Division Overview

Our Vision

We will be the leaders in the care of children with digestive diseases

Our Mission

• Care: We will deliver exceptional, safe, and affordable care
• Research: We will catalyze high-impact research in digestive diseases
• Education: We will train the future leaders of the field

Our Values

• We are respectful
• We are honest
• We speak the truth
• We value diversity
• We work as a team

Innovation in Clinical Care

The location of the division is on the eighth and ninth floors of the Clinical Sciences Building, where clinical, research, and training projects permits integration to provide the most innovative, evidence- and expert-based care for children with all forms of digestive disease. Delivery of direct patient care occurs in the Outpatient Gastroenterology Clinic and in inpatient units for Gastroenterology (A4S) and for Hepatology and Liver Transplantation (A4N). Our team also provides timely consultation to all clinical services at Cincinnati Children’s Hospital, where we work as a multi-disciplinary team to improve the care of the children we serve. The scope of care starts with the most common digestive problems and extends to the most rare and complex disorders that require ever-improving technologies to aid in diagnosis and to design new therapies. Some of our specialized services include liver and intestinal transplantation, intestinal rehabilitation, total pancreatectomy and islet cell autotransplantation, inflammatory and complex esophageal and intestinal disorders, and others (described below).

Our medical and nurse specialists also provide care in satellite clinics with the goals to bring gastroenterology expertise to our communities and improve patient experience. We hold daily clinics at Cincinnati Children's Liberty Campus focusing on gastroenterology and an increasing number of subspecialty clinics (example: nonalcoholic steatohepatitis (NASH) clinic and Neurogastroenterology / Motility clinic), and gastrointestinal endoscopies. Other satellite gastroenterology clinics are available at Cincinnati Children’s facilities in Mason, Green Township, Anderson, Northern Kentucky, and Portsmouth. Our experts also hold telehealth gastroenterology clinics with programs in Kalamazoo (MI) focused on children with liver and intestinal failure, Lexington (KY) focused on liver and pancreatic disorders, and in Erlanger (TN) focused on children with intestinal failure.

Innovation and Research

The division is a scientific hub for digestive disease research for Cincinnati Children's and the University of Cincinnati College of Medicine. We founded our research programs on the premise that defects in development, genetics, and immunology play key roles in determining the phenotypes of digestive diseases in children. We aim to discover the biological underpinnings of digestive diseases that begin in childhood. To this end, physician-scientists and researchers receive funding from the National Institutes of Health and industry to use novel model systems in the laboratory and to perform clinical trials. Our commitment is to increase the tempo of translation of new discoveries to the clinics so that the investments from our hospital and our society can translate into actionable items in the clinic and improve the outcome of children with digestive diseases. The listings below are a review of our broad research portfolio by the individual Centers of Excellence.

Innovation in Education

For over 15 years a T32 grant funds our training program. Most of our graduates are on academic positions and hold several positions as division chiefs in the U.S. We believe in our commitment to integrating the clinical and research programs into an arena of opportunities for advanced training in the field of gastroenterology and related subspecialties. Our training programs include:

• Fellowship Program in Gastroenterology, Hepatology and Nutrition
• Advanced fellowship training in Hepatology and Liver Transplantation, Neurogastroenterology / Motility, and Nutrition
• Short-term clinical observation/clerkships for U.S. and international trainees
• Research training for international scientists

Below, we present summaries and accomplishments by individual Centers of Excellence.

Digestive Health Center

Members:

Jorge Bezerra, MD, Director
Lee (Ted) Denson, MD, Associate Director
Heidi Kwalkarf, PhD, Associate Director
Cynthia Wetzel, PhD, Center Manager

The Digestive Health Center (DHC) is one of only 18 Silvio O. Conte Digestive Diseases Research Core Centers funded by the National Institutes of Health in the U.S., and the only one dedicated to pediatric digestive diseases. Aaron Zorn, PhD, from the Division of Developmental Biology, serves as an associate director. The center seeks to improve child health through better diagnosis, treatments and outcomes that will emerge from highly innovative work in our four key focus areas: 1) Liver disease modeling, 2) Digestive disease and immunity, 3) Digestive disease and obesity, and 4) Translational embryology. Three scientific cores link these research focus areas that provide investigators to have timely access to state-of-the-art technologies at the Integrative Morphology, Gene Analysis, and Pluripotent Stem Cell and Organoid Cores. An additional clinical component facilities patient-based research. With 80 investigators, the DHC contributes to the research goals of faculty from 19 divisions within the Department of Pediatrics and eight other departments within the University of Cincinnati, College of Medicine, with a total extramural grant portfolio of $35.5 million in digestive disease research and 211 digestive disease related articles during the past 12 months. To strengthen pediatric digestive disease, the DHC funds highly promising pilot and feasibility projects from junior investigators and sponsors a dynamic enrichment program of scientific seminars, workshops, and annual symposium. The DHC Pilot and Feasibility Program has invested $2.43 million among 53 early stage investigators since 2007. These investigators have since attracted $74.3 million in extramural grant funding.

In addition to the accomplishments described above, the following center investigators received national and international recognition for their clinical, research, and educational accomplishments this past year:

• Theresa Alenghat, VMD, PhD, was one of 10 recipients of the 2019 Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund
• Bezerra became president of the American Association for Studies of Liver Diseases and member of the board of Scientific Councils for NIDDK Intramural Research
• Kalkwarf is a standing member of the National Institutes of Health Neurological, Aging and Musculoskeletal Epidemiology Study Section for Scientific Review
• Takanori Takebe, MD, received the 2019 Dr. Ralph and Marian Falk Medical Trust-Catalyst Award
• Sing Sing Way, MD, PhD, elected to the Association of American Physicians.
• James Wells, PhD, was one of five recipients of the 2019 Distinguished Investigator Awards form the Paul G. Allen Frontiers Group

Advanced Nutrition

Members:

Marialena Mouzaki, MD, MSc, Director
Conrad Cole, MD, MPH, MSc
Lee (Ted) A Denson, MD
James E. Heubi, MD
Heidi Kalkwarf, RD, PhD
Samuel Kocoshis, MD
Stavra Xanthakos, MD, MS

Our mission is to optimize nutritional status of children exposed to chronic medical conditions and environmental hardships through surveillance of patients at risk, and identification and implementation of best treatment practices. We seek to improve the prevention and treatment of childhood diarrhea, obesity and undernutrition by implementing best practices and creating new knowledge through bench-to-bedside research collaborations between Cincinnati Children’s Hospital Medical Center and global partners.

Mouzaki, in collaboration with Alexander Miethke, MD, from the Division of Gastroenterology, Hepatology and Nutrition, is investigating the body composition of patients with autoimmune liver diseases and the pathophysiology of the sarcopenia seen in this context. Mouzaki and Xanthakos established a collaboration with the Department of Radiology (Andrew Trout, MD, and Jonathan Dillman, MD, MSc) and are investigating the body composition of obese youth with non-alcoholic fatty liver disease (NAFLD), as well as the links between sarcopenia and NAFLD severity. They are also studying the impact of socioeconomic deprivation on disease severity in NAFLD, including the role of food insecurity (along with Sarah Orkin, MD, advanced nutrition fellow).

Xanthakos is completing her study that compares the impact of lifestyle interventions against weight loss surgery on liver related outcomes and metabolic comorbidities of patients with NAFLD, including the role of dietary changes.

Mouzaki developed a new study to discover novel cutaneous biomarkers of NAFLD and NASH.

Kalkwarf and Xanthakos are investigating deficits in bone density among adolescents with NAFLD, and are also researching deficiencies of iron, vitamin B12 and calcium in adolescents who have undergone bariatric surgery.

Kalkwarf and Heubi are completing a study investigating trajectories of bone mineral accrual in young children and the influences of dietary intake, growth and body composition. This data will establish normal ranges for bone density based on age and enable detection of bone deficits in children with chronic medical conditions.

Denson continues collaboration with investigators at the University of Virginia and The Aga Khan University in Pakistan on patient-based studies to define the pathogenesis of environmental enteropathy in affected children. He is also leading the first multi-center RCT of the prebiotic 2’-fucosyllactose nutritional supplement in children and young adults with Crohn’s disease and ulcerative colitis.

Cole continues to have collaboration / consulting role in projects in Ghana and Sierra Leone focused on micronutrient deficiencies (zinc and iron) in undernutrition, diarrheal diseases and development of endoscopy skills and services.

Cole and Kocoshis are center investigators in clinical trials and patient-based research involving patients with intestinal failure.

Cincinnati Center for Eosinophilic Disorders

Members:

Phil Putnam, MD, GI Director
Vince Mukkada, MD, GI Associate Director
Scott Bolton, MD

The Cincinnati Center for Eosinophilic Disorders (CCED) is an established multidisciplinary referral center for evaluation and treatment of eosinophilic gastrointestinal disorders (EGID) in children and adults. Physicians representing the Divisions of Gastroenterology, Hepatology and Nutrition, Allergy and Immunology, and Pathology and Laboratory Medicine provide comprehensive clinical services supported by experienced nurses, dieticians, a psychologist and a social worker. Over 70% of our patients agree to participate in clinical and basic science research studies. Our clinical research includes important studies of both dietary and pharmacologic management of eosinophilic disorders and we are continuing to focus on identifying less invasive means of diagnosis and disease monitoring. Putnam, Bolton and Mukkada collaborate with other leading investigators in the CCED in studies of genetic and immunologic factors underlying the development of eosinophilic inflammation in the gut, and in evaluating the effectiveness of biological agents (including anti-IL-4 receptor binding antibodies, anti-IL5 receptor binding antibodies, and anti-Siglec8 antibodies) and topical glucocorticoids in the management of eosinophilic disease. The CCED team was the first to investigate eosinophil progenitor (EoP) levels in patients with eosinophilic esophagitis (EoE), leading to the identification of a potential new noninvasive biomarker, which is an essential step toward simpler disease monitoring over time, with the potential of reduced discomfort, costs and side effects.

Recent research includes a recently published manuscript demonstrating a possible role for a calcium activated chloride channel (Anoctamin 1, ANO1) in the pathogenesis of EoE. This provides a potential new pharmacologic target to try to address epithelial proliferation in active EoE. In a collaborative effort across the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), we recently published our work in demonstrating the high disease burden in patients with EGIDs as well as significant differences in symptoms and co-morbidities seen in patients with EoE vs more generalized EGID. We also recently published our experience across CEGIR in developing novel tissue (gastric transcripts) and blood based biomarker assays for eosinophilic gastritis, providing new insights into correlations between gastric molecular expression and symptoms, histology, and endoscopic findings in this poorly understood disease. We extended our previous work with the EoE Histology Scoring System to develop a novel EoE Histology Remission Score which correlates with both symptoms and several biomarkers of disease activity. We are continuing to participate in a number of clinical trials of novel therapeutics in eosinophilic GI disease, including phase III trials of a budesonide oral solution and an anti IL4a receptor blocking antibody in EoE, a phase III trial of an anti-Siglec8 antibody in eosinophilic gastritis as well as a phase II trial of the same antibody for eosinophilic esophagitis, and a phase II trial of an anti-IL5 receptor binding antibody in eosinophilic esophagitis. We also recently completed our single center trial of the IL5 receptor binding antibody benralizumab in eosinophilic gastritis and will be presenting our results shortly.

We continue to involve our trainees in cutting edge research in eosinophilic disease. Recent graduates completed projects examining the potential role of estrogen receptors in the pathogenesis of EoE, expanding on our prior work to examine the use of eosinophil progenitor cells as a non-invasive biomarker of EoE disease activity, and identifying the effect of EoE and its treatment on bone health in our local patient population. Our most recent graduating fellows completed work looking at a novel characterization of very early onset EoE compared to a control group of patients who present as adolescents, as well as examinations of the development and characteristics of EGID developing in patients who have undergone liver or small bowel transplants, as well as a description of our experience with benralizumab in patients with EoE. We have a new fellow joining our research group this year with a plan to better elucidate the molecular and clinical phenotype of eosinophilic gastritis and duodenitis over his two research years.

With support from the National Institutes of Health to Marc Rothenberg, MD, PhD, from the Division of Allergy and Immunology, the CCED leads a consortium of organizations with a common goal to conduct clinical research into eosinophilic disorders and to train investigators in how to conduct clinical research. We recently received an award for a competitive five year renewal of the consortium’s work. This CEGIR is a collaboration of clinician investigators, translational scientists, physicians, patients, families and patient advocacy groups and is part of the Rare Disease Clinical Research Network (RDCRN). Work from this collaborative group to date focuses on studies of the natural history of eosinophilic disease, particularly the comparatively rare types including eosinophilic gastritis and eosinophilic colitis, as well as determining the disease response to less-restrictive diet therapy in adult patients with EoE. A series of pilot studies supported through this consortium, include projects examining the use of the angiotensin receptor blocker losartan in the treatment of EoE, another assessing the role of elemental diet therapy for eosinophilic gastritis, and another examining a less invasive esophageal monitoring system, transnasal endoscopy compared with classic endoscopy.

Clinically, Bolton and Mukkada are beginning to train to learn new endoscopic techniques (transnasal endoscopy and EndoFlip) to provide minimally invasive diagnosis and monitoring to our patients in the future, as well as to integrate better assessments of esophageal function into our clinical practice. We, like all of our colleagues and patients, are deeply affected by the ongoing COVID-19 crisis and are contributing to our improving understanding of effects of the pandemic in chronic disease by participating in an international registry of patients with EGIDs who have contracted coronavirus (SECURE-EoE / EGID). We are hopeful that the insights gleaned from this registry will help improve the clinical care of our patient population with the novel coronavirus going forward.

IBD- The Schubert-Martin Inflammatory Bowel Disease Center

Members:

Lee “Ted” Denson, MD, Director
Michael Rosen, MD, Medical Director
Phillip Minar, MD
Jennifer Hellmann, MD
Kaitlin Whaley, MD

The Division of Gastroenterology, Hepatology and Nutrition and the IBD Center sees more than 1,000 patients with IBD each year. Over 100 new patients receive a diagnosis annually, and close to 80 second-opinion patients see physicians from the Schubert-Martin Inflammatory Bowel Disease / IBD Center from more than 20 states and abroad. These numbers reflect a steady increase in total patient volume over the last five years.

The center is an integral and leading participant in collaborative consortia like the ImproveCareNow (ICN) Quality Improvement Network and the Crohn’s and Colitis Foundation’s PRO-KIDS Clinical Research Network. Rosen, medical director of the Schubert-Martin Pediatric IBD Center, began a three year term as PRO-KIDS co-chair last year. This role reflects in superior outcomes for our patients, with 84% of IBD patients within the center being in remission, 68% in sustained remission, and 89% expressing a high level of confidence in disease management. A focus of quality improvement is behind the development of care algorithms for biologic therapy. Implementation of these is quite effective, with 99% of patients having drug levels measured, and 88% achieving target drug levels. We embraced telehealth to maintain care and these outcomes for our IBD population during the COVID-19 pandemic. The center’s website shares these outcome measures transparently, and with other ICN centers. Our Annual IBD Family Education Day, co-hosted by the local chapter of the Crohn’s and Colitis Foundation, continues to be one of the largest educational events of its kind in the country.

Physicians within the center continue to develop and lead basic, translational and clinical research to identify key etiopathogenic mechanisms for inflammatory bowel diseases, minimally invasive biomarkers for predication of disease flares and remission, development of mobile phone apps for patient engagement and self-management, and transition of patients to adult providers. A study published in the IBD Journal, defined an improved population pharmacokinetic model for predicting optimized infliximab exposure in pediatric inflammatory bowel disease. Minar is now leading the effort to incorporate this model for personalized drug dosing into clinical practice via a novel dashboard. We reported in Nature Communications genes and microbes associated with treatment response in the context of the first NIH-supported prospective inception cohort study of children with Ulcerative Colitis, the PROTECT study. In the setting of standardized therapy, we defined an inflammatory rectal gene expression signature and associated microbial shifts linked to lack of response to corticosteroids and biologic therapy. These data will guide current clinical practice, and support our ongoing NIH-supported clinical trial of the 2’-fucosyllactose prebiotic. A study in Life Science Alliance defined the critical role of the STAT5 transcription factor in maintaining Paneth cells and the stem cell niche in the setting of Clostridium difficile infection. This may point to novel approaches for this infection which contributes to substantial morbidity in IBD patients. Collaborators within the institution include members from the James M. Anderson Center for Health System Excellence, the Division of Behavioral Medicine and Clinical Psychology, the Center for Adherence and Self-Management, Pediatric Surgery, the Divisions of Allergy and Immunology, Adolescent and Transition Medicine, and the Department of Radiology continue to make significant contributions to finding a cure as well as improving outcomes and self-management skills for children suffering from IBD.

Interdisciplinary Feeding Team

Members:

Scott Pentiuk, MD
Vince Mukkada, MD

The Interdisciplinary Feeding Team (IFT) provides comprehensive evaluation for children with swallowing / feeding disorders. This multidisciplinary team includes experts from the Divisions of Gastroenterology, Hepatology and Nutrition, Otolaryngology, Speech Language Pathology, Occupational Therapy and Social Services. The IFT evaluated over 1,150 patient visits and 260+ new patients in fiscal year 2020. In addition to comprehensive consultation and care, the IFT offers unique multidisciplinary outpatient treatment sessions and child-adult relationship enhancement training for families. Ongoing research projects by IFT investigators include the development and use of the pureed by G-tube diet and methods to evaluate children with swallowing dysfunction.

Intestinal Rehabilitation and Intestinal Transplantation Programs

Members:

Conrad Cole, MD, MPH, MSc, Medical Director, Intestinal Rehabilitation Center
Samuel Kocoshis, MD, Medical Director, Intestinal Transplantation Program
Stephanie Oliveira, MD
Antoinette Adjowa Amevor, MD

These two programs continue to expand their clinical profiles and facilitate the translational and clinical research conducted by both programs. Our circumspect, thoughtful approach to intestinal rehabilitation obviates the need for intestinal transplantation for many of the patients referred for transplantation as less than one in five patients referred for intestinal transplantation receive a transplant. Our mission is to provide the best possible care for children with intestinal failure though innovation. Outcomes for both intestinal rehabilitation and intestinal transplantation are excellent. Our central line associated blood stream infection rate of 1.5/1000 catheter days is among the best in North America. We were the lead center for the expanded multicenter pediatric clinical trial funded by Shire / Takeda Pharmaceuticals for the recently approved Teduglutide (Gattex®) with Kocoshis as lead investigator, and Cole as co- investigator. Additional studies include the evaluation of the impact of quality of life of the family on the outcome of children with intestinal failure. We continue to collaborate with Nana-Hawa Yayah Jones, MD, from the Division of Endocrinology, for ongoing evaluation and developing novel therapeutic options for children with intestinal failure who develop iodine deficiency. We continue to monitor these modalities and are actively working on identifying the shortest duration of exclusive parental nutrition associated with the development of iodine deficiency. In collaboration with our colleagues in the Division of Infectious Diseases (David Haslam, MD), and Surgery (Helmrath), we are evaluating the interaction of diet and antimicrobials on intestinal microbiome and how this impacts adaptation. Helmrath continues to lead the surgical program in using unique surgical procedures associated with better outcomes in these patients. The Helmrath lab studies the biology of intestinal stem cells as a key to unravel the mechanism involved during the disease process. Two retrospective studies emerged from the transplant program. We presented data, characterizing eosinophilic bowel disease in our transplant population, and we identified profound increases in peripheral blood lymphocyte counts among those patients with exfoliative rejection. Manuscripts are currently under review. 

Our intestinal transplantation team shows that patients with combined liver / intestinal transplantation have better outcomes than with isolated intestinal transplantation. They also stratified risk for exfoliative rejection by presence or absence of allograft liver in the graft or by presence or absence of preformed or de novo donor specific antibodies (DSA). Patients with a positive DSA receive two to three times higher induction doses. Preliminary data suggest that these strategies impacted patient survival insofar as all five of our most recently transplanted patients survived from three months to three years.

Liver Care Center

Members:

Jorge A. Bezerra, MD, Director
William F. Balistreri, MD
Akihiro Asai, MD, PhD
Kathleen Campbell, MD
Chandrashekar Gandhi, PhD
James Heubi, MD
Stacey Huppert, PhD
Alexander Miethke, MD, Associate Director
Anna Peters, MD, PhD
Pranav Shivakumar, PhD
Takanori Takebe, PhD
Amy Taylor, MD
Chunyue Yin, PhD

The Pediatric Liver Care Center provides comprehensive care for children with liver diseases and serves a national and international referral population via a comprehensive evaluation of all medical and surgical aspects of liver diseases. The evaluation includes a full spectrum of metabolic analysis, autoimmune and inflammatory processes, and gene sequencing techniques to diagnose mutations that cause clinical phenotypes. The multidisciplinary nature of the comprehensive care makes the center a “one-stop-shop” in which the timely consultation with hepatologists, surgeons, pathologists, radiologists, and nutritionists with expertise in pediatric liver disease optimizes patient care. It also catalyzes patient-based research to narrow the knowledge gap and solve clinical challenges with the ultimate goal to improve outcomes.

Physicians, surgeons and scientists in the center are performing exciting research with the goals of understanding the mechanisms of liver development, advancing tissue engineering, discovering the causes and pathogenesis of pediatric liver disease and designing new therapies to block progression of liver injury. Their work receives funding from independent grants from the National Institutes of Health, foundations, and industry and aims at closing the knowledge gap in the field with a focus on translating new discoveries into improved clinical care. One example is Bezerra’s partnership with Cincinnati Children's clinical laboratories to launch a new clinical assay to quantify MMP-7 in the serum as a biomarker of biliary atresia.

Our faculty published over 20 original scientific reports last year, as shown below with a brief summary of key findings:

• Ledipasvir-Sofosbuvir treatment is a effective treatment for hepatitis C in children 3-6 years of age (Balistreri, published in Hepatology)
• Predictive modeling and therapeutic target for biliary atresia (Bezerra and Shivakumar, published in Gastroenterology) and PKD1L1 in syndromic biliary atresia (Bezerra, published in Hepatology)
• Modeling steatohepatitis with liver organoids derived from iPSCs (Takebe, published in Cell Metabolism) and modeling development of hepato-biliary-pancreatic organogenesis from iPSCs (Takebe, published in Nature)
• Outcome of cholestasis in children with Alagille syndrome (Heubi, published in Hepatology Communications) and open label continuation study of cholic acid in patients with defect in bile acid metabolism (Heubi, published in Journal Ped Gastroenterology Nutrition)
• SCOPE index as a prognostic tool in PSC (Miethke, published in Hepatology) and MRCP to differentiate types of autoimmune liver disease (Miethke, published in Abdominal Radiology)
• Sox9 and liver disease in a mouse model of Alagille (Huppert, published in the Hepatology)
• Mannose and hepatic stellate cell activation in zebrafish (Yin, published in Hepatology)
• Pro- and anti-fibrogenic function of LPS in the liver (Gandhi, published in Frontiers in Medicine) and LPS reverses hepatic stellate cell activation via transcription factors (Gandhi and Miethke, published in Hepatology)

We have several lines of ongoing and new clinical and translational investigation addressing mechanisms of disease and new treatments. Examples include Balistreri’s studies on the use of direct acting antivirals to treat hepatitis C virus infection in young children and Bezerra’s clinical trial assessing the efficacy of Tenofovir in children with chronic hepatitis B infection. Asai is using CRISPR-editing to introduce patient-specific mutation in pluripotent stem cells, generate inducible hepatocytes, and study mechanisms of cholestasis. In the Center for Autoimmune Liver Disease, Miethke leads a multi-disciplinary team studying radiological, biomarker and genetic underpinnings of autoimmune liver disease, with a focus on studies of primary sclerosing cholangitis, and Taylor is investigating family networks to understand the needs of children with autoimmune hepatitis and sclerosing cholangitis to improve clinical outcome and foster participation in clinical trials. Miethke will be a co-principal investigator in new prospective observational and interventional studies for children with primary sclerosing cholangitis as part of the NIH-funded Childhood Liver Research Network. Breaking new ground for transplantation science, Peters is applying single cell sequencing to study the cellular mechanisms underlying late-onset acute cellular rejection for liver-transplanted children.

In the laboratory, Huppert is studying mechanisms of cellular plasticity in the liver, with exciting work investigating re-programming mechanisms to regenerate the biliary epithelium. Gandhi is pursuing studies defining the role of augmenter of liver regeneration in pathogenesis of NASH, and the cellular crosstalk among sinusoidal endothelial cells, hepatic stellate cells and inflammatory cells that regulates fibrogenesis. Using zebrafish models, Yin is uncovering molecular mechanisms of cell injury and biliary secretion that drive pathogenic mechanisms of cholestatic syndromes.

Neurogastroenterology and Motility (NGM) Disorders Center

Members:

Ajay Kaul, MD, Professor and Director, NGM Center
Khalil El-Chammas, MD, MS, Associate Professor, Medical Director of MDMC Program, Director of Advanced Fellowship Program
Neha Santucci, MD, Assistant Professor, Lead for FGID Program
Kahleb Graham, MD, Assistant Professor

The Neurogastroenterology and Motility Disorders (NGM) Center, despite the pandemic, continues to experience growth, with 1,374 outpatient encounters (68% more than prior fiscal year) and performing 565 manometry procedures (96% increase from prior fiscal year) and 145 impedance studies. We added a fourth faculty, Graham, to the NGM Center with a focus on functional GI disorders (FGID). Over the past year, the center received about 40 new referrals / second opinions per month, primarily from patients outside of our primary service area. Patients came from 30 states and six from outside the country. El-Chammas, as medical director of the collaborative Multidisciplinary Motility Clinic (MDMC) along with the Colorectal Center, was instrumental in successfully managing the unprecedented growth of the program. The MDMC program had 120 clinic visits with complex motility disorders from the region and across the nation. Santucci, with her expertise in functional gastrointestinal disorders (FGID), led an effort to develop a novel program for managing children with pain-related FGID. Since its inception this year, and with the recent addition of Graham, the program experienced significant growth with a total of 428 clinic visits. Our team made a significant contribution to the evolving neuromodulation program by placing a record 59 percutaneous electric nerve field stimulation devices in patients with FGID, working with our CRC colleagues in managing patients with sacral nerve stimulators (SNS) for intractable constipation, and, more recently, gastric electric stimulation (GES) in patients with severe gastroparesis. We continue to improve our diagnostic armamentarium and treatment modalities using the latest, advanced technology and knowledge. In addition to high resolution manometry and impedance technology, we are employing newer tests like EndoFlip (11), transrectal ultrasound and temporary gastric electric stimulation in our patients with intractable GI motility disorders.

Exploring new research opportunities, the center involved itself in multicenter trials on the use of percutaneous electric nerve field stimulation in functional gastrointestinal disorders, the characterization of high resolution colon manometry studies, and the use of Mirtazapine in functional abdominal pain, amongst others. Our advanced fellowship program in pediatric NGM, one of only a few in the nation, saw two fellows graduate and join as faculty at the Children’s Hospital of Pittsburgh (University of Pittsburgh Medical Center) and Children’s Mercy Hospital (University of Missouri-Kansas City). We are currently training our third advanced motility fellow and will have our first international graduate from Israel join our program next year. Our international clinical observership program continues to thrive, with our current observer from Thailand completing his tenure on an educational scholarship from his country. Due to the COVID-19 pandemic, our team members were not able to have the fifth National Annual Workshop on Pediatric Manometry Training for physicians and nurses this year. This highly interactive and practical workshop is not suitable for delivery as a virtual experience. To continue to share knowledge and advances with the community, we are collaborating with the sponsors to start a series of educational webinars this year.

Pancreas Care Center (PCC) at Cincinnati Children's Hospital Medical Center

Members:

Maisam Abu-El-Haija, MD, MS, Medical Director
Tom K. Lin, MD, Associate Director, Endoscopy Director
David Vitale, MD

Our vision is to be the leader in delivering world class healthcare to children with pancreatic disease, through comprehensive multidisciplinary management that puts patient outcomes at the forefront of our overarching goals. We implement chronic care algorithms that enhance the care coordination and apply state of the art research methodology to lead our innovation in patient care.

The program, which is also led by Jaimie Nathan, MD, surgical director, and Deborah Elder, MD, endocrinology director, in collaboration with the Pain Management Center team and the Division of Behavioral Medicine and Clinical Psychology, currently follows more than 400 patients with various pancreatic disorders including pancreatitis, exocrine pancreatic insufficiency, congenital anomalies of the pancreas and pancreatic tumors. Since its inception in fiscal year 13, the program completed a survey of Cincinnati Children’s providers to better understand the variation in management of acute pancreatitis, assembled a multidisciplinary care team to evaluate and treat complex pancreatic disorders and established a REDCap database for patient registry. We also established a robust registry and biorepository for pancreatic surgical patients for future research initiatives. In 2020, in collaboration with endocrine team, we built a diabetes registry for post Total Pancreatectomy with Islet Autotransplantation (TPIAT) patients. The existing databases design allows generation of data that drives healthcare outcomes positively.

The Pancreatic Care Center (PCC) performed our first TPIAT operation in fiscal year 15, and performed 18 operations in fiscal year 20, which makes the total TPIATs and subtotal pancreatectomies with IAT performed at 71 operations since our program’s inception. There were 427 Gastroenterology pancreas clinic visits in fiscal year 20 of those 77 were new pancreas visits, and 33 new TPIAT evaluations in fiscal year 20. The PCC advanced endoscopists performed 171 Endoscopic Retrograde Cholangiopancreatographies (ERCPs) and 37 endoscopic ultrasounds (EUS) in fiscal year 20.

Our scientific highlights for this past year included cutting edge research findings that included publications on the role of imaging in staging pancreatic disease in children, published in the journal of Pediatric Radiology (PMID 32556574 and PMID: 32047986) and other high quality journals. Predictive models on severe acute pancreatitis and the optimal management paradigms published in Pancreas (PMID: 32132512) and the Journal of Pediatrics ( PMID: 31399249). Our unique TPIAT program generated important clinical studies on the outcomes of sterility cultures following pancreatectomy in islet isolates in the Journal of Gastrointestinal Surgery (PMID: 31745897), and the phenomena of extreme thrombocytosis following islet transplantation in the Journal of Pediatric Surgery (PMID: 31677823). The PCC is also proud to announce opening a new islet laboratory under the leadership of Balamurugan Appakalai, PhD, where we will conduct islet cell isolation and islet cell biology and physiology related studies.

Abu-El-Haija receives funding from a K23 NIDDK grant for predicting severity and improving the outcomes of acute pancreatitis, and the grant is in the third year of funding currently. Our center is participating in NIH-funded multi-center studies (first two studies listed below) that will help advance the care of children with pancreatic disorders, amongst other grants submitted and awaiting review.

PCC team extramural funding during fiscal year 20:

1. NIH U01 Abu-El-Haija (site principal investigator) - CPDPC INSPPIRE International Study Group to Study Pediatric Acute Recurrent and Chronic Pancreatitis: In Search for a Cure. Cincinnati Children's Hospital Medical Center is the highest recruiting center for three years in a row out of 19 national and international centers.
2. NIH R01 Nathan (site principal investigator) - Advancing Treatment for Pancreatitis: A Prospective Observational Study of TPIAT. Our center is the highest enrolling center for pediatric TPIAT nationally in this consortium.

We also have widely marketed our Pancreas Gene Panel that we developed and launched in collaboration with the Molecular Genetics Laboratory, and it is now a clinically available test that evaluates 10 genes known to cause inheritable pancreatitis using Next Generation Sequencing technology. Since the launch in November 2016, we steadily perform about 10 tests a month using the Pancreas Gene Panel.

Nationally, PCC members are actively involved in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), as Abu-El-Haija is the vice chair of the pancreas committee and a course director for the National Pancreas Foundation (NPF) annual meeting. Abu-El-Haija is on the American Gastroenterology Association Pancreas Selection Committee, the president-elect for the Collaborative Alliance for Pancreatic Education and Research (CAPER), and on the planning committees of NASPGHAN, CAPER and World Congress meetings. David Vitale, MD, is an active member in the NASPGHAN endoscopy committee. Lin and Vitale are active members in the NASPGHAN ERCP Special Interest Group. Nathan is part of the NASPGHAN Pancreas Committee as well. The PCC at Cincinnati Children's is one of only a select few pediatric centers that are an NPF-approved Center of Excellence for pancreatic care in the nation, and is a referral destination sought out by patients and physicians from around the nation based on its reputation for excellence in patient care and its commitment to innovative research.

Pediatric Liver Transplantation

Members:

Alexander Miethke, MD, Medical Director
Akihiro Asai, MD
William Balistreri, MD
Jorge A. Bezerra, MD
Kathleen Campbell, MD
James Heubi, MD
Anna Peters, MD, PhD
Amy Taylor, MD

The mission of the Pediatric Liver Transplant Program is to advance the care of liver transplant recipients by providing unparalleled clinical care, addressing gaps in knowledge through patient-based and basic laboratory research, improving health care delivery system through continuous quality improvement, and serving as advocates for organ donation and allocation in our community and country. As one of the largest pediatric liver transplant programs in the country, we performed 727 liver transplants since the program began in 1986. Our patient and graft survival rates are above the national average at three years post-transplant, and we are performing living donor liver transplantation. In addition to providing care for the most common pediatric liver disorders leading to transplantations we leverage institutional strengths to provide care and the best outcome available to a number of patients with rare diseases and extremely complex needs. This includes children with advanced liver tumors. Since 2007, the Cincinnati Children's Liver Transplant Team performed 35 liver transplants for pediatric patients with hepatic tumors, more than any other program in the United States. Chronic liver disease and transplantation impact other organs especially the kidneys. In collaboration with the nephrology service we provide innovative renal replacement therapies including MARS before transplant or during the surgery, protect renal function following transplant through multi-disciplinary care coordination, and for those in need we perform simultaneous liver-kidney transplants. We recently performed two combined heart-liver transplants for patients with congenital heart disease and chronic liver failure from failing Fontan physiology.

In addition to providing outstanding patient care, the Liver Transplant program is a leader in multicenter clinical and translational research studies and national quality improvement efforts. These include: Studies in Pediatric Liver Transplantation (SPLIT) quality improvement community and clinical registry and multiple local projects. For instance, we developed a quality improvement program to identify barriers for medication non-compliance to design individualized mitigation strategies in our adolescent patients with support of the James M. Anderson Center for Health Systems Excellence. In collaboration with the Center for Transplant Immunology (CTIMM), Peters is using single-cell sequencing technology to molecularly define transplant rejection responses to better understand the biological processes underpinning late-onset acute cellular rejection and ultimately personalize immunosuppression therapies.

At the program level, our multi-disciplinary teams are undertaking various QI initiatives and innovative approaches to improve patient outcomes. These include live vaccines for post-transplant patients, and a new remote home monitoring program for our freshly transplanted patients.

Steatohepatitis Center

Members:

Stavra Xanthakos, MD, MS, Director
Catalina Arce-Clachar, MD
Kristin Bramlage, MD
Marialena Mouzaki, MD, MSc, Associate Director

Understanding and treating NAFLD and NASH: The Cincinnati Steatohepatitis Center (CCSC) is a multidisciplinary program that provides care to a growing population of children and adolescents with nonalcoholic fatty liver disease, the most common cause of liver disease worldwide. NAFLD affects one in 10 children and one in three adults in the United States; up to 1/3 of these affected persons can develop a more severe form called NASH which can progress to severe fibrosis. NASH-related cirrhosis is one of the leading causes of liver transplant in adults, especially among younger adults. Early identification and intervention is critical to prevent progression to end-stage liver disease.

Because NAFLD and NASH are closely associated with obesity, cardiovascular disease, prediabetes and diabetes, the CCSC collaborates with the Center for Better Health and Nutrition, the Sleep Center, the Hypertension Clinic, the Lipid Clinic, the Type2 Diabetes Comprehensive Care Clinic and the Surgical Weight Loss Program for Teens to help identify and manage comorbid conditions and help patients achieve a healthier weight, the current first-line treatment. Our program completed over 650 patient visits in fiscal year 2020. Given the high prevalence of this disease, our program now offers clinics at our base, Liberty and Anderson locations, with four faculty members, including Arce-Clachar, Bramlage, Mouzaki and Xanthakos. Because patients of Hispanic ethnicity carry a high burden of NAFLD and may face additional barriers to accessing healthier lifestyles, we offer a clinic staffed by Arce-Clachar, who is bilingual in Spanish and English, to improve communication. In 2020, we also initiated telehealth offerings to expand patient care during the ongoing global pandemic.

Our program also seeks to develop more broadly effective prevention and intervention strategies for NAFLD. We are also investigating novel noninvasive biomarkers for the diagnosis and staging of NAFLD, to reduce need for liver biopsies, which are currently the gold standard for evaluation of severity. We are a leading pediatric site in the NIDDK-funded NASH Clinical Research Network (NASH-CRN), a multi-center consortium investigating the natural history and determinants of NASH in adults and children and conducting trials of novel therapies, including a recently completed randomized control trial of losartan for the treatment of NAFLD in children. In 2018, we also joined TARGET-NASH, a multi-center observational cohort study that will examine natural history and comparative effectiveness of diverse treatments in populations under-represented in phase II and phase III clinical trials. Published research highlights in 2020 included evaluating the association of community socioeconomic deprivation and NAFLD severity in children, which found that children from more deprived neighborhoods presented with NAFLD at an earlier age. We also examined the significance of autoantibody seropositivity in a multicenter study of 136 children with NAFLD. While one third of children had elevated autoantibodies (most commonly anti-nuclear antibody, followed by anti-smooth muscle antibody), none met criteria for autoimmune hepatitis and autoantibody seropositivity with no association with histological liver disease severity. We also demonstrated that state-of-the-art multifrequency octopolar BIA at point-of care can accurately assess body composition even in children with severe obesity, relative to DEXA-assessed body composition. The published work by the CCSC investigators is in Alimentary Pharmacology and Therapeutics, Gastroenterology, Clinical Gastroenterology and Hepatology, Obesity, New England Journal of Medicine, Nature, JAMA Pediatrics, Journal of Pediatrics, Journal of Pediatric Gastroenterology and Nutrition, Nature Reviews Gastro Hepatology, Pediatric Obesity and others.