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Concurrent Celiac Disease and Eosinophilic Esophagitis in a Pediatric Cohort: More Than a Coincidence

Bergman, Arielle; Greifer, Melanie; Levine, Jeremiah
Celiac disease (CeD) and eosinophilic esophagitis (EoE) are immune-mediated disorders that can occur in the same patient. A retrospective study at a tertiary care hospital was conducted to determine the prevalence of EoE in a pediatric population with CeD and to compare characteristics of patients with both diseases to patients with CeD-only. Among the 148 patients with CeD identified in the study, 11 patients had both CeD and EoE (7.4%). Patients with both CeD and EoE had a higher absolute eosinophil count (per μL) at diagnosis compared to patients with CeD-only (454.1 ± 122.7 vs 231.9 ± 19.4, P = .003). In conclusion, there was a higher proportion of EoE in patients with CeD than would be expected in the general population, suggesting a potential pathophysiological overlap between the 2 diseases. An elevated peripheral absolute eosinophil count may help predict which patients with CeD may additionally have EoE.
PMID: 38374667
ISSN: 1938-2707
CID: 5634062

Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study

Atia, Ohad; Shavit-Brunschwig, Zivia; Mould, Diane R; Stein, Ronen; Matar, Manar; Aloi, Marina; Ledder, Oren; Focht, Gili; Urlep, Darja; Hyams, Jeffrey; Broide, Efrat; Weiss, Batia; Levine, Jeremiah; Russell, Richard K; Turner, Dan
BACKGROUND:Scarce data are available on the use of vedolizumab in children with inflammatory bowel disease (IBD). We aimed to evaluate the safety, effectiveness, and dosing of vedolizumab to induce remission of IBD. METHODS:body surface area (up to 300 mg maximum). The primary outcome was steroid-free and exclusive enteral nutrition-free remission at 14 weeks, analysed according to the intention-to-treat principle. Serum samples were taken for analysis of drug concentration and faecal calprotectin at baseline, and at 2, 6, and 14 weeks. Adverse events were recorded in real time and classified as severe or non-severe and related or unrelated to vedolizumab. This study is registered with ClinicalTrials.gov, NCT02862132. FINDINGS/RESULTS:body surface area or 10 mg/kg. 32 (23%) of 142 children reported at least one adverse event, the most common were headache (five [4%]), myalgia (four [3%]), and fever (three [2%]). None of the adverse events were classified as severe, and only two (1%) patients discontinued treatment due to adverse events. INTERPRETATION/CONCLUSIONS:) or weight (10 mg/kg). FUNDING/BACKGROUND:The European Crohn's and Colitis Organization, the European Society for Paediatric Gastroenterology Hepatology and Nutrition, and Takeda.
PMID: 36306803
ISSN: 2468-1253
CID: 5359712

Filling in the "GAPPS": an unusual presentation of a child with gastric adenocarcinoma and proximal polyposis of the stomach

Grossman, Arielle; Colavito, John; Levine, Jeremiah; Thomas, Kristen M; Greifer, Melanie
Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a very rare gastric polyposis syndrome characterized by numerous polyps of the gastric fundus and body. We present the unusual case of a 10-year-old Polish-American male with history of eosinophilic esophagitis, who was found to have multiple fundic gland polyps (FGP) with low grade dysplasia on esophagogastroduodenoscopy. Subsequent evaluation including genetic testing confirmed the diagnosis of GAPPS, and after exhaustive multidisciplinary consultation the decision was made to proceed with prophylactic total gastrectomy given the markedly increased risk of gastric adenocarcinoma in GAPPS patients. To our knowledge, this represents the youngest patient diagnosed with GAPPS and the youngest patient who has undergone prophylactic gastrectomy for this disease at age 8 and 10 years, respectively. The pathophysiology, presentation, and treatment of GAPPS in a pediatric patient are discussed.
PMID: 34581903
ISSN: 1436-3305
CID: 5067432

Effect of a gluten-free diet on albuminuria in children with newly diagnosed celiac disease

Levine, Jeremiah; Hauptman, Leora; Moy, Libia; Trachtman, Howard
Background and objectives/UNASSIGNED:Altered gastrointestinal permeability in celiac disease (CD) is mediated by zonulin. The receptor for zonulin is expressed on podocytes. Therefore, we tested the effect of a gluten-free diet (GFD) on albuminuria in pediatric patients with newly diagnosed CD. Methods/UNASSIGNED:We performed a cohort study comparing urinary albumin (μg):creatinine (mg) ratio (ACR) in CD patients vs controls and in response to a GFD. Results/UNASSIGNED:Children with CD (n=46) had higher ACR compared to controls (n=21), 20.2±5.6 versus 8.4±1.1 μg/mg, P=0.16 and exceeded 30 μg/mg (microalbuminuria cut-off) in 7/46 cases. 17 patients had a follow-up assessment (interval 6.1±0.7 months) on a GFD. Baseline ACR was 20.7±5.2 that fell to 10.4±1.5 μg/mg, P=0.035. Conclusion/UNASSIGNED:Children and adolescents with newly diagnosed CD have low-grade albuminuria that is numerically higher than controls and that declined after implementation of a GFD. CD may be associated with reversible defects in the glomerular barrier.
PMCID:8336695
PMID: 34368799
ISSN: 2673-3633
CID: 5086952

Persistent organic pollutant exposure and celiac disease: A pilot study

Gaylord, Abigail; Trasande, Leonardo; Kannan, Kurunthachalam; Thomas, Kristen M; Lee, Sunmi; Liu, Mengling; Levine, Jeremiah
Celiac disease affects approximately 1% of the population worldwide. Little is known about environmental factors that may modulate risk in genetically susceptible populations. Persistent organic pollutants (POPs) are known endocrine disruptors and, given the interplay between the endocrine and immune systems, are plausible contributors to celiac disease. The current study aims to elucidate the association between POPs and celiac disease. We conducted a single-site pilot study of 88 patients recruited from NYU Langone's Hassenfeld Children's Hospital outpatient clinic, 30 of which were subsequently diagnosed with celiac disease using standard serology and duodenal biopsy examination. Polybrominated diphenyl ether (PBDEs), perfluoroalkyl substances (PFASs), and p,p'-dichlorodiphenyldichloroethylene (DDE) and HLA-DQ genotype category were measured in blood serum and whole blood, respectively. Multivariable logistic regressions were used to obtain odds ratios for celiac disease associated with serum POP concentrations. Controlling for sex, race, age, BMI, and genetic susceptibility score, patients with higher serum DDE concentrations had 2-fold higher odds of celiac disease (95% CI: 1.08, 3.84). After stratifying by sex, we found higher odds of celiac disease in females with serum concentrations of DDE (OR = 13.0, 95% CI = 1.54, 110), PFOS (OR = 12.8, 95% CI = 1.17, 141), perfluorooctanoic acid (OR = 20.6, 95% CI = 1.13, 375) and in males with serum BDE153, a PBDE congener (OR = 2.28, 95% CI = 1.01, 5.18). This is the first study to report on celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.
PMID: 32409013
ISSN: 1096-0953
CID: 4438232

Integrating Suicide Risk Screening into Pediatric Ambulatory Subspecialty Care

Lois, Becky H; Urban, Tamaki H; Wong, Christina; Collins, Erin; Brodzinsky, Lara; Harris, Mary Ann; Adkisson, Hayley; Armstrong, Monique; Pontieri, Jeanmarie; Delgado, Diana; Levine, Jeremiah; Liaw, K Ron-Li
Background/UNASSIGNED:Suicide risk screening is recommended in pediatric care. To date, no previous studies illustrate the implementation of suicide risk screening in pediatric subspecialty care, even though chronic medical conditions are associated with a higher risk of suicide. Methods/UNASSIGNED:A large multidivision pediatric ambulatory clinic implemented annual suicide risk screening. Patients ages 9-21 years participated in suicide risk screening using the Ask Suicide-Screening Questions during the project. A multidisciplinary team employed quality improvement methods and survey-research design methods to evaluate the feasibility and acceptability of the screening process for patients, families, and medical providers. Results/UNASSIGNED:During the quality improvement project period, 1,934 patients were offered screening; 1,301 (67.3%) patients completed screening; 82 patients (6.3% of 1,301 patients) screened positive. The monthly compliance rate held steady at 86% following several Plan-Do-Study-Act cycles of improvement. The survey results demonstrate that providers rated the suicide risk screening process positively; however, a subset of providers indicated that the screening process was out of their scope of practice or impeded their workflow. Conclusions/UNASSIGNED:Suicide risk screening is feasible in pediatric specialty care and can identify at-risk patients. Continued efforts are needed to standardize suicide risk screening practices. Future directions include identifying factors associated with suicide risk in patients in pediatric subspecialty care settings.
PMCID:7297392
PMID: 32656472
ISSN: 2472-0054
CID: 5069922

Airway and esophageal eosinophils in children with severe uncontrolled asthma

Erkman, Jessica; Vaynblat, Allen; Thomas, Kristen; Segal, Leopoldo N; Levine, Jeremiah; Moy, Libia; Greifer, Melanie; Giusti, Robert; Shah, Rasik; Kazachkov, Mikhail
AIM/OBJECTIVE:Children with severe uncontrolled asthma (SUA) have a high burden of symptoms and increased frequency of asthma exacerbations. Reflux esophagitis and eosinophilic esophagitis are important co-morbid factors for SUA. Both are associated with the presence of eosinophils in esophageal mucosa. We hypothesized that esophageal eosinophils are frequently present and correlate with the presence of airway eosinophils in children with SUA. METHOD/METHODS:We performed a retrospective analysis of a prospective database of children who underwent "triple endoscopy" (sleep laryngoscopy, bronchoscopy with bronchoalveolar lavage [BAL] and endobronchial biopsy [EBB], and esophagogastroduodenoscopy with esophageal biopsy [EsB]) at our Aerodigestive Center for evaluation of SUA. Children with known cystic fibrosis, primary ciliary dyskinesia, and aspiration-related lung disease were excluded. RESULT/RESULTS:Twenty-four children (21 males) ages 2-16 years were studied. Elevated BAL eosinophils were found in 10 (42%) patients, endobronchial eosinophils in 16 (67%); 7 (29%) had endobronchial eosinophils without elevated BAL eosinophils. Esophageal eosinophils were found in 11 (46%) patients. There was a correlation between the amount of eosinophils in BAL and EBB (R = 0.43, P = 0.05) airway eosinophils, defined as elevated BAL and/or EBB eosinophils, correlated with esophageal eosinophils (R = 0.41, P = 0.047). CONCLUSION/CONCLUSIONS:We concluded that airway and esophageal eosinophils are frequently present in children with SUA.
PMID: 30353711
ISSN: 1099-0496
CID: 3373392

Aerodigestive dysbiosis in children with chronic cough

Kazachkov, Mikhail; Kapoor, Bianca C; Malecha, Patrick W; Wu, Benjamin G; Li, Yonghua; Levine, Jeremiah; Erkman, Jessica; Fitzgerald, Kathryn; Moy, Libia; Segal, Leopoldo N
In pediatric patients with chronic cough, respiratory culture techniques commonly yield negative results. Studies using culture-independent methods have found a high relative abundance of oral microbes in the lower airways, suggesting that the topographical continuity, and dynamics of the intraluminal contents of the aerodigestive system likely influence the lower airway microbiota. We hypothesize that in subjects with chronic cough, clinical diagnosis will correlate with distinct microbial signatures detected using culture-independent methods.
PMID: 29984544
ISSN: 1099-0496
CID: 3191752

Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations

Kazachkov, Mikhail; Palma, Jose-Alberto; Norcliffe-Kaufmann, Lucy; Bar-Aluma, Bat-El; Spalink, Christy L; Barnes, Erin P; Amoroso, Nancy E; Balou, Stamatela M; Bess, Shay; Chopra, Arun; Condos, Rany; Efrati, Ori; Fitzgerald, Kathryn; Fridman, David; Goldenberg, Ronald M; Goldhaber, Ayelet; Kaufman, David A; Kothare, Sanjeev V; Levine, Jeremiah; Levy, Joseph; Lubinsky, Anthony S; Maayan, Channa; Moy, Libia C; Rivera, Pedro J; Rodriguez, Alcibiades J; Sokol, Gil; Sloane, Mark F; Tan, Tina; Kaufmann, Horacio
BACKGROUND:Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS:We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS:Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS:Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.
PMCID:6084453
PMID: 30053970
ISSN: 1532-3064
CID: 3216612

Using the Objective Structured Clinical Examination to Assess ACGME Competencies in Pediatric Gastroenterology Fellows

Solomon, Aliza B; Reed, Rachel; Benkov, Keith; Kingsbery, Joseph; Lusman, Sarah S; Malter, Lisa B; Levine, Jeremiah; Rabinowitz, Simon S; Wolff, Martin; Zabar, Sondra; Weinshel, Elizabeth
BACKGROUND:The Accreditation Council for Graduate Medical Education has described 6 core competencies with which trainees should demonstrate proficiency. Using the Objective Structured Clinical Examination (OSCE), we aimed to assess 4 of these competencies among Pediatric Gastrointestinal (GI) fellows (PGs). METHODS:Eight first-year PGs from 6 medical centers in the New York area participated in a 4-station OSCE with trained standardized patient (SP) actors. The cases included an emergency department (ED) consult, or "ED Consult" for lower gastrointestinal bleeding; "Breaking Bad News" focusing on CF nutritional complications; "Second Opinion" for abdominal pain; "Transition of Care" for inflammatory bowel disease. At each station, attending faculty observed the encounters behind a 1-way mirror. SPs and faculties provided immediate feedback to the examined fellows. Previously validated OSCE checklists were used to assess performance. On completion, fellows attended debriefing sessions and completed surveys about the educational value. RESULTS:Median overall milestone competency scores were 6.9 (PC1), 4.8 (PC2), 5.9 (MK1), 5.7 (MK2), 6.4 (ICS1), 6.9 (Prof1), and 6.7 (Prof3). Overall, fellows score highest (7/9) on the inflammatory bowel disease "Transition of Care" case, found the "Breaking Bad News" Cystic Fibrosis OSCE to be the most challenging, and were most comfortable with the "ED Consult" OSCE, as a commonly encountered scenario. Overall, the fellows rated the educational value of the program highly. CONCLUSIONS:To our knowledge, although the OSCE has been validated in other medical fields, this is the first OSCE program developed for PGs fellows. These OSCEs have included Accreditation Council for Graduate Medical Education competencies, serving to assess fellows' skills in these areas while exposing them to challenging medical and psychosocial cases that they may not frequently encounter.
PMID: 27782961
ISSN: 1536-4801
CID: 2956102