Jennifer A. Strople

Prevalence of subclinical vitamin K deficiency in cholestatic liver disease.

Background and Objective: Prothrombin time (PT), a surrogate marker of vitamin K deficiency, may underestimate the prevalence of vitamin K deficiency in cholestatic liver disease. This study investigated the frequency of vitamin K deficiency in children and adults with cholestatic liver disease by determining plasma protein induced in vitamin K absence II (PIVKA-II), and assessed the relation between plasma PIVKA-II levels and markers of cholestasis, measured PT, international normalized ratio (INR), serum undercarboxylated osteocalcin (ucOC), serum vitamins A and E, and serum 25-hydroxyvitamin D levels. Patients and Methods: Blood was collected from patients with cholestatic liver disease for liver biochemistries, PT, INR, bile acids, 25-hydroxyvitamin D, vitamin A, vitamin E, ucOC, and PIVKA-II. Results: Thirty-one patients were enrolled (age range 0.5–54 years, median age 5.7 years, 17 females). Nine patients (29%) had increased INRs, whereas 21 (68%) had elevated plasma PIVKA-II levels. All patients with increased INRs had increased plasma PIVKA-II. Fifteen of 21 patients with increased plasma PIVKA-II were receiving supplemental vitamin K therapy (range 7.8–700 μg/kg/day). Plasma PIVKA-II levels were positively correlated with serum conjugated bilirubin, bile acids, aspartate aminotransferase, alanine aminotransferase, PT, INR, and serum ucOC (P ≤ 0.02) and negatively correlated with serum 25-hydroxyvitamin D levels (P = 0.01). Twenty-two patients (71%) had vitamin D deficiency, 9 patients (29%) had vitamin A deficiency, and 2 patients (6%) had vitamin E deficiency. Conclusions: Despite vitamin K supplementation, elevation of plasma PIVKA-II suggesting ongoing vitamin K deficiency is common in cholestatic liver disease. Better strategies for vitamin K supplementation and dosing guidelines are needed.

Tubulointerstitial nephritis: an extraintestinal manifestation of Crohn disease in children.

Extraintestinal manifestations and complications occur in up to 35% of pediatric patients with inflammatory bowel disease (IBD) and can involve almost any organ system (1). The association of renal and urinary complications with Crohn disease (CD) has been well described (2,3). Although the most com

Pediatric gastroesophageal reflux disease--current perspectives.

Purpose of reviewAlthough heartburn and regurgitation are common manifestations of gastroesophageal reflux disease (GERD), otolaryngologic or respiratory symptoms may be the only indication of GERD. This review focuses on the recent developments in the pathophysiology, diagnosis, and treatment of GERD and their implications in pediatrics. Recent findingsNewer diagnostic modalities include intraesophageal impedance and Bravo wireless pH monitoring. Impedance technology measures both acid and non-acid reflux, whereas the Bravo capsule allows prolonged pH monitoring under more physiologic conditions. In managing children with GERD, there is increasing evidence that they need higher dosages of acid suppressive therapy to achieve clinical response. Alternative therapeutic options are also currently being explored, including pharmacotherapy that targets the primary mechanism for GERD. Endoluminal therapy for GERD in adults as an alternative to surgery has been an exciting development. At present, two of these procedures, Stretta (using radiofrequency energy) and Endocinch (gastroplication), have been approved by the Food and Drug Administration for use in adults. SummaryImpedance technology has increased our understanding of acid and nonacid reflux; however, normal values for children are not yet established. There are also limitations to the applicability of the new endoluminal therapies in children. Further research is needed before these developments can be recommended for use in pediatric practice.

North American Pediatric Gastroenterology Fellowship Needs Assessment in Inflammatory Bowel Disease: Trainee and Program Director Perspectives.

Background:Pediatric inflammatory bowel disease (IBD) care is complex and rapidly evolving. The Crohns and Colitis Foundation of America and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition cosponsored a needs assessment survey of pediatric gastroenterology trainees and program directors (PDs) to inform on educational programming. Methods:A Web-based, self-completed survey was provided to North American trainees and PDs during the 2013–2014 academic year. Standard descriptive statistics summarized demographics and responses. Results:One hundred sixty-six of 326 (51%) trainees (62% female) and 37 of 74 (50%) PDs responded. Median trainees per program = 5 and median total faculty = 10 (3 IBD experts); 15% of programs did not have a self-identified “IBD expert” faculty member. Sixty-nine percent of trainees were confident/somewhat confident in their IBD inpatient training, whereas 54% were confident/somewhat confident in their outpatient training. Trainees identified activities that would most improve their education, including didactics (55%), interaction with national experts (50%), trainee-centered IBD Web resources (42%), and increased patient exposure (42%). Trainees were most confident in managing inpatient active Crohns disease/ulcerative colitis, phenotype classification, managing biological therapies, and using clinical disease activity indices. They were least confident in managing J-pouch complications, performing pouchoscopy, managing extraintestinal manifestations, and ostomy-related complications. Eighty-five percent would like an IBD-focused training elective. Most directors (86%) would allow trainees to do electives at other institutions. Conclusions:This IBD needs assessment survey of pediatric gastroenterology trainees and PDs demonstrated a strong resource commitment to IBD training and clinical care. Areas for educational enrichment emerged, including pouch and ostomy complications.

Biologic Therapy in Pediatric Inflammatory Bowel Disease

The incidence of pediatric inflammatory bowel disease (IBD) has risen over the past several decades and therapeutic strategies continue to evolve. Many unique considerations must be taken into account when selecting the optimal therapy for a pediatric IBD patient, including the effect of therapy on growth parameters, the cummulative or long-term adverse effects of treatments, and the inherently longer duration of therapy give the young age at diagnosis. Biologic agents have been used to treat pediatric IBD for several decades. This chapter reviews the biologic agents currently used to treat this population, the indications for use in pediatric Crohn’s disease (CD) and ulcerative colitis (UC), outcomes associated with these medications, including impact on growth and bone health, and adverse events, specfically malignancy risks. Strategies and recommendations for vaccination of peidatric IBD patients receiving biologic therapy are also reviewed.

Serologic reactivity reflects clinical expression of ulcerative colitis in children

Background In contrast to pediatric Crohns disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.

Suboptimal Early Outcomes following Standardized Induction Therapy in Children Newly Diagnosed with Ulcerative Colitis: The Protect Study

Jeffrey S. Hyams , Sonia Davis, David R. Mack , Brendan Boyle, Anne M. Griffiths, Neal S. Leleiko, Cary G.Sauer, David J. Keljo, James Markowitz, Susan Baker, Joel Rosh, Robert N. Baldassano, Ashish Patel, Marian Pfefferkorn, Anthony Otley, Melvin Heyman, Joshua Noe, Maria OlivaHemker, Paul Rufo, Jennifer Strople, David Ziring, Stephen Guthery, Boris Sudel, Keith Benkov, Prateek Wali, Dedrick Moulton, Jonathan Evans, Michael Kappelman , Alison Marquis, Francisco A. Sylvester, Margaret H. Collins, Suresh Venkateswaran, Marla Dubinsky, Krista L. Spada, Ashley Britt, Bradley Saul, Nathan Gotman, Jose Serrano, Subra Kugathasan, Thomas Walters, Lee A. Denson

Sa1999 Patient Related Outcomes and Disease Activity Indices in New Onset Pediatric Ulcerative Colitis: The PROTECT Study

Patient Related Outcomes and Disease Activity Indices in New Onset Pediatric Ulcerative Colitis: The PROTECT Study Thomas D. Walters, David R. Mack, Brendan Boyle, Anne M. Griffiths, Cary Sauer, Neal S. Leleiko, James Markowitz, David J. Keljo, Joel R. Rosh, Susan S. Baker, Melvin B. Heyman, Ashish S. Patel, Marian D. Pfefferkorn, Robert Baldassano, Joshua D. Noe, Maria Oliva-Hemker, Anthony R. Otley, Paul A. Rufo, Keith J. Benkov, David Ziring, Prateek Wali, Jonathan Evans, Dedrick E. Moulton, Boris Sudel, Stephen L. Guthery, Jennifer A. Strople, Michael Kappelman, Neera Gupta, Krista Spada, Subra Kugathasan, Lee Denson, Jeffrey S. Hyams

Laboratory Evaluation of Inflammatory Bowel Disease

Although a thorough clinical history and physical exam may raise suspicion of Crohn disease (CD) or ulcerative colitis (UC), a focused laboratory evaluation can facilitate further differentiation between inflammatory bowel disease (IBD) and noninflammatory bowel disease – in particular, distinguishing between IBD, infectious processes and functional bowel disorders. These blood and stool studies, in combination with clinical presentation, can help determine which child may require more extensive or invasive testing, such as radiological and endoscopic evaluation to definitively diagnose IBD. Not only can a carefully chosen combination of blood and stool studies help determine which child may require more invasive testing, but they provide important information about inflammation and function of other organ systems involved. Additionally, some of these tests may provided insight into disease course (IBD serologies), be used for objective monitoring of disease activity (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and fecal calprotectin/lactoferrin) and are possible surrogates for mucosal healing (fecal calprotectin/lactoferrin), which facilitates the ability for the clinician to employ more precise targeted therapies to optimize care.