Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial.

AIMS/HYPOTHESIS: Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. METHODS: This study included adults (aged 20-86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. RESULTS: Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: -0.26 ± 0.64 vs -0.17 ± 0.62, p=0.44; GSRS: -0.35 ± 0.62 vs -0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: -0.47 ± 0.78 vs -0.33 ± 0.75, p=0.34; GSRS: -0.46 ± 0.90 vs -0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs -19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated. CONCLUSIONS/INTERPRETATION: Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04143269 FUNDING: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045).

Gastrointestinal dysmotility in rodent models of Parkinson's disease.

Multiple studies describe prodromal, nonmotor dysfunctions that affect the quality of life of patients who subsequently develop Parkinson's disease (PD). These prodromal dysfunctions comprise a wide array of autonomic issues, including severe gastrointestinal (GI) motility disorders such as dysphagia, delayed gastric emptying, and chronic constipation. Indeed, strong evidence from studies in humans and animal models suggests that the GI tract and its neural, mainly vagal, connection to the central nervous system (CNS) could have a major role in the etiology of PD. In fact, misfolded α-synuclein aggregates that form Lewy bodies and neurites, i.e., the histological hallmarks of PD, are detected in the enteric nervous system (ENS) before clinical diagnosis of PD. The aim of the present review is to provide novel insights into the pathogenesis of GI dysmotility in PD, focusing our attention on functional, neurochemical, and molecular alterations in animal models.

Gluten-related Disorders From Bench to Bedside.

Celiac disease, non-celiac gluten sensitivity, and wheat allergy comprise 3 of the main conditions with wheat- and gluten-containing foods as the symptom trigger. Distinguishing between these entities can be daunting. In this review, we compare and contrast celiac disease, non-celiac gluten sensitivity, and wheat allergy to allow clinicians to determine which diagnosis fits their patient to facilitate high-quality management and longitudinal care.

Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study.

BACKGROUND & AIMS: The estimated prevalence of irritable bowel syndrome (IBS) using Rome IV criteria in the United States (US) ranges from 4.7% to 5.3%, although these estimates arise from studies with relatively small sample sizes. This study assessed the prevalence of IBS and its associated burden of illness using a nationally representative data set with nearly 89,000 people in the US. METHODS: From May 3 to June 24, 2020, we performed an online survey described to participating adults aged ≥18 years old as a "national health survey." We recruited a representative sample of people in the US to complete the survey, which included the Rome IV IBS questionnaire, National Institutes of Health Patient-Reported Outcome Measurement Information System (PROMIS) gastrointestinal scales, and questions on health care-seeking behavior. RESULTS: Overall, 88,607 people completed the survey, of whom 5414 (6.1%) met Rome IV IBS criteria: mixed IBS (n = 1838 [33.9%]), constipation-predominant IBS (n = 1819 [33.6%]), diarrhea-predominant IBS (n = 1521 [28.1%]), and unsubtyped IBS (n = 236 [4.4%]). Women had higher odds for IBS compared with men, whereas racial/ethnic minorities had lower odds for IBS vs non-Hispanic Whites. Across the 3 main subtypes, 68.2% to 73.2% of people reported ever seeking care for their IBS symptoms, whereas 53.8% to 58.9% did so in the past 12 months. CONCLUSIONS: In this nationwide US survey, we found that Rome IV IBS is slightly more prevalent (6.1%) vs prior estimates (4.7%-5.3%). Additional research is needed to determine whether this higher prevalence is in part due to the coronavirus disease 2019 pandemic during which this study was conducted.

Evaluating the safety of high-intensity focused ultrasound treatment for rectal endometriosis: results from a French prospective multicentre study including 60 patients.

STUDY QUESTION: Is increasing the intensity of high-intensity focused ultrasound (HIFU) by 30% in the treatment of rectal endometriosis a safe procedure? SUMMARY ANSWER: This study demonstrates the safety of a 30% increase in the intensity of HIFU in the treatment of rectal endometriosis, with no Clavien-Dindo Grade III complications overall, and namely no rectovaginal fistulae. WHAT IS KNOWN ALREADY: A feasibility study including 20 patients with rectal endometriosis demonstrated, with no severe complications, a significant improvement in digestive disorders, dysmenorrhoea, dyspareunia, and health status, although the volume of the endometriosis nodule did not appear to be reduced. STUDY DESIGN, SIZE, DURATION: A prospective multicentre cohort study was conducted between 2020 and 2022 with 60 patients with symptomatic rectal endometriosis. Following the failure of medical treatment, HIFU treatment was offered as an alternative to surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: As the main objective of this study was to examine safety, all adverse events observed during the 6 months of follow-up were analysed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and Clavien-Dindo classifications. Secondary objectives included evaluating the evolution of symptoms using validated questionnaires: gynaecological and digestive pain symptoms with a visual analogue scale, health status with the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire, average post-operative daily pain level, and analgesic medication required in the 10 days following treatment. MRI was also performed at Day 1 to detect early complications. Finally, we performed a blinded MRI review of the evolution of the nodule at 6 months post-treatment. MAIN RESULTS AND THE ROLE OF CHANCE: The procedure was performed under spinal anaesthesia for 30% of the patients. The median duration of treatment was 32 min. Fifty-five patients left the hospital on Day 1. MRI scans performed on Day 1 did not highlight any early-onset post-operative complication. Using the Clavien-Dindo classification, we listed 56.7% Grade I events, 3.4% Grade II events, and no events Grade III or higher. At 1, 3, and 6 months, all gynaecologic, digestive and general symptoms, as well as health status, had significantly improved. The evolution of the nodule was also significant (P < 0.001) with a 28% decrease in volume. LIMITATIONS, REASONS FOR CAUTION: The main objective was safety and not effectiveness. The study was not randomized and there was no control group. WIDER IMPLICATIONS OF THE FINDINGS: HIFU treatment for rectal endometriosis results in an improvement of symptoms with low morbidity; as such, for selected patients, it could be a valuable alternative to surgical approaches following the failure of medical treatment. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the company EDAP TMS. Professors Dubernard and Rousset are consultants for EDAP TMS. Dubernard received travel support from EDAP-TMS. Dr F. Chavrier received industrial grants from EDAP-TMS. He has developed a device for generating focused ultrasonic waves with reduced treatment time. This device has been patented by EDAP-TMS. Dr Lafon received industrial grants from EDAP-TMS; he declares that EDAP-TMS provided funding directly to INSERM to support a young researcher chair in therapeutic ultrasound, which is unrelated to the current study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT04494568.

Diabetes distress and depression are independently associated with gastrointestinal symptoms in type 2 diabetes in Bangladesh.

BACKGROUND AND AIMS: Gastrointestinal (GI) symptoms, common in type 2 diabetes (T2D), are typically bothersome, socially embarrassing, and impact negatively on quality of life. They may also contribute to diabetes distress (DD), but this has never been formally evaluated. We aimed to investigate the relationships between GI symptoms, DD and depressive symptoms in a large cohort of individuals with T2D in Bangladesh. MATERIALS AND METHODS: 1406 unselected T2D individuals (female 58.8%; mean age 51.0 ± 12.5 years) from four diabetes clinics in Bangladesh completed validated questionnaires evaluating GI symptoms (PAGI-SYM), DD (DDS-17) and depressive symptoms (PHQ-9). RESULTS: 31.1% of participants reported GI symptoms (36.2% females, 23.7% males), while 51.1% had elevated DD and 37.8% depressive symptoms. GI symptoms exhibited independent relationships with both DD and depressive symptoms, and their likelihood was higher among those with DD (OR: 3.6 [2.2-5.6] and with depressive symptoms (OR: 5.9 [3.5-9.9]). CONCLUSIONS: GI symptoms are independently associated with both DD and depressive symptoms in people with T2D in Bangladesh.

A comparative study on dietary diversity and gut microbial diversity in children with autism spectrum disorder, attention-deficit hyperactivity disorder, their neurotypical siblings, and non-related neurotypical volunteers: a cross-sectional study.

BACKGROUND: Previous research has shown a significant link between gut microbiota in children with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). However, much remains unknown because of the heterogeneity of disorders and the potential confounders such as dietary patterns and control group variations. METHODS: Children aged 6-12 years who had been clinically diagnosed with ASD and/or ADHD, their unaffected neurotypical siblings, and non-related neurotypical volunteers were recruited cross-sectionally. The ASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule-2 (ADOS-2) in all patients, including those with ADHD. Standardized DNA extraction and sequencing methods were used to compare gut microbial alpha-diversity among the groups. Dietary diversity was calculated from a standardized dietary questionnaire form. We compared the difference in gut microbiome between patients with ASD and/or ADHD with neurotypical siblings and non-related neurotypical controls. RESULTS: Ninety-eight subjects were included in the study (18 with ASD, 19 with ADHD, 20 with both ASD and ADHD, 13 neurotypical siblings, and 28 non-related neurotypical controls). The alpha-diversity indices, such as Chao 1 and Shannon index, showed a significant difference between the groups in a Linear mixed-effect model (F(4, 93) = 4.539, p = .02), (F(4, 93) = 3.185, p = .017), respectively. In a post-hoc pairwise comparison, patients with ASD had lower alpha-diversity compared with non-related controls after Bonferroni correction. Dietary diversity shown in Shannon index did not differ among the groups (F(4, 84) = 1.494, p = .211). CONCLUSIONS: Our study indicates disorder-specific microbiome differences in patients with ASD. In future research on gut microbiota in neurodevelopmental disorders, it is necessary to consider the impact of ASD and ADHD co-occurrence, and strictly control for background information such as diet, to elucidate the gut-microbiota interaction in ASD and ADHD for exploring the potential of therapeutic interventions.

Impact of a pharmaceutical algorithm on patients with upper-gastrointestinal symptoms: A pre-post intervention study.

OBJECTIVE: To evaluate the algorithm impact on the upper gastrointestinal patients' symptoms (PROMs) and satisfaction with pharmaceutical care received (PREMs). METHODS: The algorithm was previously developed by clinicians and pharmacists, through a pre-post intervention study in Spain (June-October 2022). We included 1221 patients who were seeking advice and/or medication for symptoms at 134 community pharmacies. Patients' sociodemographic and clinical variables were assessed at baseline and were classified in accordance with the Gastroesophageal Reflux Disease Impact Scale (GIS) into patients with either epigastric, retrosternal or overlapping symptoms. Interventions included medical referral; education on healthy habits; prescription of an OTC treatment or a non-pharmacologic prescription. Fourteen days later, patients were assessed through: a) the change on the GIS score, and b) patients' satisfaction with pharmaceutical care received. RESULTS: Most patients reported overlapping symptoms (660, 54.0%), 171 (14.0%) reported epigastric symptoms and 390 (32.0%) retrosternal symptoms. Patients with epigastric symptoms did not show a difference in the GIS score after the intervention while those with retrosternal symptoms and those with overlapping symptoms did (mean 1.09 (4.28 SD), p < 0.001 and mean 3.18 (6.01 SD), p < 0.001, respectively). Patients who received education on healthy habits and those with a prescription of a pharmacological treatment (antiacids in monotherapy and alginates-antiacids) showed an increase in the GIS score. Patients' satisfaction with pharmaceutical care received was over 99.2% of sample. CONCLUSION: Implementation of the upper-gastrointestinal symptoms algorithm in Community pharmacies had a positive impact on patients' symptoms, quality of life, and satisfaction with pharmaceutical care received.

Gastrointestinal system involvement in patients with primary immunodeficiency: a single center experience.

AIM: Primary immunodeficiencies (PIDs) are a heterogeneous disorder group characterized by an impaired immune system, leading to an increased susceptibility to infections and a wide range of clinical manifestations, including gastrointestinal (GI) complications. This study aimed to assess the GI manifestations of PID patients and highlight the significance of atypical gastrointestinal symptoms in the early diagnosis of these patients. METHODS: A retrospective analysis was conducted on pediatric patients diagnosed with PIDs at Selcuk University Medical Faculty from 2011 to 2021. The study focused on demographic data, clinical presentation, genetic mutations, and GI manifestations, including endoscopic evaluation. Patients were categorized according to the International Union of Immunological Societies (IUIS) PID classifications. Statistical analyses were performed to identify significant associations between PID types and GI manifestations. RESULTS: The cohort comprised 101 patients, with 46% presenting with GI symptoms, including malnutrition and chronic diarrhea, as the most common findings. Primary antibody deficiency (PAD) emerged as the most prevalent PID with GI involvement, followed by combined immunodeficiencies (CID) with associated or syndromic features. Endoscopic evaluations revealed inflammatory bowel disease (IBD)-like colitis in a significant subgroup of patients. The analysis showed that some GI symptoms were more common in specific PID categories, highlighting the importance of early gastroenterological assessment in PID patients. CONCLUSION: Recognition of common GI symptoms in pediatric patients with PIDs may facilitate early diagnosis and prompt multidisciplinary management, potentially improving patient outcomes. The study highlights the necessity of considering PIDs in diagnosing persistent or severe GI symptoms in children.

The role of high-resolution impedance manometry to identify rumination syndrome in children with unexplained foregut symptoms.

OBJECTIVES: Diagnosis of rumination syndrome (RS) relies on Rome IV criteria. Oesophageal high-resolution impedance manometry (HRIM) can objectively demonstrate the episodes of rumination, but its role in the diagnostic pathway is not yet established. We aimed to demonstrate the clinical contribution of this tool for the timely diagnosis of RS and diagnostic work-up of children with unexplained foregut symptoms deemed to be due to other conditions. METHODS: HRIMs performed between 2012 and 2021 were searched to retrieve all diagnoses of RS. Medical records were reviewed for clinical data. RESULTS: Out of 461 HRIMs performed, 76 children had manometric diagnosis of RS (35 male, median age: 13 years). Of them, 47% were not clinically suspected as the symptoms did not fulfil clinical criteria for RS. The indications for HRIM in these cases were investigation of unexplained foregut symptoms (37%), suspected refractory gastroesophageal reflux disease (8%) and dysphagia (2%). Among all HRIMs performed for investigations of unexplained foregut symptoms (n = 80), 35% demonstrated rumination episodes. CONCLUSION: Identification of characteristic patterns of rumination on HRIM in children with unexplained foregut symptoms enables the immediate diagnosis of RS. Thus, in situations of diagnostic uncertainty, the use of HRIM at early stages of the diagnostic pathway would reduce unnecessary investigations and treatments.

Prediction of gastrointestinal symptoms trajectories using omega-3 and inflammatory biomarkers in early-stage breast cancer patients receiving chemotherapy.

PURPOSE: Gastrointestinal (GI) symptoms are common among breast cancer patients undergoing chemotherapy, negatively impacting treatment outcomes and quality of life. Evidence points to inflammatory processes as the underlying cause of chemotherapy-associated GI symptoms. Relatedly, omega-3 (n-3) has been linked to anti-inflammatory processes. The primary objective of this study was to examine the associations between baseline n-3, baseline inflammatory markers and GI symptom progression in early-stage breast cancer patients receiving chemotherapy. METHODS: In this secondary analysis of a prospective cohort study, we analyzed baseline levels of inflammatory biomarkers (measured using a Luminex bead-immunoassay) and plasma levels of DHA, EPA, and FFA (measured using enzyme-linked immunosorbent assay). GI symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire in Cancer Patients (EORTC QLQ-C30) symptom scale scores at baseline (T1) and at least 6 weeks after, during chemotherapy (T2). Inferential statistics were used to analyze associations between the variables of interest. RESULTS: The analysis included 31 female breast cancer patients (mean age ± SD = 50.5 ± 8.8; 89.6% receiving anthracycline-based chemotherapy). Higher levels of docosahexaenoic acid (DHA) and interleukin-8 (IL-8) predicted increases in appetite loss. Similarly, higher IL-8 predicted worsened nausea and vomiting. CONCLUSION: Baseline IL-8 and DHA predicted GI symptom progression in early-stage breast cancer patients undergoing chemotherapy. Future studies are required to evaluate how therapeutic intervention targeting these biomarkers may mitigate gastrointestinal symptoms in cancer patients.

Development and validation of the Gastrointestinal Symptom Severity Scale in Spanish children and adolescents.

Functional gastrointestinal disorders (FGIDs) are characterized by chronic or recurrent gastrointestinal symptoms (GS) that are not explained by structural or biochemical abnormalities. FGIDs are related to lower quality of life, increased demands on medical resources, and greater somatization and emotional instability. Furthermore, GS appears to be an indicator of dysbiosis in gut-microbiota, affecting the gut-microbiota-brain relationship. To develop and evaluate the psychometric properties of a new instrument called the Gastrointestinal Symptom Severity Scale (GSSS) using a web-based survey in a sample of neurotypical children and adolescents from Spain. Instrument development and validation processes were applied to the GSSS following its administration as part of an online survey. The sample included 1242 neurotypical children and adolescents. The mean age of participants was 13.95 years, with a standard deviation of 1.37 years. Overall, 13.8% suffered infectious diarrhea, 12.6% suffered abdominal pain, 5% suffered dyspepsia and 2.6% suffered gastro-esophageal reflux. A single-factor model produced good fit indices. Furthermore, internal consistency and test-retest reliability outcomes were acceptable. The GSSS was found to have acceptable metric measurement invariance. Significant correlations with other instruments were produced and were of expected direction and magnitude, confirming scale validity for hypothesis testing.     Conclusions: The GSSS shows promising psychometric properties for assessing GS in neurotypical Spanish adolescents and children. What is Known: • To the best of our knowledge, instruments assessing the severity of gastrointestinal symptoms in children and adolescents are still too few. What is New: • The GSSS shows promising psychometric properties for assessing GS in neurotypical adolescents and children. The GSSS may help improve understanding of GS involvement in the gut-brain microbiota axis in children and adolescents.

Dietary intake and gastrointestinal symptoms are altered in children with Autism Spectrum Disorder: the relative contribution of autism-linked traits.

BACKGROUND: Dietary and gastrointestinal (GI) problems have been frequently reported in autism spectrum disorder (ASD). However, the relative contributions of autism-linked traits to dietary and GI problems in children with ASD are poorly understood. This study firstly compared the dietary intake and GI symptoms between children with ASD and typically developing children (TDC), and then quantified the relative contributions of autism-linked traits to dietary intake, and relative contributions of autism-linked traits and dietary intake to GI symptoms within the ASD group. METHODS: A sample of 121 children with ASD and 121 age-matched TDC were eligible for this study. The dietary intake indicators included food groups intakes, food variety, and diet quality. The autism-linked traits included ASD symptom severity, restricted repetitive behaviors (RRBs), sensory profiles, mealtime behaviors, and their subtypes. Linear mixed-effects models and mixed-effects logistic regression models were used to estimate the relative contributions. RESULTS: Children with ASD had poorer diets with fewer vegetables/fruits, less variety of food, a higher degree of inadequate/unbalanced dietary intake, and more severe constipation/total GI symptoms than age-matched TDC. Within the ASD group, compulsive behavior (a subtype of RRBs) and taste/smell sensitivity were the only traits associated with lower vegetables and fruit consumption, respectively. Self-injurious behavior (a subtype of RRBs) was the only contributing trait to less variety of food. Limited variety (a subtype of mealtime behavior problems) and ASD symptom severity were the primary and secondary contributors to inadequate dietary intake, respectively. ASD symptom severity and limited variety were the primary and secondary contributors to unbalanced dietary intake, respectively. Notably, unbalanced dietary intake was a significant independent factor associated with constipation/total GI symptoms, and autism-linked traits manifested no contributions. CONCLUSIONS: ASD symptom severity and unbalanced diets were the most important contributors to unbalanced dietary intake and GI symptoms, respectively. Our findings highlight that ASD symptom severity and unbalanced diets could provide the largest benefits for the dietary and GI problems of ASD if they were targeted for early detection and optimal treatment.

Food intolerance related to gastrointestinal symptoms amongst adults living with bile acid diarrhoea: A cross-sectional study.

BACKGROUND: The role of food in managing bile acid diarrhoea (BAD) is poorly understood. The present study explored the prevalence of food intolerance amongst adults with BAD. METHODS: The study comprised a cross-sectional survey of adults with BAD determined by the 75 selenium homotaurocholic acid test (SeHCAT) living in the UK. Participants anonymously completed an online questionnaire on 39 food items. Frequency of food in general affecting BAD symptoms, as well as frequencies of diarrhoea, abdominal pain, bloating, flatulence and consequential food avoidance after food item ingestion, were assessed. Food group avoidance was also assessed. RESULTS: There were 434 participants who completed the questionnaire between April and May 2021 of whom 80% reported moderate to severe chronic diarrhoea. Food intolerances were reported by 88.0% (95% confidence interval [CI] = 84.6-90.9) of participants. Diarrhoea was reported most frequently after take-away food, fish and chips, creamy sauces, cream and large quantities of fruit (range 41.0%-33.6%). Lowest frequencies were for potato, avocado, mango, watermelon and pear (range 3.7%-7.4%) for the foods listed in the questionnaire. Similar trends were found for abdominal pain, bloating, flatulence and consequential food avoidance. Symptom-triggering within 30 min of ingestion was more prevalence than after 30 min for almost all foods. Food group avoidance was highest for fatty foods (81.2%; 95% CI = 77.8-85.3) followed by dairy (53.9%; 95% CI = 49.1-58.7). CONCLUSIONS: Perceived food intolerance amongst adults with BAD and persisting diarrhoeal symptoms is high. Important triggers were meals with a higher fat content and higher-fat dairy products. Diets amongst those with persisting diarrhoeal symptoms may be overly restrictive.

Cannabis-Induced Gastrointestinal Tract Symptoms in the Adult Population: A Systematic Review.

OBJECTIVE: Cannabinoid usage is widespread in the self-management of various medical ailments. However, adverse effects have been reported with use, especially pertaining to the gastrointestinal system in adults and aged patients. These range from nausea, vomiting, bloating, or abdominal pain. This systematic review of previously reported cannabis-induced gastrointestinal symptoms in the adult population from the literature provides an analysis of relevant data to enhance knowledge and awareness of this topic. METHODS: PubMed, Ovid MEDLINE, Cochrane Central, EMBASE, and Google Scholar databases were searched for relevant studies published from inception to March 2023. RESULTS: The search yielded 598 results, of which 13 were deemed relevant and underwent further review. These included two systematic reviews, one retrospective cohort study, one retrospective chart review, two cross-sectional studies, one survey, and six case reports. The Cochrane Risk Tool for bias analysis was applied where relevant. The total number of people in the studies selected for analysis was 79, 779. Twelve out of the thirteen included studies reported some type of gastrointestinal tract symptoms experienced in medical and/or recreational cannabis users ranging from nausea, vomiting, diarrhoea, abdominal pain to adult intussusception. CONCLUSION: Potential limitations include small sample sizes, variation in research methodologies, varied studied designs, and limited availability of data on specific populations such as geriatric users. Further research is warranted to add to current evidence pertaining to this emerging topic of significance, fill the broad knowledge gaps and contribute to evidence-based guidelines for healthcare professionals, ensuring safe prescribing practices and provision of quality care.

Clinical outcomes among young patients with Fabry disease who initiated agalsidase beta treatment before 30 years of age: An analysis from the Fabry Registry.

BACKGROUND: Clinical manifestations of classic Fabry disease (α-galactosidase A deficiency) usually occur in childhood, while complications involving major organs typically develop in adulthood. Outcomes of Fabry-specific treatment among young patients have not been extensively reported. Our aim was to analyze clinical outcomes among patients aged 5-30 years at initiation of treatment with agalsidase beta using data from the Fabry Registry (NCT00196742, sponsor: Sanofi). METHODS: Reported GLA variants were predicted to be associated with the classic phenotype or not classified in fabry-database.org. Linear mixed models were conducted to assess changes over ≥2-year follow-up in the estimated glomerular filtration rate (eGFR) stratified by low (LRI) and high (HRI) renal involvement (defined by proteinuria/albuminuria levels), and changes in interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) Z-scores stratified by median age at first treatment. Self-reports ('yes'/'no') of abdominal pain, diarrhea, chronic peripheral pain (denoting neuropathic pain), and acute pain crises at baseline were compared with reports after ≥0.5-year and ≥2.5-year follow-up using McNemar's test. RESULTS: Male (n = 117) and female patients (n = 59) with LRI initiated treatment at a median age of 19.9 and 23.6 years, respectively, and were followed for a median of 6.3 and 5.0 years, respectively. The eGFR slopes were -1.18 (Pfrom 0 <0.001) and -0.92 mL/min/1.73 m2/year (Pfrom 0 = 0.040), respectively. Males with HRI (n = 23, median UPCR 1.0 g/g), who started treatment at a median age of 26.7 years, had an eGFR slope of -2.39 mL/min/1.73 m2/year (Pfrom 0 <0.001; Pdifference = 0.055, as compared with the slope of -1.18 mL/min/1.73 m2/year for LRI males) during a median follow-up of 5.6 years. Echocardiographic variables were stable among males, regardless of age, and among young females (median follow-up >5.5 years and ≥4.5 years, respectively). Older females (treatment initiation at median age 27.5 years) had a slope of LVPWT Z-scores of 0.18/year (n = 12, Pfrom 0 = 0.028), whereas IVST Z-scores remained stable (n = 13, 0.10/year, Pfrom 0 = 0.304) during a median follow-up of ≥3.7 years. These slopes did not significantly differ from slopes of younger females. Reports of chronic peripheral pain and acute pain crises by males, and of diarrhea and acute pain crises by females, significantly reduced after a median follow-up of ≥4.0 years. After a median follow-up of ≥5.4 years, reports of all four symptoms significantly decreased among males, whereas among females only reports of abdominal pain significantly decreased. CONCLUSIONS: During sustained treatment with agalsidase beta in young Fabry patients with a predicted classic phenotype or with unclassified GLA variants with similar characteristics, the decline in eGFR was modest among male and female patients with LRI. The greater decline in eGFR among older, proteinuric (i.e., HRI) males may suggest a benefit of earlier treatment. Overall, echocardiographic variables remained stable, particularly among males and younger females. Significant reductions in symptom reports occurred primarily among males after longer follow-up and were less noticeable among females. These observed trends are suggestive of an overall improvement after treatment in young patients, but warrant larger longitudinal studies.

Helicobacter pylori infection and small intestinal bacterial overgrowth: a systematic review and meta-analysis.

BACKGROUND: There is a link between Helicobacter pylori (HP) infection and small intestinal bacterial overgrowth (SIBO) with nonspecific digestive symptoms. Nonetheless, whether HP infection is associated with SIBO in adults remains unclear. Based on a meta-analysis, we evaluated this relationship. RESULTS: Observational studies relevant to our research were identified by searching PubMed, Embase, the Cochrane Library, and the Web of Science. We evaluated between-study heterogeneity using the Cochrane Q test and estimated the I2 statistic. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used. Ten datasets from eight studies, including 874 patients, were involved in the meta-analysis. It was shown that HP infection was related to a higher odds of SIBO (odds ratio [OR]: 1.82, 95% confidence interval: 1.29 to 2.58, p < 0.001) with mild heterogeneity (p for Cochrane Q test = 0.11, I2 = 7%). Subgroup analyses showed that HP infection was related to SIBO in young patients (mean age < 48 years, OR: 2.68, 95% CI: 1.67 to 4.28, p < 0.001; I2 = 15%) but not in older patients (mean age ≥ 48 years, OR: 1.15, 95% CI: 0.69 to 1.92, p < 0.60; I2 = 1%; p for subgroup difference = 0.02). Subgroup analyses further indicated that the association was not significantly affected by the country of study, comorbidities, exposure to proton pump inhibitors, or methods of evaluating HP infection and SIBO. CONCLUSIONS: HP infection may be related to SIBO in adults, which supports the detection of SIBO in patients with digestive symptoms and HP infection.

Gastrointestinal Symptoms of Monkeypox Infection: A systematic review and meta-analysis.

Since early May 2022, outbreaks of Monkeypox (Mpox) cases have emerged and become a global concern. Studies exploring the gastrointestinal symptoms and/or liver injury of Mpox are still very limited. This systematic review and meta-analysis is the first to summarize the gastrointestinal symptoms reported by Mpox patients. We searched for Mpox studies published until October 21, 2022, in MEDLINE, EMBASE, SCOPUS, and organization websites. Mpox studies were observational studies that reported at least one of either gastrointestinal symptoms and/or liver injury in Mpox patients. Meta-analysis was done to obtain the pooled prevalence of gastrointestinal symptoms in Mpox patients. Subgroup analyses were done based on the study location, age groups, and Mpox Clades. The quality of included studies was assessed using the NIH Quality Assessment Tool. Overall, 31 studies that reported gastrointestinal symptoms and/or liver injury in Mpox patients were included. The reported gastrointestinal symptoms were abdominal pain, anorexia, diarrhea, nausea, and vomiting. There is a lack of reporting for liver injury. The most prevalent gastrointestinal symptoms in Mpox patients were anorexia (47%; 95% confidence interval [CI] 41%-53%), followed by vomiting (12%; 95% CI 11%-13%), nausea (10%; 95% CI 9%-11%), abdominal pain (9%; 95% CI 8%-10%), and diarrhea (5%; 95% CI 4%-6%). Additionally, the prevalence of proctitis, rectal/anal pain, and rectal bleeding were 11% (95% CI 11%-12%), 25% (95% CI 24%-27%), and 12% (95% CI 11%-13%), respectively. Anorexia was the most frequently reported gastrointestinal symptom in Mpox patients, followed by vomiting, nausea, abdominal pain, and diarrhea. Proctitis is a novel presentation of Mpox in the 2022 outbreak.

Gastrointestinal Symptoms After Resection of Esophagogastric Cancer: A Longitudinal Study on Their Incidence and Impact on Patient-Reported Outcomes.

BACKGROUND: This study assesses the incidence of gastrointestinal symptoms in the first year after resection of esophageal or gastric cancer and its association with health-related quality of life (HRQoL), functioning, work productivity, and daily activities. PATIENTS AND METHODS: Patients diagnosed with esophageal or gastric cancer between 2015 and 2021, who underwent a resection, and completed ≥ 2 questionnaires from the time intervals prior to resection and 0-3, 3-6, 6-9, and 9-12 months after resection were included. Multivariable generalized linear mixed models were used to assess changes in gastrointestinal symptoms over time and the impact of the number of gastrointestinal symptoms on HRQoL, functioning, work productivity, and daily activities for patients who underwent an esophagectomy or gastrectomy separately. RESULTS: The study population consisted of 961 (78.8%) and 259 (21.2%) patients who underwent an esophagectomy and gastrectomy, respectively. For both groups, the majority of gastrointestinal symptoms changed significantly over time. Most clinically relevant differences were observed 0-3 after resection compared with prior to resection and included increased diarrhea, appetite loss, and eating restrictions, and specifically after esophagectomy dry mouth, trouble with coughing, and trouble talking. At 9-12 after resection one or more severe gastrointestinal symptoms were reported by 38.9% after esophagectomy and 33.7% after gastrectomy. A higher number of gastrointestinal symptoms was associated with poorer functioning, lower HRQoL, higher impairment in daily activities, and lower work productivity. CONCLUSIONS: This study shows that gastrointestinal symptoms are frequently observed and burdensome after esophagectomy or gastrectomy, highlighting the importance to address these sequelae for high quality survivorship.

Ramadan intermittent fasting reduces visceral fat and improves gastrointestinal motility.

BACKGROUND: Ramadan is a model of intermittent fasting linked with possible beneficial effects. Scarce information, however, is available about the combined effects of Ramadan intermittent fasting (RIF) on anthropometric and metabolic indices, gastrointestinal symptoms, and motility. METHODS: In 21 healthy Muslims, we assessed the impact of RIF on caloric intake, physical activity, gastrointestinal symptoms and motility (gastric/gallbladder emptying by ultrasonography, orocaecal transit time by lactulose breath test), anthropometric indices, subcutaneous and visceral fat thickness (ultrasonography), glucose and lipid homeostasis. RESULTS: Mean caloric intake decreased from a median of 2069 kcal (range 1677-2641) before Ramadan to 1798 kcal (1289-3126) during Ramadan and increased again to 2000 kcal (1309-3485) after Ramadan. Although physical activity remained stable before, during, and after RIF, body weight, body mass index and waist circumference decreased in all subjects and in both genders, together with a significant decrease in subcutaneous and visceral fat thickness and insulin resistance. The postprandial gastric emptying speed was significantly faster after than before RIF. Fasting gallbladder volume was about 6% smaller after, than before Ramadan, with a stronger and faster postprandial gallbladder contraction. After RIF, lactulose breath test documented increased microbiota carbohydrate fermentation (postprandial H2 peak), and faster orocaecal transit time. RIF also significantly improved gastric fullness, epigastric pain and heartburn. CONCLUSIONS: RIF generates, in healthy subjects, multiple systemic beneficial effects in terms of fat burden, metabolic profile, gastrointestinal motility and symptoms. Further comprehensive studies should assess the potential beneficial effects of RIF in diseased people.