Clinical trial: 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.

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.

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.

Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.

BACKGROUND: Linaclotide, a guanylate cyclase C agonist, has been approved in the USA for the treatment of chronic idiopathic constipation and irritable bowel syndrome with predominant constipation in adults. We aimed to assess the efficacy and safety of linaclotide in paediatric patients aged 6-17 years with functional constipation. METHODS: This randomised, double-blind, placebo-controlled, multicentre, phase 3 study was done at 64 clinic or hospital sites in seven countries (USA, Canada, Israel, Italy, the Netherlands, Ukraine, and Estonia). Patients aged 6-17 years who met modified Rome III criteria for functional constipation were randomly assigned (1:1), with a block size of four and stratified by age (6-11 years and 12-17 years), to receive either oral linaclotide 72 µg or placebo once daily for 12 weeks. Participants, investigators, and data assessors were masked to assignment. The primary efficacy endpoint was change from baseline (CFB) in the 12-week frequency rate of spontaneous bowel movements (SBMs; occurring in the absence of rescue medication on the calendar day of or before the bowel movement) per week and the secondary efficacy endpoint was CFB in stool consistency over the 12-week treatment period; efficacy and safety were analysed in all patients in the randomised population who received at least one dose of study intervention (modified intention-to-treat population and safety population, respectively). The study is registered with ClinicalTrials.gov, NCT04026113, and the functional constipation part of the study is complete. FINDINGS: Between Oct 1, 2019, and March 21, 2022, 330 patients were enrolled and randomly assigned to linaclotide (n=166) or placebo (n=164). Two patients in the linaclotide group did not receive any treatment; thus, efficacy and safety endpoints were assessed in 328 patients (164 patients in each group). 293 (89%) patients completed the 12-week treatment period (148 in the linaclotide group and 145 in the placebo group). 181 (55%) of 328 patients were female and 147 (45%) were male. At baseline, the mean frequency rate for SBMs was 1·28 SBMs per week (SD 0·87) for placebo and 1·16 SBMs per week (0·83) for linaclotide, increasing to 2·29 SBMs per week (1·99) for placebo and 3·41 SBMs per week (2·76) for linaclotide during intervention. Compared with placebo (least-squares mean [LSM] CFB 1·05 SBMs per week [SE 0·19]), patients treated with linaclotide showed significant improvement in SBM frequency (LSM CFB 2·22 SBMs per week [0·19]; LSM CFB difference 1·17 SBMs per week [95% CI 0·65-1·69]; p<0·0001). Linaclotide also significantly improved stool consistency over placebo (LSM CFB 1·11 [SE 0·08] vs 0·69 [0·08]; LSM CFB difference 0·42 [95% CI 0·21-0·64]; p=0·0001). The most reported treatment-emergent adverse event (TEAE) by patients treated with linaclotide was diarrhoea (seven [4%] of 164 vs three [2%] of 164 patients in the placebo group) and by patients treated with placebo was COVID-19 (five [3%] vs four [2%] in the linaclotide group). The most frequent treatment-related TEAE was diarrhoea (linaclotide: six [4%] patients; placebo: two [1%] patients). One serious adverse event of special interest (treatment-related severe diarrhoea resulting in dehydration and hospitalisation) occurred in a female patient aged 17 years in the linaclotide group; this case resolved without sequelae after administration of intravenous fluids. No deaths occurred during the study. INTERPRETATION: Linaclotide is an efficacious and well tolerated treatment for functional constipation in paediatric patients and has subsequently been approved by the US Food and Drug Administration for this indication. FUNDING: AbbVie and Ironwood Pharmaceuticals.

The utility of balloon-based and standard impedance technology to diagnose esophageal mucosal diseases in children.

BACKGROUND: Standard impedance catheters and balloon-based mucosal impedance catheters (BBMI) have been used to assess mucosal integrity and diagnose mucosal diseases. The goal of this study was to determine the age-related technical issues associated with mucosal balloon inflation, validate the BBMI measurement against a standard impedance probe, and compare software-generated diagnoses to histologic diagnoses. METHODS: We prospectively recruited patients undergoing endoscopy, during which patients underwent standard mucosal impedance catheters and BBMI measurements. Measurements were compared to each other, to the histologic diagnoses, and to the number of eosinophils per high power field. We then compared the patients' diagnosis to that assigned by the BBMI software. KEY RESULTS: Sixty-two patients (mean age: 62 ± 62 months) were recruited, including non-GERD (N = 40), GERD (N = 15), and EoE (N = 7) patients. There were significant differences between the impedance values measured by the two technologies at each esophageal height (p < 0.003). There were significant correlations between the mean impedance values taken by the two catheters in the distal (r2 = 0.272, p = 0.04), mid (r2 = 0.371, p < 0.001), and proximal (r2 = 0.259, p = 0.05) esophagus. There were significant differences in BBMI impedance values across diagnoses in the mid and proximal esophagus (p = 0.024 and 0.025, respectively). While not statistically significant (p = 0.061-0.073), the standard catheter showed similar trends by diagnosis. Using the BBMI diagnostic prediction software, 33%-72% of patients were misclassified. CONCLUSION AND INFERENCES: While there was significant variability in impedance values between technologies within patients, regional measurements were consistent across catheters. Automated analyses lacked the sensitivity to diagnose inflammatory disorders.

The Effect of Dexmedetomidine Sedation on Lower Gastrointestinal Motility in Children-Is It Suitable for Anorectal Manometry?

Anorectal manometry is one of the most frequently performed gastrointestinal motility studies in children. It is an important study in diagnosing Hirschsprung disease (HD). These procedures can be uncomfortable, painful and emotionally distressing. Nitrous oxide or midazolam are the only pharmacologic options available, as clinical experience suggests that they do not alter manometry readings. Our study was designed to determine whether Dexmedetomidine (DEX) could provide adequate sedation without disrupting anal and rectal pressure. The effect of DEX on anorectal function has never been studied in children. This prospective study recorded anorectal manometry (ARM) measurements prior to the administration of DEX and then repeated the measurements at 1 and 5 min after DEX. The main ARM measurements included resting intra-anal sphincter pressure (IASP) and the presence and characteristics of the recto-anal inhibitory reflex (RAIR). DEX was administered as a bolus followed by a continuous infusion. Twenty patients were included (60% female; mean age 10.8 ± 4.6 years). The RAIR became absent in 2/16 (12.5%) patients after DEX administration. DEX may alter physiologic ARM and IASP recordings necessary to diagnose gastrointestinal medical conditions.

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.

Simultaneous Colonic Pressure Waves in Children and Young Adults with Gastrointestinal Motility Disorders: Artefact or Colonic Physiology?

BACKGROUND: Simultaneous pressure waves (SPW) spanning all recording sites in colonic manometry studies have been described as a potential biomarker of normal gas transit and extrinsic neural reflexes. In pediatric studies utilizing combined antroduodenal and colonic manometry, it was noted that most colonic SPWs appeared to also span all sensors in the gastric and small bowel regions. This suggests that a proportion of colonic SPWs may represent an artefact caused by forces extrinsic to the colon. Our aim was to characterize colonic SPWs and determine how many of these spanned most of the digestive tract. METHODS: In 39 combined high-resolution antroduodenal and colonic manometry traces from 27 pediatric patients, we used our purpose-built software to identify all SPWs that spanned either (i) all recording sites in the digestive tract or (ii) those restricted to the colon. RESULTS: A total of 14,565 SPWs were identified (364 ± 316 SPWs/study), with 14,550 (99.9%) spanning the entire antroduodenal and colonic recording sites. Only 15 SPWs (0.1% of the total) were restricted to the colon (all in one recording). CONCLUSIONS: Based on these findings, we suggest that, in pediatric studies, SPWs should not form part of any diagnostic criteria, as these events appear to be an artefact caused by factors outside the colon (abdominal strain, body motion).

First study to assess the reliability of commonly used pain scales in children with disorders of gut-brain interaction.

BACKGROUND: There are no validated measures to assess chronic abdominal pain (AP) in clinical trials of children with disorders of gut-brain interaction (DGBIs). Currently used AP measures are extrapolated from studies on adults or children with acute AP. The primary aim of the study was to assess the commonly used pain scales in children with DGBIs. The secondary aim of the study was to compare specific pain measures with the overall subjective assessment of AP well-being in children. METHODS: A sub-study from multicenter crossover randomized controlled trial (RCT) was conducted. Children with AP-DGBIs completed daily diaries for 7 weeks. It included three widely used AP scales: the numeric rating scale (NRS), the visual analog scale (VAS), the Faces Pain Scale Revised (FPS-R), and a global improvement question. Strength of correlations among scales and questions was assessed with the Pearson correlation coefficient (r). KEY RESULTS: Thirty subjects completed the study. Children completed 4975 of 5880 (84.6%) pain and global responses. The VAS and NRS had strongest correlation among them, r = 0.893 (p < 0.001). The FPS-R also demonstrated strong correlations with the VAS r = 0.773 (p < 0.001), NRS = 0.783 (p < 0.001). The three scales exhibited weaker but significant correlations with the global question. Strong correlations were consistent when stratified by age groups. CONCLUSION: This is the first study to assess the most used AP scales in children with DGBIs. It supports the Rome IV recommendations on using the VAS and NRS scales. It also suggests that FPS-R, that was not part of Rome IV, can also be used in RCTs. Congruent with the biopsychosocial model, there was a weaker correlation between AP measures and the global question. This suggests that the global question measures more domains than AP alone and that it should also be incorporated in DGBIs RCTs in children.

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.

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.

Clinical utility of colonic low-amplitude propagating contractions in children with functional constipation.

BACKGROUND: Colonic high-amplitude propagating contractions (HAPC) are generally accepted as a marker of neuromuscular integrity. Little is known about low-amplitude propagating contractions (LAPCs); we evaluated their clinical utility in children. METHODS: Retrospective review of children with functional constipation undergoing low-resolution colon manometry (CM) recording HAPCs and LAPCs (physiologic or bisacodyl-induced) in three groups: constipation, antegrade colonic enemas (ACE), and ileostomy. Outcome (therapy response) was compared to LAPCs in all patients and within groups. We evaluated LAPCs as potentially representing failed HAPCs. KEY RESULTS: A total of 445 patients were included (median age 9.0 years, 54% female), 73 had LAPCs. We found no association between LAPCs and outcome (all patients, p = 0.121), corroborated by logistic regression and excluding HAPCs. We found an association between physiologic LAPCs and outcome that disappears when excluding HAPCs or controlling with logistic regression. We found no association between outcome and bisacodyl-induced LAPCs or LAPC propagation. We found an association between LAPCs and outcome only in the constipation group that cancels with logistic regression and excluding HAPCs (p = 0.026, 0.062, and 0.243, respectively). We found a higher proportion of patients with LAPCs amongst those with absent or abnormally propagated (absent or partially propagated) HAPCs compared to those with fully propagated HAPCs (p = 0.001 and 0.004, respectively) suggesting LAPCs may represent failed HAPCs. CONCLUSIONS/INFERENCES: LAPCs do not seem to have added clinical significance in pediatric functional constipation; CM interpretation could rely primarily on the presence of HAPCs. LAPCs may represent failed HAPCs. Larger studies are needed to further validate these findings.

Diferencias en la duración del reflejo rectoanal inhibitorio en pacientes con constipación funcional refractaria y mielomeningocele / Differences in rectoanal inhibitory reflex duration between patients with refractory functional constipation and myelomeningocele

Introducción. Habitualmente, durante la manometría anorrectal, en lo correspondiente al reflejo rectoanal inhibitorio (RRAI) solo se pesquisa su presencia o ausencia. Estudios han reportado que su análisis detallado puede brindar datos de interés. Nuestra hipótesis es que la medición del RRAI puede dar información para reconocer causas orgánicas (médula anclada, lipoma, etc.) en pacientes en los que previamente se consideró como de causa funcional. Objetivos. Comparar la duración del reflejo rectoanal inhibitorio en la manometría anorrectal de pacientes con constipación funcional refractaria (CFR) y mielomeningocele (MMC). Población y métodos. Estudio observacional, transversal, analítico (2004-2019). Pacientes constipados crónicos con incontinencia fecal funcional y orgánica (mielomeningocele). Se les realizó manometría anorrectal con sistema de perfusión de agua y se midió la duración del RRAI con diferentes volúmenes (20, 40 y 60 cc). Grupo 1 (G1): 81 CFR. Grupo 2 (G2): 54 MMC. Se excluyeron pacientes con retraso madurativo, esfínter anal complaciente, agenesia sacra y aquellos no colaboradores. Resultados. Se incluyeron 135 sujetos (62 varones). La mediana de edad fue G1:9,57 años; G2: 9,63 años. Duración promedio G1 vs. G2 con 20 cc: 8,89 vs. 15,21 segundos; con 40 cc: 11.41 vs. 21,12 segundos; con 60 cc: 14,15 vs. 26,02 segundos. La diferencia de duración del RRAI entre ambos grupos con diferentes volúmenes fue estadísticamente significativa (p = 0,0001). Conclusión. La duración del RRAI aumenta a mayor volumen de insuflación del balón en ambas poblaciones. Pacientes con MMC tuvieron mayor duración del RRAI que aquellos con CFR. En los pacientes con RRAI prolongado, debe descartarse lesión medular.

Introduction. Usually, during anorectal manometry, only the presence or absence of rectoanal inhibitory reflex (RAIR) is investigated. Studies have reported that a detailed analysis may provide data of interest. Our hypothesis is that RAIR measurement may provide information to detect organic causes (tethered cord, lipoma, etc.) in patients in whom a functional cause had been previously considered. Objectives. To compare RAIR duration in anorectal manometry between patients with refractory functional constipation (RFC) and myelomeningocele (MMC). Population and methods. Observational, analytical, cross-sectional study (2004­2019). Patients with chronic constipation and functional and organic fecal incontinence (myelomeningocele). The anorectal manometry was performed with a water-perfused system, and the duration of RAIR was measured with different volumes (20, 40, and 60 cc). Group 1 (G1): 81 RFC. Group 2 (G2): 54 MMC. Patients with developmental delay, compliant anal sphincter, sacral agenesis and non-cooperative patients were excluded. Results. A total of 135 individuals were included (62 were male). Their median age was 9.57 years in G1 and 9.63 years in G2. Average duration in G1 versus G2 with 20 cc: 8.89 versus 15.21 seconds; 40 cc: 11.41 versus 21.12 seconds; 60 cc: 14.15 versus 26.02 seconds. The difference in RAIR duration with the varying volumes was statistically significant (p = 0.0001). Conclusion. RAIR duration was longer with increasing balloon inflation volumes in both populations. RAIR duration was longer in patients with MMC than in those with RFC. Spinal injury should be ruled out in patients with prolonged RAIR.

Differences in rectoanal inhibitory reflex duration between patients with refractory functional constipationand myelomeningocele. / Diferencias en la duración del reflejo rectoanal inhibitorio en pacientes con constipación funcional refractaria y mielomeningocele.

Introduction. Usually, during anorectal manometry, only the presence or absence of rectoanal inhibitory reflex (RAIR) is investigated. Studies have reported that a detailed analysis may provide data of interest. Our hypothesis is that RAIR measurement may provide information to detect organic causes (tethered cord, lipoma, etc.) in patients in whom a functional cause had been previously considered. Objectives. To compare RAIR duration in anorectal manometry between patients with refractory functional constipation (RFC) and myelomeningocele (MMC). Population and methods. Observational, analytical, cross-sectional study (2004-2019). Patients with chronic constipation and functional and organic fecal incontinence (myelomeningocele). The anorectal manometry was performed with a water-perfused system, and the duration of RAIR was measured with different volumes (20, 40, and 60 cc). Group 1 (G1): 81 RFC. Group 2 (G2): 54 MMC. Patients with developmental delay, compliant anal sphincter, sacral agenesis and non-cooperative patients were excluded. Results. A total of 135 individuals were included (62 were male). Their median age was 9.57 years in G1 and 9.63 years in G2. Average duration in G1 versus G2 with 20 cc: 8.89 versus 15.21 seconds; 40 cc: 11.41 versus 21.12 seconds; 60 cc: 14.15 versus 26.02 seconds. The difference in RAIR duration with the varying volumes was statistically significant (p = 0.0001). Conclusion. RAIR duration was longer with increasing balloon inflation volumes in both populations. RAIR duration was longer in patients with MMC than in those with RFC. Spinal injury should be ruled out in patients with prolonged RAIR.

Introducción. Habitualmente, durante la manometría anorrectal, en lo correspondiente al reflejo rectoanal inhibitorio (RRAI) solo se pesquisa su presencia o ausencia. Estudios han reportado que su análisis detallado puede brindar datos de interés. Nuestra hipótesis es que la medición del RRAI puede dar información para reconocer causas orgánicas (médula anclada, lipoma, etc.) en pacientes en los que previamente se consideró como de causa funcional. Objetivos. Comparar la duración del reflejo rectoanal inhibitorio en la manometría anorrectal de pacientes con constipación funcional refractaria (CFR) y mielomeningocele (MMC). Población y métodos. Estudio observacional, transversal, analítico (2004-2019). Pacientes constipados crónicos con incontinencia fecal funcional y orgánica (mielomeningocele). Se les realizó manometría anorrectal con sistema de perfusión de agua y se midió la duración del RRAI con diferentes volúmenes (20, 40 y 60 cc). Grupo 1 (G1): 81 CFR. Grupo 2 (G2): 54 MMC. Se excluyeron pacientes con retraso madurativo, esfínter anal complaciente, agenesia sacra y aquellos no colaboradores. Resultados. Se incluyeron 135 sujetos (62 varones). La mediana de edad fue G1:9,57 años; G2: 9,63 años. Duración promedio G1 vs. G2 con 20 cc: 8,89 vs. 15,21 segundos; con 40 cc: 11.41 vs. 21,12 segundos; con 60 cc: 14,15 vs. 26,02 segundos. La diferencia de duración del RRAI entre ambos grupos con diferentes volúmenes fue estadísticamente significativa (p = 0,0001). Conclusión. La duración del RRAI aumenta a mayor volumen de insuflación del balón en ambas poblaciones. Pacientes con MMC tuvieron mayor duración del RRAI que aquellos con CFR. En los pacientes con RRAI prolongado, debe descartarse lesión medular.

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.

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.

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.

A prospective study of intrapyloric botulinum toxin and EndoFLIP in children with nausea and vomiting.

BACKGROUND: Intrapyloric botulinum toxin injection (IPBI) is used to treat nausea and vomiting in children, but no prospective pediatric studies exist. The aims of the current study were to assess the efficacy of IPBI in children with refractory nausea or vomiting and to use EndoFLIP as a biomarker of IPBI response. METHODS: This was a prospective observational cohort study of pediatric patients undergoing IPBI for refractory nausea, vomiting, or feeding difficulties at a tertiary center. Patients completed validated questionnaires at baseline and 1, 2, and 3 months after IPBI. A subset of patients >10 years old underwent pyloric EndoFLIP at the time of IPBI. Symptoms were compared pre- and post-IPBI, and EndoFLIP measurements were assessed in relation to baseline characteristics and response to IPBI. KEY RESULTS: Forty-five patients (mean age 14.2 ± 6.0 years) received IPBI, and 23 of those patients underwent EndoFLIP. Twenty-nine patients (64%) had symptomatic improvement at 1-month follow-up, including improvements in overall GI symptoms (p = 0.003), nausea and vomiting (p = 0.009), and discomfort when eating (p = 0.006). Symptomatic improvements lasted up to 3 months. There was a trend towards lower pyloric distensibility in patients with delayed versus normal gastric emptying (4.5 ± 3.8 mm2 /mmHg in delayed vs. 8.9 ± 6.6 mm2 /mmHg in normal, p = 0.09), though there were no differences in EndoFLIP measurements between IPBI responders and non-responders (p > 0.05). CONCLUSIONS AND INFERENCES: The majority of patients responded to IPBI, with significant improvements seen in nausea, vomiting, and discomfort. Pyloric EndoFLIP tended to distinguish baseline delays in gastric emptying, but it did not predict IPBI response in this patient cohort.