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Background and Aims: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. Approach and Results: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of

Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. Methods: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. Results: Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. Conclusions: All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long-term outcomes in pediatric PSC patients. We evaluated GGT normalization (75% versus 75% by 1 year after PSC diagnosis predicts favorable 5-year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.

OBJECTIVEClostridium difficile infection (CDI) places a high burden on the US healthcare system. Recurrent CDI (RCDI) occurs frequently. Recently proposed guidelines from the American College of Gastroenterology (ACG) and the American Gastroenterology Association (AGA) include fecal microbiota transplantation (FMT) as a therapeutic option for RCDI. The purpose of this study was to estimate the cost-effectiveness of FMT compared with vancomycin for the treatment of RCDI in adults, specifically following guidelines proposed by the ACG and AGA.DESIGNWe constructed a decision-analytic computer simulation using inputs from the published literature to compare the standard approach using tapered vancomycin to FMT for RCDI from the third-party payer perspective. Our effectiveness measure was quality-adjusted life years (QALYs). Because simulated patients were followed for 90 days, discounting was not necessary. One-way and probabilistic sensitivity analyses were performed.RESULTSBase-case analysis showed that FMT was less costly ($1,669 vs $3,788) and more effective (0.242 QALYs vs 0.235 QALYs) than vancomycin for RCDI. One-way sensitivity analyses showed that FMT was the dominant strategy (both less expensive and more effective) if cure rates for FMT and vancomycin were ≥70% and CONCLUSIONSOur results suggest that FMT may be a cost-saving intervention in managing RCDI. Implementation of FMT for RCDI may help decrease the economic burden to the healthcare system.Infect Control Hosp Epidemiol 2014;00(0): 1–7

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC–inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. Conclusion: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC–inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518–527).

Neonatal cholestasis results from a variety of etiologies, including anatomic, infectious, and metabolic abnormalities. Hyperthyroidism, in contrast to hypothyroidism, is infrequently associated with neonatal cholestasis. Newborn screening is an important tool to detect newborn metabolic disorders, including thyroid dysfunction. However, one must exercise caution when interpreting these reports; typically only high thyroid stimulating hormone (TSH) levels are flagged as abnormal, while low or undetectable levels may not be. We present a unique case of cholestasis in a hyperthyroid neonate of an untreated, undiagnosed mother with Graves' disease; the infant's metabolic screen was not flagged as abnormal.

1. Raghu Varier, DO* 2. Laura Plencner, MD* 3. Douglas Rivard, DO† 4. Angela L. Myers, MD, MPH* 1. *Department of Pediatrics, Children's Mercy Hospitals & Clinics and The University of Missouri-Kansas City, Kansas City, MO. 2. †Department of Radiology, Children's Mercy Hospitals & Clinics and The University of Missouri-Kansas City, Kansas City, MO. A previously healthy 13-year-old girl presents to the emergency department with a 2-week history of worsening sore throat and a 4-day history of left neck swelling, pain, and fever. Results of evaluation by a prior clinician at the onset of symptoms included a negative rapid streptococcal antigen test and a positive heterophile antibody test, prompting treatment with oral corticosteroids for 5 days as an anti-inflammatory medication. The girl now reports pain with swallowing, decreased oral intake, and left-sided head tilt for the past 24 hours. On physical examination, the girl has a temperature of 38.4°C and appears to be in no acute distress. In addition, her heart rate is 91 beats/min, respiratory rate is 20 breaths/min, and blood pressure is 119/69 mm Hg. She has a warm, very tender, firm, anterior, left-sided 1.5-cm mass at the level of the thyroid gland. The mass moves when she swallows. Findings on the rest of her physical examination are normal. Laboratory investigation reveals a white blood cell count of 17.2×103/μL (17.2×109/L) with 74% neutrophils and 14% lymphocytes, hemoglobin of 13 g/dL (130 g/L), and platelet count of 423×103/μL (423×109/L). C-reactive protein (CRP) measurement is elevated at 1.6 mg/dL (normal, 0.3 to 1.0 mg/dL). Computed tomography (CT) scan of her neck with intravenous contrast enhancement suggests the diagnosis (Fig. 1). Figure 1. Axial computed tomography scan of the neck with intravenous contrast enhancement. The patient's physical and laboratory findings and CT scan of the neck are consistent with acute suppurative thyroiditis. The CT scan reveals a multilocular inflammatory phlegmon/abscess-in-evolution involving the superior pole of the …

Functional constipation (FC) is a common medical problem in children, with minimal risk of long-term complications. We determined that a large number of children were being admitted to our children's hospital for FC in which there was no neurological or anatomical cause. Our hospital experienced a patient complication in which a patient died after inpatient treatment of FC. Subsequently, we developed a standardised approach to determine when paediatric patients needed hospitalisation for FC, as well as to develop a regimented outpatient therapeutic approach for such children to prevent hospitalisation. Our quality improvement initiative resulted in a large decrease in the number of children with FC admitted into the hospital as well as a decrease in the number of children needing faecal disimpaction in the operating room. Our quality improvement process can be used to decrease hospitalisations, decrease healthcare costs and improve patient care for paediatric FC.

Clostridium difficile infection (CDI) is costly. Current guidelines recommend metronidazole as first-line therapy and vancomycin as an alternative. Recurrence is common. Faecal microbiota transplantation (FMT) is an effective therapy for recurrent CDI (RCDI). This study explores the cost-effectiveness of FMT, vancomycin and metronidazole for initial CDI. We constructed a decision-analytic computer simulation using inputs from published literature to compare FMT with a 10–14-day course of oral metronidazole or vancomycin for initial CDI. Parameters included cure rates (baseline value (range)) for metronidazole (80% (65–85%)), vancomycin (90% (88–92%)) and FMT(91% (83–100%)). Direct costs of metronidazole, vancomycin and FMT, adjusted to 2011 dollars, were $57 ($43–72), $1347 ($1195–1499) and $1086 ($815–1358), respectively. Our effectiveness measure was quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were conducted from the third-party payer perspective. Analysis using baseline values showed that FMT($1669, 0.242 QALYs) dominated (i.e. was less costly and more effective) vancomycin ($1890, 0.241 QALYs). FMT was more costly and more effective than metronidazole ($1167, 0.238 QALYs), yielding an incremental cost-effectiveness ratio (ICER) of $124 964/QALY. One-way sensitivity analyses showed that metronidazole dominated both strategies if its probability of cure were >90%; FMT dominated if it cost

Graphics Processing Units (GPUs) are becoming the workhorse of scalable computations. MADNESS is a scientific framework used especially for computational chemistry. Most MADNESS applications use operators that involve many small tensor computations, resulting in a less regular organization of computations on GPUs. A single GPU kernel may have to multiply by hundreds of small square matrices (with fixed dimension ranging from 10 to 28). We demonstrate a scalable CPU-GPU implementation of the MADNESS framework over a 500-node partition on the Titan supercomputer. For this hybrid CPU-GPU implementation, we observe up to a 2.3-times speedup compared to an equivalent CPU-only implementation with 16 cores per node. For smaller matrices, we demonstrate a speedup of 2.2-times by using a custom CUDA kernel rather than a cuBLAS-based kernel.