Correction to: Berardinelli-Seip syndrome and achalasia: a shared pathomechanism?

Although the patient has provided consent for publication of this case report and accompanying images, after publication of this article it has come to the authors' attention that Fig. 1 needs changes to better protect the privacy of the patient. A modified Fig. 1 is included in this Erratum. The original Fig. 1 has been removed to protect the patient's privacy.

Reliability of the reflux finding score for infants in flexible versus rigid laryngoscopy.

OBJECTIVES: The Reflux Finding Score for Infants (RFS-I) was developed to assess signs of laryngopharyngeal reflux (LPR) in infants. With flexible laryngoscopy, moderate inter- and highly variable intraobserver reliability was found. We hypothesized that the use of rigid laryngoscopy would increase reliability and therefore evaluated the reliability of the RFS-I for flexible versus rigid laryngoscopy in infants. METHODS: We established a set of videos of consecutively performed flexible and rigid laryngoscopies in infants. The RFS-I was scored twice by 4 otorhinolaryngologists, 2 otorhinolaryngology fellows, and 2 inexperienced observers. Cohen's and Fleiss' kappas (k) were calculated for categorical data and the intraclass correlation coefficient (ICC) was calculated for ordinal data. RESULTS: The study set consisted of laryngoscopic videos of 30 infants (median age 7.5 (0-19.8) months). Overall interobserver reliability of the RFS-I was moderate for both flexible (ICC = 0.60, 95% CI 0.44-0.76) and rigid (ICC = 0.42, 95% CI 0.26-0.62) laryngoscopy. There were no significant differences in reliability of overall RFS-I scores and individual RFS-I items for flexible versus rigid laryngoscopy. Intraobserver reliability of the total RFS-I score ranged from fair to excellent for both flexible (ICC = 0.33-0.93) and rigid (ICC = 0.39-0.86) laryngoscopies. Comparing RFS-I results for flexible versus rigid laryngoscopy per observer, reliability ranged from no to substantial (k = -0.16-0.63, mean k = 0.22), with an observed agreement of 0.08-0.35. CONCLUSION: Reliability of the RFS-I was moderate and did not differ between flexible and rigid laryngoscopies. The RFS-I is not suitable to detect signs or to guide treatment of LPR in infants, neither with flexible nor with rigid laryngoscopy.

Berardinelli-Seip syndrome and achalasia: a shared pathomechanism?

UNLABELLED: Berardinelli-Seip congenital lipodystrophy (BSCL) is an uncommon autosomal recessive disorder. Patients with BSCL present with a distinct phenotype since subcutaneous fat is largely lacking and musculature has become more prominent. During childhood, diabetes and acanthosis nigricans evolve and female patients may develop hirsutism. Different genes encoding this entity have been described. Achalasia is a rare esophageal motility disorder, characterized by its distinct motility pattern with absent or incomplete lower esophageal sphincter (LES) relaxations. The exact cause of achalasia is yet unknown. Here, we describe a patient with achalasia in the context of BSCL, which might be linked by a shared pathophysiologic background, as evaluated in this case report. CONCLUSION: In a BSCL patient presenting with gastrointestinal symptoms, a motility disorder of the gastrointestinal tract should be considered. WHAT IS KNOWN: • Berardinelli-Seip congenital lipodystrophy (BSCL) and achalasia are both disorders characterized by low prevalence. What is New: • Co-existence of both diseases is described in this report. Linkage by a potential common pathophysiologic background is discussed in this paper.

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.

Intramural pseudodiverticulosis of the esophagus: a case report.

UNLABELLED: Esophageal intramural pseudodiverticulosis (EIPD) is a rare disorder in adults, and even more in infants and children. It is characterized by the dilatation of the submucosal esophageal glands. The exact etiology and pathophysiology of EIPD is, however, unknown. Dysphagia is the predominant presenting symptom in both children and adults. CONCLUSION: Here, we present a case of a boy with persistent dysphagia who had a thorough diagnostic workup and was eventually diagnosed with EIPD.

Outcomes of endoscopy and novel pH-impedance parameters in children: is there a correlation?

OBJECTIVES: Discordance exists between outcomes of endoscopy, multichannel intraluminal impedance monitoring (pH-MII), MII baselines, and gastroesophageal reflux symptoms. The aim of the present study was to determine the association between endoscopy, pH-MII and MII baselines, in children with gastroesophageal reflux symptoms. METHODS: Endoscopies were graded for reflux esophagitis (RE). Biopsies of the distal esophagus were assessed for signs suggestive of esophagitis. Reflux index (RI), symptom association probability (SAP), number of reflux episodes, and mean baseline values were calculated. pH-MII was considered positive in children when RI was ≥ 3% and/or SAP was ≥ 95% and for infants when RI was ≥ 10% and/or SAP was ≥ 95%. Baselines were manually calculated and compared with an automated analysis. For MII baselines, patients were divided in 3 groups: normal endoscopy and negative overall pH-MII; normal endoscopy and an overall positive pH-MII; and RE. RESULTS: A total of 26 children and 14 infants were included, median age: 26.5 months (2 months-16.2 years). Thirteen (32.5%) had RE. A significant negative association was found for RI and MII baselines (P = 0.009) and between SAP and RE (P = 0.039, odds ratio 1.018). MII baseline values were predictive for neither conventional pH-MII parameters nor RE. Manual analysis and automated calculation of MII baselines showed a perfect correlation. Distal MII baselines were significantly lower in children with a positive overall pH-MII outcome compared with the proximal esophagus (P = 0.049). No significant changes were found in baselines among the different groups 1 to 3. CONCLUSIONS: Acid-related parameters are significantly related to MII baselines. A perfect correlation between manual- and automated analysis of MII baselines was found. Large prospective studies are needed to confirm the exact role of endoscopy and MII baselines.

Diagnostic accuracy of tests in pediatric gastroesophageal reflux disease.

OBJECTIVE: To systematically review the literature evaluating the diagnostic accuracy of commonly used diagnostic tests over conventional history taking and physical examination in children ≤ 18 months and >18 months suspected of gastroesophageal reflux disease (GERD). STUDY DESIGN: We searched Medline, Embase, and the Cochrane database for studies assessing the diagnostic accuracy of pH-metry, pH-impedance, esophagogastroscopy, barium contrast study, scintigraphy, and empirical treatment as diagnostic tools. Quality was assessed according to Quality Assessment of Studies of Diagnostic Accuracy Included in Systematic Reviews criteria. RESULTS: Of the 2178 studies found, 6 studies were included, containing 408 participants (age 1 month-13.6 years) and 145 controls (age 1 month-16.9 years). Studies included children with GERD symptoms; 1 included an atypical presentation. In all the studies, the diagnostic accuracy of pH-metry was investigated, and in 2 studies esophagogastroscopy was investigated as well. Sensitivity and specificity were calculated in 3 studies. The range of reported sensitivity and specificity was broad and unreliable because of poor methodological quality according to Quality Assessment of Studies of Diagnostic Accuracy Included in Systematic Reviews criteria and inadequate study design. CONCLUSION: Diagnostic accuracy of tests in children suspected of GERD remains unclear and implications for practice are hard to give. There is an urgent need of well-designed randomized controlled trials where the effect of treatment according to specific signs and symptoms will be compared with the effect of treatment based on the results of additional diagnostic tests, for patient relevant outcomes.

Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review.

INTRODUCTION: Use of proton-pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD) in children has increased enormously. However, effectiveness and safety of PPIs for pediatric GERD are under debate. OBJECTIVES: We performed a systematic review to determine effectiveness and safety of PPIs in children with GERD. METHODS: We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for randomized controlled trials and crossover studies investigating efficacy and safety of PPIs in children aged 0 to 18 years with GERD for reduction in GERD symptoms, gastric pH, histologic aberrations, and reported adverse events. RESULTS: Twelve studies were included with data from children aged 0-17 years. For infants, PPIs were more effective in 1 study (compared with hydrolyzed formula), not effective in 2 studies, and equally effective in 2 studies (compared with placebo) for the reduction of GERD symptoms. For children and adolescents, PPIs were equally effective (compared with alginates, ranitidine, or a different PPI dosage). For gastric acidity, in infants and children PPIs were more effective (compared with placebo, alginates, or ranitidine) in 4 studies. For reducing histologic aberrations, PPIs showed no difference (compared with ranitidine or alginates) in 3 studies. Six studies reported no differences in treatment-related adverse events (compared with placebo or a different PPI dosage). CONCLUSIONS: PPIs are not effective in reducing GERD symptoms in infants. Placebo-controlled trials in older children are lacking. Although PPIs seem to be well tolerated during short-term use, evidence supporting the safety of PPIs is lacking.