Liver Transplantation and Development of Diabetes in an Adolescent Male With HNF1B Disease.

Mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene cause a variety of diseases in different organ systems. Mutations have been described as causing neonatal cholestasis, maturity-onset diabetes of the young (type 5), cortical renal cysts, urogenital abnormalities, liver dysfunction, and atrophy of the pancreas. We describe a male patient who presented with cholestatic liver disease in infancy which progressed by age 14 to end-stage liver disease due to HNF1B disease. He subsequently underwent liver transplantation at age 15 and then developed diabetes requiring insulin which did not resolve after cessation of corticosteroids. To our knowledge, this is the first case reported of liver transplantation for decompensated cirrhosis secondary to HNF1B disease.

Genetic variants in DGAT1 cause diverse clinical presentations of malnutrition through a specific molecular mechanism.

BACKGROUND: DGAT1, a gene encoding a protein involved in lipid metabolism, has been recently implicated in causing a rare nutritional and digestive disease presenting as Congenital Diarrheal Disorder (CDD). Genetic causes of malnutrition can be classified as metabolic disorders, caused by loss of a specific enzyme's function. However, disease driven by genetic variants in lipid metabolism genes is not well understood, and additional information is needed to better understand these effects. METHODS: We gathered a multi-institutional cohort of undiagnosed patients with a constellation of phenotypes presenting as malnutrition and metal ion dysregulation. Clinical Whole Exome Sequencing (WES) was performed on four patients and their unaffected parents. We prioritized genetic variants based on multiple criteria including population allele frequency and presumed inheritance pattern, and identified a candidate gene. Computational modeling was used to investigate if the altered amino acids are likely to result in a dysfunctional enzyme. RESULTS: We identified a multi-institutional cohort of patients presenting with malnutrition-like symptoms and likely pathogenic genomic variants within DGAT1. Multiple approaches were used to profile the effect these variants have on protein structure and function. Laboratory and nutritional intervention studies showed rapid and robust patient responses. CONCLUSIONS: This report adds on to the database for existing mutations known within DGAT1, a gene recently implicated with CDD, and also expands its clinical spectrum. Identification of these DGAT1 mutations by WES has allowed for changes in the patients' nutritional rehabilitation, reversed growth failure and enabled them to be weaned off of total parenteral nutrition (TPN).

Interdisciplinary aerodigestive care model improves risk, cost, and efficiency.

OBJECTIVE: This study sought to evaluate the impact of an interdisciplinary care model for pediatric aerodigestive patients in terms of efficiency, risk exposure, and cost. METHODS: Patients meeting a standard clinical inclusion definition were studied before and after implementation of the aerodigestive program. RESULTS: Aerodigestive patients seen in the interdisciplinary clinic structure achieved a reduction in time to diagnosis (6 vs 150 days) with fewer required specialist consultations (5 vs 11) as compared to those seen in the same institution prior. Post-implementation patients also experienced a significant reduction in risk, with fewer radiation exposures (2 vs 4) and fewer anesthetic episodes (1 vs 2). Total cost associated with the diagnostic evaluation was significantly reduced from a median of $10,374 to $6055. CONCLUSION: This is the first study to utilize a pre-post cohort to evaluate the reduction in diagnostic time, risk exposure, and cost attributable to the reorganization of existing resources into an interdisciplinary care model. This suggests that such a model yields improvements in care quality and value for aerodigestive patients, and likely for other pediatric patients with chronic complex conditions.

Structure and Functions of Pediatric Aerodigestive Programs: A Consensus Statement.

Aerodigestive programs provide coordinated interdisciplinary care to pediatric patients with complex congenital or acquired conditions affecting breathing, swallowing, and growth. Although there has been a proliferation of programs, as well as national meetings, interest groups and early research activity, there is, as of yet, no consensus definition of an aerodigestive patient, standardized structure, and functions of an aerodigestive program or a blueprint for research prioritization. The Delphi method was used by a multidisciplinary and multi-institutional panel of aerodigestive providers to obtain consensus on 4 broad content areas related to aerodigestive care: (1) definition of an aerodigestive patient, (2) essential construct and functions of an aerodigestive program, (3) identification of aerodigestive research priorities, and (4) evaluation and recognition of aerodigestive programs and future directions. After 3 iterations of survey, consensus was obtained by either a supermajority of 75% or stability in median ranking on 33 of 36 items. This included a standard definition of an aerodigestive patient, level of participation of specific pediatric disciplines in a program, essential components of the care cycle and functions of the program, feeding and swallowing assessment and therapy, procedural scope and volume, research priorities and outcome measures, certification, coding, and funding. We propose the first consensus definition of the aerodigestive care model with specific recommendations regarding associated personnel, infrastructure, research, and outcome measures. We hope that this may provide an initial framework to further standardize care, develop clinical guidelines, and improve outcomes for aerodigestive patients.

The Association Between Celiac Disease and Eosinophilic Esophagitis: Mayo Experience and Meta-analysis of the Literature.

BACKGROUND: The association between celiac disease (CD) and eosinophilic esophagitis (EoE) has been the focus of multiple studies with variable results. Both diseases are immune mediated, and dietary triggers play a role in their pathogenesis. OBJECTIVES: The aim of the study was to analyze the risk of EoE in children with CD, assess the magnitude of association between CD and EoE in children, and report the characteristics and outcomes of children with both conditions. METHODS: We conducted a retrospective study of the Mayo Clinic Electronic medical records between January 1, 1998 and December 31, 2015. Systematic review and meta-analysis of multiple databases was conducted to include studies reporting on the same association. Random-effects model was used to report pooled odds ratio (OR) and 95% confidence interval (CI). RESULTS: In this cohort study, of 10,201 children who underwent at least 1 endoscopy, 595 had EoE, and 546 had CD. The risk of having EoE was not increased in children with CD compared to those without CD (OR, 0.29; 95% CI, 0.154-0.545). Nine of 10 children improved with gluten-free diet, topical glucocorticosteroid, and/or elimination diet. One child lost to follow-up.Meta-analysis of 5 studies showed similar results (OR, 0.525; 95% CI, 0.364-0.797). A total of 45 cases in the literature had both CD and EoE (mean age, 10 years; 64% boys; majority presenting with abdominal pain, vomiting, and diarrhea). CONCLUSIONS: Based on our cohort and the observational data, the diagnosis of CD in children is not associated with increased risk of EoE.

Postoperative gastrointestinal bleeding in orthognathic surgery patients: its estimated prevalence and possible association to known risk factors.

PURPOSE: To assess the prevalence of gastrointestinal (GI) bleeding in patients after orthognathic surgery and its relation to known risk factors. PATIENT AND METHODS: With institutional review board approval, a single-center case series was conducted with data collected retrospectively from orthognathic surgical patients' medical records from 1990 to 2010. All patients were treated by 1 primary surgeon, were limited to 21 years or younger at the time of surgery, and had no coagulopathy. The authors' hypothesis was that patients concurrently exposed to mechanical ventilation and dual anti-inflammatory drugs in the postoperative period would be at a greater risk for clinically significant GI bleeding according to the American Society of Health-System Pharmacists guideline compared with those exposed to fewer risk factors. Its prevalence and relation to known risk factors were analyzed. RESULTS: In total 498 orthognathic cases consisting of 220 male patients (median age, 17 yr; age range, 3 to 21 yr) and 262 female patients (median age, 17 yr; age range, 10 to 21 yr) were reviewed. Of 17 patients admitted to intensive care unit level of care postoperatively, 4 patients were exposed to concomitant administration of ketorolac and steroids while being mechanically ventilated. Two of these 4 patients developed esophagogastroduodenoscopy-confirmed upper GI bleeding (UGIB). There was no incidence of UGIB in patients not exposed to all 3 risk factors concurrently. CONCLUSIONS: Postoperative GI bleeding complication is rare in orthognathic surgical patients, with an estimated prevalence of 0.4%. Based on these observations, orthognathic surgical patients who require mechanical ventilation and are receiving anti-inflammatory medications may have an increased risk of GI bleeding. In the absence of active bleeding from the surgical site, persistent decrease in hemoglobin concentration should alert one to consider the possibility of UGIB.

Multiple liver lesions in an immunosuppressed patient: is infection always the answer?

Pylephlebitis with associated liver abscesses is a rare complication of Crohn's disease that usually presents in the setting of active disease and recent escalation of the immunosuppressive regimen. Here we describe a 17-year-old female patient with active Crohn's disease who presented with a clinical picture and hepatic radiographic findings concerning for pylephlebitis and associated liver abscesses but subsequently confirmed to be an atypical form of focal fatty liver infiltration. We describe the diagnostic difficulty this unique distribution of hepatic fatty infiltration can present and highlight the importance of the different imaging studies to differentiate between atypical focal fatty infiltration and pylephlebitis.

The Mayo Dysphagia Questionnaire-30: documentation of reliability and validity of a tool for interventional trials in adults with esophageal disease.

The aim of this study was to develop the Mayo Dysphagia Questionnaire-30 Day (MDQ-30), a tool to measure esophageal dysphagia, by adapting items from validated instruments for use in clinical trials, and assess its feasibility, reproducibility, and concurrent validity. Outpatients referred to endoscopy for dysphagia or seen in a specialty clinic were recruited. Feasibility testing was done to identify problematic items. Reproducibility was measured by test-retest format. Concurrent validity reflects agreement between information gathered in a structured interview versus the patients' written responses. The MDQ-30, a 28-item instrument, took 10 min (range = 5-30 min) to complete. Four hundred thirty-one outpatients [210 (49%) men; mean age = 61 years] participated. Overall, most concurrent validity kappa values for dysphagia were very good to excellent with a median of 0.78 (min 0.28, max 0.95). The majority of reproducibility kappa values for dysphagia were moderate to excellent with a median kappa value of 0.66 (min 0.07, max 1.0). Overall, concurrent validity and reproducibility kappa values for gastroesophageal reflux disease (GERD) symptoms were 0.81 (95% CI = 0.72, 0.91) and 0.66 (95% CI = 0.55, 0.77), respectively. Individual item percent agreement was generally very good to excellent. Internal consistency was excellent. We conclude that the MDQ-30 is an easy-to-complete tool to evaluate reliably dysphagia symptoms over the last 30 days.

Orthostatic intolerance and gastrointestinal motility in adolescents with nausea and abdominal pain.

OBJECTIVE: To describe the relationships between gastric emptying, autonomic function, and postural tachycardia in adolescent patients with nausea and/or abdominal discomfort. It was hypothesized that patients with both gastrointestinal symptoms and symptoms of orthostatic intolerance are more likely to show abnormal tilt table results and delayed gastric emptying. PATIENTS AND METHODS: A retrospective review was conducted of adolescent patients who came to a pediatric referral center because of nausea and dyspepsia and who subsequently underwent both autonomic reflex screening and gastric emptying testing. Patients with a heart rate change of 30 or more beats per minute on the heads-up tilt table test were assigned to the postural orthostatic tachycardia syndrome (POTS) group (n = 21), and those with a heart rate change of fewer than 30 beats per minute on the heads-up tilt table test were assigned to the non-POTS group (n = 10). RESULTS: There was no significant difference between the POTS and non-POTS groups with regard to presenting symptoms (P > 0.05). Overall, 13 (42%) individuals had abnormal gastric emptying results (delayed in 6, accelerated in 7), but gastric emptying scores were similar between the POTS and non-POTS groups. Furthermore, there was no correlation between an individual's gastric emptying results at 1, 2, and 4 hours and that person's heart rate change on HUT (r = -0.05, -0.15, and -0.19). CONCLUSIONS: Although altered gastric emptying and postural tachycardia are common in a referral population of adolescents with nausea and/or abdominal discomfort, the clinical presentation was not predictive of test results. Furthermore, delayed gastric emptying was not correlated with the current definition of postural tachycardia.