Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-analysis.

BACKGROUND & AIMS: Some brain-gut behavioral treatments (BGBTs) are beneficial for global symptoms in irritable bowel syndrome (IBS). United States management guidelines suggest their use in patients with persistent abdominal pain, but their specific effect on this symptom has not been assessed systematically. METHODS: We searched the literature through December 16, 2023, for randomized controlled trials (RCTs) assessing efficacy of BGBTs for adults with IBS, compared with each other or a control intervention. Trials provided an assessment of abdominal pain resolution or improvement at treatment completion. We extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures and reporting pooled relative risks (RRs) of abdominal pain not improving with 95% confidence intervals (CIs), ranking therapies according to the P score. RESULTS: We identified 42 eligible randomized controlled trials comprising 5220 participants. After treatment completion, the BGBTs with the largest numbers of trials and patients recruited demonstrating efficacy for abdominal pain, specifically, included self-guided/minimal contact cognitive behavioral therapy (CBT) (RR, 0.71; 95% CI, 0.54-0.95; P score, 0.58), face-to-face multicomponent behavioral therapy (RR, 0.72; 95% CI, 0.54-0.97; P score, 0.56), and face-to-face gut-directed hypnotherapy (RR, 0.77; 95% CI, 0.61-0.96; P score, 0.49). Among trials recruiting only patients with refractory global IBS symptoms, group CBT was more efficacious than routine care for abdominal pain, but no other significant differences were detected. No trials were low risk of bias across all domains, and there was evidence of funnel plot asymmetry. CONCLUSIONS: Several BGBTs, including self-guided/minimal contact CBT, face-to-face multicomponent behavioral therapy, and face-to-face gut-directed hypnotherapy may be efficacious for abdominal pain in IBS, although none was superior to another.

Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments.

Chronic visceral pain is one of the most common reasons for patients with gastrointestinal disorders, such as inflammatory bowel disease or disorders of brain-gut interaction, to seek medical attention. It represents a substantial burden to patients and is associated with anxiety, depression, reductions in quality of life, and impaired social functioning, as well as increased direct and indirect health care costs to society. Unfortunately, the diagnosis and treatment of chronic visceral pain is difficult, in part because our understanding of the underlying pathophysiologic basis is incomplete. In this review, we highlight recent advances in peripheral pain signaling and specific physiologic and pathophysiologic preclinical mechanisms that result in the sensitization of peripheral pain pathways. We focus on preclinical mechanisms that have been translated into treatment approaches and summarize the current evidence base for directing treatment toward these mechanisms of chronic visceral pain derived from clinical trials. The effective management of chronic visceral pain remains of critical importance for the quality of life of suffers. A deeper understanding of peripheral pain mechanisms is necessary and may provide the basis for novel therapeutic interventions.

Sex-Dependent Efficacy of Dietary Fiber in Pediatric Functional Abdominal Pain.

BACKGROUND & AIMS: Functional abdominal pain disorders (FAPDs) are more prevalent in female patients. Dietary fiber may alleviate FAPD symptoms; however, whether this effect is sex dependent remains unclear. We investigated the sex dependency of dietary fiber benefit on abdominal pain in children with FAPDs and explored the potential involvement of the gut microbiome. METHODS: In 2 cross-sectional cohorts of children with FAPDs (n = 209) and healthy control individuals (n = 105), we correlated dietary fiber intake with abdominal pain symptoms after stratifying by sex. We also performed sex-stratified and sex-interaction analyses on data from a double-blind trial in children with irritable bowel syndrome randomized to psyllium fiber (n = 39) or placebo (n = 49) for 6 weeks. Shotgun metagenomics was used to investigate gut microbiome community changes potentially linking dietary fiber intake with abdominal pain. RESULTS: In the cross-sectional cohorts, fiber intake inversely correlated with pain symptoms in boys (pain episodes: r = -0.24, P = .005; pain days: r = -0.24, P = 0.004) but not in girls. Similarly, in the randomized trial, psyllium fiber reduced the number of pain episodes in boys (P = .012) but not in girls. Generalized linear regression models confirmed that boys treated with psyllium fiber had greater reduction in pain episodes than girls (P = .007 for fiber × sex × time interaction). Age, sexual development, irritable bowel syndrome subtype, stool form, and microbiome composition were not significant determinants in the dietary fiber effects on pain reduction. CONCLUSIONS: Dietary fiber preferentially reduces abdominal pain frequency in boys, highlighting the importance of considering sex in future dietary intervention studies for FAPDs. (ClincialTrials.gov, Number NCT00526903).

Treatment of non-constipated irritable bowel syndrome with the histamine 1 receptor antagonist ebastine: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: We evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study. METHODS: Non-constipated patients with IBS fulfilling the Rome III criteria were randomly assigned to 20 mg ebastine or placebo for 12 weeks. Subjects scored global relief of symptoms (GRS) and abdominal pain intensity (API). A subject was considered a weekly responder for GRS if total or obvious relief was reported and a responder for API if the weekly average pain score was reduced by at least 30% vs baseline. The primary endpoints were the proportion of subjects who were weekly responders for at least 6 out of the 12 treatment weeks for both GRS and API ('GRS+API', composite endpoint) and for GRS and API separately. RESULTS: 202 participants (32±11 years, 68% female) were randomly allocated to receive ebastine (n=101) or placebo (n=101). Treatment with ebastine resulted in significantly more responders (12%, 12/92) for GRS+API compared with placebo (4%, 4/87, p=0.047) while the proportion of responders for GRS and API separately was higher for ebastine compared with placebo, although not statistically significant (placebo vs ebastine, GRS: 7% (6/87) vs 15% (14/91), p=0.072; API: 25% (20/85) vs 37% (34/92), p=0.081). CONCLUSIONS: Our study shows that ebastine is superior to placebo and should be further evaluated as novel treatment for patients with non-constipated IBS. TRIAL REGISTRATION NUMBER: The study protocol was approved by the local ethics committee of each study site (EudraCT number: 2013-001199-39; ClinicalTrials.gov identifier: NCT01908465).

Expression and function of transient receptor potential melastatin 3 in the spinal afferent innervation of the mouse colon.

Abdominal pain is a cardinal symptom of inflammatory bowel disease (IBD). Transient receptor potential (TRP) channels contribute to abdominal pain in preclinical models of IBD, and TRP melastatin 3 (TRPM3) has recently been implicated in inflammatory bladder and joint pain in rodents. We hypothesized that TRPM3 is involved in colonic sensation and is sensitized during colitis. We used immunohistochemistry, ratiometric Ca2+ imaging, and colonic afferent nerve recordings in mice to evaluate TRPM3 protein expression in colon-projecting dorsal root ganglion (DRG) neurons, as well as functional activity in DRG neurons and colonic afferent nerves. Colitis was induced using dextran sulfate sodium (DSS) in drinking water. TRPM3 protein expression was observed in 76% of colon-projecting DRG neurons and was often colocalized with calcitonin gene-related peptide. The magnitudes of intracellular Ca2+ transients in DRG neurons in response to the TRPM3 agonists CIM-0216 and pregnenolone sulfate sodium were significantly greater in neurons from mice with colitis compared with controls. In addition, the percentage of DRG neurons from mice with colitis that responded to CIM-0216 was significantly increased. CIM-0216 also increased the firing rate of colonic afferent nerves from control and mice with colitis. The TRPM3 inhibitor isosakuranetin inhibited the mechanosensitive response to distension of wide dynamic range afferent nerve units from mice with colitis but had no effect in control mice. Thus, TRPM3 contributes to colonic sensory transduction and may be a potential target for treating pain in IBD.NEW & NOTEWORTHY This is the first study to characterize TRPM3 protein expression and function in colon-projecting DRG neurons. A TRPM3 agonist excited DRG neurons and colonic afferent nerves from healthy mice. TRPM3 agonist responses in DRG neurons were elevated during colitis. Inhibiting TRPM3 reduced the firing of wide dynamic range afferent nerves from mice with colitis but had no effect in control mice.

Animal models with characteristics of irritable bowel syndrome with diarrhea: current applications and future perspectives.

Irritable bowel syndrome with diarrhea (IBS-D) is a common intestinal condition that significantly impacts work efficiency and quality of life. The use of animal models is crucial for delving into the pathophysiology of IBS-D and exploring therapeutic options. However, a wide variety of animal models for IBS-D has been employed in previous studies, posing a considerable challenge for researchers in selecting a suitable model. In this review, conducted using the Web of Science database, we searched IBS-D-related research spanning from 2014 to 2023, described the differences in animal strains and modeling methods among various IBS-D features recapitulating models, summarized the frequency of model usage, pathogenesis, and pathological characteristics of these models, and discussed their current applications, limitations, and future perspectives. The objective is to offer theoretical guidance for future researchers, aiding them in choosing suitable animal models based on their experimental designs.

Efficacy of Probiotics in Irritable Bowel Syndrome: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Some probiotics may be beneficial in irritable bowel syndrome (IBS), but differences in species and strains used, as well as endpoints reported, have hampered attempts to make specific recommendations as to which should be preferred. We updated our previous meta-analysis examining this issue. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to March 2023). Randomized controlled trials (RCTs) recruiting adults with IBS, comparing probiotics with placebo were eligible. Dichotomous symptom data were pooled to obtain a relative risk of global symptoms, abdominal pain, or abdominal bloating or distension persisting after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized mean difference with a 95% CI. Adverse events data were also pooled. RESULTS: We identified 82 eligible trials, containing 10,332 patients. Only 24 RCTs were at low risk of bias across all domains. For global symptoms, there was moderate certainty in the evidence for a benefit of Escherichia strains, low certainty for Lactobacillus strains and Lactobacillus plantarum 299V, and very low certainty for combination probiotics, LacClean Gold S, Duolac 7s, and Bacillus strains. For abdominal pain, there was low certainty in the evidence for a benefit of Saccharomyces cerevisae I-3856 and Bifidobacterium strains, and very low certainty for combination probiotics, Lactobacillus, Saccharomyces, and Bacillus strains. For abdominal bloating or distension there was very low certainty in the evidence for a benefit of combination probiotics and Bacillus strains. The relative risk of experiencing any adverse event, in 55 trials, including more than 7000 patients, was not significantly higher with probiotics. CONCLUSIONS: Some combinations of probiotics or strains may be beneficial in IBS. However, certainty in the evidence for efficacy by GRADE criteria was low to very low across almost all of our analyses.

Catechol-O-Methyltransferase Loss Drives Cell-Specific Nociceptive Signaling via the Enteric Catechol-O-Methyltransferase/microRNA-155/Tumor Necrosis Factor α Axis.

BACKGROUND & AIMS: The etiology of abdominal pain in postinfectious, diarrhea-predominant irritable bowel syndrome (PI-IBS-D) is unknown, and few treatment options exist. Catechol-O-methyltransferase (COMT), an enzyme that inactivates and degrades biologically active catecholamines, plays an important role in numerous physiologic processes, including modulation of pain perception. Our objective was to determine the mechanism(s) of how decreased colonic COMT in PI-IBS-D patients contributes to the chronic abdominal pain phenotype after enteric infections. METHODS: Colon neurons, epithelial cells, and macrophages were procured with laser capture microdissection from PI-IBS-D patients to evaluate cell-specific colonic COMT, microRNA-155 (miR-155), and tumor necrosis factor (TNF) α expression levels compared to recovered patients (infection cleared: did not develop PI-IBS-D) and control individuals. COMT-/-, colon-specific COMT-/-, and miR-155-/- mice and human colonoids were used to model phenotypic expression of COMT in PI-IBS-D patients and to investigate signaling pathways linking abdominal pain. Citrobacter rodentium and trinitrobenzene sulfonic acid animal models were used to model postinflammatory changes seen in PI-IBS-D patients. RESULTS: Colonic COMT levels were significantly decreased and correlated with increased visual analog scale abdominal pain ratings in PI-IBS-D patients compared to recovered patients and control individuals. Colonic miR-155 and TNF-α were increased in PI-IBS-D patients with diminished colonic COMT. COMT-/- mice had significantly increased expression of miR-155 and TNF-α in both colon tissues and dorsal root ganglia. Introduction of cV1q antibody (anti-TNF-α) into mice reversed visceral hypersensitivity after C rodentium and trinitrobenzene sulfonic acid. CONCLUSIONS: Decreased colonic COMT in PI-IBS-D patients drives abdominal pain phenotypes via the COMT/miR-155/TNF-α axis. These important findings will allow new treatment paradigms and more targeted and personalized medicine approaches for gastrointestinal disorders after enteric infections.

Scoring System to Evaluate Risk of Nonoperative Management Failure in Children With Intussusception.

INTRODUCTION: Typical first-line management of children with intussusception is enema reduction; however, failure necessitates surgical intervention. The number of attempts varies by clinician, and predictors of failed nonoperative management are not routinely considered in practice. The purpose of this study is to create a scoring system that predicts risk of nonoperative failure and need for surgical intervention. METHODS: Children diagnosed with intussusception upon presentation to the emergency department of a tertiary children's hospital between 2019 and 2022 were retrospectively identified. Univariable logistic regression identified predictors of nonoperative failure used as starting covariates for multivariable logistic regression with final model determined by backwards elimination. Regression coefficients for final predictors were used to create the scoring system and optimal cut-points were delineated. RESULTS: We identified 143 instances of ultrasound-documented intussusception of which 28 (19.6%) required operative intervention. Predictors of failed nonoperative management included age ≥4 y (odds ratio [OR] 32.83, 95% confidence interval [CI]: 1.91-564.23), ≥1 failed enema reduction attempts (OR 189.53, 95% CI: 19.07-1884.11), presenting heart rate ≥128 (OR 3.38, 95% CI: 0.74-15.36), presenting systolic blood pressure ≥115 mmHg (OR 6.59, 95% CI: 0.93-46.66), and trapped fluid between intussuscepted loops on ultrasound (OR 17.54, 95% CI: 0.77-397.51). Employing these factors, a novel risk scoring system was developed (area under the curve 0.96, 95% CI: 0.93-0.99). Scores range from 0 to 8; ≤2 have low (1.1%), 3-4 moderate (50.0%), and ≥5 high (100%) failure risk. CONCLUSIONS: Using known risk factors for enema failure, we produced a risk scoring system with outstanding discriminate ability for children with intussusception necessitating surgical intervention. Prospective validation is warranted prior to clinical integration.

Adult vasovagal syncope with abdominal pain diagnosed by head-up tilt combined with transcranial doppler: a preliminary study.

BACKGROUND: Syncope is a common condition that increases the risk of injury and reduces the quality of life. Abdominal pain as a precursor to vasovagal syncope (VVS) in adults is rarely reported and is often misdiagnosed.​. METHODS: We present three adult patients with VVS and presyncopal abdominal pain diagnosed by synchronous multimodal detection (transcranial Doppler [TCD] with head-up tilt [HUT]) and discuss the relevant literature. RESULTS: Case 1: A 52-year-old man presented with recurrent decreased consciousness preceded by six months of abdominal pain. Physical examinations were unremarkable. Dynamic electrocardiography, echocardiography, head and neck computed tomography angiography, magnetic resonance imaging (MRI), and video electroencephalogram showed no abnormalities. Case 2: A 57-year-old woman presented with recurrent syncope for 30 + years, accompanied by abdominal pain. Physical examination, electroencephalography, and MRI showed no abnormalities. Echocardiography showed large right-to-left shunts. Case 3: A 30-year-old woman presented with recurrent syncope for 10 + years, with abdominal pain as a precursor. Physical examination, laboratory analysis, head computed tomography, electrocardiography, and echocardiography showed no abnormalities. Syncope secondary to abdominal pain was reproduced during HUT. Further, HUT revealed vasovagal syncope, and synchronous TCD showed decreased cerebral blood flow; the final diagnosis was VVS in all cases. CONCLUSIONS: Abdominal pain may be a precursor of VVS in adults, and our findings enrich the clinical phenotypic spectrum of VVS. Prompt recognition of syncopal precursors is important to prevent incidents and assist in treatment decision-making. Abdominal pain in VVS may be a sign of sympathetic overdrive. Synchronous multimodal detection can help in diagnosing VVS and understanding hemodynamic mechanisms.

A review of 17 cases of mesenteric panniculitis in Zhengzhou Ninth People's Hospital in China.

PURPOSE: Mesenteric panniculitis (MP) represents the uncommon, benign and chronic inflammatory disorder affecting the mesenteric adipose tissues. Its etiology, diagnosis and treatment remain unnoticed. Our report focused on shedding more lights on this condition. PATIENTS AND METHODS: Seventeen MP patients were identified by searching the electronic medical record system in the Zhengzhou Ninth People's Hospital using the search terms "Mesenteric panniculitis" from October 2015 to March 2023. All cases were diagnosed with MP through computed tomography (CT). Their clinical features and treatments were analyzed. RESULTS: There were altogether 17 cases enrolled for this analysis. The male to female ratio was 8:9, and the median age at diagnosis was 64 (range: 37-96) years. There were 15 patients (88.2%) showing abdominal pain to varying degrees. The proportions of symptoms of nausea, vomiting and fever were 23.5%, 23.5% and 41.2%, respectively. Neoplastic disease was present in 3 patients (17.6%). Meanwhile, 9 patients (52.9%) had gallstones, 3 (17.6%) had cholecystitis and 1 (5.9%) had gallbladder polyps. Six patients (35.3%) received antibiotics treatment only and 1 (5.9%) received oral antibiotics and prednisone. One patient (5.9%) received antibiotics followed by prednisone treatment, because the symptoms were significantly relieved after antibiotic treatment, while the disease recurred soon after, and the symptoms improved again after prednisone treatment. The abdominal pain in 9 patients (52.9%) was relieved spontaneously. Two patients (11.8%) died, including one due to respiratory failure caused by pneumonia and the other one because of pancreatic cancer with lung and liver metastases. CONCLUSION: MP is a poorly understood chronic inflammatory disease. Patients often have abdominal pain as the main symptom, accompanied by comorbidities in the gallbladder, and the prognosis is usually good after correct diagnosis and treatment, Therefore, the present report aims to promote the awareness among clinicians of patients with non-classic abdominal symptoms, so as to avoid misdiagnosis or missed diagnosis.

Effect of cognitive-behavior therapy for children with functional abdominal pain: a meta-analysis.

BACKGROUND: Cognitive-Behavior Therapy (CBT) is the validated non-pharmacological treatment for chronic pain in pediatric patients. While some suggested CBT were comparable to the usual care in reducing children's functional abdominal pain. This meta-analysis was designed to systematically review the literature for RCTs that investigated the efficacy of CBT in children with functional abdominal pain (FAP). METHODS: PubMed, Embase, and the Cochrane library were searched for papers published up to October 2022. Studies applying different CBT delivery methods (in-person, web-based, phone-based) were included in this meta-analysis to evaluate the comprehensive effectiveness of CBT compared with usual care. Weighted and standardized mean difference with the 95% confidence intervals were used for the synthesis of the results. Primary outcome was the decrease of functional disability inventory (FDI) and the secondary outcomes were the decrease of severity in pain intensity, depression, anxiety, gastrointestinal symptoms, and improvement in physical quality of life (QoL). RESULTS: A total of 10 RCTs with 1187 children were included in the final analysis. The results showed that CBT resulted in better effect in reducing functional disability inventory (SMD=-2.282, 95%CI: -4.537 to -0.027, P = 0.047), pain intensity (SMD=-0.594, 95%CI: -1.147 to -0.040, P = 0.036), and improving QoL (SMD = 14.097, 95%CI: 0.901 to 27.292, P = 0.036) compared with the control groups. Comparable effects were observed in the severity of depression (SMD=-0.493, 95%CI: -1.594 to 0.608, P = 0.380), anxiety (SMD=-0.062, 95%CI: -0.640 to 0.517, P = 0.835), and gastrointestinal symptoms (SMD=-1.096 95%CI: -2.243 to 0.050, P = 0.061) between CBT and usual treatment. CONCLUSIONS: We observed the differences in post-treatment FAP and pain intensity for children receiving CBT compared with children receiving treatment as usual. CBT in the setting of FAP demonstrates promising developments and highlights the need for future research.

The Adult Carbohydrate Perception Questionnaire Identifies Patients with Lactose or Fructose Intolerance Who Respond to Diet.

INTRODUCTION: There is no evidence that a positive breath test is a good predictor of the success of a carbohydrate-restricted diet. Our objective was to investigate whether patients in whom lactose intolerance (LIT) or fructose intolerance (FIT) is diagnosed by validated symptom measurement respond to diet. METHODS: Patients referred for evaluation of LIT or FIT underwent hydrogen/methane breath testing (malabsorption test) and symptom measurement with the adult Carbohydrate Perception Questionnaire (aCPQ, intolerance test) before and after 50 g lactose or 25 g fructose. Patients with a positive aCPQ received instructions on specific diets and supplements. Severity of abdominal pain, bloating, diarrhoea, flatulence, and nausea were measured using a visual analogue scale (VAS) before (VAS1, mm) and after (VAS2, mm) diet. The change in VAS for individual symptoms and overall symptoms after diet is expressed as deltaVAS (mm) and as change relative to VAS1 (%). RESULTS: Forty-one patients were included (23 LIT, 8 FIT, 10 LIT+FIT). Eight patients had negative breath tests (no malabsorption). After 2 months of diet, the overall VAS and the individual symptoms decreased (p < 0.001). Overall VAS1 and the VAS1 for individual symptoms correlated significantly with the decrease in deltaVAS (mm) after diet. Nineteen patients (46%) had total recovery, and additional 13 patients (32%) had improvement of >50%. Response to diet was independent of breath test results. CONCLUSION: This uncontrolled and unblinded study suggests that patients with carbohydrate intolerance diagnosed by aCPQ benefit significantly from diet, independent of the presence of malabsorption. Controlled studies are required to confirm these results in larger patient groups.

Histoplasmosis peritonitis in an immunocompetent patient: case report.

Histoplasmosis is a fungal infection most frequently seen in immunocompromised patients. It is endemic in Central and South America and in Africa. The infection is usually asymptomatic in a healthy individual. Extrapulmonary dissemination can be seen in immunocompromised hosts. Gastrointestinal manifestations frequently involve the terminal ileum and cecum, mimicking Crohn's disease or malignancy. We describe the case of a 36-year-old healthy man from Cameroon, living in Switzerland for 13 years and without any medical nor surgical history, who presented peritonitis not responding to antibiotics. CT-scan showed bowel obstruction and signs of peritonitis. We opted for an explorative laparoscopy, which was converted to laparotomy with extensive adhesiolysis. Diagnostic of histoplasmosis was confirmed by histology and PCR analysis on biopsy. To our knowledge, this is the first described case of peritonitis as main outcome of a disseminated histoplasmosis involving the peritoneum in an immunocompetent patient.

Assessment of dietary interventions including low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet as management for fructose intolerance.

OBJECTIVES: Abdominal pain remains one of the most common referral reasons to pediatric gastroenterology. Dietary intolerances are often considered but due to various factors are hardly pursued. We observed that diet review in large number of children with abdominal pain was high in sugary foods which led to food intolerance investigation and dietary intervention. METHODS: A retrospective review was conducted of patients presenting with abdominal pain, diarrhea, or vomiting and negative GI evaluation, who underwent fructose breath testing. Patients younger than 20 years old who were seen between June 1, 2018 and March 1, 2021 were included. Statistical analysis was performed in R. RESULTS: There were 110 pediatric patients during the study period who underwent fructose breath testing, with 31% male and 69% female. The average age was 12.14 ± 4.01 years, and the average BMI was 21.21 ± 6.12. Abdominal pain was the most common presenting symptom (74.5%) followed by diarrhea and vomiting. Seventy-seven patients (70%) had a positive fructose breath test and were diagnosed with dietary intolerance to fructose. The 56 (67.5%) of those patients experienced symptoms during the breath test. Forty-three patients improved with dietary intervention. Twenty-seven on low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet and 16 on other diets. CONCLUSIONS: Based on analysis of our cohort of children with abdominal pain and high incidence of fructose intolerance as well as improvement in symptoms, following dietary changes, this condition should be considered and treated. Further investigation is needed to improve diagnostic testing but also into understanding mechanisms behind symptom presentation in this population.

Clinical presentation and outcomes of Helicobacter heilmannii gastritis in children in the New England region of the United States.

OBJECTIVE: To describe the clinical, endoscopic, histologic, and treatment outcomes of Helicobacter heilmannii (H. heilmannii) associated gastritis in children in the New England region of the United States. METHODS: Retrospective study of children (1-18 years) with H. heilmannii identified on gastric mucosal biopsies from two pediatric centers over a 21-year period, January 2000-December 2021. Cases were identified by querying pathology databases at each institution. Demographic and clinical data were obtained from the medical record. Endoscopic and histologic findings were extracted from endoscopy and pathology reports, respectively. RESULTS: Thirty-eight children were diagnosed with H. heilmannii-associated gastritis during the study period. The mean age at diagnosis was 10.1 ± 5.3 years, and 25/38 (66%) cases were male. Abdominal pain (32%) and nausea with or without vomiting (26%) were the most common symptoms. Thirty-two children (84%) had endoscopic findings including gastric nodularity (55%) and erythema (26%). All children had histologic signs of chronic gastritis, including those with normal endoscopic exams. Antibiotic regimens used for treating Helicobacter pylori were frequently prescribed. Of the 17 children who underwent a follow-up endoscopy (range 2-68 months), 15 (88%) did not have H. heilmannii identified on gastric biopsies. CONCLUSION: H. heilmannii was an infrequent but potential cause of epigastric abdominal pain and nausea in our cohort of New England children. While morphologically distinct from H. pylori, the bacteria can result in similar endoscopic and histologic findings of nodularity and chronic gastritis, respectively. The rate of eradication, as assessed by histology following treatment with H. pylori therapies, was below the 90% recommended goal for antimicrobial therapies.

Safety and efficacy of linaclotide in children aged 7-17 years with irritable bowel syndrome with constipation.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for the treatment of children 6-17 years old with functional constipation. This study evaluated the safety and efficacy of various linaclotide doses in children 7-17 years old with irritable bowel syndrome with constipation (IBS-C). METHODS: In this 4-week, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study, children with IBS-C were randomized to once-daily placebo or linaclotide (Dose A: 18 or 36 µg, B: 36 or 72 µg, and C: 72 µg or 145 µg, or 290 µg); those aged 7-11 years in a 1:1:1:1 allocation based on weight (18 to <35 kg:18 µg, 36 µg, or 72 µg; or ≥35 kg: 36 µg, 72 µg, or 145 µg), and those aged 12-17 years in a 1:1:1:1:1 allocation (the higher option of Doses A-C or 290 µg). The primary efficacy endpoint was a change from baseline in 4-week overall spontaneous bowel movement (SBM) frequency rate over the treatment period. Adverse events and clinical laboratory measures were also assessed. RESULTS: Efficacy, safety, and tolerability were assessed in 101 patients. In the intent-to-treat population, numerical improvement was observed in overall SBM frequency rate with increasing linaclotide doses (A: 1.62, B: 1.52, and C: 2.30, 290 µg: 3.26) compared with placebo. The most reported treatment-emergent adverse events were diarrhea and pain, with most cases being mild and none being severe. CONCLUSIONS: Linaclotide was tolerated well in this pediatric population, showing numerical improvement in SBM frequency compared with placebo.

Role of peripheral and tissue eosinophils and eosinophil cationic protein in pediatric inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease (IBD), eosinophilic gastrointestinal disease (EGID), and functional abdominal pain disorder (FAPD) present with nonspecific gastrointestinal (GI) symptoms clinically and also have some similarities in pathogeneses associated with eosinophils. Therefore, we aimed to evaluate the role of eosinophils in IBD compared to EGID and FAPD by investigating eosinophils in peripheral blood and GI tissue and eosinophil cationic protein (ECP). METHODS: Pediatric patients with chronic GI symptoms who underwent endoscopic biopsies were enrolled. Complete blood cell counts, inflammatory markers, immunoglobulin E (IgE), serum ECP levels, and endoscopic and histopathologic findings were retrospectively reviewed. RESULTS: A total of 387 patients were included: 179 with EGID, 107 with IBDs, and 82 with FAPD. Peripheral absolute eosinophil count (AEC), total IgE, and serum ECP were significantly higher in both IBD and EGID than in FAPD (all p < 0.05). Statistically significant differences were noted among the three groups in tissue eosinophil counts in each segment of GI tract except for the esophagus (p < 0.05). Significant differences were observed in tissue eosinophil counts in the ascending, sigmoid colon, and rectum between EGID and IBD (p < 0.05). Peripheral and tissue eosinophils in the stomach and duodenum revealed positive correlation in both EGID and IBD (both p < 0.001). CONCLUSION: Elevated eosinophil-related markers, as well as increased tissue eosinophilic infiltration in the affected areas of the GI tract in both IBD and EGID compared to FAPD, suggest that eosinophils might play a common important role in the pathogeneses of both diseases.

Getting the BS out of Irritable Bowel Syndrome with Diarrhea (IBS-D): Let's Make a Diagnosis.

PURPOSE OF REVIEW: Irritable bowel syndrome with diarrhea (IBS-D) is diagnosed when chronic symptoms of abdominal pain accompany loose stools, and alarm features, such as fever, anemia, rectal bleeding, and weight loss are absent. This combination of symptoms makes structural disorders, such as inflammatory bowel disease or cancer, unlikely, but does not exclude other conditions that cause these symptoms. The question is whether making a "positive diagnosis" of IBS-D based on symptoms alone and instituting therapy based on that diagnosis still makes sense. RECENT FINDINGS: Clinical observations suggest that at least two-thirds of cases of IBS-D can be explained by three mechanisms: a) food intolerances (~ 30-40%), b) bile acid diarrhea (~ 20-30%), and c) disturbed microbial flora (~ 15-20%). Other conditions that are less frequent but can cause IBS symptoms or be confused with IBS include: celiac disease, microscopic colitis, mastocytosis/mast cell activation, and drug side-effects. Many cases of IBS-D have a discoverable, underlying cause that can direct therapy more efficiently.

Rising Prevalence of Mild Chronic Gastritis in Children: A Single Center Experience.

OBJECTIVES AND METHODS: We analyzed upper endoscopic and histological findings in 3 cohorts of children undergoing upper gastrointestinal endoscopy over a 10-year period. Five hundred seventy-nine patients were identified, with 244 (42%), 199 (35%), and 136 (23%) in the 2011, 2015, and 2019 cohorts, respectively. The most common symptoms and signs were abdominal pain, vomiting, failure to thrive, and diarrhea. RESULTS: The number of patients who had histological evidence of chronic gastritis increased from 2011 (n = 70, 29%) to 2015 (n = 106, 53%) and 2019 (n = 92, 68%; P < .001). The prevalence of "normal" endoscopic gastric findings was higher in controls (n = 247, 90%) compared to cases (n = 201, 76%; P < .001). There was a small but statistically significant difference in endoscopic esophageal grading (P = .008) over time, with lower grades being more prevalent in 2011 compared to 2015 (P = .026) and 2019 (P = .001). Crude comparisons of the predictors (sex, weight percentile, payor type, month of endoscopy, symptom duration, PPI exposure, and endoscopic stomach findings) yielded no difference between cases and controls. CONCLUSIONS: There has been a significant rise in the prevalence of mild chronic gastritis or non-specific gastritis over the last decade in our population.