, positively correlating with psychological scores. Non-responders showed significantly higher (p < 0.05, family-wise error (few) corrected) RSFC in regions of the lateral visual network as compared to controls. Regarding between-network RSFC, responders showed significantly higher anti-correlation between executive control and salience networks (p < 0.05, FWE corrected) with respect to both controls and non-responders. Significant positive correlation (Spearman rho = 0.48, p = 0.0012) was found between % of excess weight loss and executive control-salience network RSFC. CONCLUSION: There are differences in brain functional connectivity in either responders or non-responders patients to SG. The present results offer new insights into the neural correlates of outcome in patients who undergo SG and expand knowledge about neural mechanisms which may be related to surgical response.

Accuracy of controlled attenuation parameter for assessing liver steatosis in individuals with morbid obesity before bariatric surgery.

BACKGROUND & AIMS: The ultrasound-based controlled attenuation parameter (CAP) is a non-invasive tool widely validated for assessing liver steatosis across different etiologies. However, few studies, with liver biopsy available, have investigated its performance in individuals with morbid obesity. Herein, we aimed to evaluate the diagnostic accuracy of CAP in participants with morbid obesity from the MAFALDA study before bariatric surgery. METHODS: A total of 120 individuals with valid examinations within three months from bariatric surgery were included. Clinical, laboratory, FibroScan® (XL probe), and liver biopsy data were collected using standardized procedures. The overall accuracy of CAP for detecting liver steatosis was estimated by the area under the receiver-operating characteristics curve (AUROC). Optimal cut-offs were chosen at points with the highest Youden index. RESULTS: The AUROCs of CAP for detecting S ≥ S1, S ≥ S2, and S = S3 were 0.91 (95% CI 0.86-0.97), 0.83 (95% CI 0.76-0.90), and 0.86 (95% CI 0.79-0.94), respectively. The best CAP cut-offs for S ≥ S1, S ≥ S2, and S = S3 were 300 dB/m (95% CI 275-316), 328 dB/m (95% CI 296-345), and 344 dB/m (95% CI 343-352), respectively. CAP values were independently influenced by steatosis grade (estimate 20.60, 95% CI 12.70-28.40, P = 1.05 × 10-6 ). The AUROC of FibroScan-AST (FAST) score for detecting progressive non-alcoholic steatohepatitis was 0.76 (95% CI 0.66-0.86). CONCLUSIONS: In individuals with morbid obesity, CAP measured by XL probe is an accurate non-invasive tool for grading liver steatosis. Measurement of liver fat content by CAP may help identify those eligible for bariatric procedures and estimate the effect of bariatric surgery on hepatic steatosis. LAY SUMMARY: The ultrasound-based controlled attenuation parameter (CAP) by using the XL probe has an excellent performance for grading liver steatosis among individuals with morbid obesity. CAP may represent an accurate tool for the non-invasive assessment of liver steatosis among individuals with morbid obesity before and after bariatric surgery.

Enhanced recovery after bariatric surgery: an Italian consensus statement.

BACKGROUND: Enhanced recovery after bariatric surgery (ERABS) is an approach developed to improve outcomes in obese surgical patients. Unfortunately, it is not evenly implemented in Italy. The Italian Society for the Surgery of Obesity and Metabolic Diseases and the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care joined in drafting an official statement on ERABS. METHODS: To assess the effectiveness and safety of ERABS and to develop evidence-based recommendations with regard to pre-, intra-, and post-operative care for obese patients undergoing ERABS, a 13-member expert task force of surgeons and anesthesiologists from Italian certified IFSO center of excellence in bariatric surgery was established and a review of English-language papers conducted. Oxford 2011 Levels of Evidence and U.S. Preventive Services Task Force Grade Definitions were used to grade the level of evidence and the strength of recommendations, respectively. The supporting evidence and recommendations were reviewed and discussed by the entire group at meetings to achieve a final consensus. RESULTS: Compared to the conventional approach, ERABS reduces the length of hospital stay and does not heighten the risk of major post-operative complications, re-operations, and hospital re-admissions, nor does it increase the overall surgical costs. A total of 25 recommendations were proposed, covering pre-operative evaluation and care (7 items), intra-operative management (1 item, 11 sub-items), and post-operative care and discharge (6 items). CONCLUSIONS: ERABS is an effective and safe approach. The recommendations allow the proper management of obese patients undergoing ERABS for a better outcome.

The gastro-jejunal anastomosis site influences dumping syndrome and weight regain in patients with obesity undergoing Laparoscopic Roux-en-Y Gastric Bypass.

PURPOSE: The Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is an effective weight loss procedure. The gastro-jejunal (GJ) anastomosis required can be performed on the anterior or posterior gastric pouch wall. No studies have compared these variants in terms of efficacy and onset of dumping syndrome (DS) and weight regain (WR). We aimed at assessing the prevalence of DS in relation to the site of anastomosis together with identifying prognostic factors of DS and WR. METHODS: Patients who had undergone LRYGB with anterior (AGJ) or posterior (PGJ) anastomosis in 2010-2019 were retrospectively analyzed. We collected demographic data, medical history and the prevalence of DS evaluated through the Sigstad Score, together with WR data. RESULTS: 213 patients were enrolled, of which 51.6% had an AGJ and 48.4% had a PGJ. The mean follow-up time was 81 ± 18 and 27 ± 13 months in the AGJ and PGJ group, respectively (p < 0.0001). Excess weight loss was 77.59% and 94.13% in patients with AGJ and PGJ, respectively (p < 0.001). WR rate was 16% and 4% in the AGJ and PGJ population, respectively (p < 0.001). DS prevalence was 38% and 76% in the AGJ and the PGJ population, respectively (p < 0.0001). The site of anastomosis was identified as an independent predictor of DS (OR5.15; 95% CI 2.82-9.41; p < 0.0001) and WR (OR5.31; 95% CI 2.32-12.15; p < 0.0001). Obesity-related complications significantly improved after surgery independent of the anastomosis site. CONCLUSION: LRYGB is effective in determining long-term weight loss and improvement of complications. AGJ is associated with lower prevalence of DS but more frequent WR. The anastomosis site is a factor to be considered when performing LRYGB. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Laparoscopic-Guided Transversus Abdominis Plane (TAP) Block Combined with Port-Site Infiltration (PSI) for Laparoscopic Sleeve Gastrectomy in an ERABS Pathway: A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial.

PURPOSE: Patients undergoing laparoscopic sleeve gastrectomy (LSG) commonly experience moderate to severe postoperative pain. We conducted a randomized, prospective double-blind placebo-controlled study to evaluate the analgesic effect of laparoscopic-guided TAP (LG-TAP) block after LSG in a high-volume bariatric center, applying an enhanced recovery after bariatric surgery (ERABS) pathway. MATERIAL AND METHODS: One hundred ten patients were randomly allocated to receive LG-TAP block with local anesthetic (LA) or saline solution (placebo), both combined with port-site infiltration with LA (LA-PSI). Primary outcome was pain score measured in post-anesthesia care unit (PACU) and at 6, 12, and 24 h after surgery. Secondary outcomes included postoperative nausea and/or vomiting (PONV), analgesic requirement, time to walking, time to flatus, length of hospital stay (LOS), and surgical complications. RESULTS: No significant differences were observed between LG-TAP and placebo groups in postoperative analgesia, with a median (IQR) NRS of 2 (4.75-0) vs. 2 (5.25-0) in PACU, 5.5 (7-3) vs. 6 (7-4) at 6 h, 2 (6-0) vs. 3 (5.25-1.75) at 12 h, and 2 (3.75-0) vs. 1 (2-0) at 24 h; all p > 0.05. A significant difference was found in PONV in PACU (LG-TAP, 46%; placebo, 25%, p-value, 0.019) and at 6 h postoperatively (LG-TAP, 69%, placebo, 41%, p-value, 0.003). No differences were observed as regards other secondary outcomes. CONCLUSION: Our results suggest that LG-TAP block is not related to more effective postoperative analgesia compared to placebo when LA-PSI is performed.

Impact of Sleeve Gastrectomy on Brain Structural Integrity.

INTRODUCTION: Potential brain structural differences in people with obesity (PwO) who achieve over or less than 50% excess weight loss (EWL) after sleeve gastrectomy (SG) are currently unknown. We compared measures of gray matter volume (GMV) and white matter (WM) microstructural integrity of PwO who achieved over or less than 50% EWL after SG with a group of controls with obesity (CwO) without a past history of metabolic bariatric surgery. METHODS: Sixty-two PwO underwent 1.5 T MRI scanning: 24 who achieved more than 50% of EWL after SG ("group a"), 18 who achieved less than 50% EWL after SG ("group b"), and 20 CwO ("group c"). Voxel-based morphometry and tract-based spatial Statistics analyses were performed to investigate GMV and WM differences among groups. Multiple regression analyses were performed to investigate relationships between structural and psychological measures. RESULTS: Group a demonstrated significantly lower GMV loss and higher WM microstructural integrity with respect to group b and c in some cortical regions and several WM tracts. Positive correlations were observed in group a between WM integrity and several psychological measures; the lower the WM integrity, the higher the mental distress, emotional dysregulation, and binge eating behavior. CONCLUSION: The present results gain a new understanding of the neural mechanisms of outcome in patients who undergo SG. We found limited GMV changes and extensive WM microstructural differences between PwO who achieved over or less than 50% EWL after SG, which may be due to higher vulnerability of WM to the metabolic dysfunction present in PwO.

IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids.

Steatotic liver disease (SLD) prevails as the most common chronic liver disease yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, the mechanistic link between IL-32 and intracellular triglyceride metabolism remains to be elucidated. We demonstrate in vitro that incubation with IL-32ß protein leads to an increase in intracellular triglyceride synthesis, while downregulation of IL32 by small interfering RNA leads to lower triglyceride synthesis and secretion in organoids from human primary hepatocytes. This reduction requires the upregulation of Phospholipase A2 group IIA (PLA2G2A). Furthermore, downregulation of IL32 results in lower intracellular type I collagen levels in di-lineage human primary hepatic organoids. Finally, we identify a genetic variant of IL32 (rs76580947) associated with lower circulating IL-32 and protection against SLD measured by non-invasive tests. These data suggest that IL32 downregulation may be beneficial against SLD.

Sex difference in the safety and efficacy of bariatric procedures: a systematic review and meta-analysis.

With the prevalence of obesity alarmingly increasing, it is of primary interest to identify those factors predicting the success of anti-obesity therapeutic strategies currently adopted in clinical practice, and in particular, those of bariatric procedures showing the greatest success in terms of weight loss and maintenance in both the short and long term. Given sex-related differences in psychosocial status, hormonal homeostasis, and body fat distribution, it is likely that the response to different weight management strategies differs by sex. The objective was to elucidate the effect of sex on different bariatric procedures' efficacy and safety outcomes. Searches of PubMed, Cochrane, and Embase databases were performed, followed by hand-searching of reference lists from all relevant articles. We included all the studies evaluating the effect of bariatric procedures on body mass index loss (BMIL), and/or percentage excess weight loss (%EWL), and/or percentage excess body mass index loss, and/or percentage of responders, and/or short-/long-term complications and co-morbidity resolution, broken down by sex. Twenty-seven studies with a total of 114,919 patients were included. Men were more likely to achieve greater BMIL, consistent with higher male baseline BMI, and women were 2.87 times more likely to be classified as weight responders (95% confidence interval [CI]: 1.90-4.34), as well as to perform better in terms of %EWL (95% CI: .13-.54). Upon subgroup analysis based on bariatric procedure, women were more likely to be successful in terms of %EWL upon bioenteric intragastric balloon (BIB) placement (.72, 95% CI: .42-1.02). There was no sex difference regarding investigated co-morbidity resolution (hypertension, diabetes, and obstructive sleep apnea syndrome) or occurrence of short-term complications, whereas women were more likely to develop long-term complications, with an odds ratio of 1.97 (95% CI: 1.57-2.49). Sex does not have a clear effect on efficacy outcomes of bariatric procedures. Differentiating by procedure, BIB may be more effective in women, although results are discordant based on the weight loss outcome considered. If the short-term postoperative complication rate is similar across both sexes, long-term complications occur more frequently in women. To clarify the real effect of sex on bariatric procedure-derived health benefits, it is crucial to report sex-stratified results in future studies, as well as evaluate body composition changes that go beyond simple body weight reduction.

Advice of General Practitioner, of Surgeon, of Endocrinologist, and Self-determination: the Italian Road to Bariatric Surgery.

PURPOSE: Bariatric surgery (BS) is considered the most efficient treatment for severe obesity. International guidelines recommend multidisciplinary approach to BS (general practitioners, endocrinologists, surgeons, psychologists, or psychiatrists), and access to BS should be the final part of a protocol of treatment of obesity. However, there are indications that general practitioners (GPs) are not fully aware of the possible benefits of BS, that specialty physicians are reluctant to refer their patients to surgeons, and that patients with obesity choose self-management of their own obesity, including internet-based choices. There are no data on the pathways chosen by physicians and patients to undergo BS in the real world in Italy. METHODS: An exploratory exam was performed for 6 months in three pilot regions (Lombardy, Lazio, Campania) in twenty-three tertiary centers for the treatment of morbid obesity, to describe the real pathways to BS in Italy. RESULTS: Charts of 2686 patients (788 men and 1895 women, 75.5% in the age range 30-59 years) were evaluated by physicians and surgeons of the participating centers. A chronic condition of obesity was evident for the majority of patients, as indicated by duration of obesity, by presence of several associated medical problems, and by frequency of previous dietary attempts to weight loss. The vast majority (75.8%) patients were self-presenting or referred by bariatric surgeons, 24.2% patients referred by GPs and other specialists. Self-presenting patients were younger, more educated, more professional, and more mobile than patients referred by other physicians. Patients above the age of 40 years or with a duration of obesity greater than 10 years had a higher prevalence of all associated medical problems. CONCLUSIONS: The majority of patients referred to a tertiary center for the treatment of morbid obesity have a valid indication for BS. Most patients self-refer to the centers, with a minority referred by a GP or by specialists. Self-presenting patients are younger, more educated, more professional, and more mobile than patients referred by other physicians. Older patients and with a longer duration of obesity are probably representative of the conservative approach to BS, often regarded as the last resort in an endless story.

Conversion from laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) to one anastomosis gastric bypass (OAGB): preliminary data from a multicenter retrospective study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most commonly performed bariatric procedure, while laparoscopic adjustable gastric banding (LAGB) has been for a decade one of the most popular interventions for weight loss. After LSG and LAGB, some patients may require a second surgery due to weight regain or late complications. One anastomosis gastric bypass (OAGB) is a promising bariatric procedure, which provides effective long-term weight loss and has a favorable effect on type 2 diabetes. OBJECTIVES: To retrospectively analyze data from 10 Italian centers on conversion from LAGB and LSG to OAGB. SETTING: High-volume centers for bariatric surgery. METHODS: Prospectively collected data from 10 high-volume centers were retrospectively reviewed. Body mass index (BMI), percentage of excess BMI loss, reasons for redo, remission from co-morbidities (hypertension, diabetes, gastroesophageal reflux, and dyslipidemia), and major complications were recorded. RESULTS: Three hundred patients were included in the study; 196 patients underwent conversion from LAGB to OAGB and 104 were converted from LSG. BMI was 45.1 ± 7 kg/m2 at the time of first intervention, 41.8 ± 6.3 kg/m2 at redo time, and 30.5 ± 5.5 kg/m2 at last follow-up appointment. Mean percentage of excess BMI loss was 13.2 ± 28.2 at conversion and 73.4 ± 27.5 after OAGB. Remission rates from hypertension, diabetes, gastroesophageal reflux, and dyslipidemia were 40%, 62.5%, 58.7% and 52%, respectively. Mean follow-up was 20.8 (range, 6-156) months and overall complications rate was 8.6%. CONCLUSION: Our data show that OAGB is a safe and effective revisional procedure after failed restrictive bariatric surgery.

Selected treatments for duodenal perforation after ERCP. A report of three cases.

Perforation is one of the most serious complications of endoscopic sphincterotomy. In the last decade, the management has shifted towards a more selective approach. Three cases are reported here involving three different treatments. In one case, the patient was submitted to a surgical procedure, while a conservative strategy was preferred in the other two, consisting in a naso-biliary drain and endoscopic clip placement, respectively. In this way, the safety of surgical and nonsurgical management of ERCP-related duodenal perforations was tested.

[Laparoscopic appendectomy: retrospective studies of 172 consecutive procedures]. / Appendicectomia laparoscopica: analisi retrospettiva su 172 procedure consecutive.

The aim of our study was to assess the efficacy and safety of laparoscopic appendectomy, as performed by experienced and trainee surgeons in a Unit of General Surgery. From June 1997 to May 2002, 172 patients underwent laparoscopic appendectomy. Age below 13 years was an exclusion criterion. There was no single protocol for the diagnosis and surgical technique adopted by the different surgeons. The average operating time was 65.3 min (range: 41-106 min). There were 9 conversions to open surgery (5.2%) and 9 postoperative complications (5.5%) out of a total of 162 patients undergoing the laparoscopic procedure. Oral intake was resumed on post-operative day 2 and the average hospital stay was 3.4 days (range: 3-5 days). In conclusion, laparoscopic appendectomy proved to be safe and effective, even when performed by surgeons with only limited experience of minimally invasive surgery.