Mechanical Skin Injury Promotes Food Anaphylaxis by Driving Intestinal Mast Cell Expansion.

Mast cell (MC) mediator release after crosslinking of surface-bound IgE antibody by ingested antigen underlies food allergy. However, IgE antibodies are not uniformly associated with food allergy, and intestinal MC load is an important determinant. Atopic dermatitis (AD), characterized by pruritis and cutaneous sensitization to allergens, including foods, is strongly associated with food allergy. Tape stripping mouse skin, a surrogate for scratching, caused expansion and activation of small intestinal MCs, increased intestinal permeability, and promoted food anaphylaxis in sensitized mice. Tape stripping caused keratinocytes to systemically release interleukin-33 (IL-33), which synergized with intestinal tuft-cell-derived IL-25 to drive the expansion and activation of intestinal type-2 innate lymphoid cells (ILC2s). These provided IL-4, which targeted MCs to expand in the intestine. Duodenal MCs were expanded in AD. In addition to promoting cutaneous sensitization to foods, scratching may promote food anaphylaxis in AD by expanding and activating intestinal MCs.

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.

Safety and efficacy of linaclotide in children aged 2-5 years with functional constipation: Phase 2, randomized study.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for the treatment of children 6-17 years of age with functional constipation (FC). This study evaluated the dose-response, safety, and efficacy of 4 weeks of linaclotide compared with placebo in children 2-5 years of age with FC. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, multidose study, 35 children with FC (based on Rome III criteria) were randomized 3:1 to receive linaclotide (18, 36, or 72 µg, for groups 1, 2, and 3, respectively) and 5:1 to receive linaclotide 9, 18, 36, or 72 µg (group 4), or matching placebo. Key endpoints were the changes from baseline in overall spontaneous bowel movement (SBM) frequency (SBMs/week), stool consistency, and straining, as well as the proportion of days with fecal incontinence during the study intervention period. Adverse events (AEs) were recorded. RESULTS: Of the randomized patients, 34 (97.1%) completed the treatment period and 33 (94.3%) completed the posttreatment period. Mean change from baseline over the treatment period for three of the four key efficacy endpoints showed greater improvement in the linaclotide 72 µg group versus placebo. A dose-response trend was seen for stool consistency in patients receiving linaclotide. Four patients randomized to linaclotide experienced treatment-emergent AEs, one of which was treatment-related (mild diarrhea). All AEs were mild or moderate and none were severe. CONCLUSIONS: Linaclotide was well tolerated in this pediatric population and an efficacy trend was seen with linaclotide 72 µg versus placebo.

Randomized controlled trial of linaclotide in children aged 6-17 years with functional constipation.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for treatment of children 6-17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6-17 years old with FC. METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 2 study, 173 children with FC (based on Rome III criteria) were randomized to once-daily linaclotide (A: 9 or 18 µg, B: 18 or 36 µg, or C: 36 or 72 µg) or placebo in a 1:1:1:1 ratio for 6- to 11-year-olds (dosage determined by weight: 18 to <35 or ≥35 kg) and linaclotide (18, 36, 72, or 145 µg) or placebo in a 1:1:1:1:1 ratio for 12- to 17-year-olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4-week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored. RESULTS: Efficacy and safety were assessed in 173 patients (52.0% aged 6-11 years; 48.0% aged 12-17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBM frequency was observed with increasing linaclotide doses (1.90 in 6- to 11-year-olds [36 or 72 µg] and 2.86 in 12- to 17-year-olds [72 µg]). The most reported treatment-emergent AE was diarrhea, with most cases being mild; none were severe. CONCLUSIONS: Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation.

A multicenter registry study on percutaneous electrical nerve field stimulation for pediatric disorders of gut-brain interaction.

OBJECTIVES: Percutaneous electrical nerve field stimulation (PENFS) has demonstrated promise in single-center trials for pediatric abdominal pain-related disorders of gut-brain interaction (DGBI). Our aim was to explore efficacy of PENFS as standard therapy for DGBI in a registry involving multiple pediatric gastroenterology referral centers. METHODS: This was a multicenter, prospective open-label registry of children (8-18 years) undergoing PENFS for DGBI at seven tertiary care gastroenterology clinics. DGBI subtypes were classified by Rome IV criteria. Parents and patients completed Abdominal Pain Index (API), Nausea Severity Scale (NSS), and Functional Disability Inventory (FDI) questionnaires before, during therapy and at follow-up visits up to 1 year later. RESULTS: A total of 292 subjects were included. Majority (74%) were female with median (interquartile range [IQR]) age 16.3 (14.0, 17.7) years. Most (68%) met criteria for functional dyspepsia and 61% had failed ≥4 pharmacologic therapies. API, NSS, and FDI scores showed significant declines within 3 weeks of therapy, persisting long-term in a subset. Baseline (n = 288) median (IQR) child-reported API scores decreased from 2.68 (1.84, 3.58) to 1.99 (1.13, 3.27) at 3 weeks (p < 0.001) and 1.81 (0.85, 3.20) at 3 months (n = 75; p < 0.001). NSS scores similarly improved from baseline, persisting at three (n = 74; p < 0.001) and 6 months later (n = 55; p < 0.001). FDI scores displayed similar reductions at 3 months (n = 76; p = 0.01) but not beyond. Parent-reported scores were consistent with child reports. CONCLUSIONS: This large, comprehensive, multicenter registry highlights efficacy of PENFS for gastrointestinal symptoms and functionality for pediatric DGBI.

Impact of Coronavirus disease 2019 pandemic in children with functional abdominal pain disorders: Data from long-term follow-up.

OBJECTIVE: We aimed to compare symptom frequency and severity in children with functional abdominal pain disorders (FAPDs) and to evaluate anxiety, quality of life (QoL) and global health during Coronavirus disease 2019 (COVID-19) related quarantine and after 17 months. METHODS: Children diagnosed with FAPDs between October 2019 and February 2020 at 5 different centers were enrolled and prospectively interviewed during the COVID-19 quarantine and 17 months later when schools, hospital services, and routine activities had re-opened to the public. The patients were asked to complete the Rome IV questionnaire, the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) Generic Core Scale, the Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and global health questionnaires. Data about COVID-19 infection and its clinical outcome were also collected. RESULTS: Ninety-nine out of 180 (55%) children completed the follow-up. The number of patients reporting a worsening of their symptoms was significantly higher at follow-up when compared to the quarantine period (24/99 [24.2%] vs. 12/99 [12.1%]; p = 0.04). The PedsQL 4.0 subtotal score at follow-up significantly decreased at 17 months of follow-up (65.57 [0-100]) when compared to the quarantine (71 [0-100], p = 0.03). Emotional functioning was the most significantly reduced (Follow-up: 64.7 [0-100] vs. Quarantine: 75 [0-100]; p = 0.006). We did not identify significant differences in symptoms and QoL between COVID-19 infected children and the remaining cohort at the two time points. CONCLUSIONS: An improvement of symptoms and QoL was observed during the quarantine, followed by a worsening at-follow-up. These findings reinforce the hypothesis that the nest effect overweighted COVID-19 fears during the quarantine and highlight the importance of psychological factors in symptom exacerbation.

Airway Impedance: A Novel Diagnostic Tool to Predict Extraesophageal Airway Inflammation.

OBJECTIVE: To validate a novel biomarker, airway impedance for extraesophageal disease. STUDY DESIGN: We prospectively recruited patients with respiratory symptoms undergoing combined endoscopy and direct laryngoscopy for the evaluation of symptoms. The direct laryngoscopy was performed and videotaped for blinded scoring by 3 otolaryngologists and an impedance catheter was placed onto the posterior larynx to obtain measurements. Following this, an endoscopy was performed and impedance measurements and biopsies were taken at 3 esophageal heights. Impedance values were compared within and between patients. RESULTS: Eighty-eight patients were recruited, of which 73 had complete airway and endoscopic exams. There was no significant correlation between airway impedance values and mean reflux finding scores (r2 = 0.45, P = .07). There was no significant positive correlation between airway impedance and esophageal impedance values (r2 = 0.097-0.138, P > .2). Patients taking proton pump inhibitors had significantly lower mean airway impedance values (706 ± 450 Ω) than patients not taking them (1069 ± 809 Ω, P = .06). Patients who had evidence of aspiration on video fluoroscopic swallow studies had lower airway impedance (871 ± 615 Ω) than patients without aspiration (1247 ± 360 Ω, P = .008). Inhaled steroids did not impact airway impedance levels (P = .7). CONCLUSIONS: Airway impedance may be an important diagnostic tool to diagnose gastroesophageal reflux or aspiration, eliminating the subjectivity of airway appearance alone.

Clinical Utility of Ileal Motility in Children With Defecation Disorders and Children With Chronic Intestinal Pseudo-Obstruction.

BACKGROUND: Little is known about ileal motility patterns and their utility in children. Here, we present our experience with children undergoing ileal manometry (IM). METHODS: A retrospective review of children with ileostomy comparing IM between 2 groups: A [chronic intestinal pseudo-obstruction (CIPO)] and B (feasibility of ileostomy closure in children with defecation disorders). We also compared the IM findings with those from antroduodenal manometry (ADM), and evaluated the joint effect of age, sex, and study indication group on IM results. RESULTS: A total of 27 children (median age 5.8 years old, range 0.5-16.74 years, 16 were female) were included (12 in group A and 15 in group B). There was no association between IM interpretation and sex; however younger age was associated with abnormal IM ( P = 0.021). We found a significantly higher proportion of patients with presence of phase III of the migrating motor complex (MMC) during fasting and normal postprandial response in group B than in group A ( P < 0.001). Logistic regression analysis revealed that only Group B was associated with normal IM ( P < 0.001). We found a moderate agreement for the presence of phase III MMC and postprandial response between IM and ADM (kappa = 0.698, P = 0.008 and kappa = 0.683, P = 0.009, respectively). CONCLUSION: IM is abnormal in patients with CIPO and normal in patients with defecation disorders, suggesting that IM may be not needed for ostomy closure in those with defecation disorders. IM has a moderate agreement with ADM and could be used as a surrogate for small bowel motility.

Award Recipients for Pediatric Gastroenterology: A Descriptive Analysis of Gender Distribution.

Society awards are an important component of recognition in medicine and for career advancement such as promotion. Multiple studies conducted in pediatrics and gastroenterology have shown underrepresentation of women awardees even in fields with a higher proportion of women than men. To our knowledge, no such studies have been conducted in pediatric gastroenterology. We hypothesized that among all recipients, women would be underrepresented when compared to men and that women were more likely to be given teaching awards compared to other career achievement awards. We collected data on recipients of major recognition award presented by The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition from 1987 to 2022. We found that 80.90% of the awards had been given to men and that most nominators were men. This study highlights inequities in women recipients for major awards and presents an opportunity for a call for action to examine and address the factors contributing to this gender inequity.

The Clinical Utility of Antroduodenal Manometry in the Evaluation of Children with Upper Gastrointestinal Symptoms.

OBJECTIVES: Antroduodenal manometry (ADM) measures antral and small bowel motility and is clinically used to evaluate upper gastrointestinal (UGI) symptoms. We aimed to evaluate its utility in guiding treatment, predicting response, and association with clinical findings. METHODS: Retrospective review of 200 children undergoing ADM. ADM interpretation and parameters were compared to outcomes (response to first therapy after ADM and overall response), predominant symptom (group A, abdominal distention and/or vomiting and group B, abdominal pain and/or nausea), etiology (idiopathic or with known comorbidity), and ADM indication [suspected chronic intestinal pseudo-obstruction (CIPO) or unexplained UGI symptoms]. RESULTS: We found an association between a normal intestinal phase III of the migrating motor complex (MMC) and idiopathic etiology, group B symptoms and unexplained UGI symptoms. No variable was associated with initial successful response. However, normal small bowel phase III of the MMC and idiopathic etiology were associated with overall successful response to treatment (including feeding tolerance and weaning of parenteral nutrition). No antral ADM parameter was associated with outcomes or other comparisons. The time to overall successful treatment response was significantly shorter in patients with a normal ADM and presence of a normal phase III of the MMC. CONCLUSIONS: The presence of the phase III of the MMC was the single ADM parameter predictive of overall treatment response, also associated to group B symptoms and idiopathic etiology. Our findings suggest that small bowel ADM parameters are more useful to predict outcomes and ADM should be performed primarily in patients presenting with abdominal distention and/or vomiting and those being evaluated for CIPO.

A Review of the Evidence and Recommendations on Communication Skills and the Patient-Provider Relationship: A Rome Foundation Working Team Report.

BACKGROUND & AIMS: Over several decades, changes in health care have negatively impacted meaningful communication between the patient and provider and adversely affected their relationship. Under increasing time pressure, physicians rely more on technology than face-to-face time gathering data to make clinical decisions. As a result, they find it more challenging to understand the illness context and fully address patient needs. Patients experience dissatisfaction and a diminution of their role in the care process. For patients with disorders of gut-brain interaction, stigma leads to greater care dissatisfaction, as there is no apparent structural basis to legitimize the symptoms. Recent evidence suggests that practical communication skills can improve the patient-provider relationship (PPR) and clinical outcomes, but these data are limited. METHODS: The Rome Foundation convened a multidisciplinary working team to review the scientific evidence with the following aims: a) to study the effect of communication skills on patient satisfaction and outcomes by performing an evidence-based review; b) to characterize the influence of sociocultural factors, health care system constraints, patient perspective, and telehealth on the PPR; c) to review the measurement and impact of communication skills training on these outcomes; and d) to make recommendations to improve communication skills training and the PPR. RESULTS: Evidence supports the fact that interventions targeting patient-provider interactions improve population health, patient and provider experience, and costs. Communication skills training leads to improved patient satisfaction and outcomes. The following are relevant factors to consider in establishing an effective PPR: addressing health care system constraints; incorporating sociocultural factors and the role of gender, age, and chronic illness; and considering the changing role of telehealth on the PPR. CONCLUSIONS: We concluded that effective communication skills can improve the PPR and health outcomes. This is an achievable goal through training and system change. More research is needed to confirm these findings.

Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension.

BACKGROUND & AIMS: Pediatric functional constipation (PFC) is a common problem in children that causes distress and presents treatment challenges to health care professionals. We conducted a randomized, placebo-controlled trial (study 1) in patients with PFC (6-17 years of age) to evaluate the efficacy and safety of lubiprostone, followed by an open-label extension for those who completed the placebo-controlled phase (study 2). METHODS: Study 1 (NCT02042183) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 12-week study evaluating the efficacy and safety of lubiprostone 12 µg twice daily (BID) and 24 µg BID. Study 2 (NCT02138136) was a phase 3, long-term, open-label extension of study 1. In both studies, lubiprostone doses were based on patients' weight. Efficacy was assessed solely based on study 1, with a primary endpoint of overall spontaneous bowel movement (SBM) response (increase of ≥1 SBM/wk vs baseline and ≥3 SBMs/wk for ≥9 weeks, including 3 of the final 4 weeks). RESULTS: 606 patients were randomized to treatment (placebo: n = 202; lubiprostone: n = 404) in study 1. No statistically significant difference in overall SBM response rate was observed between the lubiprostone and placebo groups (18.5% vs 14.4%; P = .2245). Both the 12-µg BID and 24-µg BID doses of lubiprostone were well tolerated in the double-blind and extension phases, with a safety profile consistent with that seen in adult studies. CONCLUSIONS: Lubiprostone did not demonstrate statistically significant effectiveness over placebo in children and adolescents with PFC but did demonstrate a safety profile similar to that in adults. (ClinicalTrials.gov: Number: NCT02042183; Number: NCT02138136).

Pediatric Aspects of Nutrition Interventions for Disorders of Gut-Brain Interaction.

Dietary factors may play an important role in the generation of symptoms in children with disorders of gut-brain interaction (DGBIs). Although dietary modification may provide successful treatment, there is a relative paucity of controlled trials that have shown the effectiveness of dietary interventions. This study is a narrative review that explores the existing literature on food and pediatric DGBIs. The following have been shown to be beneficial: (i) in infants with colic, removing cow's milk from the infant's diet or from the maternal diet in those who are breastfed; (ii) in infants with regurgitation, adding thickeners to the formula or removing cow's milk protein from the infant's diet or the maternal diet in those who are breastfed; and (iii) in children with pain-predominant DGBIs, using soluble fiber supplementation or a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet. In children with functional constipation, there is no evidence that adding fiber is beneficial. Given that most dietary interventions include restriction of different foods in children, a thoughtful approach and close follow-up are needed.

Impact of Coronavirus Disease 2019 on the Pediatric Population with Aerodigestive Disease.

OBJECTIVE: To determine the impact of the coronavirus disease 2019 (COVID-19) quarantine on baseline health, medication use, health anxiety, and healthcare use in pediatric patients with aerodigestive disease and to evaluate for associations of commonly prescribed medications with the risk of COVID-19 illness. STUDY DESIGN: Prospective study of patients presenting in person to pediatric neurogastroenterology clinics between July 2020 and March 2021. RESULTS: Of 202 recruited patients, 71.3% were seen in the aerodigestive diseases center and 28.7% in the functional abdominal pain (FAP)/motility clinic. Of all patients, 25.1% reported improved overall health during quarantine; patients with aerodigestive disease (35.3%) reported higher rates of improved overall health compared with patients with FAP/motility disorders (3.6%, P = .0001). Patients with aerodigestive disease had fewer airway symptoms (P < .05) and less medication use during quarantine (inhaled steroids, P < .05 and albuterol, P < .05). Despite objective improvement, there was significant health-related anxiety, with greater anxiety scores reported during and at the end of quarantine (P < .05), with no difference between patient groups (P > .11). Patients continued to access healthcare during quarantine. In total, 28.7% of patients were seen in the emergency department (patients with FAP more than patients with aerodigestive disease, P = .02), and 19.8% were hospitalized. COVID-19 testing was performed in 58.4% of patients and 2.0% (n = 4) of the entire cohort tested positive. CONCLUSIONS: Patients with aerodigestive disease show improvement of airway symptoms and decreased use of medications during the pandemic, despite increased health-related anxiety. Despite complexities of accessing care due to the widespread lockdown, all patient groups continued to access healthcare.

A Quality Improvement Initiative to Reduce Abdominal X-ray use in Pediatric Patients Presenting with Constipation.

OBJECTIVE: To decrease the percentage of patients undergoing an abdominal radiograph for evaluation of constipation within 24 hours of their initial gastroenterology visit. STUDY DESIGN: In January 2015, we implemented a quality improvement, evidence-based guideline (EBG) aimed at standardizing the initial assessment of patients presenting for a new outpatient gastroenterology visit with a primary complaint of constipation. Over the subsequent 5 years, we followed the clinical impact of this guideline initiation with the goal of decreasing unnecessary abdominal radiograph use by 10% within 1 year of EBG launch. Patients older than 6 months and younger than 19 years were included. RESULTS: In total, 6723 patients completed new patient gastroenterology visits for a primary diagnosis of constipation between 2013 and 2019. Of these, 993 (14.8%) patients had abdominal radiographs taken within 24 hours of their initial visit. Over the 7 years of this project, a mean frequency of abdominal radiograph use decreased from 24% to less than 11%. In addition, a 57% decrease in hospital charges related to decreased radiograph use for constipation was found. No increases in subsequent emergency department visits or hospitalization for constipation within 30 days of patients' initial visits were seen. CONCLUSIONS: Through local adoption of an EBG, routine use of abdominal radiographs taken during a patient's initial outpatient gastroenterology visit for constipation decreased by more than 50%. This reduction was maintained over a subsequent 5-year period without any detrimental side effects.

Can Propofol Be Used to Assess the Presence of the Rectoanal Inhibitory Reflex During Anorectal Manometry Studies?

OBJECTIVES: To study changes in intra-anal pressure (IAP) and characteristics of the rectoanal inhibitory reflex (RAIR) during anorectal manometry (ARM) in patients undergoing anesthesia induction with propofol. METHODS: Prospective study in which ARM was performed at baseline while patients were awake and repeated after propofol-induced anesthesia. We studied IAP and the presence and characteristics of the RAIR before and after propofol. RESULTS: A total of 27 patients were included (63% male; 9.2 years). Three patients had obstructive symptoms after Hirschsprung disease repair (HSCR), and 24 had intractable constipation. At baseline, the RAIR was present on 21 of 27 patients and absent on 6 of 27. Of the six patients with an absent RAIR, it remained absent in four of six (three known HSCR, and one new diagnosis of IAS achalasia), and two of six had a normal RAIR during propofol. Therefore, RAIR was present in all patients with constipation. The mean resting IAP was significantly lower after propofol. The percentage of IAS relaxation after lower balloon volume inflations was significantly higher during propofol (P < 0.05). No difference was observed over the latency time or the total relaxation time after propofol. CONCLUSIONS: Propofol can be used to assess the presence of the RAIR during ARM in children who are uncooperative and undergoing other procedures under anesthesia. On the other hand, propofol significantly reduces the resting IAP and increases the percentage of internal anal sphincter relaxation after balloon distention. These findings may impact the interpretation to decide if an intervention is needed, or if there is a possible spinal neuropathy.

Diverting Ileostomy in Children With Functional Constipation: A Study Evaluating the Utility of Colon Manometry.

OBJECTIVES: Pediatric functional constipation (FC) may require invasive evaluations [like colon manometry (CM)] and surgical interventions [including diverting ostomy (DO)]. We evaluated the utility of CM in guiding surgery after DO. METHODS: Children with medically refractory FC undergoing an ostomy were included. Institutional Review Board approval was obtained for this retrospective study. Demographics and CM variables [high amplitude propagating contractions (HAPCs)] were recorded. Outcome measures: response to ostomy closure defined as successful if no need for further surgery after ostomy closure, and improvement on baseline CM after ostomy. A CM-guided ostomy closure algorithm was developed based on previous studies. We evaluated the association between response to ostomy closure and demographics, ostomy indication and CM improvement, and evaluated the role of CM predicting response using algorithm. RESULTS: A total of 60 children underwent ostomy for FC (median age: 7.1 years, range 0.15-23.6 years, 50% female). Ostomy was closed in 30 patients and deemed successful in 23 of 30. CM was performed in 42 of 60 patients before ostomy and in 29 of 30 before ostomy closure. We found no association between ostomy outcome and age, gender, weight, imaging studies, follow-up time, time with ostomy, HAPCs, and CM improvement. We found an association between failed response and ostomy indication of antegrade colonic enemas (ACE) failure ( P = 0.026) and successful response when ostomy closure was guided by algorithm ( P = 0.03). CONCLUSIONS: DO is a useful intervention in selected children with medically refractory FC, improving colon motility in most. CM can successfully guide the timing and type of ostomy closure. Larger studies are needed to further validate our findings.

The Utility of Functional Luminal Imaging Probes Measurements to Diagnose Dysmotility and Their Relationship to Impaired Bolus Clearance.

BACKGROUND: Functional luminal imaging probes (FLIP) have been used by multiple centers to assess esophagogastric junction (EGJ) function in patients at risk for esophageal obstruction but its role in diagnosing peristaltic disorders is less well studied. In particular, there are no studies comparing the sensitivity of FLIP to diagnose motility abnormalities and impaired bolus transit by high-resolution esophageal manometry with impedance. METHODS: We prospectively recruited 42 patients undergoing high-resolution esophageal manometry with impedance (HRIM) who also underwent FLIP between 2018 and 2020. HRIM parameters were analyzed using Swallow Gateway software to determine peristaltic and lower esophageal sphincter pressure measurements as well as bolus flow parameters. FLIP tracings were analyzed for the presence of repetitive antegrade contractions (RACs), EGJ distensibility, and associated parameters. RESULTS: Forty-two patients were included (11 controls, 7 achalasia, 16 fundoplication, 8 dysmotility). The mean age of patients was 10.1 ±â€Š0.9 years. There were significant differences in bolus flow parameters across diagnosis with longer bolus presence (BPT) in control patients compared with fundoplication and dysmotility patients. There was a significant correlation between EGJ diameter, EGJ distensibility and bolus flow time (BFT) for solid foods (r2 > 0.518, P < 0.02). The presence of RACs and EGJ relaxation during RACs was associated with a greater BFT and BPT across textures (P < 0.05). Forty-two percentage of patients with absent RACs, however, had clear peristalsis by HRIM. CONCLUSIONS: The presence of RACs and EGJ relaxation by FLIP correlate with improved bolus flow. Patients with an absence of RACs need HRIM to confirm any diagnoses of dysmotility.

Melanosis Coli Is Not Associated with Colonic Dysmotility Nor Severity of Pediatric Functional Constipation.

BACKGROUND: Sennosides are commonly used for the treatment of constipation and associated with melanosis coli. In the present study, we evaluated the utility of melanosis coli as a marker of severity and its association with colonic motility in children with functional constipation. METHODS: Prospective study includes pediatric patients undergoing colonic manometry and colonic biopsies. Demographic data, medication history, surgical history, colonic manometry results (gastrocolonic response to a meal, high-amplitude propagating contractions, and nonpropagating contractions), colonic manometry catheter position, and pathologic results were collected and analyzed. We compared those variables with outcome (need for surgery) between both patient groups (presence or absence of melanosis coli). RESULTS: A total of 150 patients were included, median age was 9.9 years (range 2.1-18) and 77 (51.3%) were female, 17 had melanosis. Patients who took sennosides had higher rates of melanosis coli compared to those who did not (adjusted OR 13.88; 95% CI 4.05-47.57; P < 0.001), and we did not find an association between melanosis coli and use of other medications (osmotic laxatives, bisacodyl, lubiprostone), age, gender, weight, and height. We found no significant difference in the results colonic manometry between patients with and without melanosis coli. The rates of surgery for constipation between patients with and without melanosis coli were not statistically different. (OR 3.00; 95% CI 0.45-20.07; P = 0.257). CONCLUSIONS: Melanosis coli is associated with sennosides use, but it does not influence colonic motility nor is associated with increased subsequent need for surgery in pediatric functional constipation.

Duodenal and proximal jejunal motility inhibition associated with bisacodyl-induced colonic high-amplitude propagating contractions.

Bisacodyl is a stimulant laxative often used in manometric studies of pediatric constipation to determine if it can initiate propulsive high-amplitude propagating contractions (HAPCs). Whereas the effects of bisacodyl infusion on colonic motility are well described, the effects of the drug on other regions of the gut after colonic infusion are not known. The aim of the present study was to characterize the effects of bisacodyl on both colonic and small bowel motility. Twenty-seven children (9.3 ± 1.2 yr) undergoing simultaneous high-resolution antroduodenal and colonic manometry were included. Small bowel and colonic motor patterns were assessed before and after colonic infusion of bisacodyl. Patients were divided into two groups: responders and nonresponders based on the presence of high-amplitude propagating contractions (HAPCs) after bisacodyl infusion. Nineteen patients were responders. A total of 188 postbisacodyl HAPCs was identified with a mean count of 10.4 ± 5.5 (range, 3-22), at a frequency of 0.6 ± 0.2/min and mean amplitude of 119.8 ± 23.6 mmHg. No motor patterns were induced in the small bowel. However, in the 19 responders the onset of HAPCs was associated with a significant decrease in small bowel contractile activity. In the nonresponders, there was no detectable change in small bowel motility after bisacodyl infusion. Bisacodyl-induced HAPCs are associated with a significant reduction in small bowel motility probably mediated by extrinsic sympathetic reflex pathways. This inhibition is potentially related to rectal distension, caused by the HAPC anal propulsion of colonic content.NEW & NOTEWORTHY The present study has shown, for the first time, that the presence of high-amplitude propagating contractions induced by bisacodyl is associated with a significant reduction in small bowel motility. These findings support of possible existence of a reflex pathway that causes inhibition of small bowel motility in response to rectal distension.