High prevalence of gastrointestinal disorders in a large cohort of patients with joint hypermobility.

The gastrointestinal (GI) manifestations in children with hypermobile Ehlers-Danlos syndrome/joint hypermobility syndrome (hEDS/JHS) are not well described. We investigated the prevalence of GI disorders in children and young adults with hEDS/JHS through a single-center retrospective review. Demographic data, clinical history, symptoms, and diagnostic studies were reviewed. Of 435 patients with hEDS/JHS, 66% were females (age 5-28 years). We noted a high prevalence of constipation (61%), dysphagia (32%), dyspepsia and/or gastroparesis (25%), eosinophilic esophagitis (EoE) (21%), and celiac disease (4%) in our cohort. Upper endoscopy and gastric emptying scans had the highest yield to detect abnormalities. Motility studies were abnormal in 31% of the 80 patients who underwent them. Dysphagia symptoms are significantly associated with EoE. Thirty-three percent of dysphagia patients had EoE, versus 16% of non-dysphagia patients (p < 0.001). Screening hEDS/JHS patients for GI issues should be routine, with further investigations and referrals guided by identified symptoms.

Safety and Effectiveness of Prucalopride in Children with Functional Constipation with and without Upper Symptoms.

INTRODUCTION: Pediatric prucalopride studies for treatment of gastrointestinal (GI) disorders have reported mixed results. We aimed to assess the safety and effectiveness of prucalopride in functional constipation (FC) with and without upper GI symptoms. METHODS: Retrospective data on patients with FC receiving combined prucalopride and conventional therapy was compared with those receiving conventional therapy alone within 12 months. Thirty patients on combined therapy and those on conventional therapy were each matched on the basis of age, gender, race, and presence of fecal soiling. Response (complete, partial, or no resolution) was compared. Similarly, response to concurrent functional upper GI symptoms (postprandial pain, bloating, weight loss, vomiting, early satiety, or nausea) and dysphagia, as well as adverse effects, were evaluated in the combined group. RESULTS: Mean age of 57 cases was 14.7 ± 4.9 years and 68% were female. Comorbidities included functional upper GI (UGI) symptoms (84%), dysphagia (12%), mood disorders (49%), and hypermobility spectrum disorder (37%). Unmatched cases reported 63% improvement to FC; response did not differ between the matched cohorts (70% versus 76.6%, p = 0.84). Cases showed a 56% improvement in functional UGI symptoms and 100% in dysphagia. Adverse effects were reported in 30%, abdominal cramps being most common. Four (7%) patients with a known mood disorder reported worsened mood, of which two endorsed suicidal ideation. CONCLUSION: Prucalopride efficaciously treated concurrent UGI symptoms and dysphagia in constipated pediatric patients and was overall well tolerated. Preexisting mood disorders seemed to worsen in a small subset of cases.

Percutaneous Electrical Nerve Field Stimulation in Children and Adolescents With Functional Dyspepsia-Integrating a Behavioral Intervention.

OBJECTIVES: Functional dyspepsia (FD) includes postprandial distress and epigastric pain syndrome. Percutaneous electrical nerve field stimulation (PENFS) in addition to behavioral interventions (BI) has shown benefits in children with functional abdominal pain but not specifically in FD. We aimed to assess the efficacy of PENFS for treating FD and compare the outcomes with those who received the combination of PENFS + BI. MATERIALS AND METHODS: Charts of patients with FD who completed four weeks of PENFS were evaluated. A subset of patients received concurrent BI. Demographic data, medical history, and symptoms were documented. Outcomes at different time points included subjective symptom responses and validated questionnaires collected clinically (Abdominal Pain Index [API], Nausea Severity Scale [NSS], Functional Disability Inventory [FDI], Pittsburgh Sleep Quality Index [PSQI], Children's Somatic Symptoms Inventory [CSSI], Patient-Reported Outcomes Measurement Information Systems [PROMIS] Pediatric Anxiety and Depression scales). RESULT: Of 84 patients, 61% received PENFS + BI, and 39% received PENFS alone. In the entire cohort, API (p < 0.0001), NSS (p = 0.001), FDI (p = 0.001), CSSI (p < 0.0001), PSQI (p = 0.01), PROMIS anxiety (p = 0.02), and depression (p = 0.01) scores improved from baseline to three weeks and at three months. Subjective responses showed nausea improvement (p = 0.01) and a trend for improvement in abdominal pain (p = 0.07) at week three. Abdominal pain subjectively improved at week three and three months (p = 0.003 and 0.02, respectively), nausea at week three and three months (p = 0.01 and 0.04, respectively), and a trend for improvement in sleep disturbances at week three and three months (p = 0.08 and p = 0.07, respectively) in the PENFS + BI group vs PENFS alone. CONCLUSION: Abdominal pain, nausea, functioning, somatization, sleep disturbances, anxiety, and depression improved at three weeks and three months after PENFS in pediatric FD. Subjective pain and nausea improvement were greater in the PENFS + BI group than in the group with PENFS alone, suggesting an additive effect of psychologic therapy.

Percutaneous electrical nerve field stimulation compared to standard medical therapy in adolescents with functional abdominal pain disorders.

Introduction: Standard medical therapy (SMT) in children with functional abdominal pain disorders (FAPD) includes cyproheptadine and amitriptyline. While percutaneous electrical nerve field stimulation (PENFS) has shown benefit, no study has compared outcomes of PENFS to SMT. We aimed to examine changes in abdominal pain, nausea and disability before and after treatment and compare outcomes between treatments. Methods: The records of FAPD patients ages 11-21 years, treated with 4 weeks of PENFS, cyproheptadine or amitriptyline were reviewed. Outcomes were evaluated using validated questionnaires [Abdominal Pain Index (API), Nausea Severity Scale (NSS), and the Functional Disability Inventory (FDI)] at baseline and follow-up within 3 months (FU). Result: Of 101 patients, 48% received PENFS, 31% cyproheptadine and 21% received amitriptyline. Median ages were 17 (15-19), 16 (15-18) and 15 (11-16) years respectively and the majority were females (75%, 90% and 52% respectively). In the PENFS group, API (p = 0.001), NSS (p = 0.059) and FDI (p = 0.048) were significantly lower at FU. API (p = 0.034) but not NSS and FDI (p > 0.05) decreased significantly at FU in the amitriptyline group. API, NSS and FDI did not change significantly with cyproheptadine at FU (p > 0.05). FU API scores were lower in PENFS vs. cyproheptadine (p = 0.04) but not vs. amitriptyline (p = 0.64). The FDI scores were significantly lower in the amitriptyline vs. cyproheptadine group (p = 0.03). Conclusion: Therapy with PENFS showed improvements in abdominal pain, nausea and disability while amitriptyline showed improvements in abdominal pain within 3 months of treatment. PENFS was more effective than cyproheptadine in improving abdominal pain. Amitriptyline improved disability scores more than cyproheptadine and showed promise for treatment. PENFS may be a good non-pharmacologic alternative for FAPD.

Pediatric gastrointestinal neuromodulation: A review.

Neuromodulation, also known as bioelectric neuromodulation or neurostimulation, is the therapeutic use of electrical stimulation of nerves or brain centers. Neuromodulation has been trialed in an increasing range of human diseases as well as gastrointestinal disorders. The application of neuromodulation to treat pediatric motility and functional disorders is an exciting recent development. This review aims to briefly discuss the use of neuromodulation for the treatment of pediatric gastroparesis, constipation, and visceral hyperalgesia.

Effect of percutaneous electrical nerve field stimulation on mechanosensitivity, sleep, and psychological comorbidities in adolescents with functional abdominal pain disorders.

BACKGROUND: Percutaneous electrical nerve field stimulation (PENFS) improves symptoms in adolescents with functional abdominal pain disorders (FAPDs). However, little is known about its impact on sleep and psychological functioning. We evaluated the effects of PENFS on resting and evoked pain and nausea, sleep and psychological functioning, and long-term outcomes. METHODS: Patient ages 11-19 years with FAPD requiring PENFS as standard care were recruited. Evoked pain was elicited by a Water Load Symptom Provocation Task (WL-SPT) before and after four weeks of treatment. Pain, gastrointestinal symptoms, sleep, somatic symptoms, and physical and psychological functioning were assessed. Actigraphy was used to measure daily sleep-wake patterns. KEY RESULTS: Twenty patients (14.3 ± 2.2 years old) with FAPD were enrolled. Most patients were females (70%) and white (95%). During pain evoked by WL-SPT, visual analog scale (VAS) pain intensity and nausea were lower following PENFS compared with baseline (p = 0.004 and p = 0.02, respectively). After PENFS, resting VAS pain unpleasantness (p = 0.03), abdominal pain (p < 0.0001), pain catastrophizing (p = 0.0004), somatic complaints (0.01), functional disability (p = 0.04), and anxiety (p = 0.02) exhibited significant improvements, and some were sustained long-term. Self-reported sleep improved after PENFS (p's < 0.05) as well as actigraphy-derived sleep onset latency (p = 0.03). CONCLUSIONS AND INFERENCES: We demonstrated improvements in resting and evoked pain and nausea, sleep, disability, pain catastrophizing, somatic complaints, and anxiety after four weeks of PENFS therapy. Some effects were sustained at 6-12 months post-treatment. This suggests that PENFS is a suitable alternative to pharmacologic therapy.

Outcomes of combined pyloric botulinum toxin injection and balloon dilation in dyspepsia with and without delayed gastric emptying.

Background: Pyloric botulinum toxin injection has improved symptoms in children with delayed gastric emptying. We aimed to determine the clinical response to combined endoscopic intra-pyloric botulinum toxin injection and pyloric balloon dilation (IPBT-BD) in patients with dyspepsia. Methods: Electronic medical records were reviewed to gather demographic data, symptoms, and follow-up on patients with dyspepsia. Cases were defined as those who underwent IPBT-BD in addition to their ongoing management. Controls received pharmacotherapy, behavioral intervention, or dietary management alone. Clinical response was defined as no change, partial, or complete improvement in symptoms within 12 months. Propensity score matching based on age, gender, and symptom duration was used to pair cases and controls. Results: In total, 79 cases and 83 controls were identified. After propensity matching, 63 patients were included in each group. The mean age for cases was 14.5 ± 3.9y; 62% were females and 98% were Caucasian. Further, 83% of 46 cases and 94% of 49 controls who had scintigraphy scans showed delayed gastric emptying. After matching, 76% of cases showed partial or complete improvement compared with 49% controls within 12 months (P = 0.004). Younger children tended to respond more favorably to the procedure (P = 0.08). Conclusions: In our propensity-matched analysis, combined IPBT-BD in addition to pharmacotherapy, behavioral, or dietary management clearly showed a benefit over these modalities alone. This favorable response lasted up to 12 months.

Esophageal dysmotility: An intrinsic feature of megacystis, microcolon, hypoperistalsis syndrome (MMIHS).

OBJECTIVES: Megacystis-microcolon-hypoperistalsis syndrome (MMIHS) also called Berdon's Syndrome, is a smooth muscle myopathy that results in an enlarged bladder, microcolon, and small bowel hypoperistalsis. In our series of six patients with this disorder, all had disordered swallowing. Therefore, we prospectively characterized esophageal structure and function in all. METHODS: Diagnoses had been established by contrast radiography, small bowel manometry, and urodynamic studies. To investigate the esophagus, we endoscoped and biopsied the esophagus of each patient on multiple occasions. All patients also underwent water soluble contrast esophagography and esophageal manometry. RESULTS: Upon careful questioning, all patients had swallowing dysfunction, and the majority of their enteral intake was via gastrostomy or gastrojejunostomy. All took some oral alimentation, but eating was slow and none could aliment themselves completely by the oral route, receiving 50% or less of their calories by mouth. Four had megaesophagus whereas the esophagus of the two youngest was of normal caliber. All had eosinophilic esophagitis and/or esophageal Candidiasis from time to time, but successful treatment of these findings failed to improve their symptoms. Manometry revealed normal lower esophageal sphincter (LES) resting tone and normal LES relaxation, but for all, peristalsis was absent in the esophageal body. CONCLUSIONS: This series expands the spectrum of findings in MMIHS, to include a primary motility disorder of the esophageal body. As patients age, the esophageal caliber appears to increase. Successful treatment of neither esophageal eosinophilia nor Candidiasis is effective in ameliorating the motility disorder. If our findings are confirmed in more patients with MMIHS, this disorder should be renamed, megacystis-microcolon-intestinal-and esophageal hypoperistalsis syndrome. TYPE OF STUDY: Prognosis study, Level IV (case series).

Rectal prolapse and cystic fibrosis.

Screening for cystic fibrosis (CF) is suggested in patients with rectal prolapse (RP). Little is known about the association between CF and RP in the era of newborn screening for CF. Our retrospective review showed that 3.6% of patients with RP had CF, and 3.5% of patients with CF had RP. No demographic or clinical factors appear to predict the likelihood of RP in patients with CF. Sweat chloride testing for patients with RP has a low yield in the era of newborn screening but may still need to be considered in children with RP to avoid missing the rare child with CF.

Colon high-resolution manometry: using pressure topography plots to evaluate pediatric colon motility.

OBJECTIVES: Colon manometry is usually performed using the 8-pressure sensor water-perfused manometry system. High-resolution manometry (HRM), using closely spaced solid-state pressure recording sensors, provides more detailed information of gut luminal pressure changes, and, by displaying the HRM data as a pressure topography plot (PTP), helps with data interpretation. Our aim was to compare the colon and rectal luminal pressure data obtained using 8 pressure sensors and displayed as conventional line plot (CLP) with data obtained using a custom-made solid state manometry catheter with 36 pressure recording sensors and displayed as PTP. METHODS: We evaluated colon manometry patterns during fasting, response to meal, and bisacodyl stimulation in 10 patients with constipation and stool expulsion disorders. The data from 8 pressure sensors were displayed as CLP and data from 36 pressure sensors as PTP. Two gastroenterologists independently interpreted these studies. We calculated variability in interpreting colon, rectal, and anal manometry data. RESULTS: Intermode, interobserver, and intraobserver reliability were good to excellent for recognizing colon contraction patterns when data are displayed as PTP compared with when displayed as CLP, whereas the reliability for recognizing anal contractions were poor to excellent. CONCLUSIONS: Colonic and anal manometry patterns are easily recognized when HRM data are expressed as PTP. Obtaining information of colonic luminal pressure changes with rectum and anal pressure changes using HRM can help better understand the pathophysiology of pediatric constipation and stool expulsion disorders.

Pancreatic insufficiency in Toriello-Carey syndrome: report of a second patient.

Toriello-Carey syndrome is characterized by multiple congenital anomalies. Pancreatic insufficiency is suspected when patients present with poor weight gain, diarrhea, or maldigestion. The diagnosis is confirmed by low stool elastase and pancreatic stimulation testing. To our knowledge, only one patient with Toriello-Carey syndrome has been reported to have pancreatic insufficiency. We report on a second patient with Toriello-Carey syndrome and pancreatic insufficiency, and describe the management of pancreatic insufficiency in patients with this syndrome.

Do oro-anal transit markers predict which children would benefit from colonic manometry studies?

OBJECTIVES: The aim of the study was to compare oro-anal transit time (OTT) measured by radio-opaque markers with colon motility (CM) findings in children with chronic constipation and to assess clinical outcomes in children with chronic constipation evaluated by OTT and CM studies. METHODS: Twenty-four children with chronic constipation (12 girls; median age 12 years [3-18 years]; median symptoms 87 months [6-186 months]) who underwent OTT and CM studies were reviewed. The OTT was determined using commercially available Sitzmarks. Patients were studied for a median of 23 months (4-60 months) and outcomes reviewed. RESULTS: All 5 children with normal OTT had normal CM; however, only 47% (9/19) of children with slow OTT had an abnormal CM. The abnormal CM findings were total colonic pseudo-obstruction in 3 and left colonic pseudo-obstruction in 6 children. Of the 9 children with abnormal CM, 5 were managed surgically, 1 with medicine escalation, and 3 were lost to follow-up; all 6 children with known follow-up have more bowel movements and less soiling. Of the 15 children with normal CM, 10 were managed with medication escalation, 3 with behavioral intervention, and 2 surgically. Of these 15 children, 8 improved, 1 did not change, 2 worsened, and 4 were lost to follow-up. CONCLUSIONS: OTT studies may be helpful to predict which children should be referred for CM studies. Normal OTT studies may predict normal colon manometry; however, abnormal OTT studies may not predict abnormalities in colonic manometry in children with chronic constipation. Therefore, patients with slow transit marker studies should be assessed by colon manometry to evaluate colon neuromuscular integrity.

Bloodstream infections in febrile neutropenic patients at a tertiary care center in Lebanon: a view of the past decade.

OBJECTIVES: Previous studies from Lebanon have shown Gram-negative organisms to be the predominant agents in febrile neutropenic patients. The objective of this study was to evaluate the most current epidemiological trends among patients with neutropenic fever. METHODS: This prospective observational cohort study, the largest to date in the country, was conducted at the American University of Beirut Medical Center between January 2001 and December 2003, with the objective of describing the characteristics of patients with neutropenic fever and to assess temporal trends. RESULTS: We included 177 episodes of neutropenic fever. The most common underlying malignancy was lymphoma (42.4%). Gastrointestinal and abdominal infections were predominant (31.6%) and 23.7% of cases represented fever of unknown origin. Gram-negative organisms were responsible for 78.8% (26/33) of bloodstream infections compared to 33.3% (11/33) with Gram-positive organisms. The in-hospital mortality rate in this study (12.1%) was considerably lower than in previous years. CONCLUSIONS: Gram-negative organisms are persistently predominant in our center. In a developing country like Lebanon with limited resources, lower mortality rates commensurate with worldwide reports were successfully achieved in this high-risk patient population. Protocols and guidelines should be adapted to the characteristics of individual institutions to ensure delivery of appropriate care to febrile neutropenic patients.