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.

Diverticular disease: update on pathophysiology, classification and management.

Colonic diverticulosis is prevalent, affecting approximately 70% of the western population by 80 years of age. Incidence is rapidly increasing in younger age groups. Between 10% and 25% of those with diverticular disease (DD) will experience acute diverticulitis. A further 15% will develop complications including abscess, bleeding and perforation. Such complications are associated with significant morbidity and mortality and constitute a worldwide health burden. Furthermore, chronic symptoms associated with DD are difficult to manage and present a further significant healthcare burden. The pathophysiology of DD is complex due to multifactorial contributing factors. These include diet, colonic wall structure, intestinal motility and genetic predispositions. Thus, targeted preventative measures have proved difficult to establish. Recently, commonly held conceptions on DD have been challenged. This review explores the latest understanding on pathophysiology, risk factors, classification and treatment options.

MorphGI: A Self-Propelling Soft Robotic Endoscope Through Morphing Shape.

Colonoscopy is currently the best method for detecting bowel cancer, but fundamental design and construction have not changed significantly in decades. Conventional colonoscope (CC) is difficult to maneuver and can lead to pain with a risk of damaging the bowel due to its rigidity. We present the MorphGI, a robotic endoscope system that is self-propelling and made of soft material, thus easy to operate and inherently safe to patient. After verifying kinematic control of the distal bending segment, the system was evaluated in: a benchtop colon simulator, using multiple colon configurations; a colon simulator with force sensors; and surgically removed pig colon tissue. In the colon simulator, the MorphGI completed a colonoscopy in an average of 10.84 min. The MorphGI showed an average of 77% and 62% reduction in peak forces compared to a CC in high- and low-stiffness modes, respectively. Self-propulsion was demonstrated in the excised tissue test but not in the live pig test, due to anatomical differences between pig and human colons. This work demonstrates the core features of MorphGI.

Adult stem cell activity in naked mole rats for long-term tissue maintenance.

The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity and tissue function with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5+) in their native in vivo state, we find an expanded pool of Lgr5+ cells in NMRs, and these cells specifically at the crypt base (Lgr5+CBC) exhibit slower division rates compared to those in short-lived mice but have a similar turnover as human LGR5+CBC cells. Instead of entering quiescence (G0), NMR Lgr5+CBC cells reduce their division rates by prolonging arrest in the G1 and/or G2 phases of the cell cycle. Moreover, we also observe a higher proportion of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust pro-apoptotic, anti-proliferative response within the stem/progenitor cell zone.

A grumbling concern: an international survey of gastrointestinal symptoms in cystic fibrosis in the modulator era.

Background: Gastrointestinal symptoms in cystic fibrosis (CF) are common and intrusive to daily life. Relieving gastrointestinal symptoms was identified as an important research priority and previously explored in an international survey in 2018. However, following the widespread introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators in 2019, the landscape of CF treatment has changed. We repeated an online survey to further describe gastrointestinal symptoms and their effect on quality of life (QoL) in the CFTR modulator era. Methods: An electronic survey consisting of closed questions and free text responses was distributed via social media and professional networks for a period of one month between March - April 2022. People with CF (pwCF), their family and friends, and healthcare professionals (HCPs) were invited to take part. Results: There were 164 respondents: 88 pwCF (54%), 22 (13%) family, and 54 (33%) healthcare professionals (HCPs). A total of 89/110 (81%) pwCF or family members reported CFTR modulator treatment. The most commonly reported symptoms were wind / gas, rumbling stomach noises, loose motions (modulator) and bloating (no modulator). Abdominal pain and bloating had the greatest impact on QoL.For those on a CFTR modulator, the proportion of pwCF reporting "no change" or "worse" for all of the symptoms surveyed was greater than the proportion reporting an improvement. Following modulator introduction, dietary changes were recommended by 28/35 (80%) of HCPs and reported by 38/76 (50%) lay respondents. Changes in medication were recommended by 19/35 (54%) HCPs and reported by 44/76 (58%) of patients and family members. Conclusion: This survey has shown that gastrointestinal symptoms remain prevalent in pwCF in the CFTR modulator era, though the nature of these symptoms may have changed. A better understanding of the underlying pathophysiology of these symptoms is essential. Future clinical studies should focus on improving symptoms and QoL.

WHAT IS ALREADY KNOWN: Gastrointestinal symptoms are common and intrusive to everyday life for people with cystic fibrosis (CF), however the majority of studies reporting gastrointestinal symptoms in CF are published prior to the widespread introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies. These are medications which target the underlying defect in CF rather than the consequences of CFTR failure. WHAT THIS STUDY ADDS: Through this survey, we describe the similarities and differences of gastrointestinal symptoms for people with CF on modulator therapy compared to those not receiving modulators. Comparisons were also made to our previous work which was completed in 2018 prior to the licencing of the newest, and most widely used modulator, Elexacaftor / Tezacaftor / Ivacaftor (ETI). How this study might affect future research: This survey provides a snapshot into gastrointestinal symptoms for people with CF which will be of benefit for researchers as well as clinicians caring for people with CF. These results will inform the development of a CF-specific gastrointestinal patient reported outcome measure for people with CF that can be used in clinical trials.

All-or-Nothing Behavior and Catastrophic Thinking Predict Fatigue in Inflammatory Bowel Disease: A Prospective Cohort Study.

Patients with inflammatory bowel disease (IBD) often report fatigue. However, the reasons for this are poorly understood. In this study of people with IBD, we demonstrate that all-or-nothing behavior (being very active then needing to resting a while) and catastrophic thinking (making very negative assumptions about outcomes) both predict worsening in fatigue over time.

Towards NHS Zero: greener gastroenterology and the impact of virtual clinics on carbon emissions and patient outcomes. A multisite, observational, cross-sectional study.

Objective: The National Health Service (NHS) produces more carbon emissions than any public sector organisation in England. In 2020, it became the first health service worldwide to commit to becoming carbon net zero, the same year as the COVID-19 pandemic forced healthcare systems globally to rapidly adapt service delivery. As part of this, outpatient appointments became largely remote. Although the environmental benefit of this change may seem intuitive the impact on patient outcomes must remain a priority. Previous studies have evaluated the impact of telemedicine on emission reduction and patient outcomes but never before in the gastroenterology outpatient setting. Method: 2140 appointments from general gastroenterology clinics across 11 Trusts were retrospectively analysed prior to and during the pandemic. 100 consecutive appointments during two periods of time, from 1 June 2019 (prepandemic) to 1 June 2020 (during the pandemic), were used. Patients were telephoned to confirm the mode of transport used to attend their appointment and electronic patient records reviewed to assess did-not-attend (DNA) rates, 90-day admission rates and 90-day mortality rates. Results: Remote consultations greatly reduced the carbon emissions associated with each appointment. Although more patients DNA their remote consultations and doctors more frequently requested follow-up blood tests when reviewing patients face-to-face, there was no significant difference in patient 90-day admissions or mortality when consultations were remote. Conclusion: Teleconsultations can provide patients with a flexible and safe means of being reviewed in outpatient clinics while simultaneously having a major impact on the reduction of carbon emissions created by the NHS.

DECIDE: Delphi Expert Consensus Statement on Inflammatory Bowel Disease Dysplasia Shared Management Decision-Making.

BACKGROUND AND AIMS: Inflammatory bowel disease colitis-associated dysplasia is managed with either enhanced surveillance and endoscopic resection or prophylactic surgery. The rate of progression to cancer after a dysplasia diagnosis remains uncertain in many cases and patients have high thresholds for accepting proctocolectomy. Individualised discussion of management options is encouraged to take place between patients and their multidisciplinary teams for best outcomes. We aimed to develop a toolkit to support a structured, multidisciplinary and shared decision-making approach to discussions about dysplasia management options between clinicians and their patients. METHODS: Evidence from systematic literature reviews, mixed-methods studies conducted with key stakeholders, and decision-making expert recommendations were consolidated to draft consensus statements by the DECIDE steering group. These were then subjected to an international, multidisciplinary modified electronic Delphi process until an a priori threshold of 80% agreement was achieved to establish consensus for each statement. RESULTS: In all, 31 members [15 gastroenterologists, 14 colorectal surgeons and two nurse specialists] from nine countries formed the Delphi panel. We present the 18 consensus statements generated after two iterative rounds of anonymous voting. CONCLUSIONS: By consolidating evidence for best practice using literature review and key stakeholder and decision-making expert consultation, we have developed international consensus recommendations to support health care professionals counselling patients on the management of high cancer risk colitis-associated dysplasia. The final toolkit includes clinician and patient decision aids to facilitate shared decision-making.

Artificial Intelligence Enabled Histological Prediction of Remission or Activity and Clinical Outcomes in Ulcerative Colitis.

BACKGROUND & AIMS: Microscopic inflammation has significant prognostic value in ulcerative colitis (UC); however, its assessment is complex with high interobserver variability. We aimed to develop and validate an artificial intelligence (AI) computer-aided diagnosis system to evaluate UC biopsies and predict prognosis. METHODS: A total of 535 digitalized biopsies (273 patients) were graded according to the PICaSSO Histologic Remission Index (PHRI), Robarts, and Nancy Histological Index. A convolutional neural network classifier was trained to distinguish remission from activity on a subset of 118 biopsies, calibrated on 42 and tested on 375. The model was additionally tested to predict the corresponding endoscopic assessment and occurrence of flares at 12 months. The system output was compared with human assessment. Diagnostic performance was reported as sensitivity, specificity, prognostic prediction through Kaplan-Meier, and hazard ratios of flares between active and remission groups. We externally validated the model in 154 biopsies (58 patients) with similar characteristics but more histologically active patients. RESULTS: The system distinguished histological activity/remission with sensitivity and specificity of 89% and 85% (PHRI), 94% and 76% (Robarts Histological Index), and 89% and 79% (Nancy Histological Index). The model predicted the corresponding endoscopic remission/activity with 79% and 82% accuracy for UC endoscopic index of severity and Paddington International virtual ChromoendoScopy ScOre, respectively. The hazard ratio for disease flare-up between histological activity/remission groups according to pathologist-assessed PHRI was 3.56, and 4.64 for AI-assessed PHRI. Both histology and outcome prediction were confirmed in the external validation cohort. CONCLUSION: We developed and validated an AI model that distinguishes histologic remission/activity in biopsies of UC and predicts flare-ups. This can expedite, standardize, and enhance histologic assessment in practice and trials.

Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome.

BACKGROUND: Gut-brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide. METHODS: We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete-linkage hierarchical cluster analysis of metabolites discriminant for PD-status was performed. RESULTS: Longer colonic transit was linked to deficits in faecal short-chain-fatty acids outside PD, to a 'tryptophan-containing metabolite cluster' overall. Phenotypic cluster analysis aggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan-cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole-ring compound (anti-fungals) and vitamin B3 (anti-inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid-cluster deficit was linked to (well-recognised) lower caffeine and alcohol intakes, tryptophan-cluster deficit to higher maltose intake. Free-sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton-pump inhibitors (p = .001)], with 16% of PD-probands exceeding a cut-point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut-point. CONCLUSIONS: Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory response syndrome.

High burden of polyp mischaracterisation in tertiary centre referrals for endoscopic resection may be alleviated by telestration.

Objective: Endoscopic resection (ER) often involves referral to tertiary centres with high volume practices. Lesions can be subject to prior manipulation and mischaracterisation of features required for accurate planning, leading to prolonged or cancelled procedures. As potential solutions, repeating diagnostic procedures is burdensome for services and patients, while even enriched written reports and still images provide insufficient information to plan ER. This project sought to determine the frequency and implications of polyp mischaracterisation and whether the use of telestration might prevent it. Design/method: A retrospective data analysis of ER referrals to four tertiary centres was conducted for the period July-December 2019. Prospective telestration with a novel digital platform was then performed between centres to achieve consensus on polyp features and ER planning. Results: 163 lesions (163 patients; mean age 67.9±12.2 y; F=62) referred from regional hospitals, were included. Lesion site was mismatched in 11 (6.7%). Size was not mentioned in the referral in 27/163 (16.6%) and incorrect in 81/136 (51.5%), more commonly underestimated by the referring centre (<0.0001), by a mean factor of 1.85±0.79. Incurred procedure time (in units of 20 min) was significantly greater than that allocated (p=0.0085). For 10 cases discussed prospectively, rapid consensus on lesion features was achieved, with agreement between experts on time required for ER. Conclusions: Polyp mischaracterisation is a frequent feature of ER referrals, but could be corrected by the use of telestration between centres. Our study involved expert-to-expert consensus, so extending to 'real-world' referring centres would offer additional learning for a digital pathway.

Green endoscopy: British Society of Gastroenterology (BSG), Joint Accreditation Group (JAG) and Centre for Sustainable Health (CSH) joint consensus on practical measures for environmental sustainability in endoscopy.

GI endoscopy is highly resource-intensive with a significant contribution to greenhouse gas (GHG) emissions and waste generation. Sustainable endoscopy in the context of climate change is now the focus of mainstream discussions between endoscopy providers, units and professional societies. In addition to broader global challenges, there are some specific measures relevant to endoscopy units and their practices, which could significantly reduce environmental impact. Awareness of these issues and guidance on practical interventions to mitigate the carbon footprint of GI endoscopy are lacking. In this consensus, we discuss practical measures to reduce the impact of endoscopy on the environment applicable to endoscopy units and practitioners. Adoption of these measures will facilitate and promote new practices and the evolution of a more sustainable specialty.

Faecal calprotectin is a surrogate marker of biliary inflammation in primary sclerosing cholangitis associated inflammatory bowel disease.

Objective: Faecal calprotectin (fCAL) is an established marker of intestinal inflammation in inflammatory bowel disease (IBD). Disproportionally high fCAL levels, for the severity of intestinal inflammation, have been previously observed in primary sclerosing cholangitis associated IBD (PSC-IBD). The aim of this study was to test the hypothesis that fCAL is a marker of biliary injury in PSC-IBD. Methods: We used two cohorts: (1) post hoc analysis of a colonoscopic surveillance study allowing correlation of fCAL to endoscopic severity as measured by the ulcerative colitis endoscopic index of severity (UCEIS) in PSC-IBD (n=20) and ulcerative colitis (UC, n=20) and (2) prospective recruitment of patients attending for endoscopic retrograde cholangiopancreatography allowed the correlation of fCAL to biliary calprotectin (n=8). Results: A strong correlation was seen between fCAL and UCEIS in UC (r=0.821, 95% CI (0.585 to 0.929), p<0.0001). In PSC-IBD, the correlation was weaker (r=0.596, 95% CI (0.195 to 0.8260), p=0.006). PSC-IBD patients with endoscopically quiescent colitis (UCEIS: 0-1) had higher fCAL than patients with UC (279 µg/g, IQR (68-601) vs 30 µg/g, IQR (14-107), p=0.015). This was associated with higher risk of biliary complications like need for antibiotics or instrumentation (HR 16.39, 95% CI (2.98 to 90.25)) rather than colitis flares (follow-up: 12 months). Calprotectin measured in faeces correlated positively with biliary calprotectin (r=0.898, p=0.0024). Conclusion: fCAL is a surrogate marker for biliary inflammation in PSC-IBD. Trial registration number: NCT02543021.

Daily life difficulties among patients with ulcerative colitis in Japan and the United Kingdom: A comparative study.

The difficulty of life scale (DLS) instrument is used to measure specific life problems in patients with ulcerative colitis (UC). Importantly, health care providers should consider the characteristics of the country in which they support patients with UC. This cross-cultural comparison study investigated DLS among patients with UC in Japan and the United Kingdom (UK). Outpatients attending one hospital in London and one in Osaka were included. We collected patient information using the DLS questionnaire, which comprises 18 items in three domains. Mean differences between Japan and the UK were compared for the total score and each domain of the DLS. Variables with P < .05 in univariate analysis were entered into a multiple regression model. We included 142 patients from Japan and 100 patients from the UK in the analysis. Univariate results showed that UK patients had more difficulties than Japanese patients in all three domains. Multivariate results showed that only "decline of vitality or vigor" showed significantly lower difficulty scores in Japanese patients. Having four or more bowel movements per day, visible bleeding, and being a homemaker or unemployed were significantly associated with greater difficulty according to the DLS total score. The level of daily life difficulties assessed using the DLS was greater among patients in the UK than among Japanese patients. This comparative study between patients with UC in Japan and the UK demonstrated certain country-related features for domain 3, "decline of vitality or vigor," of the DLS. The reasons why UK patients felt greater decline in vitality or vigor may be that these patients may have symptoms other than bowel symptoms; also, Japanese patients are more hesitant to express discomfort. The findings of this study might lead to a better understanding of culturally sensitive perceptions of daily life difficulties in UC.

Cytokine responsive networks in human colonic epithelial organoids unveil a molecular classification of inflammatory bowel disease.

Interactions between the epithelium and the immune system are critical in the pathogenesis of inflammatory bowel disease (IBD). In this study, we mapped the transcriptional landscape of human colonic epithelial organoids in response to different cytokines responsible for mediating canonical mucosal immune responses. By profiling the transcriptome of human colonic organoids treated with the canonical cytokines interferon gamma, interleukin-13, -17A, and tumor necrosis factor alpha with next-generation sequencing, we unveil shared and distinct regulation patterns of epithelial function by different cytokines. An integrative analysis of cytokine responses in diseased tissue from patients with IBD (n = 1,009) reveals a molecular classification of mucosal inflammation defined by gradients of cytokine-responsive transcriptional signatures. Our systems biology approach detected signaling bottlenecks in cytokine-responsive networks and highlighted their translational potential as theragnostic targets in intestinal inflammation.

Reducing the environmental footprint of gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) Position Statement.

Climate change and the destruction of ecosystems by human activities are among the greatest challenges of the 21st century and require urgent action. Health care activities significantly contribute to the emission of greenhouse gases and waste production, with gastrointestinal (GI) endoscopy being one of the largest contributors. This Position Statement aims to raise awareness of the ecological footprint of GI endoscopy and provides guidance to reduce its environmental impact. The European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) outline suggestions and recommendations for health care providers, patients, governments, and industry. MAIN STATEMENTS 1: GI endoscopy is a resource-intensive activity with a significant yet poorly assessed environmental impact. 2: ESGE-ESGENA recommend adopting immediate actions to reduce the environmental impact of GI endoscopy. 3: ESGE-ESGENA recommend adherence to guidelines and implementation of audit strategies on the appropriateness of GI endoscopy to avoid the environmental impact of unnecessary procedures. 4: ESGE-ESGENA recommend the embedding of reduce, reuse, and recycle programs in the GI endoscopy unit. 5: ESGE-ESGENA suggest that there is an urgent need to reassess and reduce the environmental and economic impact of single-use GI endoscopic devices. 6: ESGE-ESGENA suggest against routine use of single-use GI endoscopes. However, their use could be considered in highly selected patients on a case-by-case basis. 7: ESGE-ESGENA recommend inclusion of sustainability in the training curricula of GI endoscopy and as a quality domain. 8: ESGE-ESGENA recommend conducting high quality research to quantify and minimize the environmental impact of GI endoscopy. 9: ESGE-ESGENA recommend that GI endoscopy companies assess, disclose, and audit the environmental impact of their value chain. 10:  ESGE-ESGENA recommend that GI endoscopy should become a net-zero greenhouse gas emissions practice by 2050.