American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

Biliary cast syndrome after liver transplantation: A cholangiographic evolution study.

BACKGROUND AND AIM: The aim of this study is to describe the cholangiographic features and endoscopic management of biliary cast syndrome (BCS), a rare specific ischemic cholangiopathy following liver transplantation. METHODS: Patients with biliary complications were identified from prospectively collected database records of patients who underwent liver transplantation at the Erasme Hospital from January 2005 to December 2014. After excluding patients with hepatico-jejunostomy or no suspicion of stricture, cholangiograms obtained during endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance imaging were systematically reviewed. Biliary complications were categorized as anastomotic (AS) and non-AS strictures, and patients with BCS were identified. Clinical, radiological, and endoscopic data were reviewed. RESULTS: Out of 311 liver transplantations, 14 cases were identified with BCS (4.5%) and treated with ERCP. Intraductal hyperintense signal on T1-weighted magnetic resonance and a "duct-in-a-duct" image were the most frequent features of BCS on magnetic resonance imaging. On initial ERCP, 57% of patients had no stricture. Complete cast extraction was achieved in 12/14, and one of these had cast recurrence. On follow-up, 85% of the patients developed biliary strictures that were treated with multiple plastic stents reaching 60% complete stricture resolution, but 40% of them had recurrence. After a median follow-up of 58 months, BCS patients had lower overall and graft survival (42.9% and 42.9%) compared with non-AS (68.8% and 56.3%) and AS (83.3% and 80.6%), respectively. CONCLUSIONS: Particular magnetic resonance-cholangiographic and ERCP-cholangiographic features of BCS have been identified. Outcomes for BCS are characterized by high complete cast extraction rates, high incidence of secondary strictures, and poorer prognosis.

Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes.

Type 2 diabetes is a pandemic disease with an incidence that has risen steadily over recent decades. Experimental evidence in animals has demonstrated that intestinal bypass surgery of the upper small intestine, particularly the duodenum, has an important role in glucose homoeostasis. Furthermore, Roux-en-Y bypass performed as bariatric surgery has shown to correct hyperglycaemia from the first postoperative days in obese diabetic patients. Therefore, on the basis of these considerations, duodenal mucosal resurfacing was studied in type 2 diabetes patients as a minimally invasive procedure that could offer an alternative treatment for these patients. Further studies, and particularly large controlled trials, are needed to determine the place of this procedure in the treatment of type 2 diabetes as well as other metabolic diseases such as non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.

Dietary strategies in non-alcoholic fatty liver disease patients: From evidence to daily clinical practice, a systematic review.

Lifestyle modification comprising calorie restriction (CR) and increased physical activity enabling weight loss is the first-line of treatment for non-alcoholic fatty liver disease (NAFLD). However, CR alone is not optimal and evidence suggests that dietary pattern and composition are also critical in NAFLD management. Accordingly, high consumption of red and processed meat, saturated fat, added sugar, and sweetened beverages are associated with an increased risk of developing NAFLD and hepatocellular carcinoma, while other foods and compounds such as fish, olive oil, and polyphenols are, in contrast, beneficial for metabolic disorders. Therefore, several dietary interventions have been studied in order to determine which strategy would be the most beneficial for NAFLD. The evidence regarding the effectiveness of different dietary interventions such as low carbohydrate/low-fat diet, time-restricted eating diet, CR, and the well-studied Mediterranean diet is summarized.

Cold atmospheric plasma differentially affects cell renewal and differentiation of stem cells and APC-deficient-derived tumor cells in intestinal organoids.

Cold atmospheric plasma (CAP) treatment has been proposed as a potentially innovative therapeutic tool in the biomedical field, notably for cancer due to its proposed toxic selectivity on cancer cells versus healthy cells. In the present study, we addressed the relevance of three-dimensional organoid technology to investigate the biological effects of CAP on normal epithelial stem cells and tumor cells isolated from mouse small intestine. CAP treatment exerted dose-dependent cytotoxicity on normal organoids and induced major transcriptomic changes associated with the global response to oxidative stress, fetal-like regeneration reprogramming, and apoptosis-mediated cell death. Moreover, we explored the potential selectivity of CAP on tumor-like Apc-deficient versus normal organoids in the same genetic background. Unexpectedly, tumor organoids exhibited higher resistance to CAP treatment, correlating with higher antioxidant activity at baseline as compared to normal organoids. This pilot study suggests that the ex vivo culture system could be a relevant alternative model to further investigate translational medical applications of CAP technology.

Endoscopic duodenal mucosal resurfacing for nonalcoholic steatohepatitis (NASH): a pilot study.

Background and study aims Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide with limited treatment options. Duodenal mucosal resurfacing (DMR) has been associated with improvement in glycaemic parameters and liver function tests (LFTs) in type 2 diabetes. This study aimed to assess the effect of DMR in patients with NASH. Patients and methods This was a single-center, open-label pilot study. Patients with definite, biopsy-proven NASH (nonalcoholic fatty liver disease activity score [NAS] ≥ 4) underwent a single DMR procedure followed by a 2-week postprocedural diet, without lifestyle intervention. The primary outcome was either resolution of NASH with no worsening of fibrosis or improvement in fibrosis (≥ 1 stage) with no worsening of NASH at 12 months. Secondary outcomes were changes in key histological parameters of NASH, surrogate markers of fibrosis, LFTs, and metabolic factors at 12 months. Results From 2017 to 2019, 14 patients underwent successful DMR, of whom 11 were included in the analysis. After 12 months, no resolution of NASH was observed, while three patients (27 %) had marginal improvement in fibrosis with no worsening of NASH. Serious adverse events related to the procedure were reported in two patients out of 14 (14 %). Neither weight loss nor improvement in NAS score, or in the other secondary outcomes, were observed at 12 months. Conclusions In this small and heterogenous study population, we found that DMR, in the absence of lifestyle intervention, did not induce NASH resolution and marginally improved liver fibrosis at 12 months.

Noninvasive diagnosis in alcohol-related liver disease.

BACKGROUND: Alcohol-related liver disease (ALD) represents a major cause of death worldwide, and unfortunately, most patients are diagnosed at an advanced stage of the disease, which is related to poorer outcomes. Liver biopsy has historically been the gold standard for identifying advanced hepatic fibrosis, but this approach has several limitations, including invasiveness, low applicability, sampling variability, and cost. MAIN TEXT: In order to detect earlier features of advanced liver fibrosis, surrogate biomarkers and techniques have been developed. While these were initially developed for chronic liver diseases such as viral hepatitis and nonalcoholic fatty liver disease (NAFLD), their performance in ALD has also been recently studied. Among the noninvasive surrogate markers and techniques used to detect liver fibrosis, the Enhanced Liver Fibrosis test, FibroTest, and Transient Elastography are the most accurate and validated techniques. In this review, we summarize the current status of the noninvasive assessment of liver disease in ALD and provide a synthesis of how these noninvasive tools can be used in clinical practice. Finally, we briefly outline novel biomarkers that are currently being investigated and discuss future directions and new opportunities in the noninvasive diagnosis of ALD.

Metabolic endoscopy: Today's science-tomorrow's treatment.

Obesity, type 2 diabetes mellitus (T2DM) and nonalcoholic steatohepatitis are increasing pandemic metabolic disorders. Lifestyle intervention (LSI) is the cornerstone treatment for these but is successful as standard care alone in only a few patients, given the modest weight loss at mid and long term. Conversely, bariatric surgery is the only proven effective treatment for these metabolic disorders, albeit offered only in a small percentage of cases because of its invasiveness and cost. The so-called endoscopic bariatric and metabolic therapies (EBMTs) include new, less-invasive technologies such as intragastric balloons, aspiration therapy, endoscopic sleeve gastroplasty, diversion devices, and duodenal mucosal resurfacing, currently at various stages of development. EBMTs, as an add-on to LSI, might represent an effective treatment filling the gap between medical and surgical management, taking into account, however, that obesity and its associated comorbidities constitute a chronic disease that needs lifelong therapy. In this review we describe the current scientific evidence surrounding EBMTs as well as future opportunities for such treatments in managing obesity and metabolic disorders.

Left ventricular adaptation to high altitude: speckle tracking echocardiography in lowlanders, healthy highlanders and highlanders with chronic mountain sickness.

Hypoxic exposure depresses myocardial contractility in vitro, but has been associated with indices of increased cardiac performance in intact animals and in humans, possibly related to sympathetic nervous system activation. We explored left ventricular (LV) function using speckle tracking echocardiography and sympathetic tone by spectral analysis of heart rate variability (HRV) in recently acclimatized lowlanders versus adapted or maladapted highlanders at high altitude. Twenty-six recently acclimatized lowlanders, 14 healthy highlanders and 12 highlanders with chronic mountain sickness (CMS) were studied. Control measurements at sea level were also obtained in the lowlanders. Altitude exposure in the lowlanders was associated with slightly increased blood pressure, decreased LV volumes and decreased longitudinal strain with a trend to increased prevalence of post-systolic shortening (p = 0.06), whereas the low frequency/high frequency (LF/HF) ratio increased (1.62 ± 0.81 vs. 5.08 ± 4.13, p < 0.05) indicating sympathetic activation. Highlanders had a similarly raised LF/HF ratio, but no alteration in LV deformation. Highlanders with CMS had no change in LV deformation, no significant increase in LF/HF, but decreased global HRV still suggestive of increased sympathetic tone, and lower mitral E/A ratio compared to healthy highlanders. Short-term altitude exposure in lowlanders alters indices of LV systolic function and increases sympathetic nervous system tone. Life-long altitude exposure in highlanders is associated with similar sympathetic hyperactivity, but preserved parameters of LV function, whereas diastolic function may be altered in those with CMS. Altered LV systolic function in recently acclimatized lowlanders may be explained by combined effects of hypoxia and changes in loading conditions.

Left ventricular adaptation to acute hypoxia: a speckle-tracking echocardiography study.

BACKGROUND: Hypoxia depresses myocardial contractility in vitro but does not affect or may even improve indices of myocardial performance in vivo, possibly through associated changes in autonomic nervous system tone. The aim of this study was to explore the effects of hypoxic breathing on speckle-tracking echocardiographic indices of left ventricular function, with and without ß1-adrenergic inhibition. METHODS: Speckle-tracking echocardiography was performed in 21 healthy volunteers in normoxia and after 30 min of hypoxic breathing (fraction of inspired oxygen, 0.12). Measurements were also obtained after the administration of atropine in normoxia (n = 21) and after bisoprolol intake in normoxia (n = 6) and in hypoxia (n = 10). RESULTS: Hypoxia increased heart rate (from 68 ± 11 to 74 ± 9 beats/min, P = .001), without changing mean blood pressure (P = NS), and decreased total peripheral resistance (P = .003). Myocardial deformation magnitude increased (circumferential strain, -19.6 ± 1.9% vs -21.2 ± 2.5%; radial strain, 19.2 ± 3.7% vs 22.6 ± 4.1%, P < .05; longitudinal and circumferential strain rate, -0.88 ± 0.11 vs -0.99 ± 0.15 sec(-1) and -1.03 ± 0.16 vs -1.18 ± 0.18 sec(-1), respectively, P < .05 for both; peak twist, 8.98 ± 3.2° vs 11.1 ± 2.9°, P < .05). Except for peak twist, these deformation parameters were correlated with total peripheral resistance (P < .05). Atropine increased only longitudinal strain rate magnitude (-0.88 ± 0.11 vs -0.97 ± 0.14 sec(-1), P < .05). The increased magnitude of myocardial deformation persisted in hypoxia under bisoprolol (P < .05). In normoxia, bisoprolol decreased heart rate (73 ± 10 vs 54 ± 7 beats/min, P = .0005), mean blood pressure (88 ± 7 vs 81 ± 4 mm Hg, P = .0027), without altering deformation. CONCLUSIONS: Hypoxic breathing increases left ventricular deformation magnitude in normal subjects, and this effect may not be attributed to hypoxia-induced tachycardia or ß1-adrenergic pathway changes but to hypoxia-induced systemic vasodilation.