Browsing by Author "Heyman, Melvin B."
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Item Analysis of Using the Total White Blood Cell Count to Define Severe New-onset Ulcerative Colitis in Children(Wolters Kluwer, 2020-09) Mack, David R.; Saul, Bradley; Boyle, Brendan; Griffiths, Anne; Sauer, Cary; Markowitz, James; LeLeiko, Neal; Keljo, David; Rosh, Joel R.; Baker, Susan S.; Steiner, Steve; Heyman, Melvin B.; Patel, Ashish S.; Baldassano, Robert; Noe, Joshua; Rufo, Paul; Kugathasan, Subra; Walters, Thomas; Marquis, Alison; Thomas, Sonia M.; Denson, Lee; Hyams, Jeffrey; Pediatrics, School of MedicineObjectives: The aim of this study was to assess common laboratory tests in identifying severe ulcerative colitis in children at diagnosis. Methods: A cohort of 427 children 4 to 17 years of age newly diagnosed with ulcerative colitis (UC) was prospectively enrolled. Boosted classification trees were used to characterize predictive ability of disease attributes based on clinical disease severity using Pediatric Ulcerative Colitis Activity Index (PUCAI), severe (65+) versus not severe (<65) and total Mayo score, severe (10-12) versus not severe (<10); mucosal disease by Mayo endoscopic subscore, severe (3) versus not severe (<3); and extensive disease versus not extensive (left-sided and proctosigmoiditis). Results: Mean age was 12.7 years; 49.6% (n = 212) were girls, and 83% (n = 351) were Caucasian. Severe total Mayo score was present in 28% (n = 120), mean PUCAI score was 49.8 ± 20.1, and 33% (n = 142) had severe mucosal disease with extensive involvement in 82% (n = 353). Classification and regression trees identified white blood cell count, erythrocyte sedimentation rate, and platelet count (PLT) as the set of 3 best blood laboratory tests to predict disease extent and severity. For mucosal severity, albumin (Alb) replaced PLT. Classification models for PUCAI and total Mayo provided sensitivity of at least 0.65 using standard clinical cut-points with misclassification rates of approximately 30%. Conclusions: A combination of the white blood cell count, erythrocyte sedimentation rate, and either PLT or albumin is the best predictive subset of standard laboratory tests to identify severe from nonsevere clinical or mucosal disease at diagnosis in relation to objective clinical scores.Item Association of Baseline Luminal Narrowing With Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn Disease(Oxford University Press, 2021) Ta, Allison D.; Ollberding, Nicholas J.; Karns, Rebekah; Haberman, Yael; Alazraki, Adina L.; Hercules, David; Baldassano, Robert; Markowitz, James; Heyman, Melvin B.; Kim, Sandra; Kirschner, Barbara; Shapiro, Jason M.; Noe, Joshua; Oliva-Hemker, Maria; Otley, Anthony; Pfefferkorn, Marian; Kellermayer, Richard; Snapper, Scott; Rabizadeh, Shervin; Xavier, Ramnik; Dubinsky, Marla; Hyams, Jeffrey; Kugathasan, Subra; Jegga, Anil G.; Dillman, Jonathan R.; Denson, Lee A.; Pediatrics, School of MedicineBackground: Transmural healing (TH) is associated with better long-term outcomes in Crohn disease (CD), whereas pretreatment ileal gene signatures encoding myeloid inflammatory responses and extracellular matrix production are associated with stricturing. We aimed to develop a predictive model for ileal TH and to identify ileal genes and microbes associated with baseline luminal narrowing (LN), a precursor to strictures. Materials and methods: Baseline small bowel imaging obtained in the RISK pediatric CD cohort study was graded for LN. Ileal gene expression was determined by RNASeq, and the ileal microbial community composition was characterized using 16S rRNA amplicon sequencing. Clinical, demographic, radiologic, and genomic variables were tested for association with baseline LN and future TH. Results: After controlling for ileal location, baseline ileal LN (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.8), increasing serum albumin (OR, 4; 95% CI, 1.3-12.3), and anti-Saccharomyces cerevisiae antibodies IgG serology (OR, 0.97; 95% CI, 0.95-1) were associated with subsequent TH. A multivariable regression model including these factors had excellent discriminant power for TH (area under the curve, 0.86; positive predictive value, 80%; negative predictive value, 87%). Patients with baseline LN exhibited increased Enterobacteriaceae and inflammatory and extracellular matrix gene signatures, coupled with reduced levels of butyrate-producing commensals and a respiratory electron transport gene signature. Taxa including Lachnospiraceae and the genus Roseburia were associated with increased respiratory and decreased inflammatory gene signatures, and Aggregatibacter and Blautia bacteria were associated with reduced extracellular matrix gene expression. Conclusions: Pediatric patients with CD with LN at diagnosis are less likely to achieve TH. The association between specific microbiota, wound healing gene programs, and LN may suggest future therapeutic targets.Item Chronic pancreatitis: Pediatric and adult cohorts show similarities in disease progress despite different risk factors(Lippincott, Williams & Wilkins, 2020-04) Schwarzenberg, Sarah J.; Uc, Aliye; Zimmerman, Bridget; Wilschanski, Michael; Wilcox, C. Mel; Whitcomb, David C.; Werlin, Steven L.; Troendle, David; Tang, Gong; Slivka, Adam; Singh, Vikesh K.; Sherman, Stuart; Shah, Uzma; Sandhu, Bimaljit S.; Romagnuolo, Joseph; Rhee, Sue; Pohl, John F.; Perito, Emily R.; Ooi, Chee Y.; Nathan, Jaimie D.; Muniraj, Thiruvengadam; Morinville, Veronique D.; McFerron, Brian; Mascarenhas, Maria; Maqbool, Asim; Liu, Quin; Lin, Tom K.; Lewis, Michele; Husain, Sohail Z.; Himes, Ryan; Heyman, Melvin B.; Guda, Nalini; Gonska, Tanja; Giefer, Matthew J.; Gelrud, Andres; Gariepy, Cheryl E.; Gardner, Timothy B.; Freedman, Steven D.; Forsmark, Christopher E.; Fishman, Douglas S.; Cote, Gregory A.; Conwell, Darwin; Brand, Randall E.; Bellin, Melena; Barth, Bradley; Banks, Peter A.; Anderson, Michelle A.; Amann, Stephen T.; Alkaade, Samer; Abu-El-Haija, Maisam; Abberbock, Judah N.; Lowe, Mark E.; Yadav, Dhiraj; Medicine, School of MedicineObjectives: To investigate the natural history of chronic pancreatitis (CP), patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared. Methods: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1,063 adults were compared using appropriate statistical tests for categorical and continuous variables. Results: Alcohol was a risk in 53% of adults and 1% of children (p<0.0001); tobacco in 50% of adults and 7% of children (p<0.0001). Obstructive factors were more common in children (29% vs 19% in adults, p=0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, p=0.107). Diabetes was more common in adults than children (36% vs 4% respectively, p<0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared to INSPPIRE subjects. These two cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, p=0.011). Conclusions: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.Item Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From the INSPPIRE Study(Wolters Kluwer, 2020-07) Dike, Chinenye R.; Zimmerman, Bridget; Zheng, Yuhua; Wilschanski, Michael; Werlin, Steven L.; Troendle, David; Shah, Uzma; Schwarzenberg, Sarah Jane; Pohl, John; Perito, Emily R.; Ooi, Chee Y.; Nathan, Jaimie D.; Morinville, Veronique D.; McFerron, Brian; Mascarenhas, Maria; Maqbool, Asim; Liu, Quin; Lin, Tom K.; Husain, Sohail Z.; Heyman, Melvin B.; Gonska, Tanja; Giefer, Matthew J.; Gariepy, Cheryl E.; Fishman, Douglas S.; Bellin, Melena; Barth, Bradley; Abu-El-Haija, Maisam; Lowe, Mark E.; Uc, Aliye; Pediatrics, School of MedicineObjective: The aim of the study was to determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a cuRE) sites. Study design: Data were collected from INSPPIRE and analyzed per US regions and "non-US" sites. Between-group differences were compared by Pearson chi-square test. Differences in disease burden were compared by Kruskal-Wallis test. Results: Out of the 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South, and 84 (18%) at non-US sites. Hispanic ethnicity was more common in South (P < 0.0001); white race in Northeast (P = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (P = 0.0002 and P = 0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (P = 0.002). Gallstones were more frequent in South (P = 0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non-United States (P < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly as total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non-US sites (P < 0.0001). Conclusions: This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non-United States sites need to be further explored.Item Health-Related Quality of Life in Pediatric Acute Recurrent or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors(Wiley, 2022) Tham, See Wan; Wang, Fuchenchu; Gariepy, Cheryl E.; Cress, Gretchen A.; Abu-El-Haija, Maisam A.; Bellin, Melena D.; Ellery, Kate M.; Fishman, Douglas S.; Gonska, Tanja; Heyman, Melvin B.; Lin, Tom K.; Maqbool, Asim; McFerron, Brian A.; Morinville, Veronique D.; Nathan, Jaimie D.; Ooi, Chee Y.; Perito, Emily R.; Schwarzenberg, Sarah Jane; Sellers, Zachary M.; Shah, Uzma; Troendle, David M.; Wilschanski, Michael; Zheng, Yuhua; Yuan, Ying; Lowe, Mark E.; Uc, Aliye; Palermo, Tonya M.; INternational Study Group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) and Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC); Pediatrics, School of MedicineObjectives: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL. Methods: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment. Results: The sample included 368 children (54.3% girls, mean age = 12.7years, standard deviation [SD] = 3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (M = 38.5, SD = 16.0) was demonstrated while psychosocial HRQOL (M = 49.5, SD = 10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (B = -10.28, P < 0.001), episodic and constant abdominal pain (B = 04.66, P = 0.03; B = -13.25, P < 0.001) were associated with low physical HRQOL, after accounting for ARP/CP status, age, sex, exocrine, and endocrine disease (F [9, 271] = 8.34, P < 0.001). Borderline and clinical levels of emotional and behavioral problems (B = -10.18, P < 0.001; B = -15.98, P < 0.001), and constant pain (B = -4.46, P < 0.001) were associated with low psychosocial HRQOL (F [9, 271] = 17.18, P < 0.001). Conclusions: Findings highlight the importance of assessing HRQOL and treating pain and psychosocial problems in this vulnerable group of children.Item Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis(Wolters Kluwer, 2018-09) Uc, Aliye; Zimmerman, M. Bridget; Wilschanski, Michael; Werlin, Steven L.; Troendle, David; Shah, Uzma; Schwarzenberg, Sarah Jane; Rhee, Sue; Pohl, John F.; Perito, Emily R.; Palermo, Joseph J.; Ooi, Chee Y.; Liu, Quin; Lin, Tom K.; Morinville, Veronique D.; McFerron, Brian A.; Husain, Sohail Z.; Himes, Ryan; Heyman, Melvin B.; Gonska, Tanja; Giefer, Matthew J.; Gariepy, Cheryl E.; Freedman, Steven D.; Fishman, Douglas S.; Bellin, Melena D.; Barth, Bradley; Abu-El-Haija, Maisam; Lowe, Mark E.; Pediatrics, School of MedicineOBJECTIVE: The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). METHODS: We determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations. RESULTS: Of 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups. CONCLUSIONS: Obesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study.Item INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE Cohort Study: Design and Rationale for INSPPIRE 2 From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer(Wolters Kluwer, 2018-11) Uc, Aliye; Perito, Emily R.; Pohl, John F.; Shah, Uzma; Abu-El-Haija, Maisam; Barth, Bradley; Bellin, Melena D.; Ellery, Kate M.; Fishman, Douglas S.; Gariepy, Cheryl E.; Giefer, Matthew J.; Gonska, Tanja; Heyman, Melvin B.; Himes, Ryan W.; Husain, Sohail Z.; Maqbool, Asim; Mascarenhas, Maria R.; McFerron, Brian A.; Morinville, Veronique D.; Lin, Tom K.; Liu, Quin Y.; Nathan, Jaimie D.; Rhee, Sue J.; Ooi, Chee Y.; Sellers, Zachary M.; Schwarzenberg, Sarah Jane; Serrano, Jose; Troendle, David M.; Werlin, Steven L.; Wilschanski, Michael; Zheng, Yuhua; Yuan, Ying; Lowe, Mark E.; Pediatrics, School of MedicineWe created the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE 2) cohort to study the risk factors, natural history, and outcomes of pediatric acute recurrent pancreatitis and chronic pancreatitis (CP). Patient and physician questionnaires collect information on demographics, clinical history, family and social history, and disease outcomes. Health-related quality of life, depression, and anxiety are measured using validated questionnaires. Information entered on paper questionnaires is transferred into a database managed by Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer's Coordinating and Data Management Center. Biosamples are collected for DNA isolation and analysis of most common pancreatitis-associated genes.Twenty-two sites (18 in the United States, 2 in Canada, and 1 each in Israel and Australia) are participating in the INSPPIRE 2 study. These sites have enrolled 211 subjects into the INSPPIRE 2 database toward our goal to recruit more than 800 patients in 2 years. The INSPPIRE 2 cohort study is an extension of the INSPPIRE cohort study with a larger and more diverse patient population. Our goals have expanded to include evaluating risk factors for CP, its sequelae, and psychosocial factors associated with pediatric acute recurrent pancreatitis and CP.Item Pancreas Divisum in Pediatric Acute Recurrent and Chronic Pancreatitis: Report From INSPPIRE(Wolters Kluwer, 2019-07-01) Lin, Tom K.; Abu-El-Haija, Maisam; Nathan, Jaimie D.; Palermo, Joseph P.; Barth, Bradley; Bellin, Melena; Fishman, Douglas S.; Freedman, Steven D.; Gariepy, Cheryl E.; Giefer, Matthew J.; Gonska, Tanja; Heyman, Melvin B.; Himes, Ryan; Husain, Sohail Z.; Liu, Quin; Maqbool, Asim; Mascarenhas, Maria; McFerron, Brian; Morinville, Veronique D.; Ooi, Chee Y.; Perito, Emily; Pohl, John F.; Rhee, Sue; Schwarzenberg, Sarah Jane; Shah, Uzma; Troendle, David; Werlin, Steven L.; Wilschanski, Michael; Zimmerman, M. Bridget; Lowe, Mark E.; Uc, Aliye; Pediatrics, School of MedicineThe significance of pancreas divisum (PD) as a risk factor for pancreatitis is controversial. We analyzed the characteristics of children with PD associated with acute recurrent or chronic pancreatitis to better understand its impact. Patients and Methods: We compared children with or without PD in the well-phenotyped INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables, Pearson χ2 or Fisher exact test for categorical variables. Results: PD was found in 52 of 359 (14.5%) subjects, a higher prevalence than the general population (∼7%). Females more commonly had PD (71% vs. 55%; P=0.02). Children with PD did not have a higher incidence of mutations in SPINK1, CFTR, CTRC compared with children with no PD. Children with PD were less likely to have PRSS1 mutations (10% vs. 34%; P<0.01) or a family history of pancreatitis (P<0.05), and more likely to have hypertriglyceridemia (11% vs. 3%; P=0.03). Children with PD underwent significantly more endoscopic procedures and pancreatic sphincterotomy. Patients with PD had fewer attacks of acute pancreatitis (P=0.03) and were less likely to develop exocrine pancreatic insufficiency (P=0.01). Therapeutic endoscopic retrograde cholangiopancreatography was considered most helpful if pancreatic duct was impacted with stones (83% helpful). Conclusions: PD is likely a risk factor for acute recurrent pancreatitis and chronic pancreatitis in children that appears to act independently of genetic risk factors. Patients with PD and stones obstructing the pancreatic duct benefit most from therapeutic endoscopic retrograde cholangiopancreatography.Item Pediatric chronic pancreatitis without prior acute or acute recurrent pancreatitis: A report from the INSPPIRE consortium(Elsevier, 2020-06) Abu-El-Haija, Maisam; Lowe, Mark; Barth, Bradley; Bellin, Melena D.; Fishman, Douglas S.; Freedman, Steve; Gariepy, Cheryl; Giefer, Matthew J.; Gonska, Tanja; Heyman, Melvin B.; Himes, Ryan; Husain, Sohail; Lin, Tom K.; Liu, Quin; Mascarenhas, Maria R.; Maqbool, Asim; McFerron, Brian; Morinville, Veronique; Nathan, Jaimie; Ooi, Chee Y.; Perito, Emily; Pohl, John F.; Schwarzenberg, Sarah Jane; Shah, Uzma; Troendle, David; Werlin, Steven; Wilschanski, Michael; Zimmerman, Bridget; Uc, Aliye; Pediatrics, School of MedicineItem Risk Factors for Rapid Progression From Acute Recurrent to Chronic Pancreatitis in Children: Report From INSPPIRE(Wolters Kluwer, 2019-08-01) Liu, Quin Y.; Abu-El-Haija, Maisam; Husain, Sohail Z.; Barth, Bradley; Bellin, Melena; Fishman, Douglas S.; Freedman, Steven D.; Gariepy, Cheryl E.; Giefer, Matthew J.; Gonska, Tanja; Heyman, Melvin B.; Himes, Ryan; Lin, Tom K.; Maqbool, Asim; Mascarenhas, Maria; McFerron, Brian A.; Morinville, Veronique D.; Nathan, Jaimie D.; Ooi, Chee Y.; Perito, Emily R.; Pohl, John F.; Rhee, Sue; Schwarzenberg, Sarah J.; Shah, Uzma; Troendle, David; Werlin, Steven L.; Wilschanski, Michael; Zimmerman, M. Bridget; Lowe, Mark E.; Uc, Aliye; Pediatrics, School of MedicineObjective To determine the rate of progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children and assess risk factors. Study Design Data were collected from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) cohort. Kaplan-Meier curves were constructed to calculate duration of progression from initial attack of acute pancreatitis (AP) to CP. Log-rank test was used to compare survival (non-progression) probability distribution between groups. Cox proportional hazard regression models were fitted to obtain hazard ratio (with 95% CI) of progression for each risk variable. Results Of 442 children, 251 had ARP, 191 CP. The median time of progression from initial attack of AP to CP was 3.79 years. The progression was faster in those age ≥6 years at the first episode of AP compared to those age <6 years (median time to CP: 2.91 vs 4.92 years; p=0.01). Children with pathogenic PRSS1 variants progressed more rapidly to CP compared to children without PRSS1 variants (median time to CP: 2.52 vs 4.48 years; p=0.003). Within six years after the initial AP attack, cumulative proportion with exocrine pancreatic insufficiency (EPI) was 18.0% (95% CI: 12.4%, 25.6%); diabetes mellitus was 7.7% (95% CI: 4.2%, 14.1%). Conclusions Children with ARP rapidly progress to CP, EPI and diabetes. The progression to CP is faster in children who were ≥6 years at the first episode of AP or with pathogenic PRSS1 variants. The factors that impact the aggressive disease course in childhood warrant further investigation.