Raza Patel

Treatment With High-dose Proton Pump Inhibitors Helps Distinguish Eosinophilic Esophagitis From Noneosinophilic Esophagitis

Background: Eosinophilic esophagitis (EE) is a clinical entity that is recognized increasingly in children. The treatment of EE has been debated since its identification as a clinical entity separate from reflux esophagitis. We hypothesize that the treatment with a high-dose proton pump inhibitor (HDPPI) helps differentiate EE from noneosinophilic esophagitis (NEE). Patients and Methods: Retrospective review of 2221 patients who underwent esophagogastroduodenoscopy (EGD) with biopsies was undertaken. Sixty-nine patients had more than or equal to 15 eosinophils/high-power field (eos/HPF) in 1 or more esophageal levels. Of those, 36 were initially treated with HDPPI for 3 months followed by repeat EGD. Patients who demonstrated histologic response were classified as NEE. Patients with no histologic response were diagnosed as having EE and treated with HDPPI + swallowed fluticasone for 3 months followed by repeat EGD. Results: Of the 36 patients, histologic response was seen in 14 (39%) after treatment with HDPPI; 95% confidence interval (0.23–0.54). Swallowed fluticasone was added to the treatment of the 22 patients who did not show histologic response to HDPPI alone. Of those, 15 patients underwent repeat endoscopies. Seven patients were lost to follow-up or did not have repeated EGDs. Histologic response was observed in 9 of 15 (60%) patients. Of the nonresponders (6 of 15), 5 of 6 (83%) self-reported noncompliance with the swallowed fluticasone. Patients with more than or equal to 15 eos/HPF at all 3 levels (25 of 36) were less likely to respond to HDPPI alone and more likely to be categorized as EE (18 of 25), P = <0.043. Symptomatically, 28 of 36 patients reported resolution of symptoms after HDPPI therapy alone, P = <0.0001, regardless of histology. Visual endoscopic findings during the first and second EGDs did not show any significance in differentiating EE from NEE, P = 0.625 and P = 0.2405, respectively. Conclusions: The study demonstrates that HDPPI can be used to help differentiate EE from NEE histologically. Moreover, patients with more than or equal to 15 eos/HPF at all 3 levels are less likely to respond to HDPPI than patients with more than or equal to 15 eos/HPF at fewer than 3 levels. Therefore, having more than or equal to 15 eos/HPF at 1 or 2 biopsy levels does not necessarily establish the diagnosis of EE. Symptomatic response to HDPPI does not correlate with histologic findings. Clinical management guided by EGD with biopsy helps distinguish patients with EE from those with NEE.

Lipid in the livers of adolescents with nonalcoholic steatohepatitis: combined effects of pathways on steatosis

Fatty liver is a prerequisite for the development of nonalcoholic steatohepatitis (NASH). The homeostasis of hepatic lipid is determined by the dynamic balance of multiple pathways introducing lipids into or removing lipids from hepatocytes. We aim to study the different contributions of major lipid pathways to fat deposition in NASH livers. Expression of the lipid metabolism-related genes was analyzed by microarray and quantitative real-time polymerase chain reaction analysis. The expression levels of genes responsible for the rate-limiting steps of fatty acid uptake (CD36, FABPpm, SLC27A2, and SLC27A5), de novo synthesis (ACACB), oxidation (CPT-1), and very low-density lipoprotein (VLDL) secretion (ApoB) were used to evaluate the relative activity of each pathway. The expression levels for CD36 and CPT-1 were confirmed by Western blot analysis. Fatty acid uptake pathways were up-regulated to a higher degree than other pathways. The de novo synthesis pathway was also up-regulated more than both VLDL secretion and fatty acid oxidation pathways. In contrast to other NASH livers, one NASH liver exhibited lower ApoB and CPT-1 expression levels than normal controls. The increased fatty acid uptake and de novo synthesis were the most common causes for steatosis in NASH patients. In a rare case, impaired VLDL secretion and fatty acid oxidation contributed to the development of steatosis. Our study promises a simple method for the determination of why hepatic steatosis occurs in individual patients. This method may allow specific targeting of therapeutic treatments in individual patients.

Effect of Dietary Advanced Glycation End Products on Mouse Liver

The exact pathophysiology of non-alcoholic steatohepatitis (NASH) is not known. Previous studies suggest that dietary advanced glycation end products (AGEs) can cause oxidative stress in liver. We aim to study the effects of dietary AGEs on liver health and their possible role in the pathogenesis of NASH. METHODS: Two groups of mice were fed the same diet except the AGE content varied. One group was fed a high AGE diet and the second group was fed a regular AGE diet. Liver histology, alanine aminotransferase, aspartate aminotransferase, fasting glucose, fasting insulin, insulin resistance and glucose tolerance were assessed. RESULTS: Histology revealed that neutrophil infiltration occurred in the livers of the high AGE group at week 26; steatosis did not accompany liver inflammation. At week 39 livers from both groups exhibited macro- or micro-steatosis, yet no inflammation was detected. Higher insulin levels were detected in the regular AGE group at week 26 (P = 0.034), compared to the high AGE group. At week 39, the regular AGE group showed higher levels of alanine aminotransferase (P<0.01) and aspartate aminotransferase (P = 0.02) than those of the high AGE group. CONCLUSIONS: We demonstrate that a high AGE diet can cause liver inflammation in the absence of steatosis. Our results show that dietary AGEs could play a role in initiating liver inflammation contributing to the disease progression of NASH. Our observation that the inflammation caused by high AGE alone did not persist suggests interesting future directions to investigate how AGEs contribute to pro-oxidative and anti-oxidative pathways in the liver.

Increasing Incidence of Community-Associated Atypical Clostridium difficile Disease in Children

Forty-one children with a variety of gastrointestinal complaints were diagnosed with Clostridium difficile infections as part of a routine screen over 3 years. The infection had not been suspected prior to the screen. Each child responded to treatment with metronidazole with resolution of their symptoms. These data suggest that community-associated C difficile is increasing and may produce atypical disease and lead to misdiagnosis.

Delays in discharge in a tertiary care pediatric hospital

BACKGROUND Delays in discharges affect both efficiency and timeliness of care; 2 measures of quality of inpatient care. OBJECTIVE Describe number, length, and type of delays in hospital discharges. Characterize impact of delays on overall length of stay (LOS) and costs. DESIGN Prospective observational cohort study. SETTING Tertiary-care childrens hospital. PATIENTS All children on 2 medical teams during August 2004. INTERVENTION Two research assistants presented detailed data of patient care (from daily rounds) to 2 physicians who identified delays and classified the delay type. Discharge was identified as delayed if there was no medical reason for the patient to be in the hospital on a given day. MEASUREMENTS Delays were classified using a validated and reliable instrument, the Delay Tool. LOS and costs were extracted from an administrative database. RESULTS Two teams cared for 171 patients. Mean LOS and costs were 7.3 days (standard deviation [SD] 14.3) and

Clostridium difficile Infection and Proton Pump Inhibitor Use in Hospitalized Pediatric Cystic Fibrosis Patients

15,197 (SD 38,395), respectively: 22.8% of patients experienced at least 1 delay, accounting for 82 delay-related hospital days (9% of total hospital days) and

Varicella immunity in inflammatory bowel disease.

170,000 in costs (8.9% of hospital costs); 42.3% of the delays resulted from physician behavior, 21.8% were related to discharge planning, 14.1% were related to consultation, and 12.8% were related to test scheduling. CONCLUSIONS Almost one-fourth of patients in this 1-month period could have been discharged sooner than they were. Impact of delays on LOS and costs are substantial. Interventions will need to address variations in physician criteria for discharge, more efficient discharge planning, and timely scheduling of consultation and diagnostic testing.

Endoscopy in the diagnosis of intestinal graft-versus-host disease: Is lower endoscopy with biopsy as effective in diagnosis as upper endoscopy combined with lower endoscopy?

Children with cystic fibrosis (CF) often take proton pump inhibitors (PPIs), which helps improve efficacy of fat absorption with pancreatic enzyme replacement therapy. However, PPI use is known to be associated with Clostridium difficile-(C. diff-) associated diarrhea (CDAD). We retrospectively evaluated the incidence of C. diff infection from all pediatric hospital admissions over a 5-year period at a single tertiary childrens hospital. We found significantly more C. diff-positive stool tests in hospitalized patients with CF compared to patients with no diagnosis of CF. However, use of a PPI was not associated with an increased risk of CDAD in hospitalized CF patients. In summary, C. diff infection is more common in hospitalized pediatric CF patients although PPI use may not be a risk factor for CDAD development in this patient population.

Two Cases of Helicobacter pylori-Negative Gastric Outlet Obstruction in Children

Objectives: Varicella zoster is a childhood disease that can cause devastating illness and death in immunocompromised individuals, including those who are taking steroids. Inflammatory bowel disease (IBD) is managed by decreasing or controlling the inflammation using immunosuppression. Our objective was to show that at least 90% of patients newly diagnosed as having IBD had antibodies against varicella zoster and were protected by vaccination or natural disease. Materials and Methods: Retrospective review of all of the charts of the patients diagnosed with IBD at the University of Buffalos Digestive Diseases and Nutrition Center for 5 years from January 1, 2005 to December 31, 2009. Results: There were 163 new diagnoses of IBD during this time; 57% were boys. Mean age was 12 years (range 1–19 years); 62% had Crohn disease, 33% ulcerative colitis, and 5% indeterminate colitis. A total of 66% of all of the patients had a history of disease or vaccination. Measurable titers against varicella were found in only 77% of all of the patients. Conclusions: Lack of varicella immunity is common in children and adolescents at the time of diagnosis of IBD. Routine screening for varicella immune status may be warranted. Offering immunization to susceptible patients should confer protection, but this may be difficult to achieve once immune suppression has begun.

Vitamin D deficiency in pediatric patients with cystic fibrosis: associated risk factors in the northern United States.

Graft‐versus‐host disease (GvHD) causes morbidity and mortality in recipients of hematopoietic stem cell transplantation (SCT). This study assessed the distribution of GvHD in gastrointestinal (GI) biopsies from the upper and lower GI tract in pediatric patients who had undergone SCT and evaluated if there was correlation between biopsy findings and possible extra‐intestinal manifestations of GvHD.