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| 1 | Visceral hypersensitivity and electromechanical dysfunction as therapeutic targets in pediatric functional dyspepsia显示文摘Functional gastrointestinal disorders(FGID) are common clinical syndromes diagnosed in the absence of biochemical,structural,or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age,geography,and culture. Etiology of abdominal pain associated FGIDs,including functional dyspepsia(FD),remains incompletely understood,but growing evidence implicates the importance of visceral hypersensitivity and electromechanical dysfunction. This manuscript explores data supporting the role of visceral hypersensitivity and electromechanical dysfunction in FD,with focus on pediatric data when available,and provides a summary of potential therapeutic targets. | John M Rosen Jose T Cocjin Jennifer V Schurman Jennifer M Colombo Craig A Friesen | 2014 | World Journal of Gastrointestinal Pharmacology and Therapeutics2014，5，3： | 16 |
| 2 | Therapeutic effect of melatonin on pediatric functional dyspepsia: A pilot study显示文摘AIM: To study the effectiveness of melatonin vs placebo in children with functional dyspepsia(FD).METHODS: The study was conducted as a double blind, randomized, placebo controlled crossover trial. Subjects were aged 8-17 years and diagnosed with FD based on Rome Ⅲ criteria. All subjects had failed to respond to 4 wk of acid suppression. Subjects receive a continuous two weeks of placebo and a continuous two weeks of melatonin in an order blinded to the participant and the study team. A Global Clinical Score was obtained to assess changes in abdominal pain. Pain was self-reported to be worse(grade 1), no change(grade 2), moderate improvement(grade 3), good(grade 4; minimal pain and not interfering with daily activities), or excellent(grade 5; no pain), respectively. A positive clinical response was defined as a grade 3 or greater response. Subjects wore an actigraph to assess sleep during a one week baseline period and during each treatment period. Subjects' sleep latency and total sleep time were recorded throughout the duration of the study. RESULTS: Fourteen subjects were enrolled and 12 completed the study. One withdrew prior to starting both melatonin and placebo and the other before starting melatonin. A positive clinical response(grade 3-5) was achieved in 42% of subjects on melatonin vs 50% of subjects on placebo(NS). Effect size was calculated and revealed a Cohen's D of 0.343 which demonstrates a medium effect favoring placebo. A grade 4 or grade 5 response was seen in 4 patients on melatonin and 5 patients on placebo. Baseline sleep parameters were in the healthy range with the longest sleep latency being just over 20 min(mean 7.46 ± 8.53 min) and the shortest sleep duration just over 7 h(mean 10.09 ± 2.72 h). The mean latency did not differ between periods of treatment with melatonin as compared to placebo(4.48 ± 6.45 min vs 3.58 ± 4.24 min; NS). The mean sleep duration did not differ between periods of treatment with melatonin as compared to placebo(9.90 ± 3.53 h vs 9.41 ± 2.70 h; NS).CONCLUSION: Melatonin does not appear to have efficacy in relieving pain in unselected pediatric FD. Future studies should consider FD subtypes, pathophysiologic mechanisms, and baseline sleep disturbances. | Katherine Zybach Craig A Friesen Jennifer V Schurman | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，1： | 6 |
| 3 | Eosinophils and mast cells as therapeutic targets in pediatric functional dyspepsia显示文摘There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation may serve as a mediator between psychologic and physiologic functions.This manuscript reviews the literature implicating two inflammatory cell types,mast cells and eosinophils,in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD.There are a number of inciting events which may initiate an inflammatory response,and the subsequent recruitment and activation of mast cells and eosinophils.These include internal triggers such as stress and anxiety,as well as external triggers such as microbes and allergens.Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils.Evidence exists to suggest that combining 'anti-inflammatory' medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD. | Craig A Friesen Jennifer V Schurman Jennifer M Colombo Susan M Abdel-Rahman | 2013 | World Journal of Gastrointestinal Pharmacology and Therapeutics2013，4，4： | 4 |
| 4 | Comparison of the use of wireless capsule endoscopy with magnetic resonance enterography in children with inflammatory bowel disease显示文摘BACKGROUND Magnetic resonance enterography (MRE) and wireless capsule endoscopy (WCE) are equally accepted modalities for noninvasive screening of small bowel involvement (SBI) in children with Crohn’s disease (CD) and indeterminate colitis (IC) albeit there is a paucity of data comparing the two and thereby guiding the clinician in selecting the ideal diagnostic approach. Therefore, the goal of this study is to provide additional evidence for capsule endoscopy role in the evaluation of established Crohn’s disease exacerbation compared to MRE in relation to Pediatric Crohn's Disease Activity Index (PCDAI), and histological indices. AIM To prospectively compare the findings of MRE and WCE and their agreement with PCDAI or histology in children with CD or IC. METHODS Consecutive patients diagnosed with CD and IC were screened for inclusion. After informed consent, patient’s demographic and clinical data was abstracted. The current pediatric disease activity index (PCDAI) and endoscopic findings were included. Patients underwent MRE and WCE including preprocedural patency capsule within a maximum of 7 d of each other. Pathological presence of active small bowel disease in ileal and duodenal biopsies were collected if the endoscopy was performed within 2 mo of the WCE study. Patients who failed to pass the PC were excluded from the study. WCE was read by two different experienced gastroenterologists (Attard TM and Colombo JM) blinded to each other's findings and to the findings on MRE (Mardis NJ). Agreement between WCE reviewers, WCE and MRE findings and concordance between positive PCDAI and SBI based on MRE compared with WCE was computed. RESULTS Forty-five patients were included in the study, 18 withdrew and 27 (20 males and 20 CD), mean age (standard deviation) 13.46 (2.4) years, completed the study protocol. There were no instances of capsule retention. Concordance between gastroenterologist reviewers was excellent for the diagnosis of small intestinal CD with good correlation between the two Lewis scores (r=0.875, P<0.001). Concordance between WCE and MRE was poor (69%). In CD patients, when both MRE and WCE were compared using PCDAI>10 as the standard reference reflecting active small intestinal CD, the sensitivity of MRE and WCE were 100% and 83% respectively and the specificity of MRE and WCE were 57.14% and 78.6%, respectively. If the histology in ileum or/and duodenum was used as the reference for active small bowel involvement, WCE had a higher specificity as compared to MRE (83.3% vs 50%). In patients with Crohn’s disease, those with a positive PCDAI (>10) were more likely to have a positive WCE as compared to those with a negative PCDAI (83% vs 21%;P=0.018). CONCLUSION We suggest that MRE and WCE have a complementary role in the assessment of SBI in CD. WCE detected SBI with a much higher specificity while MRE had a higher sensitivity. | Nadia Mazen Hijaz Thomas Mario Attard Jennifer Marie Colombo Neil Joseph Mardis Craig Alan Friesen | 2019 | World Journal of Gastroenterology2019，25，28： | 3 |
| 5 | Present state and future challenges in pediatric abdominal pain therapeutics research: Looking beyond the forest显示文摘At the present time, it is nearly impossible to treat pediatric functional gastrointestinal disorders associated with pain in an evidence based fashion. This is due to the overall lack of controlled studies and, even more importantly, the complexity of the contributors to disease phenotype which are not controlled or accounted for in most therapeutic trials. In this manuscript, we review the challenges of defining entry criteria, controlling for the large number of biopsychosocial factors which may effect outcomes, and understanding pharmacokinetic and pharmacodynamic factors when designing therapeutic trials for abdominal pain in children. We also review the current state of pediatric abdominal pain therapeutics and discuss trial design considerations as we move forward. | Craig A Friesen Jennifer V Schurman Susan M Abdel-Rahman | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 3 |
| 6 | Symptoms and Subtypes in Pediatric Functional Dyspepsia: Relation to Mucosal Inflammation and Psychological Functioning显示文摘 | Jennifer V Schurman Meenal Singh Vivekanand Singh Nancy Neilan Craig A Friesen | 2010 | Journal of Pediatric Gastroenterology and Nutrition2010，，3： | 2 |
| 7 | Treatment of eosinophilic gastroenteritis with montelukast显示文摘 | Mark R. Neustrom Craig Friesen | 1999 | The Journal of Allergy and Clinical Immunology1999，，2： | 1 |
| 8 | Conceptualization and Treatment of Chronic Abdominal Pain in Pediatric Gastroenterology Practice显示文摘 | Jennifer V Schurman Heather L Hunter Craig A Friesen | 2010 | Journal of Pediatric Gastroenterology and Nutrition2010，，1： | 1 |
| 9 | An Evaluation of Adult Electrogastrography Criteria in Healthy Children显示文摘 | Craig A. Friesen Zhiyue Lin Jennifer Verril Schurman Linda Andre Richard W. McCallum | 2006 | Digestive Diseases and Sciences2006，，10： | 1 |
| 10 | Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils显示文摘BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group. | Panamdeep Kaur Rachel Chevalier Craig Friesen Jamie Ryan Ashley Sherman Stephanie Page | 2023 | World Journal of Gastrointestinal Endoscopy2023，15，5： | 0 |
| 11 | Evaluation of clinical outcomes in an interdisciplinary abdominal pain clinic: A retrospective, exploratory review显示文摘BACKGROUND Pediatric functional gastrointestinal disorders(FGIDs)are common and wellaccepted to be etiologically complex in terms of the contribution of biological,psychological,and social factors to symptom presentations.Nonetheless,despite its documented benefits,interdisciplinary treatment,designed to address all of these factors,for pediatric FGIDs remains rare.The current study hypothesized that the majority of pediatric patients seen in an interdisciplinary abdominal pain clinic(APC)would demonstrate clinical resolution of symptoms during the study period and that specific psychosocial variables would be significantly predictive of GI symptom improvement.AIM To evaluate outcomes with interdisciplinary treatment in pediatric patients with pain-related FGIDs and identify patient characteristics that predicted clinical outcomes.METHODS Participants were 392 children,ages 8-18[M=13.8;standard deviation(SD)=2.7],seen between August 1,2013 and June 15,2016 in an interdisciplinary APC housed within the Division of Gastroenterology in a medium-sized Midwestern children's hospital.To be eligible,patients had to be 8 years of age or older and have had abdominal pain for≥8 wk at the time of initial evaluation.Medical and psychosocial data collected as part of standard of care were retrospectively reviewed and analyzed in the context of the observational study.Logistic regression was used to model odds of reporting vs never reporting improvement,as well as to differentiate rapid from slower improvers.RESULTS Nearly 70%of patients followed during the study period achieved resolution on at least one of the employed outcome indices.Among those who achieved resolution during follow up,43%to 49%did so by the first follow up(i.e.,within roughly 2 mo after initial evaluation and initiation of interdisciplinary treatment).Patient age,sleep,ease of relaxation,and depression all significantly predicted the likelihood of resolution.More specifically,the odds of clinical resolution were 14%to 16%lower per additional year of patient age(P<0.001 to P=0.016).The odds of resolution were 28%to 42%lower per 1-standard deviation(SD)increase on a pediatric sleep measure(P=0.006 to P<0.040).Additionally,odds of clinical resolution were 58%lower per 1-SD increase on parent-reported measure of depression(P=0.006),and doubled in cases where parents agreed that their children found it easy to relax(P=0.045).Furthermore,sleep predicted the rapidity of clinical resolution;that is,the odds of achieving resolution by the first follow up visit were 47%to 60%lower per 1-SD increase on the pediatric sleep measure(P=0.002).CONCLUSION Outcomes for youth with FGIDs may be significantly improved by paying specific attention to sleep,ensuring adequate skills for relaxation,and screening of and referral for treatment of comorbid depression. | Amanda D Deacy Craig A Friesen Vincent S Staggs Jennifer V Schurman | 2019 | World Journal of Gastroenterology2019，25，24： | 0 |
| 12 | Validation of methods to assess potential biomarkers in pediatric patients with esophageal eosinophilia显示文摘AIM:To validate methods for determining mast cell density,extracellular major basic protein content,and presence of fibrosis in esophageal eosinophilia.METHODS:Twenty specimens with > 20 eosinophils/high-power field(hpf) classified as high eosinophil density(HE) and 20 specimens with < 5 eosinophils/hpf classified as low esophageal density(LE) were identified.All 40 specimens underwent immunohistochemical staining and trichrome staining.Mast cell density,extracellular major basic protein(MBP) density,and presence of subepithelial fibrosis were assessed in a standardized manner.All specimens were evaluated by two separate observers and by a single observer on two separate occasions to evaluate reproducibility of the methods.RESULTS:A strong inter-observer correlation was noted for both peak and mean mast cell counts(r = 0.725,P < 0.0001 and r = 0.823,P < 0.0001).A strong intraobserver correlation also was noted for both peak and mean mast cell counts(r = 0.752,P < 0.0001 and r =0.878,P < 0.0001).A very strong inter-observer correlation was noted for both peak(τ = 0.867,P < 0.0001)and mean extracellular MBP densities(r = 0.925,P <0.0001).A very strong intra-observer correlation was noted for both peak(τ = 0.875;P < 0.0001) and mean extracellular MBP densities(r = 0.956,P < 0.0001).Excellent inter-rater reliability was found for fibrosis(κ= 0.887).Mast cell and MBP densities,as well as presence of fibrosis,were significantly increased in HE vs LE.The HE group had significantly higher intraepithelial mast cell peak(29.35 ± 21.61 vs 12.45 ± 8.26,P =0.002) and mean(19.84 ± 15.81 vs 6.35 ± 4.5,P =0.001) densities than the LE group.The HE group had significantly higher peak extracellular MBP(2.35 ± 0.67vs 0.45 ± 0.61,P < 0.001) and mean extracellular MBP(1.95 ± 0.76 vs 0.20 ± 0.29,P < 0.0001) densities than the LE group.Seventy-three percent of patients with HE(11/15) had fibrosis,whereas only 10% of patients with LE(1/10) had fibrosis(P < 0.01).MBP performed the best in predicting classification of HE vs LE,with mean MBP demonstrating 100% sensitivity and95% specificity at the optimal cut point.CONCLUSION:This study provides methodology and proof-of-concept for future evaluation of these biomarkers for differentiating esophageal eosinophilic diseases such as reflux esophagitis and eosinophilic esophagitis. | Jennifer M Colombo Nancy A Neilan Jennifer Verrill Schurman Craig A Friesen | 2013 | World Journal of Gastrointestinal Pharmacology and Therapeutics2013，4，4： | 0 |
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