Diagnosis and management in Rubinstein-Taybi syndrome: first international consensus statement.

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.

Age-dependent normal values for the 'Infant Gastroesophageal Reflux Questionnaire Revised'.

The Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) is used to score and evaluate gastroesophageal reflux (GER) related symptoms such as regurgitation, irritability and crying. A cut-off of ≥ 16 has been suggested to discriminate between GER and GER-disease. However, age-specific normal values were not assessed. Aim of this study was to determine age-specific normal values in healthy infants. Cross-sectional survey in healthy infants aged 0-24 months during their regular check-ups at well-baby clinics and through an online questionnaire using the I-GERQ-R. Infants with a history of (suspected) GER-disease were excluded. Spearman's correlation coefficient was calculated to explore age-related trends. A total of 979 healthy infants (47% male, median age 6 [0-24] months) were included. Median I-GERQ-R score, regardless of age, was 6 (range: 0-27). I-GERQ-R scores significantly decreased with age (rs = -0.569, p < 0.001). Of all infants, 49 (5%) had a score of ≥ 16 which previously has been considered 'suggestive of GER-disease'. Scores of ≥ 16 were most frequently seen in newborns aged 0-4 months (16% in 0-1 months to 4% in 3-4 months) and disappeared after the age of 16 months. High scores in the first months of life were caused by a high prevalence of regurgitation, colic-associated symptoms and hiccup frequency.  Conclusion: Age-dependent normal values for the I-GERQ-R show that reflux symptoms decrease in the first 24 months of life in healthy infants. Scores of ≥ 16 should not necessarily be considered abnormal in young infants. Validation as a diagnostic tool for GER-disease using age-appropriate normal values is needed. What is Known: • The Infant Gastro Esophageal Reflux Questionnaire Revised (I-GERQ-R) was developed to objectively score and evaluate GER-related symptoms in infants. • Previously a cut off of ≥ 16 has been suggested to differentiate between gastro esophageal reflux (GER) and GER-disease. What is New: • We present age-specific normal values of the I-GERQ-R in healthy infants. • I-GERQ-R scores clearly decrease with age and up to 16% of young healthy infants have a score that is above the previously suggested cut-off score of 16 for GER-disease.

Fatal gastrointestinal complications in Pitt-Hopkins syndrome.

Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by mutations of the transcription factor 4 (Tcf4) gene. Individuals with PTHS often suffer from severe abdominal bloating and constipation. In this short communication, we discuss two individuals with PTHS who died unexpectedly due to gastrointestinal complications. We aim to increase awareness among healthcare professionals who care for individuals with PTHS, to ensure adequate screening and management of gastrointestinal symptoms in this population. Moreover, we discuss how fatal gastrointestinal complications may be related to PTHS and provide an overview of the literature.

Development and validation of a condition-specific quality of life instrument for adults with esophageal atresia: the SQEA questionnaire.

The importance of multidisciplinary long-term follow-up for adults born with esophageal atresia (EA) is increasingly recognized. Hence, a valid, condition-specific instrument to measure health-related quality of life (HRQoL) becomes imperative. This study aimed to develop and validate such an instrument for adults with EA. The Specific Quality of life in Esophageal atresia Adults (SQEA) questionnaire was developed through focus group-based item generation, pilot testing, item reduction and a multicenter, nationwide field test to evaluate the feasibility, reliability (internal and retest) and validity (structural, construct, criterion and convergent), in compliance with the consensus-based standards for the selection of health measurement instruments guidelines. After pilot testing (n = 42), items were reduced from 144 to 36 questions. After field testing (n = 447), three items were discarded based on item-response theory results. The final SQEA questionnaire (33 items) forms a unidimensional scale generating an unweighted total score. Feasibility, internal reliability (Cronbach's alpha 0.94) and test-retest agreement (intra-class coefficient 0.92) were good. Construct validity was discriminative for esophageal replacement (P < 0.001), dysphagia (P < 0.001) and airway obstruction (P = 0.029). Criterion validity showed a good correlation with dysphagia (area under the receiver operating characteristic 0.736). SQEA scores correlated well with other validated disease-specific HRQoL scales such as the GIQLI and SGRQ, but poorly with the more generic RAND-36. Overall, this first condition-specific instrument for EA adults showed satisfactory feasibility, reliability and validity. Additionally, it shows discriminative ability to detect disease burden. Therefore, the SQEA questionnaire is both a valid instrument to assess the HRQoL in EA adults and an interesting signaling tool, enabling clinicians to recognize more severely affected patients.

First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn's disease: an open-label multicentre randomised controlled trial.

OBJECTIVE: In newly diagnosed paediatric patients with moderate-to-severe Crohn's disease (CD), infliximab (IFX) is initiated once exclusive enteral nutrition (EEN), corticosteroid and immunomodulator therapies have failed. We aimed to investigate whether starting first-line IFX (FL-IFX) is more effective to achieve and maintain remission than conventional treatment. DESIGN: In this multicentre open-label randomised controlled trial, untreated patients with a new diagnosis of CD (3-17 years old, weighted Paediatric CD Activity Index score (wPCDAI) >40) were assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14 and 22 (FL-IFX), or EEN or oral prednisolone (1 mg/kg, maximum 40 mg) (conventional). The primary outcome was clinical remission on azathioprine, defined as a wPCDAI <12.5 at week 52, without need for treatment escalation, using intention-to-treat analysis. RESULTS: 100 patients were included, 50 in the FL-IFX group and 50 in the conventional group. Four patients did not receive treatment as per protocol. At week 10, a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001). At week 52, the proportion of patients in clinical remission was not significantly different (p=0.421). However, 19/46 (41%) patients in the FL-IFX group were in clinical remission on azathioprine monotherapy without need for treatment escalation vs 7/48 (15%) in the conventional group (p=0.004). CONCLUSIONS: FL-IFX was superior to conventional treatment in achieving short-term clinical and endoscopic remission, and had greater likelihood of maintaining clinical remission at week 52 on azathioprine monotherapy. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02517684).

Management of Gastroesophageal Reflux Disease in Esophageal Atresia Patients: A Cross-Sectional Survey amongst International Clinicians.

OBJECTIVES: After surgical repair, up to 70% of esophageal atresia (EA) patients suffer from gastroesophageal reflux disease (GERD). The ESPGHAN/NASPGHAN guidelines on management of gastrointestinal complications in EA patients were published in 2016. Yet, the implementation of recommendations on GERD management remains poor.We aimed to assess GERD management in EA patients in more detail, to identify management inconsistencies, gaps in current knowledge, and future directions for research. METHODS: A digital questionnaire on GERD management in EA patients was sent to all members of the ESPGHAN EA working group and members of the International network of esophageal atresia (INoEA). RESULTS: Forty responses were received. Thirty-five (87.5%) clinicians routinely prescribed acid suppressive therapy for 1-24 (median 12) months. A fundoplication was considered by 90.0% of clinicians in case of refractory GERD with persistent symptoms despite maximal acid suppressive therapy and in 92.5% of clinicians in case of GERD with presence of esophagitis on EGD. Half of clinicians referred patients with recurrent strictures or dependence on transpyloric feeds. Up to 25.0% of clinicians also referred all long-gap EA patients for fundoplication, those with long-term need of acid suppressants, recurrent chest infections and feedings difficulties. CONCLUSIONS: Respondents' opinions on the optimal duration for routine acid suppressive therapy and indications for fundoplication in EA patients varied widely. To improve evidence-based care for EA patients, future prospective multicenter outcome studies should compare different diagnostic and treatment regimes for GERD in patients with EA. Complications of therapy should be one of the main outcome measures in such trials.

Colonic Function Investigations in Children: Review by the ESPGHAN Motility Working Group.

ABSTRACT: Disorders of colonic motility, most often presenting as constipation, comprise one of the commonest causes of outpatient visits in pediatric gastroenterology. This review, discussed and created by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Motility Working Group, is a practical guide, which highlights the recent advances in pediatric colonic motility testing including indications, technical principles of the tests, patient preparation, performance and basis of the results' analysis of the tests. classical methods, such as colonic transit time (cTT) with radiopaque markers and colonic scintigraphy, as well as manometry and novel techniques, such as wireless motility capsule and electromagnetic capsule tracking systems are discussed.

Adverse Events of Thiopurine Therapy in Pediatric Inflammatory Bowel Disease and Correlations with Metabolites: A Cohort Study.

BACKGROUND: In the recent era of growing availability of biological agents, the role of thiopurines needs to be reassessed with the focus on toxicity. AIMS: We assessed the incidence and predictive factors of thiopurine-induced adverse events (AE) resulting in therapy cessation in pediatric inflammatory bowel disease (IBD), related to thiopurine metabolites and biochemical abnormalities, and determined overall drug survival. METHODS: We performed a retrospective, single-center study of children diagnosed with IBD between 2000 and 2019 and treated with thiopurine therapy. The incidence of AE and overall drug survival of thiopurines were evaluated using the Kaplan-Meier method. Correlations between thiopurine metabolites and biochemical tests were computed using Spearman's correlation coefficient. RESULTS: Of 391 patients with IBD, 233 patients (162 Crohn's disease, 62 ulcerative colitis, and 9 IBD-unclassified) were prescribed thiopurines (230 azathioprine and 3 mercaptopurine), of whom 50 patients (22%) discontinued treatment, at least temporary, due to thiopurine-induced AE (median follow-up 20.7 months). Twenty-six patients (52%) were rechallenged and 18 of them (70%) tolerated this. Sixteen patients (6%) switched to a second thiopurine agent after azathioprine intolerance and 10 of them (63%) tolerated this. No predictive factors for development of AE could be identified. Concentrations of 6-thioguanine nucleotides (6-TGN) were significantly correlated with white blood cell and neutrophil count, 6-methylmercaptopurine (6-MMP) concentrations with alanine aminotransferase and gamma-glutamyltranspeptidase. CONCLUSIONS: Approximately 20% of pediatric patients with IBD discontinued thiopurine treatment due to AE. A rechallenge or switch to mercaptopurine is an effective strategy after development of AE. Concentrations of 6-TGN and 6-MMP are associated with biochemical abnormalities.

Evaluation of exclusive enteral nutrition and corticosteroid induction treatment in new-onset moderate-to-severe luminal paediatric Crohn's disease.

To induce remission in luminal paediatric Crohn's disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the "TISKids" study assigned to the conventional treatment arm. Patients were aged 3-17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI) > 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score < 3 without treatment escalation at week 10. Secondary outcomes included proportion of patients without treatment escalation at week 52. In total, 27/47 patients received EEN and 20/47 corticosteroids. At baseline, patient demographics and several inflammation parameters were similar between the two treatment groups. At 10 weeks, clinical remission rates were 7/23 (30%) for EEN and 7/19 (37%) for corticosteroids (p = 0.661). Twenty-nine of 47 consented to endoscopy at 10 weeks, showing endoscopic remission rates without treatment escalation in 2/16 (13%) of EEN-treated patients and in 1/13 (8%) of corticosteroid-treated patients (p = 1.00). At week 52, 23/27 (85%) EEN-treated patients received treatment escalation (median 14 weeks) and 13/20 (65%) corticosteroid-treated patients (median 27 weeks), p = 0.070.Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10. Trial registration number: NCT02517684 What is Known: • Endoscopic remission is associated with a low risk of disease progression. • FL-IFX was superior to conventional treatment in achieving and maintaining remission in paediatric patients with moderate-to-severe CD the first year from diagnosis. What is New: • In children with newly diagnosed moderate-to-severe CD, clinical remission rates and endoscopic remission rates without treatment escalation at week 10 were 30% and 13% after EEN and 37% and 8% after corticosteroid induction treatment. • The current treatment target was often not achieved by either EEN or corticosteroid induction treatment after bridging to azathioprine.

Fundoplication in children with esophageal atresia: preoperative workup and outcome.

Up to 45% of esophageal atresia (EA) patients undergo fundoplication during childhood. Their esophageal dysmotility may predispose to worse fundoplication outcomes compared with patients without EA. We therefore compared fundoplication outcomes and symptoms pre- and post-fundoplication in EA patients with matched patients without EA. A retrospective review of patients with- and without EA who underwent a fundoplication was performed between 2006 and 2017. Therapeutic success was defined as complete sustained resolution of symptoms that were the reason to perform fundoplication. Fundoplication indications of 39 EA patients (49% male; median age 1.1 [0.1-17.0] yrs) and 39 non-EA patients (46% male; median age 1.3 [0.3-17.0] yrs) included respiratory symptoms, brief resolved unexplained events, typical symptoms of gastroesophageal reflux disease, recurrent strictures and respiratory problems. Post-fundoplication, therapeutic success was achieved in 5 (13%) EA patients versus 29 (74%) non-EA patients (P<0.001). Despite therapeutic success, all 5 (13%) EA patients developed postoperative sustained symptoms/complications versus 12 (31%) non-EA patients. Eleven (28%) EA patients versus 3 (8%) non-EA patients did not achieve any therapeutic success (P=0.036). Remaining patients achieved partial therapeutic success. EA patients suffered significantly more often from postoperative sustained dysphagia (41% vs. 13%; P=0.039), gagging (33% vs. 23%; P<0.001) and bloating (40% vs. 17%; P=0.022). Fundoplication outcomes in EA patients are poor and EA patients are more susceptible to post-fundoplication sustained symptoms and complications compared with patients without EA. The decision to perform fundoplication in EA patients with proven gastroesophageal reflux disease needs to be made with caution after thorough multidisciplinary evaluation.

Clinical Experience With Performing Esophageal Function Testing in Children.

OBJECTIVES: Pediatric high-resolution manometry (HRM) and 24-hour pH-impedance with/without ambulatory manometry (pH-MII+/-mano) tests are generally performed using adult-derived protocols. We aimed to assess the feasibility of these protocols in children, the occurrence of patient-related imperfections and their influence on test interpretability. METHODS: Esophageal function tests performed between 2015 and 2018 were retrospectively analyzed. All tests were subcategorized into uninterpretable or interpretable tests (regardless of occurrence of patient-related imperfections). For HRM, the following patient-related imperfections were scored: patient-related artefacts, multiple swallowing and/or inability to establish baseline characteristics. For pH-MII(+/-mano), incorrect symptom registration and/or premature catheter removal were scored. Results were compared between age-groups (0-3, 4-12, and >12 years). RESULTS: In total 106 HRM, 60 pH-MII, and 23 pH-MII-mano could be fully analyzed. Of these, 94.8% HRM, 91.9% pH-MII, and 95.7% pH-MII-mano were interpretable. Overall, HRM contained imperfections in 78.3% overall and in 8/8 (100%) in the youngest age group, 36/42 (85.7%) in 4 to 12 years and in 37/56 (66.1%) in children above 12 years; P = 0.011. These imperfections led to uninterpretable results in 4 HRM (3.8%), of which 3 were in the youngest age group (3/8, 37.5%). Imperfections were found in 10% of pH-MII and 17.4% of pH-MII-mano. These led to uninterpretable results in 5.0% and 4.3%, respectively. No age-effect was found. CONCLUSIONS: Esophageal function tests in children are interpretable in more than 90% overall. In children under the age of 4 years, all patients had imperfect HRM and 3/8 tests were uninterpretable. HRM in older children and pH-MII+/-mano were interpretable in the vast majority.

Measurement of Salivary Pepsin to Detect Gastroesophageal Reflux Disease Is Not Ready for Clinical Application.

A noninvasive test for gastroesophageal reflux disease (GERD) is desirable for adults and children. Salivary pepsin measurement has been proposed as such a test.1-3 A previous study from our group demonstrated that a maximal salivary pepsin cutoff of >210 ng/mL using the PepTest device (RD Biomed, Hull, United Kingdom) had excellent specificity of 96% but modest sensitivity of 44% to diagnose GERD,4 leading to optimism about its potential use. In this study, we aimed to confirm the previously reported sensitivity and specificity in healthy volunteers and patients with heartburn, evaluate the association between a positive PepTest and response to proton pump inhibitor (PPI) therapy, assess if test-sensitivity can be improved for GERD when samples are taken over a 72-hour sampling period, and establish normal values of salivary pepsin in infants.

Clinical Management of Pediatric Achalasia: A Survey of Current Practice.

OBJECTIVES: Pediatric achalasia is a rare neurodegenerative disorder of the esophagus that requires treatment. Different diagnostic and treatment modalities are available, but there are no data that show how children can best be diagnosed and treated. We aimed to identify current practices regarding the diagnostic and therapeutic approach toward children with achalasia. METHODS: Information on the current practice regarding the management of pediatric achalasia was collected by an online-based survey sent to members of the European and North American Societies for Pediatric Gastroenterology Hepatology and Nutrition involved in pediatric achalasia care. RESULTS: The survey was completed by 38 centers from 24 countries. Within these centers, 108 children were diagnosed with achalasia in the last year (median 2, range 0-15). Achalasia was primarily managed by a pediatric gastroenterologist (76%) and involved a multidisciplinary team in 84% of centers, also including a surgeon (87%), radiologist (61%), dietician (37%), speech pathologist (8%), and psychologist (5%). Medical history taking and physical examination were considered most important to establish the diagnosis (50%), followed by (a combination of) manometry (45%) or contrast swallow (21%). Treatment of first choice was Heller myotomy (58%), followed by pneumatic dilation (46%) and peroral endoscopic myotomy (29%). CONCLUSION: This study shows a great heterogeneity in the management of pediatric achalasia amongst different centers worldwide. These findings stress the need for well-designed intervention trials in children with achalasia. Given the rarity of this disease, we recommend that achalasia care should be managed in centers with access to appropriate diagnostic and treatment modalities.

Evaluation of Gastroesophageal Reflux in Children Born With Esophageal Atresia Using pH and Impedance Monitoring.

OBJECTIVES: The aim of the study was to evaluate acid and nonacid gastroesophageal reflux in infants and school-aged children with esophageal atresia (EA) using pH-impedance (pH-MII) monitoring. METHODS: Between 2012 and 2017, all 24-hour pH-MII studies performed in infants (≤18 months) and 8-year olds with EA were included. Antiacid therapy was discontinued before study. Exclusion criteria were: isolated tracheoesophageal fistula; esophageal replacement therapy; tube feeding; and monitoring <18 hours. Automatically detected retrograde bolus movements (RBM) were manually reviewed and modified/deleted if necessary. RESULTS: We included 57 children (51% boys; 2% isolated EA; 44% thoracoscopic EA repair): 24 infants (median age 0.6 years) and 33 school-aged children (median age 8.2 years). Of the automatically detected 3313 RBM, 1292 were manually deleted from the tracings: 52% of nonacid RBM and 8% of acid RBM (mainly misinterpreted swallows or 1 event recognized as several events). In infants, median reflux index (RI; pH <4) was 2.6% (abnormal in n = 2), median RBM was 61 (62% nonacid, 58% mixed), and median of the mean BCT was 11 seconds. In older children, median RI was 0.3% (abnormal in n = 4), median RBM was 21 (64% nonacid; 75% mixed), and median of the mean BCT was 13 seconds. CONCLUSIONS: Most children with EA off medication have a normal RI, yet experience a significant number of nonacid RBM. After manual revision of the tracings, a high percentage of RBM was deleted. Our data show that automated impedance analysis software needs refinement for use in infants and children with EA and question the need for standard antiacid therapy in these patients.

Novel Pressure-Impedance Parameters for Evaluating Esophageal Function in Pediatric Achalasia.

OBJECTIVE: In achalasia, absent peristalsis and reduced esophagogastric junction (EGJ) relaxation and compliance underlie dysphagia symptoms. Novel high-resolution impedance manometry variables, that is, bolus presence time (BPT) and trans-EGJ-bolus flow time (BFT) have been developed to estimate the duration of EGJ opening and trans-EGJ bolus flow. The aim of this study was to evaluate esophageal motor function and bolus flow in children diagnosed with achalasia using these variables. METHODS: High-resolution impedance manometry recordings from 20 children who fulfilled the Chicago Classification (V3) criteria for achalasia were compared with recordings of 15 children with normal esophageal high-resolution manometry findings and no other evidence suggestive of achalasia. Matlab-based analysis software was used to calculate BPT and BFT. RESULTS: Both BPT and BFT were significantly reduced in achalasia patients compared with children with normal esophageal motility (BPT 3.3 s vs 5.1 s P < 0.01; BFT 1.4 s vs 4.3 s P < 0.001). BFT was significantly lower than BPT (achalasia difference 1.9 s ±â€Š1.3 s, P = 0.001 and normal difference 0.9 ±â€Š0.3 s, P = 0.001). Overall, there was a significant correlation between BPT and BFT (r = 0.825, P < 0.001). We observed a 2-way differentiation of achalasia patients; those in whom the BPT and BFT were proportional, but significantly lower than in patients with normal peristalsis, and those in whom BFT was disproportionately lower than BPT. CONCLUSIONS: Calculation of BPT and BFT may help determine whether esophageal bolus transport to the EGJ and/or esophageal emptying through the EGJ are aberrant. For achalasia, this may detect flow resistance at the EGJ, potentially improving both diagnosis and objective assessment of therapeutic effects.

Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial.

OBJECTIVE: The long-term efficacy and safety of polyethylene glycol (PEG) in constipated children are unknown, and a head-to-head comparison of the different PEG formulations is lacking. We aimed to investigate noninferiority of PEG3350 with electrolytes (PEG3350 + E) compared to PEG4000 without electrolytes (PEG4000). METHODS: In this double-blind trial, children aged 0.5 to 16 years with constipation, defined as a defecation frequency of <3 times per week, were randomized to receive either PEG3350 + E or PEG4000. Primary outcomes were change in total sum score (TSS) at week 52 compared to baseline, and dose range determination. TSS was the sum of the severity of 5 constipation symptoms rated on a 4-point scale (0-3). Noninferiority margin was a difference in TSS of ≤1.5 based on a 95%-confidence interval [CI]. Treatment success was defined as a defecation frequency of ≥3 per week with <1 episode of fecal incontinence. RESULTS: Ninety-seven subjects were included, of whom 82 completed the study. Mean reduction in TSS was -3.81 (95% CI: -4.96 to -2.65) and -3.74 (95%CI: -5.08 to -2.40), for PEG3350 + E and PEG4000, respectively. Noninferiority criteria were not met (maximum difference between groups: -1.81 to 1.68). Daily sachet use was: 0 to 2 years: 0.4 to 2.3 and 0.9 to 2.1; 2 to 4 years: 0.1 to 3.5 and 1.2 to 3.2; 4 to 8 years: 1.1 to 2.8 and 0.7 to 3.8; 8 to 16 years 0.6 to 3.7 and 1.0 to 3.7, in PEG3350 + E and PEG4000, respectively. Treatment success after 52 weeks was achieved in 50% and 45% of children, respectively (P = 0.69). Rates of adverse events were similar between groups, and no drug-related serious adverse events occurred. CONCLUSIONS: Noninferiority regarding long-term constipation-related symptoms of PEG3350 + E compared to PEG4000 was not demonstrated. However, analysis of secondary outcomes suggests similar efficacy and safety of these agents.

Pressure-flow characteristics of normal and disordered esophageal motor patterns.

OBJECTIVE: To perform pressure-flow analysis (PFA) in a cohort of pediatric patients who were referred for diagnostic manometric investigation. STUDY DESIGN: PFA was performed using purpose designed Matlab-based software. The pressure-flow index (PFI), a composite measure of bolus pressurization relative to flow and the impedance ratio, a measure of the extent of bolus clearance failure were calculated. RESULTS: Tracings of 76 pediatric patients (32 males; 9.1 ± 0.7 years) and 25 healthy adult controls (7 males; 36.1 ± 2.2 years) were analyzed. Patients mostly had normal motility (50%) or a category 4 disorder and usually weak peristalsis (31.5%) according to the Chicago Classification. PFA of healthy controls defined reference ranges for PFI ≤142 and impedance ratio ≤0.49. Pediatric patients with pressure-flow (PF) characteristics within these limits had normal motility (62%), most patients with PF characteristics outside these limits also had an abnormal Chicago Classification (61%). Patients with high PFI and disordered motor patterns all had esophagogastric junction outflow obstruction. CONCLUSIONS: Disordered PF characteristics are associated with disordered esophageal motor patterns. By defining the degree of over-pressurization and/or extent of clearance failure, PFA may be a useful adjunct to esophageal pressure topography-based classification.

Follow-up after pH-metry and pH impedance in pediatric gastroesophageal reflux disease.

OBJECTIVES: It is unclear how diagnostic tests for gastroesophageal reflux disease (GERD) in children relate to the course of symptoms during follow-up. METHODS: During 1 year, all children (ages 0-18 years), who underwent pH-metry and/or pH multichannel intraluminal impedance (MII), were included after written informed consent was obtained. pH-metry and pH-MII test characteristics, such as reflux index (RI, % time that esophageal pH < 4), were obtained from the measurements. A questionnaire containing subcategories (medical history, gastrointestinal [GI] symptoms, extraesophageal symptoms, symptom burden, and therapeutic agents) was used; subjects were asked to fill the questionnaire at the time of inclusion and 3, 6, and 12 months afterward. RESULTS: A total of 162 infants and 42 children were included. pH-MII was performed in 15.4% and 57.4% of infants and children, respectively. All of the other subjects underwent pH-metry. Median RI was 2.0% (interquartile range 3.4) in infants and 1.7% (interquartile range 2.3) in children. RI was considered positive in 6.8% and 12.8% of infants and children, respectively. In infants, RI at baseline was significantly associated with symptom burden at baseline and at 3 and 12 months of follow-up. RI at baseline and reported GI symptoms at 3 months were also significantly associated. In infants and children using medication, symptom burden was significantly higher compared with those not using medication. This difference was found at baseline, after 3 and 12 months. CONCLUSIONS: In infants, an initial high RI is associated with persistence of GI symptoms at 3 months and a higher burden of symptoms during the course of 1 year. In children there were no such findings.

Development of the reflux finding score for infants and its observer agreement.

OBJECTIVE: It is hypothesized that laryngeal edema is caused by laryngopharyngeal reflux (LPR) (ie, gastroesophageal reflux extending into the larynx and pharynx). The validated reflux finding score (RFS) assesses LPR disease in adults. We, therefore, aimed to develop an adapted RFS for infants (RFS-I) and assess its observer agreement. STUDY DESIGN: Visibility of laryngeal anatomic landmarks was assessed by determining observer agreement. The RFS-I was developed based on the RFS, the found observer agreement, and expert opinion. An educational tutorial was developed which was presented to 3 pediatric otorhinolaryngologists, 2 otorhinolaryngologists, and 2 gastroenterology fellows. They then scored videos of flexible laryngoscopy procedures of infants who were either diagnosed with or specifically without laryngeal edema. RESULTS: In total, 52 infants were included with a median age of 19.5 (0-70) weeks, with 12 and 40 infants, respectively, for the assessment of the laryngeal anatomic landmarks and the assessment of the RFS-I. Overall interobserver agreement of the RFS-I was moderate (intraclass correlation coefficient = 0.45). Intraobserver agreement ranged from moderate to excellent agreement (intraclass correlation coefficient = 0.50-0.87). CONCLUSION: A standardized scoring instrument was developed for the diagnosis of LPR disease using flexible laryngoscopy. Using this tool, only moderate interobserver agreement was reached with a highly variable intraobserver agreement. Because a valid scoring system for flexible laryngoscopy is lacking up until now, the RFS-I and flexible laryngoscopy should not be used solely to clinically assess LPR related findings of the larynx, nor to guide treatment.

Unintentional Suture Fistula Between the Proximal and Distal Esophagus in a Preterm Neonate with Type C Esophageal Atresia.

We present the case of a patient with gross type C esophageal atresia in a preterm neonate (gestational age of 31 weeks + 1 day) with a birth weight of 1,470 g. The fistula was released via a thoracotomy, but no primary anastomosis could be made, due to an unexpected long gap. The distal esophagus was closed and approximated to the blind pouch using traction sutures until an adjacent position was reached. A gastrostomy was created for enteral feeding. Although a second attempt to make an anastomosis was unsuccessful, the patient unexpectedly developed a suture fistula 6 weeks after the first procedure, enabling feeding via a nasogastric tube. Over time, six dilations were necessary. Full enteral feeding was achieved at the age of 6 months. Our case confirms sparse reports that deliberately creating a suture fistula may be a solution in esophageal atresia patients when an unexpected long gap prohibits a primary anastomosis.