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by by ranked innineclinicalspecialties andnationally of University ofPittsburgh School Pittsburgh isaffiliated withthe UPMC Children’s Hospitalof Spring 2019 •  •  •  •  •  In This Issue •  •  •  U.S. News&World Report and Nutrition , Podcast Series Division Faculty IBD Center the Importance ofDiet Aspects, Barriersto Care, New Pediatric Research Recent Publications From About theUPMCChildren’s Pediatric IBD:Unique New MotilityCenter About the Division of About theDivisionof UPMC Resources GI Research Spotlight Pediatric Insights

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An Update from theDivisionofPediatric Gastroenterology, Hepatology, andNutrition emerging technologies for diagnosisandmanagement ofpatientswithdysmotility. “Pediatric motility andneurogastroenterology isarapidly progressing field,with exciting type ofEhlers-Danlos syndrome. to studythespectrumofgastrointestinal andmotility disorders inpatientswithahypermobile Center. Duringherfellowship training, ofherresearch, asapart Dr. Soodhadtheopportunity motility andneuro-gastroenterology fellowship attheCincinnati Children’s HospitalMedical additional oftraining inmotility disorders. Shehascompleted ayear ofadvanced pediatric and functionalgastrointestinal disorders inchildren, whicheventually ledherto pursue an inWashington D.C. WhileatGeorgetown, Dr. Sooddeveloped aninterest inmotility the divisionofpediatricgastroenterology andhepatology atMedStarGeorgetown University University ofRochester MedicalCenter). Uponcompletion ofher fellowship, Dr. Soodjoined Dr. Soodisfellowship-trained inpediatricgastroenterology (Golisano Children’s Hospitalatthe GI Patients at UPMCChildren’s Treatment Optionsfor Pediatric New MotilityCenter Will Expand stimulation (gastric pacemaker) for gastroparesis. electro auriculardevice (EAD) for functionalgastrointestinal disorders, and gastric electrical neuromodulation devices, includingsacral nerve stimulation(SNS) for intractable constipation, Dr. Sood,whohas gained experience intakingcare ofpatientswhohave received various Neuromodulation isanexciting andemerging fieldwithinneurogastroenterology, explains of thesestudiesintheclinicalrealm. esophageal, andanorectal manometryprocedures, alongwithinterpretation andapplication Dr. Soodbringswithherto UPMC Children’s proficiency inperforming colonic, antroduodenal disorders, includingcolorectal disorders, inchildren,” says Dr. Sood. My fellowship training exposed meto awidegamut ofcomplex gastrointestinal motility of Gastroenterology, Hepatology, andNutritionwelcomed In Janua patients withmot the new motility andneurogastroenterology program for pediatric Vibha Sood,MD ry, UPMC Children’s HospitalofPittsburgh Division , asitsnewest faculty memberanddirector of ility orfunctionalgastrointestinal disorders. Continued onPage 5

2 Pediatric Insights: Gastroenterology, Hepatology, and Nutrition Spring 2019

Pediatric IBD: Unique Aspects, Barriers to Care, the Importance of Diet

Sandra Kim, MD, is a nationally recognized expert in pediatric and adolescent inflammatory bowel diseases (IBD). Dr. Kim co-directs the Inflammatory Bowel Disease Center at UPMC Children’s Hospital of Pittsburgh with David Keljo, MD, PhD, (founder of the IBD center.) She is an associate professor of at the University of Pittsburgh School of Medicine.

Dr. Kim has published extensively on Committee and sits on their National pediatric and adolescent IBD. Her clinical Scientific Advisory Committee. She is an and research interests focus on pediatric organizer of and frequent speaker at national “It is important for to IBD including adolescent transitioning and physician meetings such as Digestive Disease understand and remember that quality improvement. She has experience Week and Advances in IBD as well as national in basic science research on the impact of retreats for Pediatric GI Fellows. She has been pediatric IBD has characteristics gastrointestinal­ microbiota in IBD. She has awarded the Rosenthal Award by the mentored numerous fellows on IBD-related Foundation in 2011 and 2018 due to her that differ significantly from the research projects. leadership roles in patient education and same disease in adults. Keeping advocacy for individuals living with IBD. Dr. Kim sits on the Physician Leadership this in mind is of the utmost Committee of ImproveCareNow, and together with Sapana Shah, MD, began UPMC Children’s Unique Aspects of Pediatric IBD importance in the provision of participation in this national multicenter Dr. Kim continually emphasizes one care and therapeutic options.” quality improvement collaborative. fundamental aspect of IBD in pediatric patients that she believes ought to be a Dr. Kim has worked closely with the Crohn’s ­— Sandra Kim, MD defining mantra for the care of young patients and Colitis Foundation for more than 20 years with the disease: children with IBD are not and is currently Chair of the Foundation’s small adults with IBD. Government and Industry Affairs/Advocacy UPMCPhysicianResources.com/Pediatrics 3

“It is important for physicians to understand and remember that pediatric IBD has characteristics that differ significantly from the same disease in adults. Keeping this in mind is of the utmost importance in the provision of care and therapeutic options,” says Dr. Kim.

Dr. Kim explains that while symptomatology in children and adults may be similar, children with the disease often have a much more severe clinical presentation and manifestation of symptoms. Importantly, children also can be profoundly affected in terms of their growth and physiological development during childhood and adolescence. Furthermore, while both populations of patients can and often do have significant social and psychological impact that affect quality of life, IBD often hits About the UPMC Children’s IBD Center young patient much harder in this respect. The Inflammatory Bowel Disease (IBD) Center at UPMC Children’s employs a “These aspects of IBD in pediatric patients multidisciplinary team approach to provide each patient with the most advanced medical deserve significant attention by treating care available and compassionate support for the entire family. The team is comprised of physicians. However, there is another factor pediatric gastroenterologists, , IBD nurse practitioner, nurses, dietitian, of care in this disease that disproportionately psychologists, social worker, quality improvement specialist, and research coordinators affects children: the cost of care. Recent dedicated to improving the care of all children living with IBD. Currently, they care for over studies show that for patients under the age 900 children and young adults living with IBD in Pennsylvania and surrounding states. of 19, there exists an almost two-fold increase in the annual cost of IBD-related medical care The IBD Center provides comprehensive, state-of-the-art clinical care to control the versus adult aged patients. The reasons for symptoms of IBD and to improve the quality-of-life for children with the disease. this are numerous, and the problem globally The Center’s clinical services include: is of great importance in my work, research, • Individualiz ed clinical teaching sessions for newly diagnosed patients and advocacy on the national front to improve upon the disparities and barriers of care that • A full range of diagnostic services, such as upper , colonoscopy and currently exist for children and teens with IBD capsule endoscopy and their families,” says Dr. Kim. • Nutritional services to optimize children’s diets to treat their disease and facilitate growth

Advocacy for and Improving • C omplete services, including CT scans, MRI, and Access to Care • C omplete pediatric surgical services including minimally invasive Dr. Kim and other colleagues both at UPMC • A ccess to the latest, most innovative Children’s and nationally are involved in IBD care advocacy through the Crohn’s and Colitis • C linical trials for novel therapeutics Foundation. As the chair for government • In volvement in ImproveCareNow, a pediatric IBD quality improvement collaborative affairs and advocacy for the organization, she is involved in several ongoing projects Furthermore, the IBD Center is committed to providing educational and social support to improve access to care. to patients and families living with IBD. The Center hosts an annual education day for teenagers living with IBD (“IBD Grow”). In addition, the IBD Center is actively involved in Nutritional therapies for the treatment the Western PA chapter of the Crohn’s and Colitis Foundation. Members of the Center of IBD are in most instances not covered serve on the Board of Directors, volunteer in the Camp Oasis program, and donate time by insurance carriers. Formula therapies or and other efforts in all philanthropic events. nutritional supplements routinely can approach $1,000 or more per month. Continued on Page 4 4 Pediatric Insights: Gastroenterology, Hepatology, and Nutrition Spring 2019

Pediatric IBD Continued from Page 3

However, these therapies overall are less with colleagues to develop a position paper There is much research at UPMC Children’s expensive than many of the medications used for the Crohn’s and Colitis Foundation on on the basic and translational aspects of IBD, to treat IBD, which can often exceed $10,000 addressing medical nutrition access for along with active clinical trials for new per infusion or injection depending on the patients living with IBD. therapeutic agents with Dr. Kim and her medication/biologic agents but are generally colleagues in the gastroenterology and covered by insurance. However, nutritional “I have always believed that barriers to pediatric surgery divisions, but they also have therapies/medical foods usually are not care or access to effective therapies should ongoing projects examining how to improved covered by insurance companies; therefore, never be influenced by your doctor, your utilization and understanding of specific the patients and their families bear the brunt socioeconomic status, or where you happen defined diets as part of treatment in their of covering these costs. to live. Every child should have the same pediatric IBD patients. access to care,” says Dr. Kim. Work to combat this discrepancy and gap in One specific aspect of dietary that most insurance coverage is ongoing through Dr. Kim and colleagues advocate for at UPMC Diet and Dietary Therapies and the development and advocacy for a medical Their Importance to IBD Care Children’s is the use of the Crohn’s Disease nutrition equity access bill. Organizations Exclusion Diet (CDED). This diet addresses such as the American Academy of Pediatrics Diet and dietary compliance are highly a number of components that are thought (AAP), North American Society for Gastro­ important aspects to not only the clinical to be pro-inflammatory and lead to worse enterology, Hepatology, and Nutrition care of IBD patients but also to much ongoing symptoms and disease progression. (NASPGHAN), and the Crohn’s and Colitis research in the field — basic science and Foundation are actively advocating for this mechanistic studies and translational and “This type of diet for IBD patients excludes bill’s passage, and Dr. Kim and numerous clinical trials. The role of diet in general, in processed foods and components such as physician colleagues across the country terms of patients living with Crohn’s disease emulsifiers and additives that have been are working with these organizations to or ulcerative colitis, has produced significant shown in animal studies to breakdown the push for its adoption. research in recent years examining its lining of the intestinal tract and cause importance in broad populations, and how inflammation. It also cuts out simple sugars, “This measure would ensure that health diet affects the risks of developing IBD reflecting studies in both humans and animal insurance providers provide coverage for the as well as the course of the disease. models alike that show a high simple sugar formulas that are crucial or essential parts of diet can facilitate or increase the growth of many IBD patients’ ongoing care. Part of what ‘We know that diets consisting of high pro-inflammatory microbes. Saturated fats this act says is that if you have a condition proportions of processed foods and the can also lead to similar inflammatory that requires the use of these formulas/ additives they contain such as emulsifiers, responses,” says Dr. Kim. medical necessary foods, it is a part of your saturated fats, simple sugars, and others therapy and should be covered. As clinicians factor into the complexity of increasing not To be sure, the impact of dietary factors on and researchers, we can develop new and only the risk for developing IBD but worsening IBD is multifactorial. Diet plays roles in GI highly effective diets or formulas for our of inflammatory responses in those that tract permeability, immune cell activation, patients, but if they cannot get access to already have the condition. There is a food antigen recognition, and other aspects them either because they are prohibitively tremendous amount of research being that we are learning more about with each expensive or because insurance does not conducted examining the mechanistic role passing year. Dr. Kim explains that enteral cover it as a part of therapy, patients will of diet in relation to disease, how various diets therapy is useful as both induction and needlessly suffer,” says Dr. Kim or dietary components mechanistically alter maintenance regimens in pediatric Crohn’s disease progression and severity, inflammation, disease, and that specific diets such as the Dr. Kim and colleagues also are working locally bacterial composition of the gut, and how specific carbohydrate diet (SCD) or Crohn’s at UPMC Children’s to better understand all of this affects the development and disease exclusion diet (CDED) may be the barriers to care and therapeutic options progression of the disease,” says Dr. Kim. This effective in uncomplicated cases of IBD so that they can improve access to these ongoing research in the field is informing how (primary and adjunct). More research is effective parts of IBD care. One of the current clinicians utilize dietary interventions alone needed in all these areas, but Dr. Kim and her pediatric GI fellows, Angela Sandell, MD, and in conjunction with other medical and IBD colleagues are actively pursuing answers is working alongside Dr. Kim on several surgical treatments to improve the disease to many of these questions. advocacy and research projects examining profile and manifestations in patients. barriers to care, and Dr. Sandell is working UPMCPhysicianResources.com/Pediatrics 5

Pediatric IBD Continued from Page 3 New Motility Center Continued from Page 1

Designing a Motility Program In the long-term, Dr. Sood’s goal for the colleagues, and others, such as colorectal program is to make UPMC Children’s a surgery, small bowel transplant and intestinal Dr. Sood’s primary objective in her early regional and national referral center for rehabilitation programs. work at UPMC Children’s is to formally patients with complex motility and functional establish, staff, and grow the motility and GI disorders, and to provide training in “A motility program such as we are building neurogastroenterology program. Prior these disorders to new generations of will allow additional care and expertise to be to the establishment of this program at gastroenterology specialists. provided to some of our more complex UPMC Children’s, patients with motility patients, including our intestinal transplant and functional gastrointestinal disorders patients. I am looking forward to developing in need of specialized diagnostics studies and Multidisciplinary collaborations with my colleagues in that and procedures had to be referred to other Collaborations program, and to helping care for these institutions. The closest referral centers to The breadth of services and care that is patients who need long-term, complex Pittsburgh are in Cincinnati or Columbus, provided at UPMC Children’s will allow for follow-up,” says Dr. Sood. Ohio, which could mean travel of hundreds many collaborative efforts in the future of miles and many hours for some patients. Dr. Sood’s also plans to work in close between Dr. Sood, her gastroenterology collaboration with colleagues in colorectal Dr. Sood’s program now will allow these surgery and assist in developing a patients to remain at UPMC Children’s for multidisciplinary approach to taking care their entire spectrum of care, eliminating the of patients with longstanding, severe need for long trips and time away from home, Disorders Treated in the constipation issues or complicated anorectal improving continuity of care, and provision Neurogastroenterology malformation disorders. of seamless communications and patient and Motility Program discussions — all within the campus of “I think a combined approach to caring UPMC Children’s. for these patients is highly desirable, and • Anorectal malformations I hope that we will be able to establish a Dr. Sood has several goals for the new motility • Colonic dysmotility collaborative working methodology where and neurogastroenterology program that go I can lend my expertise in motility and beyond building the necessary infrastructure • Hirschsprung disease functional disorders to the care of these and staffing for the program. patients,” says Dr. Sood. • Intractable constipation and “Our goals are to build the program encopresis Another collaborative way that Dr. Sood into a center of excellence that provides ultimately sees her expertise being leveraged comprehensive evaluation and treatment • Dysphagia and feeding disorders in the patient care arena at UPMC Children’s of pediatric patients with complex motility is by extending the utilization of motility and functional gastrointestinal disorders, • Rumination studies in existing multidisciplinary and to build a multidisciplinary care aerodigestive program with her colleagues • Achalasia service with , intestinal in pediatric otolaryngology and rehabilitation, and the intestinal transplant who care for children with complex feeding • Gastroparesis center and aerodigestive programs for and ENT problems. the co-management of patients with • Intestinal pseudo-obstruction esophageal, intestinal, and colonic dysmotility,” says Dr. Sood. • Pre- and post-small bowel transplant motility evaluation

• Functional gastrointestinal disorders

• Aerodigestive disorders 6 Pediatric Insights: Gastroenterology, Hepatology, and Nutrition Spring 2019

Recent Publications From Division Faculty

Boggs K, Wang T, Orabi AI, Mukherjee A, Ooi CY, Perito E, Pohl JF, Rhee S, Hyams JS, Davis S, Mack DR, Boyle B, Eisses JF, Sun T, Wen L, Javed TA, Esni F, Schwarzenberg SJ, Shah U, Troendle D, Griffiths AM, LeLeiko NS, Sauer CG,Keljo DJ, Chen W, Husain SZ. Pancreatic Gene Werlin SL, Wilschanski M, Zimmerman MB, Markowitz J, Baker SS, Rosh J, Baldassano RN, Expression During Recovery After Pancreatitis Lowe ME, Uc A. Pancreas Divisum in Pediatric Patel A, Pfefferkorn M, Otley A, Heyman M, Reveals Unique Transcriptome Profiles. Acute Recurrent and : Noe J, Oliva-Hemker M, Rufo P, Strople J, Sci Rep. 2018 Jan 23; 8(1): 1406. Report From INSPPIRE. Ziring D, Guthery SL, Sudel B, Benkov K, J Clin Gastroenterol. 2018 Jun 2. Wali P, Moulton D, Evans J, Kappelman MD, Abu-El-Haija M, Kumar S, Quiros JA, Marquis A, Sylvester FA, Collins MH, Balakrishnan K, Barth B, Bitton S, Eisses JF, Abu-El-Haija M, Kumar S, Quiros JA, Venkateswaran S, Dubinsky M, Tangpricha V, Foglio EJ, Fox V, Francis D, Freeman AJ, Husain S, Morinville V. Plasma Exchange Spada KL, Britt A, Saul B, Gotman N, Wang J, Gonska T, Grover AS, Husain SZ, Kumar R, in Hypertriglyceridemic Pancreatitis in Serrano J, Kugathasan S, Walters T, Denson Lapsia S, Lin T, Liu QY, Maqbool A, Sellers ZM, Children. J Pediatr Gastroenterol Nutr. 2018 LA. Factors Associated With Early Outcomes Szabo F, Uc A, Werlin SL, Morinville VD. Jun; 66(6): e163. Following Standardised Therapy in Children Management of Acute Pancreatitis in the Párniczky A, Abu-El-Haija M, Husain S, With Ulcerative Colitis (PROTECT): Pediatric Population: A Clinical Report From Lowe M, Oracz G, Sahin-Tóth M, Szabó FK, A Multicentre Inception Cohort Study. the North American Society for Pediatric Uc A, Wilschanski M, Witt H, Czakó L, Lancet Gastroenterol Hepatol. 2017 Dec; Gastroenterology, Hepatology and Nutrition Grammatikopoulos T, Rasmussen IC, Sutton 2(12): 855-868. Pancreas Committee. J Pediatr Gastroenterol R, Hegyi P. EPC/HPSG Evidence-based Nutr. 2018 Jan; 66(1): 159-176. Lindoso L, Mondal K, Venkateswaran S, Guidelines for the Management of Pediatric Somineni HK, Ballengee C, Walters TD, Eisses JF, Husain SZ. Pancreatic Development. Pancreatitis. Pancreatology. 2018 Mar; Griffiths A, Noe JD, Crandall W, Snapper S, In Pediatric Gastrointestinal and , 18(2): 146-160. Rabizadeh S, Rosh JR, LeLeiko N, Guthery S, 6th Edition. Wyllie R, Hyams JS, Kay M, eds. Scheers I, Palermo JJ, Freedman S, Mack D, Kellermayer R, Gulati AS, Pfefferkorn Elsevier Saunders, Philadelphia, PA USA. (2018). Wilschanski M, Shah U, Abu-El-Haija M, MD, Moulton DE, Keljo D, Cohen S, Oliva- Feranchak AP. Cystic Fibrosis Transmembrane Barth B, Fishman DS, Gariepy C, Giefer MJ, Hemker M, Heyman MB, Otley A, Baker SS, Conductance Regulator: Actin(G) as a Master Heyman MB, Himes RW, Husain SZ, Lin TK, Evans JS, Kirschner BS, Patel AS, Ziring D, Regulator of Cholangiocyte Function. Liu Q, Lowe M, Mascarenhas M, Morinville V, Stephens MC, Baldassano R, Dubinsky MC, Hepatology. 2018 Mar; 67(3): 833-836. Ooi CY, Perito ER, Piccoli DA, Pohl JF, Markowitz J, Denson LA, Hyams J, Schwarzenberg SJ, Troendle D, Werlin S, Kugathasan S, Ananthakrishnan AN. King CD, Singh D, Holden K, Govan AB, Zimmerman B, Uc A, Gonska T. Recommen­ The Effect of Early-Life Environmental Keith SA, Ghazi A, Robinson RAS. Proteomic dations for Diagnosis and Management of Exposures on Disease Phenotype and Identification of Virulence-Related Factors in Autoimmune Pancreatitis in Childhood: Clinical Course of Crohn’s Disease in Children. Young and Aging C. Elegans Infected With Consensus from INSPPIRE. J Pediatr Am J Gastroenterol. 2018 Sep 28. doi: 10.1038/ Pseudomonas Aeruginosa. J Proteomics. 2018 Gastroenterol Nutr. 2018 May 9. s41395-018-0239-9. Jun 15; 181: 92-103. Sellers ZM, Abu-El-Haija M, Husain SZ, Spencer EA, Davis SM, Mack DR, Boyle BM, Amrit FRG, Naim N, Ratnappan R, Mason C, Morinville V. New Management Guidelines Griffiths AM, LeLeiko NS, Sauer CG,Keljo DJ, Steenberge L, McClendon TB, Wang G, for Both Children and Adults With Acute Markowitz JF, Baker SS, Rosh JR, Baldassano Driscoll M, Yanowitz JL, Ghazi A. The Pancreatitis. Gastroenterology. 2018 Jun 8. RN, Oliva-Hemker M, Pfefferkorn MD, Otley Longevity-promoting Factor, TCER-1, scts pii: S0016-5085(18)34528-1. AR, Heyman MB, Noe JD, Patel AS, Rufo PA; Cell Non-autonomously to Repress Stress PROTECT Study Group , Alison Marquis M, Resistance and Innate Immunity. In revision, Barth B, Mehta M, Husain SZ. Anatomy, Walters TD, Collins MH, Kugathasan S, Nature Communications. Histology, and Developmental Anomalies of Denson LA, Hyams JS, Dubinsky MC. the Pancreas. In Sleisenger and Fordtran’s Lin TK, Abu-El-Haija M, Nathan JD, Palermo Serologic Reactivity Reflects Clinical Gastrointestinal and Liver Disease, 10th JP, Barth B, Bellin M, Fishman DS, Freedman Expression of Ulcerative Colitis in Children. Edition. Feldman M, Freidman LS, Brandt LJ SD, Gariepy CE, Giefer MJ, Gonska T, Heyman Inflamm Bowel Dis.2018 May 18;24(6):1335- eds. Saunders Elsevier, Philadelphia, PA MB, Himes R, Husain SZ, Liu Q, Maqbool A, 1343. doi: 10.1093/ibd/izy009. PMID: 29718391 USA. (2018). Mascarenhas M, McFerron B, Morinville VD, UPMCPhysicianResources.com/Pediatrics 7

Venkateswaran S, Prince J, Cutler DJ, Shaikhkhalil AK, Boyle B, Smith J, Dotson JL, Baumann U, Adam R, Duvoux C, Mikolajczyk Marigorta UM, Okou DT, Prahalad S, Mack D, Donegan A, Kim SC, Maltz RM, Crandall W. R, Karam V, D’Antiga L, Chardot C, Coker A, Boyle B, Walters T, Griffiths A, Sauer CG, Utilizing Quality Improvement to Increase Colledan M, Ericzon BG, Line PD, Hadzic N, LeLeiko N, Keljo D, Markowitz J, Baker SS, Enteral Therapy in Pediatric Crohn’s Disease: Isoniemi H, Klempnauer JL, Reding R, Rosh J, Pfefferkorn M, Heyman MB, Patel A, Results and Outcomes. JPGN. 2018; 66(6): McKiernan PJ, McLin V, Paul A, Salizzoni M, Otley A, Baldassano R, Noe J, Rufo P, Oliva- 909-914. Furtado ESB, Schneeberger S, Karch A. Hemker M, Davis S, Zwick ME, Gibson G, Survival of Children After Liver Transplantation Maltz RM, Keirsey J, Kim SC, Mackos AR, Denson LA, Hyams J, Kugathasan S. Enhanced for Hepatocellular Carcinoma. Liver Transplant. Gharaibeh RZ, Moore CC, Xu J, Contribution of HLA in Pediatric Onset 2018; 24: 246-55. Bakthavatchalu V, Somogyi A, Bailey MT. Ulcerative Colitis. Inflamm Bowel Dis. 2018 Prolonged Restraint Stressor Exposure in Guest JF, Ingram A, Ayoub N, Hendriksz CJ, Mar 19; 24(4): 829-838. Outbred CD-1 Mice Impacts Microbiota, Murphy E, Rahman Y, McKiernan P, Mundy H, Proksell SS, Greer JB, Theisen BK, Davis PL, Colonic Inflammation, and Short Chain Fatty Deegan P. Healthcare Resource Use and Rosh JR, Keljo DJ, Goyal A, Shah SA, Brand Acids. PLoS One. 2018; 13(5): e0196961. Costs of Managing Children and Adults With MH, Herfarth HH, Cross RK, Siegel CA, Koltun Lysosomal Acid Lipase Deficiency at a Tertiary Sridhar S, Maltz RM, Boyle BM, Kim SC. WA, Isaacs KL, Regueiro MD. IBD LIVE Case Referral Centre in the United Kingdom. PloS Dermatologic Manifestations in Pediatric Series: Case 9: Do Race and Extraintestinal One. 2018; 13:e0191945. Patients With Inflammatory Bowel Diseases Manifestations Affect Treatment of Severe On Anti-TNF Therapy. 2018. Inflamm Bowel Vajro P, Fischler B, Burra P, Debray D, Dezsofi Crohn’s Colitis? Inflamm Bowel Dis. 2018 Dis (epub). PMID: 29718343. A, Guercio Nuzio S, Hadzic N, Hierro L, Jahnel Mar 19; 24(4): 698-713. J, Lamireau T, McKiernan P, McLin V, Nobili V, Barfield E, Sockolow R, Hoffenberg E, Saeed S, Sauer CG, Loop MS, Venkateswaran S, Socha P, Smets F, Baumann U, Verkade HJ. Kim S, Siebold L, Picoraro J, Moses J, Dykes D, Tangpricha V, Ziegler TR, Dhawan A, McCall The Transition of Youth With Grossman A, Wahbeh G, Park KT. Assuring C, Bonkowski E, Mack DR, Boyle B, Griffiths Liver Disease Into the Adult Health System: Quality for Non-hospital-based Biologic AM, Leleiko NS, Keljo DJ, Markowitz J, Baker Position Paper From ESPGHAN and EASL. Infusions in Pediatric Inflammatory Bowel SS, Rosh J, Baldassano RN, Davis S, Patel S, J Pediatr Gastroenterol Nutr. 2018; 66: 976-90. Disease: A Clinical Report From the North Wang J, Marquis A, Spada KL, Kugathasan S, American Society for Pediatric Gastro­ Johansen L, McKiernan P, Sharif K, McGuirk S. Walters T, Hyams JS, Denson LA. Free and enterology, Hepatology and Nutrition. JPGN. Transjugular Intrahepatic Portosystemic Bioavailable 25-Hydroxyvitamin D Concen­ 2018; 66(4): 680-686. Shunt Insertion for the Management of trations are Associated With Disease Activity Portal Hypertension in Children. J Pediatr in Pediatric Patients With Newly Diagnosed Yokota S, Ono Y, Nakao T, Zhang P, Gastroenterol Nutr. 2018. Treatment Naïve Ulcerative Colitis. Inflamm Michalopoulos GK, Khan Z. Partial Bile Bowel Dis. 2018 Feb 15; 24(3): 641-650. Duct Ligation in the Mouse: A Controlled Goldschmidt I, Karch A, Mikolajczyk R, Model of Localized Obstructive Cholestasis. Mutschler F, Junge N, Pfister ED, Mohring T, Haberman Y, BenShoshan M, Di Segni A, J Vis Exp. 2018 Mar 28; (133). d’Antiga L, McKiernan P, Kelly D, Debray D, Dexheimer PJ, Braun T, Weiss B, Walters TD, McLin V, Pawlowska J, Hierro L, Daemen K, Baldassano RN, Noe JD, Markowitz J, Rosh J, Qin Li, Amal Dutta, Charles Kresge, Abhijit Keil J, Falk C, Baumann U. Immune Monitoring Heyman MB, Griffiths AM, Crandall WV, Bugde, and Andrew P. Feranchak. Bile Acids After Pediatric Liver Transplantation — The Mack DR, Baker SS, Kellermayer R, Patel A, Stimulate Cholangiocyte Fluid Secretion Prospective Chilsfree Cohort Study. BMC Otley A, Steiner SJ, Gulati AS, Guthery SL, by Activation of Membrane tmem16a Cl- Gastroenterology. 2018; 18: 63. LeLeiko N, Moulton D, Kirschner BS, Snapper Channels. Hepatology. 2018; 68(1). S, Avivi C, Barshack I, Oliva-Hemker M, Cohen Toft A, Taylor R, Claridge L, Clowes C, Kienstra NS, van Reemst HE, van Ginkel WG, SA, Keljo DJ, Ziring D, Anikster Y, Aronow B, Ferguson J, Hind J, Jones R, McClean P, Daly A, van Dam E, MacDonald A, Burgerhof Hyams JS, Kugathasan S, Denson LA. Long McKiernan P, Samyn M, Coad J. The JGM, de Blaauw P, McKiernan PJ, Heiner- ncRNA Landscape in the Ileum of Treatment- Experiences of Young Liver Patients Fokkema MR, van Spronsen FJ. Daily Variation Naive Early-Onset Crohn Disease. Inflamm Transferring From Children’s to Adult Services of NTBC and Its Relation to Succinylacetone Bowel Dis. 2018 Jan 18; 24(2): 346-360. and Their Support Needs for a Successful in Type 1 Patients Comparing a Transition. Prog Transplant. 2018: Serpico M, Maltz R, Crandall WV, Bricker J, Single Dose to Two Doses aDay. J Inherit 1526924818781567. Dotson JL, Kim SC, Boyle B. Combination Metabol Dis. 2018; 41: 181-186. Therapy With Thiopurines and Allopurinol Warner S, McKiernan PJ, Hartley J, et al. Mitchell E, Ranganathan S, McKiernan P, in Children With Inflammatory Bowel Hepatopulmonary Syndrome in Children: Squires RH, Strauss K, Soltys K, Mazariegos Diseases. JPGN. 2018; 67(3): 341-345. A 20-Year Review of Presenting Symptoms, G, Squires JE. Hepatic Parenchymal Injury in Clinical Progression, and Transplant Outcome. Crigler-Najjar Type I. J Pediatr Gastroenterol Liver Transplantation. 2018; 24(9): 1271-9. Nutr. 2018; 66: 588-94. Continued on Page 8 8 Pediatric Insights: Gastroenterology, Hepatology, and Nutrition Spring 2019

Recent Publications Continued from Page 7

Critelli K, McKiernan P, Vockley J, et al. Liver Squires JE, Squires RH. Evaluation of the Eberhard L, Quammie C, Alonso E, Englesbe M, Transplantation for Propionic Acidemia and Infant and Child With Liver Disease. In: Lin H, Hsu E, Furuya K, Gupta NA, Venkat V, Methylmalonic Acidemia: Perioperative Rudolph’s Pediatrics (23rd Edition). Chapter Daniel JF, Leonis M, Miloh T, Telega GW, Yap J, Management and Clinical Outcomes. Liver 414 Kline MW. Eds McGraw-Hill Companies. Menedez J, Book L, Himes RW, Sundaram SS, Transplantation. 2018; 24(9): 1260-70. New York. 2018. Parekh R, Sonneday C, Bucuvalas J, Ng VL, Kamath BM. Frailty in Children With Liver Grammatikopoulos T, McKiernan PJ, Dhawan Di Segni A, Braun T, BenShoshan M, Farage Disease. J Pediatr. 2018 Mar; 194: 109-115.e4. A. Portal Hypertension and its Management in Barhom S, Glick Saar E, Cesarkas K, Squires JE, Children. Arch Dis Child. 2018; 103(2): 186-91. Keller N, Haberman Y. Guided Protocol Al Qatarneh S, Michel H, Lindblad D, Ozolek for Fecal Microbial Characterization by 16S J, Venkat V, Weiner D. Pancreatic Cystosis McKiernan P, Soltys K. Liver Transplantation rRNA-Amplicon Sequencing. J Vis Exp. 2018 and Intrahepatic Biliopathy in a Young Adult for Metabolic Disease. Liver Transplantation: Mar 19; 133. with Cystic Fibrosis. Pediatr. 2018 Jul 2. pii: World Scientific. 2018; 307-25. S0022-3476(18)30767-4. Squires JE, Soltys KA, McKiernan PJ, Squires Mukherjee A, Hidvegi T, Araya P Ewing M, RH, Strom SC, Fox IJ, Soto-Gutierrez A. Alonso EM, Ye W, Hawthorne K, Venkat V, Stolz DB, Perlmutter DH. NFκB Mitigates Clinical Hepatocyte Transplantation: What Loomes KM, Mack CL, Hertel PM, Karpen SJ, the Pathological Effects of Misfolded is Next? Curr Transpl Rep. 2017 Dec; 4(4): Kerkar N, Molleston JP, Murray KF, Romero R, α1-antitrypsin by Activating Autophagy 280-289. Rosenthal P, Schwarz KB, Shneider BL, Suchy FJ, and an Integrated Program of Proteostasis Turmelle YP, Wang KS, Sherker AH, Sokol RJ, Mechanisms. Cell Death & Differentiation. Ng VL, Sorensen LG, Alonso EM, Fredericks Bezerra JA, Magee JC, the ChiLDReN Network. 2018; PMID: 29795336. DOI: 10.1038/ EM, Ye W, Moore J, Karpen SJ, Shneider BL, “Impact of Steroid Therapy on Early Growth in s41418-018-0130-7. Kamath BM, Molleston JP, Bezerra JA, Murray Infants With : The Multi-center KF, Loomes KM, Whitington PF, Rosenthal P, Li Qin, Dutta A, Kresge C, Bugde A, START Trial”. J Pediatr. 2018 Sep 21. Epub Squires RH, Wang K, Guthery SL, Arnon R, Feranchak AP. Bile Acids Stimulate ahead of print. Schwarz KB, Turmelle YP, Haber BH, Sherker Cholangiocyte Fluid Secretion by Activation AH, Magee JC, Sokol RJ and the Childhood Wen L, Javed TA, Yimlamai D, Mukherjee A, of Membranetmem16a Cl- Channels. Liver Disease Research Network (ChiLDReN). Xiao X, Husain SZ. Transient High Pressure Hepatology. 2018; VOL. 68(1). Neurodevelopmental Outcome of Young in Pancreatic Ducts Promotes Inflammation Celik N, Mazariegos GV, Soltys K, Rudolph JA, Children with Biliary Atresia and Native Liver: and Alters Tight Junctions Via Calcineurin Shi Y, Bond GJ, Sindhi R, Ganoza A. Pediatric Results from the Childhood Liver Diseases Signaling in Mice. Gastroenterology. 2018 Jun Intestinal Transplantation. Gastroenterol Clin Research Network (ChiLDReN). J Pediatr 19. pii: S0016-5085(18)34658-4. North Am. 2018 Jun47(2)355-368. 2018; 196: 139-47. Cox AG, Tsomides A, Yimlamai D, Hwang K, Irving SY, Rempel G, Lyman B, Sevilla WMA, Sorensen LG, Neighbors K, Hardison RM, Miesfeld J, Galli G, Fowl B, Fort M, Ma K, Northington L, Guenter P, and the American Varni JW, Ng VL, Squires RH, and Alonso EM Sullivan M, Hosios A, Snay E, Yuan M, Brown Society for Parenteral and Enteral Nutrition. for the Pediatric Acute Liver Failure Study K, Lien E, Chhangawala S, Steinhauser M, Pediatric Nasogastric Tube Placement and Group. Health Related Quality of Life and Asara JM, Houvras Y. Link BA, Vander Heiden Verification: Best Practice Recommendations Neuropsychological Outcomes in the First MG, Camargo FD, Goessling W, Yap J. From The Novel Project. Nutr Clin Pract. Year After Pediatric Acute Liver Failure. Regulates Glucose Utilization and Sustains 2018; 00:1-7. J Pediatr. 2018; 196: 129-138. Nucleotide Synthesis to Enable Organ Growth. EMBO Journal. Accepted. Harvie LM, Norris A, Sevilla WMA. Soluble Mitchell E, Loomes KM, Squires RH, Goldberg Fiber Use in Pediatric Short Bowel Syndrome: D. Variability in Acceptance of Organ Offers A Survey on Prevailing Practices. Nutr Clin by Pediatric Transplant Centers and Its Impact Prac. 2018; 33(4): 539-544. on Waitlist Mortality. Liver Transplant. 2018; Ganoza A, Goldstein S, Squires JE, 24: 803-809. Mazariegos G. Peri Transplant Determinants Bryce CL, Chang CCH, Ren Y, Yabes J, of Outcome. In: Dunn and Horslen’s Solid Zenarosa G, Iyer A, Tomko H, Squires RH, in Infants and Children Roberts MS. Using Time-Varying Models to (1st Edition). Springer, Philadelphia PA Estimate Post-Transplant Survival in Pediatric pp 485-501. June 2018. Liver Transplant Recipients. PLoS One. 2018; (5): e0198132. UPMCPhysicianResources.com/Pediatrics 9

UPMC Children’s Hospital of Pittsburgh Launches New Pediatric Research Podcast Series

UPMC Children’s Hospital of Pittsburgh has launched a new medical podcast series for physicians, scientists and other health care professionals featuring the hospital’s leading researchers and clinicians.

Episodes of “That’s Pediatrics” will include UPMC Children’s Hospital “Mysteries That Affect Our compelling interviews with scientists at UPMC “Neonatal Cardiovascular Children” with Terence Children’s Hospital who are performing Research” with Thomas Dermody, MD, Vira I. Heinz innovative basic, translational, and clinical Diacovo, MD, chief, UPMC Professor and chair, research. New episodes will be released Newborn Medicine Program, Department of Pediatrics; every two weeks. and director of Neonatal Physician-in-Chief and Cardiovascular Research, Heart Institute at Scientific Director, UPMC Children’s Hospital. “Going back to the polio UPMC Children’s Hospital vaccine, Pittsburgh has always In addition to Dr. Williams, been a hub of very innovative “In Pursuit of the Self-Healing Heart” with “That’s Pediatrics” hosts are: research, and in recent years Bernhard Kühn, MD, associate director, really has become a nexus for Richard King Mellon Foundation Institute for Carolyn Coyne, PhD, director, Center some groundbreaking research Pediatric Research, and director, Research in for , UPMC in pediatric medicine,” said John Williams, MD, at UPMC Children’s Hospital Children’s Hospital chief of the Division of Pediatric Infectious Diseases at UPMC Children’s and one of the “A History of Pediatric Liver Stephanie Dewar, MD, director, Pediatric podcast hosts. “There is a spirit of collabora­ ­ Transplantation” with George Training Program, UPMC tion here in Pittsburgh that makes it somewhat Mazariegos, MD, chief, Children’s Hospital unique nationally and we really want to Pediatric Transplantation Brian Martin, DMD, vice president, Medical explore the research that is happening here Affairs, UPMC Children’s Hospital and how we have a real opportunity to change the way pediatric medicine is practiced “A Passion for Pediatric ” around the world.” with Mioara Manole, MD, president, Children’s Community Pediatrics, and chief, Current episodes of Division of General Academic Pediatrics “That’s Pediatrics” include: “Let’s Talk About Ears” with Alejandro “Gene Therapy” with George Gittes, MD, Hoberman, MD director of the Richard King Mellon Foundation­ Institute for Pediatric Research and co- “From the U.S. Navy to UTIs” with Tim Shope, scientific director, UPMC Children’s Hospital MD, MPH, professor of pediatrics

“All About Acute Flaccid Myelitis” with “The First Handshake” with Tim Hand, PhD John Williams, MD, chief, Division of Pediatric Subscribe to “That’s Pediatrics” in iTunes or Infectious Diseases “Beyond Corn and Carrots: The Future of Pediatric Diabetes” Google Play Music to have new episodes automatically download to your phone for “Don’t Rule Out Brain Injuries” with Radhika Muzumdar, MD, free when they become available. with Rachel Berger, MD, MPH, chief, Division of Pediatric chief, Child Advocacy Center, , Diabetes, and UPMC Children’s Hospital Metabolism 10 Pediatric Insights: Gastroenterology, Hepatology, and Nutrition Spring 2019

GI Research Spotlight

In October 2018 in the journal Gastroenterology, researchers from the Division of Pediatric Gastroenterology, Hepatology, and Nutrition, including Sohail Husain, MD; Dean Yimlamai, MD, PhD; Amitava Mukherjee, PhD; Li Wen, MD, PhD; and Tanveer Javed published new findings on the origins of pancreatitis after endoscopic retrograde cholangio­ pancrea­tography (PEP). Their basic science study examined how and what effects arise from hydrostatic pressure on pancreatitis in a murine model in which acute pancreatitis is induced via clamping of the proximal common bile duct in conjunction with retrograde biliopancreatic ductal or intraductal saline infusion at constant pressures. The researchers found that intraductal pressures at both 100 mm Hg and 150 mm Hg, respectively, both were responsible for inducing pancreatitis in the models. The 100 mm Hg threshold was lower than pressures UPMC Physician Resources from previous studies in similar murine models For the latest free CME courses, videos, news, and events for physicians, please visit where 130 mm Hg of pressure induced an UPMCPhysicianResources.com/PedsGI. inflammatory response in the pancreas. CME Courses in Pediatric Gastroenterology, Hepatology, and Nutrition The responses in the models to the various intraductal pressures for short periods of Blood, Sweat, and Cheers! Scientific Discovery and Cystic Fibrosis Research time (10 minutes in the current experiments) Presented by Andrew Feranchak, MD showed activation of calcineurin within the Chief, Division of Pediatric Gastroenterology, Hepatology, and Nutrition pancreas, highlighting not only the importance Dr. Feranchak gives a presentation on the history of cystic fibrosis and of calcineurin signaling for the development important research discoveries impacting the disorder. of acute pancreatic inflammation and pancreatitis, but also that the calcineurin Video Rounds pathway may be a viable target for pharmaco­ ­logical therapies able to inhibit Video Rounds is a series of short, informative, and educational videos created for physicians, the calcineurin response and prevent the covering a variety of medical and surgical disciplines. onset of acute pancreatitis. Pediatric Metabolic Liver Disease Treatment of Acute The research team is continuing their Presented by Patrick McKiernan, MD Liver Failure experiments and will be investigating the Director, Pediatric Hepatology Presented by Robert Squires, MD effects of inhibiting the calcineurin pathway Program further in future studies.

Treating Pediatric Inflammatory References Bowel Disease Wen L, Javed TA, Yimlamai D, Mukherjee A, Presented by David Keljo, MD, PhD Xiao X, Husain SZ. Transient High Pressure Director, Inflammatory Bowel in Pancreatic Ducts Promotes Inflammation Disease Center and Alters Tight Junctions via Calcineurin Signaling in Mice. Gastroenterology. 2018; 155(4): 1250-1263. UPMCPhysicianResources.com/Pediatrics 11

About the Division of Gastroenterology, Hepatology and Nutrition at UPMC Children’s Hospital of Pittsburgh

The Division of Pediatric Gastroenterology, Hepatology and Nutrition provides a full range of diagnostic procedures and treatments related to the gastrointestinal tract, liver, and pancreas. Procedures performed include endoscopy of the upper and lower gastrointestinal tracts; biopsy of the esophagus, stomach, small bowel, large bowel and liver; ; sclerotherapy of varices; capsule endoscopy; tests of secretory function of the pancreas; pH probe testing for gastroesophageal reflux; and breath hydrogen testing.

Enterostomal therapy is offered for children • Intestinal Care and Rehabilitation with stomas, incontinence, dermal ulcers and Center (ICARE) Division Faculty and Clinical Providers other select skin conditions or those needing UPMC Children’s Intestinal Care and wound care. Rehabilitation Center (ICARE) provides expert Andrew Feranchak, MD — Division Chief care for patients with complex intestinal Jeffrey Rudolph, MD — Clinical Director, • Special Programs disease. It follows children with poorly and Director, ICARE In combination with colleagues in the functioning intestines and provides expert Feras Alissa, MD Hillman Center for Pediatric Transplantation care for children with complicated nutritional Maria Ines Clavell, MD and the Division of Pediatric General and needs including those on parenteral nutrition. Kristen Critelli, MD Thoracic Surgery, the Division of Pediatric The Division of Pediatric General and Thoracic John Eisses, MD, PhD Gastroenterology offers care in several Surgery and the transplant team participate in Kate Ellery, DO multidisciplinary programs. this center. Moreover, Children’s small-bowel Sohail Husain, MD transplant program is one of the largest • Hepatology Center in the country. David Keljo, MD, PhD Zahida Khan, MD, PhD The Hepatology Center offers consultative services and comprehensive care for children • Medical Coping Sandra Kim, MD Dale King, MD with a wide range of hepatobiliary disorders. The Medical Coping Clinic is an integral part of Services provided include inpatient and the Division of Pediatric Gastroenterology and Douglas Linblad, MD outpatient consultation; diagnosis using a provides expertise in treating issues related to Patrick McKiernan, MD variety of methods; collaborative consultation coping with a chronic illness using a broad Wednesday Sevilla, MD, MPH, CNSC and care with the Hillman Center for Pediatric range of treatment options. The Medical Sapana Shah, MD Transplantation and the Division of Pediatric Coping Clinic provides comprehensive, state- Leah Siebold, MD General and Thoracic Surgery; care plan of-the-art clinical care to improve the quality Vibha Sood, MD coordination; long-term follow-up care; and of life for children with GI-related problems. James Squires, MD, MS state-of-the-art clinical research. Robert Squires, MD • Pancreatic Center Arvind Srinath, MD, MS • Inflammatory Bowel Disease Children with acute recurrent or chronic Whitney Sunseri, MD (IBD) Center pancreatitis can find hope at the Pancreatic Veena Venkat, MD The IBD Center uses a team approach to Center at UPMC Children’s Hospital of Dean Yimlamai, MD, PhD provide each patient with the most advanced Pittsburgh. Here families will find a team of Leslie Coda, CRNP medical care available and compassionate doctors who understand pancreatitis, have a Whitney Gray, CRNP support for the whole family. The center wealth of experience caring for children who Anne Grenci, CRNP provides comprehensive, state-of-the-art have this condition, and can answer the many clinical care to control the symptoms of IBD questions families often have about it. Rebecca Piazza, CRNP and to improve the quality of life for children Carol Earl, PA-C with the disease.  Brianna Rothbauer, PA-C 4401 Penn Ave. Pittsburgh, PA 15224

About UPMC Children’s Hospital of Pittsburgh Regionally, nationally, and globally, UPMC Children’s Hospital of Pittsburgh is a leader in the treatment of childhood conditions and diseases, a pioneer in the development of new and improved therapies, and a top educator of the next generation of pediatricians and pediatric subspecialists. With generous community support, UPMC Children’s Hospital has fulfilled this mission since its founding in 1890. UPMC Children’s is recognized consistently for its clinical, research, educational, and advocacy-related accomplishments, including ranking 15th among children’s and schools of medicine in funding for pediatric research provided by the National Institutes of Health (FY2018).

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