Prateek Wali

Ghrelin and obestatin levels in children with failure to thrive and obesity.

Objectives: Ghrelin and obestatin are 2 gastric hormones with opposite effects on food intake and body weight. We investigated plasma ghrelin and obestatin in children with failure to thrive (FTT) and obesity as compared with age-matched controls. Methods: A total of 63 children were included in the study: 13 with FTT, 17 with obesity, and 33 age-matched controls. Children fasted for at least 8 hours before specimen collection. Both hormones were measured using commercially available enzyme immunoassay kits. Results: Ghrelin and obestatin levels in children with FTT were not significantly different from that of the age-matched controls (P >0.05). In children with obesity, the total ghrelin levels were significantly lower (P = 0.0003) and the obestatin levels significantly higher (P = 0.029) compared with those in controls. In the control group, the fasting ghrelin level was significantly higher in the younger (<3 years) than in the older children (>3 years; P = 0.0004). Obestatin levels correlated positively with weight-for-age percentiles in the obese group (P = 0.011) and negatively in the control group >3 years (P = 0.019). Conclusions: Compared with the levels in age-matched controls, fasting ghrelin and obestatin levels did not differ significantly in children with FTT. In the children with obesity, the decreased ghrelin and increased obestatin levels suggest a possible adaptive process to positive energy balance. Ghrelin had pronounced age-related changes, and obestatin was associated with the weight status. This may suggest that these 2 hormones use different mechanisms to regulate energy balance and weight.

Serologic reactivity reflects clinical expression of ulcerative colitis in children

Background In contrast to pediatric Crohns disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.

Suboptimal Early Outcomes following Standardized Induction Therapy in Children Newly Diagnosed with Ulcerative Colitis: The Protect Study

Jeffrey S. Hyams , Sonia Davis, David R. Mack , Brendan Boyle, Anne M. Griffiths, Neal S. Leleiko, Cary G.Sauer, David J. Keljo, James Markowitz, Susan Baker, Joel Rosh, Robert N. Baldassano, Ashish Patel, Marian Pfefferkorn, Anthony Otley, Melvin Heyman, Joshua Noe, Maria OlivaHemker, Paul Rufo, Jennifer Strople, David Ziring, Stephen Guthery, Boris Sudel, Keith Benkov, Prateek Wali, Dedrick Moulton, Jonathan Evans, Michael Kappelman , Alison Marquis, Francisco A. Sylvester, Margaret H. Collins, Suresh Venkateswaran, Marla Dubinsky, Krista L. Spada, Ashley Britt, Bradley Saul, Nathan Gotman, Jose Serrano, Subra Kugathasan, Thomas Walters, Lee A. Denson

Autoimmune hepatitis in a child presenting with hepatopulmonary syndrome (HPS).

HPS has been described in 9–20% of children with end‐stage liver disease. We present a case of a previously, asymptomatic nine‐yr‐old incidentally found to have low oxygen saturation. Physical exam was remarkable for digital clubbing, splenomegaly and orthodeoxia. Laboratory evaluation revealed a low platelet count, hyperammonemia, and prolonged coagulation studies. Sonography showed evidence of splenomegaly and portal venous hypertension. High resolution CT thorax and CTA were normal. HPS was confirmed by agitated saline contrast enhanced echocardiography and Tc‐99m MAA scan with evidence of intrapulmonary vascular dilatations. Liver biopsy was performed and consistent with autoimmune hepatitis. A high clinical index of suspicion should be maintained for HPS in pediatric patients who have unexplained hypoxemia as typical signs and symptoms of severe liver disease are often absent. In this report, we discuss a case of HPS complicated AIH in a pediatric patient and review the relevant literature.

An Adolescent With Cough and Dyspepsia

A 17-year-old Caucasian male previously healthy presents with a 4-month history of persistent dry cough, dyspnea with exertion, and dyspepsia. A chest X-ray showed no acute disease. Empiric asthma therapy with fluticasone was ineffective. He was treated for possible gastroesophageal reflux with ranitidine, followed by pantoprazole, still with no improvement in symptoms. Another chest X-ray was done for worsening nighttime cough and revealed bilateral patchy infiltrates, suggestive of atypical pneumonia. He was treated with 5 days of azithromycin with no clinical improvement. Due to his persistent dyspepsia and new-onset epigastric pain, he was referred to pediatric gastroenterology. An upper endoscopy revealed erythema of the distal esophagus and an ulcerated mass in the gastric fundus with diffuse congestion of the gastric body (Figure 1). The pathology results of the mass biopsy were consistent with a poorly differentiated adenocarcinoma, with positivity for CK7 CDX-2 and negative for chromogranin, confirming a tumor of gastric origin (Figures 2 and 3). Staining for CD34, CD31, and D-240 outlined multiple areas of lymphatic space invasion by tumor cells in the esophagus and the stomach. Immunohistochemistry studies were negative. Laboratory data included lactate dehydrogenase 783 U/L, alanine aminotransferase 173 U/L, aspartate aminotransferase 109 U/L, and lipase 191 U/L. Tumor marker results included cancer antigen 19-9 of 247 U/mL, carcinoembryonic antigen of 12.7 ng/mL, and cancer antigen 125 of 518 U/mL. The testing for Helicobacter pylori was negative. Computed tomography of the chest, abdomen, and pelvis, for tumor staging, revealed metastatic lesions in the lungs with bilateral pleural effusion and mediastinal, hilar, gastrohepatic ligament, bilateral retrocrural, periaortic and mesenteric lymphadenopathy (Figure 4).

Sa1999 Patient Related Outcomes and Disease Activity Indices in New Onset Pediatric Ulcerative Colitis: The PROTECT Study

Patient Related Outcomes and Disease Activity Indices in New Onset Pediatric Ulcerative Colitis: The PROTECT Study Thomas D. Walters, David R. Mack, Brendan Boyle, Anne M. Griffiths, Cary Sauer, Neal S. Leleiko, James Markowitz, David J. Keljo, Joel R. Rosh, Susan S. Baker, Melvin B. Heyman, Ashish S. Patel, Marian D. Pfefferkorn, Robert Baldassano, Joshua D. Noe, Maria Oliva-Hemker, Anthony R. Otley, Paul A. Rufo, Keith J. Benkov, David Ziring, Prateek Wali, Jonathan Evans, Dedrick E. Moulton, Boris Sudel, Stephen L. Guthery, Jennifer A. Strople, Michael Kappelman, Neera Gupta, Krista Spada, Subra Kugathasan, Lee Denson, Jeffrey S. Hyams

Su1234 Histologic Correlates of Clinical and Endoscopic Severity in Newly Diagnosed Pediatric Ulcerative Colitis: The PROTECT Study

Histologic Correlates of Clinical and Endoscopic Severity in Newly Diagnosed Pediatric Ulcerative Colitis: The PROTECT Study Brendan Boyle, Margaret H. Collins, Zhu Wang, David R. Mack, Anne M. Griffiths, Cary Sauer, James Markowitz, Neal S. Leleiko, David J. Keljo, Joel R. Rosh, Susan S. Baker, Marian D. Pfefferkorn, Melvin B. Heyman, Ashish S. Patel, Maria Oliva-Hemker, Robert Baldassano, Joshua D. Noe, Paul A. Rufo, Anthony R. Otley, Keith J. Benkov, Prateek Wali, Subra Kugathasan, Thomas D. Walters, Lee Denson, Jeffrey S. Hyams