Impact of Pregnancy on Weight Loss After Endoscopic Sleeve Gastroplasty.

PURPOSE: Obesity and pregnancy are strictly related: on the one hand, obesity-one of the most common comorbidities in women of reproductive age-contributes to infertility and obesity-related pregnancy complications, whereas pregnancy is a condition in which, physiologically, the pregnant woman undergoes weight gain. Endoscopic sleeve gastroplasty (ESG) may be used for the treatment of obesity in women of childbearing age. MATERIALS AND METHODS: A retrospective analysis was conducted to evaluate weight trajectories, the evolution of obesity-related comorbidities, and lifestyle modification in women who became pregnant after ESG. A comparison was made between childbearing-age women who became pregnant after ESG and non-pregnant women. RESULTS: A total of 150 childbearing-age women underwent ESG at a large tertiary medical center. Of these, 11 patients (33.4 ± 6.2 years) became pregnant after the procedure, following a mean time interval of 5.5 ± 3.9 months. Three women (two affected by polycystic ovary syndrome) reported difficulty getting pregnant before undergoing ESG. The mean preconception BMI was 31.9±4.0 kg/m2 (-7.24 ± 4.0 kg/m2 after ESG). Total body weight loss (TBWL, %) was 18.08 ± 8.00, 11.00 ± 11.08, and 12.08 ± 8.49, at the beginning of pregnancy, at the delivery, and at the first follow-up (19.6 ± 7.8 months after ESG). TBWL of at least 5% was achieved before pregnancy in all patients (73% reached a TBWL ≥ 10%). No significant differences in weight loss and QoL were found between the pregnancy and non-pregnancy groups up to 24 months after ESG. CONCLUSIONS: Endoscopic sleeve gastroplasty allows for adequate weight loss before and after pregnancy in patients with obesity.

Dynamics of liver stiffness predicts complications in patients with HCV related cirrhosis treated with direct-acting antivirals.

BACKGROUND: Direct acting antivirals(DAAs) are effective in reducing inflammatory ant fibrotic markers in patients with chronic hepatitis C virus(HCV) infection and to prevent liver-related complications. Two-dimensional shear wave elastography(2D-SWE) is an effective technique for the assessment of liver fibrosis. AIM: To evaluate changes in liver stiffness(LS) in HCV cirrhotic patients undergoing DAA therapy and to identify non-invasive parameters that predict the occurrence of liver-related events. METHODS: We enrolled 229 patients who received DAAs between January 2015 and October 2018. Ultrasound parameters and laboratory data were assessed before treatment and 24(T1) and 48(T2) weeks after end of treatment. Patients were followed up every 6 months to evaluate the development of HCC and other liver related complications. Multiple Cox regression analysis was used to determine parameters associated with the development of complications. RESULTS: Model for End-stage Liver Disease(MELD) score(HR 1.16; CI 95% 1.01-1.33; p = 0.026) and a change in LS at T2(1-year Delta LS) < 20%(HR 2.98; CI 95% 1.01-8.1; p = 0.03) were independently associated with HCC risk. One-year Delta-LS <20% was independently associated with the development of ascites(HR 5.08; CI 95% 1.03 - 25.14; p = 0.04). CONCLUSIONS: Dynamic changes of 2D-SWE-measured LS after DAA therapy may be a useful tool to identify patients who are at higher risk of liver related complications.

A Combined Raman Spectroscopy and Atomic Force Microscopy System for In Situ and Real-Time Measures in Electrochemical Cells.

An innovative and versatile set-up for in situ and real time measures in an electrochemical cell is described. An original coupling between micro-Raman spectroscopy and atomic force microscopy enables one to collect data on opaque electrodes. This system allows for the correlation of topographic images with chemical maps during the charge exchange occurring in oxidation/reduction processes. The proposed set-up plays a crucial role when reactions, both reversible and non-reversible, are studied step by step during electrochemical reactions and/or when local chemical analysis is required.

Long-term Outcomes of Transoral Outlet Reduction (TORe) for Dumping Syndrome and Weight Regain After Roux-en-Y Gastric Bypass.

BACKGROUND: Both weight regain and dumping syndrome (DS) after Roux-en-Y gastric bypass (RYGB) have been related to the dilation of gastro-jejunal anastomosis. The aim of this study is to assess the safety and long-term efficacy of endoscopic transoral outlet reduction (TORe) for DS and/or weight regain after RYBG. MATERIALS AND METHODS: A retrospective analysis was performed on a prospective database. Sigstad's score, early and late Arts Dumping Score (ADS) questionnaires, absolute weight loss (AWL), percentage of total body weight loss (%TBWL), and percentage of excess weight loss (%EWL) were assessed at baseline and at 6, 12, and 24 months after TORe. RESULTS: Eighty-seven patients (median age 46 years, 79% female) underwent TORe. The median baseline BMI was 36.2 kg/m2. Out of 87 patients, 58 were classified as "dumpers" due to Sigstad's score ≥ 7. The resolution rate of DS (Sigstad's score < 7) was 68.9%, 66.7%, and 57.2% at 6, 12, and 24 months after TORe, respectively. A significant decrease in Sigstad's score as well as in early and late ADS questionnaires was observed (p < 0.001). The median Sigstad's score dropped from 15 (11-8.5) pre-operatively to 2 (0-12) at 24 months. The %TBWL was 10.5%, 9.9%, and 8.1% at 6, 12, and 24 months, respectively. Further, "dumpers" with resolution of DS showed better weight loss results compared with those with persistent DS (p < 0.001). The only adverse event observed was a perigastric fluid collection successfully managed conservatively. CONCLUSION: TORe is a minimally invasive treatment for DS and/or weight regain after RYGB, with evidence of long-term efficacy.

Weight Recidivism and Dumping Syndrome after Roux-En-Y Gastric Bypass: Exploring the Therapeutic Role of Transoral Outlet Reduction.

Obesity is a chronic, relapsing disease representing a global epidemic. To date, bariatric surgery is the most effective treatment for morbid obesity in the long-term. Roux-en-Y gastric bypass (RYGB) is one of the most performed bariatric interventions, with excellent long-term outcomes. However, about one-third of patients may experience weight regain over time, as well as dumping syndrome. Both these conditions are challenging to manage and require a multidisciplinary and personalized approach. The dilation of the gastro-jejunal anastomosis is a recognized etiological factor for both weight regain and dumping syndrome. Dietary modifications, behavioral interventions, and medications represent the first therapeutic step. Revisional surgery is the traditional approach when non-invasive treatments fail. However, re-interventions may be technically difficult and are associated with increased morbidity and mortality. Transoral outlet reduction (TORe) is an endoscopic procedure aimed at reducing the size of the anastomosis and is proposed as a minimally invasive treatment of weight regain and/or dumping syndrome refractory to conservative therapies. This review is aimed at providing a narrative overview of the role of TORe as part of the multidisciplinary therapeutic toolkit nowadays available to approach weight regain and dumping syndrome after RYGB.

Outcomes of Endoscopic Sleeve Gastroplasty in the Elder Population.

PURPOSE: With the aging of the population and the epidemic spread of obesity, the frequency of older individuals with obesity is steadily growing. To date, no data evaluating the use of endoscopic sleeve gastroplasty (ESG) in the elderly have been published. In this case series, we evaluate the short- and medium-term outcomes of ESG in patients with obesity aged 65 years and older. MATERIALS AND METHODS: A retrospective analysis was done on a prospective database; patients aged 65 years and older were included in our analysis. EWL%, TBWL%, the Bariatric Analysis and Reporting Outcome System (BAROS) questionnaire, and the presence of comorbidities were assessed. RESULTS: Eighteen patients aged 65 years and older underwent ESG between November 2017 and July 2021. The median age was 67 years and the mean baseline BMI was 41.2 kg/m2. After ESG, the median TBWL% was 15.1%, 15.5%, and 15.5% at 6, 12, and 24 months, while the median %EWL was 39%, 37%, and 41% at 6, 12, and 24 months, respectively. The median BAROS score was 3.0, 3.4, and 2.5 at 6, 12, and 24 months, respectively. Six out of twelve patients with hypertension and 3/4 diabetic patients reduced or removed their medications within 12 months following ESG. Two out of six patients with OSA stopped therapy with CPAP. No adverse events were recorded. CONCLUSION: According to our experience, ESG is a promising therapeutic option for elder individuals with obesity who fail non-invasive methods, and who refuse or are deemed not suitable for bariatric surgery because of age and comorbidities.

Food Emulsifiers and Metabolic Syndrome: The Role of the Gut Microbiota.

The use of emulsifiers in processed foods and the rapid epidemic development of metabolic syndrome in Western countries over the past 20 years have generated growing interest. Evidence for the role of emulsifiers in metabolic syndrome through gut microbiota has not been clearly established, thus making it challenging for clinical nutritionists and dietitians to make evidence-based associations between the nature and the quantity of emulsifiers and metabolic disorders. This narrative review summarizes the highest quality clinical evidence currently available about the impact of food emulsifiers on gut microbiota composition and functions and the potential development of metabolic syndrome. The state-of-the-art of the different common emulsifiers is performed, highlighting where they are present in daily foods and their roles. Recent findings of in vitro, in vivo, and human studies assessing the effect of different emulsifiers on gut microbiota have been recently published. There is some progress in understanding how some food emulsifiers could contribute to developing metabolic diseases through gut microbiota alterations while others could have prebiotic effects. However, there are still many unanswered questions regarding daily consumption amounts and the synergic effects between emulsifiers' intake and responses by the microbial signatures of each individual.

Dietary Habits and Gut Microbiota in Healthy Adults: Focusing on the Right Diet. A Systematic Review.

Diet is the first to affect our intestinal microbiota and therefore the state of eubiosis. Several studies are highlighting the potential benefits of taking certain nutritional supplements, but a dietary regime that can ensure the health of the intestinal microbiota, and the many pathways it governs, is not yet clearly defined. We performed a systematic review of the main studies concerning the impact of an omnivorous diet on the composition of the microbiota and the production of short-chain fatty acids (SCFAs). Some genera and phyla of interest emerged significantly and about half of the studies evaluated consider them to have an equally significant impact on the production of SCFAs, to be a source of nutrition for our colon cells, and many other processes. Although numerous randomized trials are still needed, the Mediterranean diet could play a valuable role in ensuring our health through direct interaction with our microbiota.

Liver function following hepatitis C virus eradication by direct acting antivirals in patients with liver cirrhosis: data from the PITER cohort.

BACKGROUND: The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA. METHODS: Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication. RESULTS: We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8-47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0-44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00-6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18-3.36), platelet count < 100,000/µl (HR = 1.75; 95% CI 1.08-2.85) and increased INR (HR = 2.41; 95% CI 1.51-3.84). Following viral eradication, in 7 of 15 coinfected (46.6%) and in 61 of 133 (45.8%) monoinfected patients with previous history of decompensation, a new decompensating event occurred. A first decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients (p = 0.83). CONCLUSIONS: Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.

Feasibility and safety of a new endoscopic synthetic sealant nebulizing device over gastric endoscopic submucosal dissections.

BACKGROUND: Endoscopic Submucosal Dissection (ESD) is the treatment of choice of superficial neoplastic gastrointestinal lesions. Delayed bleedings and perforations are still current clinical concerns. Glubran 2 is a synthetic cyanoacrylate-derived glue nowadays already widely used as an effective tissue adhesive. ENDONEB is a novel device thought for enabling the sealant nebulization over a specific targeted surface during laparotomy, laparoscopy, and thoracotomy. The aim of this single-center preclinical animal trial is to evaluate the feasibility and safety of the same nebulization technique during ESD in the perspective that further clinical studies would demonstrate the efficacy of Glubran 2 in preventing post-ESD adverse events. METHODS: Four live Landrace pigs were enrolled. Two approximately 30-mm-wide gastric ESDs were performed in each pig (experimental ESD and control ESD). About 0.5 mL of Glubran 2 was nebulized on the experimental ESDs. Subjective perception of the feasibility of the Glubran 2 nebulization was reported. Pigs were clinically monitored at follow-up and upper GI endoscopy was performed at 24 and 48 hours, when animals were euthanized to perform a macroscopic and histological analysis of the specimens. RESULTS: No peri-procedural adverse events were reported. Glubran 2 nebulization over experimental ESDs showed to be technically easy and time-effective. Clinical and endoscopic animal monitoring was negative at follow-up. At 24 hours, the Glubran 2 film was clearly visible on the eschar of the ESDs and signs of initial hydrolysis were discernable at 48 hours. No signs of peritoneal reaction were observed at the macroscopic examination. Equal transmural inflammation was described at the histological examination of both types of ESDs. CONCLUSIONS: Safety and feasibility profiles of Glubran 2 nebulizing ENDONEB device over ESD surfaces were excellent. Further evidences and human trials are needed to investigate its effectiveness in ESDs' eschars sealing and, thus, in delayed micro-perforations and bleedings prevention and treatment.

Gut and Reproductive Tract Microbiota Adaptation during Pregnancy: New Insights for Pregnancy-Related Complications and Therapy.

Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.

Cancer-associated fibroblast secretion of PDGFC promotes gastrointestinal stromal tumor growth and metastasis.

Targeted therapies for gastrointestinal stromal tumor (GIST) are modestly effective, but GIST cannot be cured with single agent tyrosine kinase inhibitors. In this study, we sought to identify new therapeutic targets in GIST by investigating the tumor microenvironment. Here, we identified a paracrine signaling network by which cancer-associated fibroblasts (CAFs) drive GIST growth and metastasis. Specifically, CAFs isolated from human tumors were found to produce high levels of platelet-derived growth factor C (PDGFC), which activated PDGFC-PDGFRA signal transduction in GIST cells that regulated the expression of SLUG, an epithelial-mesenchymal transition (EMT) transcription factor and downstream target of PDGFRA signaling. Together, this paracrine induce signal transduction cascade promoted tumor growth and metastasis in vivo. Moreover, in metastatic GIST patients, SLUG expression positively correlated with tumor size and mitotic index. Given that CAF paracrine signaling modulated GIST biology, we directly targeted CAFs with a dual PI3K/mTOR inhibitor, which synergized with imatinib to increase tumor cell killing and in vivo disease response. Taken together, we identified a previously unappreciated cellular target for GIST therapy in order to improve disease control and cure rates.

From obesity through gut microbiota to cardiovascular diseases: a dangerous journey.

The co-existence of humans and gut microbiota started millions of years ago. Until now, a balance gradually developed between gut bacteria and their hosts. It is now recognized that gut microbiota are key to form adequate immune and metabolic functions and, more in general, for the maintenance of good health. Gut microbiota are established before birth under the influence of maternal nutrition and metabolic status, which can impact the future metabolic risk of the offspring in terms of obesity, diabetes, and cardiometabolic disorders during the lifespan. Obesity and diabetes are prone to disrupt the gut microbiota and alter the gut barrier permeability, leading to metabolic endotoxaemia with its detrimental consequences on health. Specific bacterial sequences are now viewed as peculiar signatures of the metabolic syndrome across life stages in each individual, and are linked to pathogenesis of cardiovascular diseases (CVDs) via metabolic products (metabolites) and immune modulation. These mechanisms have been linked, in association with abnormalities in microbial richness and diversity, to an increased risk of developing arterial hypertension, systemic inflammation, nonalcoholic fatty liver disease, coronary artery disease, chronic kidney disease, and heart failure. Emerging strategies for the manipulation of intestinal microbiota represent a promising therapeutic option for the prevention and treatment of CVD especially in individuals prone to CV events.