- Email: [email protected]
Tu2008 Severity of Hepatic Fibrosis in Children With Biliary Atresia Using Non Invasive Markers vs Liver Biopsy
AGA Abstracts Figure: Immunohistochemical analysis of EGFR expression in esophageal biopsies obtained from children with eosinophilic esophagitis (A and B) showing diffuse full thickness staining, and from controls (C and D) showing faint basal staining.
Severely thickened, erythematous and exudative gastric folds diffusely throughout the entire stomach. Tu2007
Tu2006
Prenatal Microbial Exposure Induces Epigenetic Changes and Modulates TLRSignaling Pathway Associated Gene Expression in the Immature Intestine Lei Lu, Yueyue Yu, Yana Filipovich, Hirsch Emmet, Erika Claud
A Case of Phlegmonous Gastritis in a 10-Year Old Child With Newly Diagnosed Ulcerative Colitis Jonathan Cordova, Tiffany Patton, Ruba Azzam, Barbara S. Kirschner, Ranjana R. Gokhale
Background: Many disorders of preterm infants are inflammatory in nature including neonatal necrotizing enterocolitis (NEC). NEC affects approximately 10% of premature infants <1500gm and is associated with an increased inflammatory response of the immature enterocyte to both commensal and pathogenic bacteria. At least 40% of preterm births are associated with intrauterine infection. Intrauterine infection results in maternal/fetal inflammatory responses that are to a large extent dependent upon toll-like receptor (TLR)mediated innate immune responses. Studies have demonstrated that when TLRs recognize pathogens and respond to systemic infections, epigenetic alterations reprogram distinct functional sets of genes to both activate and repress transcription of hundreds of other genes. We hypothesis that intrauterine microbial exposure induces epigenetic changes in TLR signaling molecules thus modulating postnatal inflammatory responses in the immature small intestine. Methods: Heat killed E. coli or PBS was administered into the gestational compartment of pregnant CD1 mice on E14.5. The resulting viable pups at term or nearterm that survived the neonatal period were subjected to further analysis. 10-day-old pup ileum genomic DNA and total RNA were extracted and used in the analysis of both TLRsignaling pathway-focused profiling of DNA methylation status (22 genes) and gene expression levels (84 genes) by qRT-PCR. Results: Intrauterine exposure to heat-killed E. coli resulted in changes in the DNA-methylation profile of TLR-signaling genes in the mouse ileum. Using a TLR-signaling pathway DNA methylation PCR Array system, we detected differential DNA methylation of major TLR-signaling molecules including Tlr-2, Irak-1, 2, CD14, Hspa1a (HSP70), Hspd1, Il-6ra, Irf-1 and Irf-3 genes (n = 6 per group). We also observed down-regulation of mRNA expression levels of many genes associated with TLRsignaling. The downregulated genes (≤ -2 fold) were TLRs: Tlr1, Tlr4, Tlr6, Tlr7, Tlr8, Tlr9, and to a lesser degree Tlr2, 3 and 5; TLR signaling molecules: Cd14, Irak1, 2, Ticam1, Tradd; proinflammatory genes: Il-1, Il-12a, Ifnb1, Ifng, Tnf, Ccl2; and transcription factors: Nfkb2, Ppara, and other genes involved in immunomodulatory functions: Btk, Il6ra, Il-10, Il-2, Cd80, Ly86, Ube2v1, Csf2, Clec4e. Intrauterine infection induced upregulation of Csf3 and Fos genes (≥ 2). Conclusions: Together, these data suggest that antenatal intrauterine inflammation induces DNA methylation changes as well as a downregulation of mRNA expressions in TLR-related genes in the small intestines of offspring. These changes may result in a tolerance/inhibition of innate immune/inflammatory responses in the immature gut upon subsequent postnatal infectious/inflammatory challenge.
Introduction Phlegmonous gastritis is a life-threatening condition described as a rapidly progressive suppurative bacterial infection of the stomach that can lead to necrotizing or gangrenous gastritis. We report a case of acute phlegmonous gastritis in a child who was newly diagnosed with ulcerative colitis. Case Description A.M. is a 10 year old female with no significant past medical history who presented to our emergency department with a ten day history of bloody diarrhea, emesis and abdominal pain. Initial labs revealed an elevated WBC 15.9 x103/μL and hemoglobin 8.7 g/dL requiring a transfusion. Stool studies were negative with a fecal calprotectin >2500 μg/g feces. She became febrile and was started on ampicillin, gentamicin and metronidazole. On day 3 of admission she underwent an ileocolonoscopy that was consistent with ulcerative colitis. An EGD showe chronic, mildly active antral gastritis. Solumedrol was started at 1 mg/kg twice daily. She remained febrile with worsening abdominal pain and emesis and, on day 4 of admission, a CT of the abdomen/ pelvis showed pan-colitis without evidence of an intra-abdominal abscess. Over the following 10 days, she developed persistent bloody emesis, severe worsening abdominal pain, hypotension, anemia and new onset pancreatitis. An ongoing fever (despite antibiotics) and an elevated WBC 34 x103/μL with coagulopathy (INR 1.5) led to a repeat CT of the abdomen. CT results showed pancreatitis (without pseudocyst or necrosis) as well as severe, diffuse gastritis with thickened gastric folds and scattered hypoechoic foci within the gastric wall concerning for phlegmonous gastritis. As a result, antibiotics were broadened to include vancomycin and meropenem and steroids were decreased to 0.5 mg/kg twice daily to improve the eradication of the infection while continuing to induce remission of ulcerative colitis. On day 15 of admission, A.M. underwent a repeat EGD due to persistent anemia and ongoing upper GI bleeding that showed severe and diffuse exudative gastritis, deep ulcerations and clots of adherent blood. Histological findings including severe neutrophilic inflammation further support a diagnosis of phlegmonous gastritis. Sub-mucosal gastric biopsies were collected without an identifiable organism isolated. A.M.'s clinical status improved dramatically on broad spectrum antibiotics, over the following few days, with resolution of the upper GI bleed. A 1-month course of antibiotics was completed as treatment of phlegmonous gastritis. At this time, patient remains in clinical remission. Conclusion Phlegmonous gastritis is a rare bacterial infection of the stomach that has a high level of mortality and should be on the differential diagnosis for any patient who develops severe abdominal pain, hematemesis and fever, particularly while on immunosuppressive therapy.
Tu2008 Severity of Hepatic Fibrosis in Children With Biliary Atresia Using Non Invasive Markers vs Liver Biopsy Teena Sebastian, Parvathi Mohan Biliary atresia (BA) is an idiopathic neonatal obstructive cholangiopathy characterized by a progressive obliteration of the large bile ducts that presents uniquely in the first few months of life. It is the most common cholestatic liver disorder requiring a liver transplantation in infants and children. Hepatic fibrosis is a universal and prominent feature of BA even after a portoenterostomy. Therefore assessing the stage of fibrosis is an important tool to predict the course of biliary atresia. A liver biopsy is the gold standard for diagnosis but is associated with certain risks. Currently available non-invasive markers for fibrosis are not validated in children. Several authors, using routine laboratory data have constructed a simple model -AST (aspartate transaminase) to platelet ratio index (APRI)- to predict fibrosis in chronic viral hepatitis and in BA (1,2). Our aim was to examine the spectrum of hepatic histopathology in patients with BA at our institution from 2008 to 2013 and to examine laboratory markers as correlates of fibrosis specifically APRI vs. liver histology. Methods: A retrospective chart review study of 15 patients with BA who had initial liver biopsies at diagnosis was performed. Age at liver biopsy, laboratory data including serum AST, total Bilirubin (TB), platelet count, INR at the time of biopsy were correlated with histological changes, specifically stage of fibrosis. Results: The mean age at biopsy 61.9 ± 30 days (Mean ± SD). The histologic changes in 15 biopsies included portal fibrosis (stage 1, 2) in 9, bridging fibrosis (stage 3) in 4 and cirrhosis (stage 4) in 2. At biopsy AST ranged from 61- 405U /L (mean ± SD 208.5 ± 117), Platelet count 203-762 (109/L) (487 ± 167 x 109/L), Total bilirubin 4.9-12.6mg/dL (8.27 ± 2.34) and APRI 1.21 ± 0.74. Correlation of total bilirubin with APRI was not significant (Pearson correlation coefficient = 0.22) (p = 0.41); Correlation of APRI with biopsy staging was also not significant (r = 0.24 and p = 0.44.) 8 of the 15 patients underwent liver
Thickened gastric folds with a ragged appearance; hypoechoic foci within gastric wall
AGA Abstracts
S-958
marrow done 3 weeks later showed aplastic marrow. Soon after, she had fevers and invasive Aspergillus was noted in right upper lobe on chest CT, while MRI of head and spine showed extensive sinus fungal disease. She was taken to the OR for sinus debridement and started on voriconazole. However, fevers persisted with deteriorating clinical condition. She then had a significant hemoglobin drop with multiple large bloody stools as well as bloody output from the nasogastric tube. EGD showed multiple 2-5 cm circular areas of denuded deep ulcers in various stages of bleeding throughout the stomach. In the mid-esophagus, a light green mass 3 cm in length was noted to project from a denuded circular ulcer-like lesion in the esophageal wall. This mass was connected to the ulcer via a thin stalk that was unable to be clearly visualized. Using a biopsy forceps, this mass was separated from its base and removed through the mouth. Histologic evaluation confirmed this mass as an aspergilloma with evidence of full-thickness esophageal necrotic tissue. She was started on octreotide IV drip, pantoprazole IV drip, sulcrafate, and continued on voriconazole. GI bleeding stabilized and patient underwent repeat EGD three weeks later which showed near complete resolution of previously seen gastric ulcers. There were no esophageal masses or lesions. Clinical improvement continued with no further significant GI bleeding and she was discharged with outpatient management of HLH. Discussion: Though Aspergillus can disseminate to the gastrointestinal system, reports of esophageal invasion are rare. Moreover, case reports of esophageal aspergilloma have been associated with fatal outcomes. In our patient, we theorize that the aspergilloma may have been continually seeding sites of gastric infection and endoscopically removing this fungal mass eliminated the key nidus of persistent infection. This may explain why the patient showed remarkable clinical improvement and resolution of gastric lesions on follow-up endoscopy while on the same anti-fungal therapy.
Tu2009 Host and Pathogen Risk Factors for Recurrent Clostridium difficile Infection in Children Maribeth Nicholson, Jonathan D. Crews, Zhi-Dong Jiang, Herbert DuPont, Kathryn M. Edwards Background: The treatment of Clostridium difficile infection (CDI) in children is complicated by high rates of recurrence (rCDI). Our studies and those of others have indicated rates of 20-30%. To date, no studies have prospectively evaluated host and pathogen risk factors associated with recurrent disease in children. Objective: To compare host genetics, immune responses, cytokine profiles, and Clostridium difficile strain type in children with and without rCDI. Methods: Pediatric patients ages 12 months through <18 years with CDI were identified through review of hospital laboratory records at two tertiary care children's hospitals. Subjects were enrolled from March 2013 through May 2014. Blood and stool samples were obtained to evaluate host IL-8 polymorphisms, host anti-toxin A antibody levels, cytokines, and C.difficile strain type. Patient medication exposures were determined for thirty days prior to symptom onset. Thirty days post enrollment a follow-up serum sample was obtained to evaluate antibody response. Patients were contacted 60 days after enrollment to assess for rCDI. Patients with and without recurrent disease were compared using Fisher's exact test for categorical data and Wilcoxon rank-sum test for continuous data. Results: Of the 28 pediatric patients enrolled, 27 completed the 60 day follow-up and were included in analysis of the primary endpoint. Of these 27 patients, 8(30%) experienced rCDI. The mean age of enrolled patients was 7.2 years and 50% of the patients were male. There were no statistically significant differences in demographic variables in patients with and without rCDI. In the 30 days prior to disease onset, patients with rCDI had a greater number of days of antibiotic use (16 vs. 13, P=0.4) and more antibiotic classes used (3 vs. 2, P=0.76). They were also more likely to have used proton pump inhibitors prior to symptom onset (50% vs 21%, P=0.15). Patients with rCDI had a trend toward increased stool calprotectin (14.4 vs. 8.6 ug/g, P=0.38), lactoferrin (18,525.8 vs. 825.5 ng/mL, P=0.17), and IL-8 (44 vs. 0 ng/mL, P=0.25) but these differences did not reach statistical significance, likely related to an overall small sample size (Table 1). Laboratory studies characterizing host IL-8 genetics, host antibody responses, serum cytokines, and C.difficile strain type are ongoing. Conclusions: The rate of rCDI in our pediatric cohort was 30%. Children with recurrent disease had a higher rate of proton pump inhibitor use as well as a larger number of days and classes of antibiotic use. Patients with rCDI also had a trend toward higher stool cytokines at the time of primary infection with C. difficile. Stool cytokines should be studied to determine value in predicting risk of recurrent disease in children. Relationship Between Host Variables and Recurrent CDI
Tu2011 Resolution of Antibiotic-Induced and Idiopathic Diarrhea in Infants With a Serum-Derived Bovine Immunoglobulin Preparation Manisha Dave, Christopher Fourment, Bruce P. Burnett Infants treated with antibiotics have a high rate of antibiotic-induced diarrhea which can result in dehydration, growth limitations, and failure to thrive. Some infants also experience idiopathic diarrhea. Serum-derived bovine immunoglobulin/protein isolate (SBI) is a specially formulated prescription medical food intended for use in patients with chronic loose and frequent stools under physician supervision. In adult populations with HIV-associated enteropathy and IBS-D, SBI has been shown to improve stool consistency and reduce daily bowel movements. SBI has also been shown to be safe in children as young as 6 months of age with duration of administration of up to 8 months. Two male infants experiencing daily, severe diarrhea for ~1 month were given SBI 5 g/day in an attempt to manage their diarrheal conditions. The first infant (9 months) was initially treated with antibiotics for an ear infection. He subsequently presented with fussiness, multiple episodes of diarrhea, and poor appetite. Stool cultures were positive for Clostridium difficile. The patient was administered metronidazole and a probiotic containing Saccharomyces boulardii lyo for 1-week without resolution of symptoms. Treatment with vancomycin followed by another course of metronidazole was unsuccessful. The infant began to lose weight from the continued diarrhea. So an esophagogastroduodenoscopy (EGD)/colonoscopy was performed with a repeat stool culture evaluation for C. difficile during the colonoscopy. The stool was negative and all biopsies were normal. SBI was added to his Similac® Sensitive formula daily at 5 g/day. On the second day, the patient was having 1-2 formed stools a day. His appetite had increased, he appeared content and the appropriate weight gain resumed. The second infant (18 months) experienced 4-weeks of idiopathic diarrhea with 5 watery stools per day and weight
CDI: Clostridium difficile infection, CA-CDAD: Community associated Clostridium difficile associated disease, HO-HCFA: Healthcare facility-onset healthcare facility-associated, COHCFA: Community-onset healthcare facility-associated, 1 Fisher's exact test; 2 Wilcoxon test Tu2010 Esophageal Aspergilloma in 3-Year-Old With HLH and Massive GI Bleed Khoa Tran, Garrett Zella, Jyoti Ramakrishna Introduction: Aspergillus is a frequent cause of opportunistic infection in immunocompromised patients with high mortality. The gastrointestinal tract is a common location for dissemination and symptoms can include abdominal pain and gastrointestinal bleeding. In particular, esophageal Aspergillus is associated with poor outcomes. Case: A previously healthy 3-year-old female presented with fever of unknown origin and elevated LFTs that quickly progressed to sepsis and multi-system organ failure. She was diagnosed with Hemophagocytic Lymphohistiocytosis (HLH) based on pancytopenia, markedly elevated ferritin, liver dysfunction, and bone marrow biopsy. She was treated with an individualized HLH chemotherapy protocol and broad spectrum antibiotics including fluconazole prophylaxis. Repeat bone
S-959
AGA Abstracts
AGA Abstracts
transplant at less than 1 year of age, 3 are currently listed and 4 did not require transplant. There was no correlation between APRI and early transplantation Conclusion: The progression of fibrosis in BA is unpredictable and varied. Based on our retrospective review we did not find APRI to be a useful surrogate non-invasive marker for fibrosis. Since our sample size was small, further study of a larger cohort is necessary to ascertain the value of APRI or similar markers as a screening tool for fibrosis in this patient group. References: 1. Wai et al Hepatology 2003;38:518. 2. Kim et al JPGN 2010;51: 198.
Severely thickened, erythematous and exudative gastric folds diffusely throughout the entire stomach. Tu2007
Tu2006
Prenatal Microbial Exposure Induces Epigenetic Changes and Modulates TLRSignaling Pathway Associated Gene Expression in the Immature Intestine Lei Lu, Yueyue Yu, Yana Filipovich, Hirsch Emmet, Erika Claud
A Case of Phlegmonous Gastritis in a 10-Year Old Child With Newly Diagnosed Ulcerative Colitis Jonathan Cordova, Tiffany Patton, Ruba Azzam, Barbara S. Kirschner, Ranjana R. Gokhale
Background: Many disorders of preterm infants are inflammatory in nature including neonatal necrotizing enterocolitis (NEC). NEC affects approximately 10% of premature infants <1500gm and is associated with an increased inflammatory response of the immature enterocyte to both commensal and pathogenic bacteria. At least 40% of preterm births are associated with intrauterine infection. Intrauterine infection results in maternal/fetal inflammatory responses that are to a large extent dependent upon toll-like receptor (TLR)mediated innate immune responses. Studies have demonstrated that when TLRs recognize pathogens and respond to systemic infections, epigenetic alterations reprogram distinct functional sets of genes to both activate and repress transcription of hundreds of other genes. We hypothesis that intrauterine microbial exposure induces epigenetic changes in TLR signaling molecules thus modulating postnatal inflammatory responses in the immature small intestine. Methods: Heat killed E. coli or PBS was administered into the gestational compartment of pregnant CD1 mice on E14.5. The resulting viable pups at term or nearterm that survived the neonatal period were subjected to further analysis. 10-day-old pup ileum genomic DNA and total RNA were extracted and used in the analysis of both TLRsignaling pathway-focused profiling of DNA methylation status (22 genes) and gene expression levels (84 genes) by qRT-PCR. Results: Intrauterine exposure to heat-killed E. coli resulted in changes in the DNA-methylation profile of TLR-signaling genes in the mouse ileum. Using a TLR-signaling pathway DNA methylation PCR Array system, we detected differential DNA methylation of major TLR-signaling molecules including Tlr-2, Irak-1, 2, CD14, Hspa1a (HSP70), Hspd1, Il-6ra, Irf-1 and Irf-3 genes (n = 6 per group). We also observed down-regulation of mRNA expression levels of many genes associated with TLRsignaling. The downregulated genes (≤ -2 fold) were TLRs: Tlr1, Tlr4, Tlr6, Tlr7, Tlr8, Tlr9, and to a lesser degree Tlr2, 3 and 5; TLR signaling molecules: Cd14, Irak1, 2, Ticam1, Tradd; proinflammatory genes: Il-1, Il-12a, Ifnb1, Ifng, Tnf, Ccl2; and transcription factors: Nfkb2, Ppara, and other genes involved in immunomodulatory functions: Btk, Il6ra, Il-10, Il-2, Cd80, Ly86, Ube2v1, Csf2, Clec4e. Intrauterine infection induced upregulation of Csf3 and Fos genes (≥ 2). Conclusions: Together, these data suggest that antenatal intrauterine inflammation induces DNA methylation changes as well as a downregulation of mRNA expressions in TLR-related genes in the small intestines of offspring. These changes may result in a tolerance/inhibition of innate immune/inflammatory responses in the immature gut upon subsequent postnatal infectious/inflammatory challenge.
Introduction Phlegmonous gastritis is a life-threatening condition described as a rapidly progressive suppurative bacterial infection of the stomach that can lead to necrotizing or gangrenous gastritis. We report a case of acute phlegmonous gastritis in a child who was newly diagnosed with ulcerative colitis. Case Description A.M. is a 10 year old female with no significant past medical history who presented to our emergency department with a ten day history of bloody diarrhea, emesis and abdominal pain. Initial labs revealed an elevated WBC 15.9 x103/μL and hemoglobin 8.7 g/dL requiring a transfusion. Stool studies were negative with a fecal calprotectin >2500 μg/g feces. She became febrile and was started on ampicillin, gentamicin and metronidazole. On day 3 of admission she underwent an ileocolonoscopy that was consistent with ulcerative colitis. An EGD showe chronic, mildly active antral gastritis. Solumedrol was started at 1 mg/kg twice daily. She remained febrile with worsening abdominal pain and emesis and, on day 4 of admission, a CT of the abdomen/ pelvis showed pan-colitis without evidence of an intra-abdominal abscess. Over the following 10 days, she developed persistent bloody emesis, severe worsening abdominal pain, hypotension, anemia and new onset pancreatitis. An ongoing fever (despite antibiotics) and an elevated WBC 34 x103/μL with coagulopathy (INR 1.5) led to a repeat CT of the abdomen. CT results showed pancreatitis (without pseudocyst or necrosis) as well as severe, diffuse gastritis with thickened gastric folds and scattered hypoechoic foci within the gastric wall concerning for phlegmonous gastritis. As a result, antibiotics were broadened to include vancomycin and meropenem and steroids were decreased to 0.5 mg/kg twice daily to improve the eradication of the infection while continuing to induce remission of ulcerative colitis. On day 15 of admission, A.M. underwent a repeat EGD due to persistent anemia and ongoing upper GI bleeding that showed severe and diffuse exudative gastritis, deep ulcerations and clots of adherent blood. Histological findings including severe neutrophilic inflammation further support a diagnosis of phlegmonous gastritis. Sub-mucosal gastric biopsies were collected without an identifiable organism isolated. A.M.'s clinical status improved dramatically on broad spectrum antibiotics, over the following few days, with resolution of the upper GI bleed. A 1-month course of antibiotics was completed as treatment of phlegmonous gastritis. At this time, patient remains in clinical remission. Conclusion Phlegmonous gastritis is a rare bacterial infection of the stomach that has a high level of mortality and should be on the differential diagnosis for any patient who develops severe abdominal pain, hematemesis and fever, particularly while on immunosuppressive therapy.
Tu2008 Severity of Hepatic Fibrosis in Children With Biliary Atresia Using Non Invasive Markers vs Liver Biopsy Teena Sebastian, Parvathi Mohan Biliary atresia (BA) is an idiopathic neonatal obstructive cholangiopathy characterized by a progressive obliteration of the large bile ducts that presents uniquely in the first few months of life. It is the most common cholestatic liver disorder requiring a liver transplantation in infants and children. Hepatic fibrosis is a universal and prominent feature of BA even after a portoenterostomy. Therefore assessing the stage of fibrosis is an important tool to predict the course of biliary atresia. A liver biopsy is the gold standard for diagnosis but is associated with certain risks. Currently available non-invasive markers for fibrosis are not validated in children. Several authors, using routine laboratory data have constructed a simple model -AST (aspartate transaminase) to platelet ratio index (APRI)- to predict fibrosis in chronic viral hepatitis and in BA (1,2). Our aim was to examine the spectrum of hepatic histopathology in patients with BA at our institution from 2008 to 2013 and to examine laboratory markers as correlates of fibrosis specifically APRI vs. liver histology. Methods: A retrospective chart review study of 15 patients with BA who had initial liver biopsies at diagnosis was performed. Age at liver biopsy, laboratory data including serum AST, total Bilirubin (TB), platelet count, INR at the time of biopsy were correlated with histological changes, specifically stage of fibrosis. Results: The mean age at biopsy 61.9 ± 30 days (Mean ± SD). The histologic changes in 15 biopsies included portal fibrosis (stage 1, 2) in 9, bridging fibrosis (stage 3) in 4 and cirrhosis (stage 4) in 2. At biopsy AST ranged from 61- 405U /L (mean ± SD 208.5 ± 117), Platelet count 203-762 (109/L) (487 ± 167 x 109/L), Total bilirubin 4.9-12.6mg/dL (8.27 ± 2.34) and APRI 1.21 ± 0.74. Correlation of total bilirubin with APRI was not significant (Pearson correlation coefficient = 0.22) (p = 0.41); Correlation of APRI with biopsy staging was also not significant (r = 0.24 and p = 0.44.) 8 of the 15 patients underwent liver
Thickened gastric folds with a ragged appearance; hypoechoic foci within gastric wall
AGA Abstracts
S-958
marrow done 3 weeks later showed aplastic marrow. Soon after, she had fevers and invasive Aspergillus was noted in right upper lobe on chest CT, while MRI of head and spine showed extensive sinus fungal disease. She was taken to the OR for sinus debridement and started on voriconazole. However, fevers persisted with deteriorating clinical condition. She then had a significant hemoglobin drop with multiple large bloody stools as well as bloody output from the nasogastric tube. EGD showed multiple 2-5 cm circular areas of denuded deep ulcers in various stages of bleeding throughout the stomach. In the mid-esophagus, a light green mass 3 cm in length was noted to project from a denuded circular ulcer-like lesion in the esophageal wall. This mass was connected to the ulcer via a thin stalk that was unable to be clearly visualized. Using a biopsy forceps, this mass was separated from its base and removed through the mouth. Histologic evaluation confirmed this mass as an aspergilloma with evidence of full-thickness esophageal necrotic tissue. She was started on octreotide IV drip, pantoprazole IV drip, sulcrafate, and continued on voriconazole. GI bleeding stabilized and patient underwent repeat EGD three weeks later which showed near complete resolution of previously seen gastric ulcers. There were no esophageal masses or lesions. Clinical improvement continued with no further significant GI bleeding and she was discharged with outpatient management of HLH. Discussion: Though Aspergillus can disseminate to the gastrointestinal system, reports of esophageal invasion are rare. Moreover, case reports of esophageal aspergilloma have been associated with fatal outcomes. In our patient, we theorize that the aspergilloma may have been continually seeding sites of gastric infection and endoscopically removing this fungal mass eliminated the key nidus of persistent infection. This may explain why the patient showed remarkable clinical improvement and resolution of gastric lesions on follow-up endoscopy while on the same anti-fungal therapy.
Tu2009 Host and Pathogen Risk Factors for Recurrent Clostridium difficile Infection in Children Maribeth Nicholson, Jonathan D. Crews, Zhi-Dong Jiang, Herbert DuPont, Kathryn M. Edwards Background: The treatment of Clostridium difficile infection (CDI) in children is complicated by high rates of recurrence (rCDI). Our studies and those of others have indicated rates of 20-30%. To date, no studies have prospectively evaluated host and pathogen risk factors associated with recurrent disease in children. Objective: To compare host genetics, immune responses, cytokine profiles, and Clostridium difficile strain type in children with and without rCDI. Methods: Pediatric patients ages 12 months through <18 years with CDI were identified through review of hospital laboratory records at two tertiary care children's hospitals. Subjects were enrolled from March 2013 through May 2014. Blood and stool samples were obtained to evaluate host IL-8 polymorphisms, host anti-toxin A antibody levels, cytokines, and C.difficile strain type. Patient medication exposures were determined for thirty days prior to symptom onset. Thirty days post enrollment a follow-up serum sample was obtained to evaluate antibody response. Patients were contacted 60 days after enrollment to assess for rCDI. Patients with and without recurrent disease were compared using Fisher's exact test for categorical data and Wilcoxon rank-sum test for continuous data. Results: Of the 28 pediatric patients enrolled, 27 completed the 60 day follow-up and were included in analysis of the primary endpoint. Of these 27 patients, 8(30%) experienced rCDI. The mean age of enrolled patients was 7.2 years and 50% of the patients were male. There were no statistically significant differences in demographic variables in patients with and without rCDI. In the 30 days prior to disease onset, patients with rCDI had a greater number of days of antibiotic use (16 vs. 13, P=0.4) and more antibiotic classes used (3 vs. 2, P=0.76). They were also more likely to have used proton pump inhibitors prior to symptom onset (50% vs 21%, P=0.15). Patients with rCDI had a trend toward increased stool calprotectin (14.4 vs. 8.6 ug/g, P=0.38), lactoferrin (18,525.8 vs. 825.5 ng/mL, P=0.17), and IL-8 (44 vs. 0 ng/mL, P=0.25) but these differences did not reach statistical significance, likely related to an overall small sample size (Table 1). Laboratory studies characterizing host IL-8 genetics, host antibody responses, serum cytokines, and C.difficile strain type are ongoing. Conclusions: The rate of rCDI in our pediatric cohort was 30%. Children with recurrent disease had a higher rate of proton pump inhibitor use as well as a larger number of days and classes of antibiotic use. Patients with rCDI also had a trend toward higher stool cytokines at the time of primary infection with C. difficile. Stool cytokines should be studied to determine value in predicting risk of recurrent disease in children. Relationship Between Host Variables and Recurrent CDI
Tu2011 Resolution of Antibiotic-Induced and Idiopathic Diarrhea in Infants With a Serum-Derived Bovine Immunoglobulin Preparation Manisha Dave, Christopher Fourment, Bruce P. Burnett Infants treated with antibiotics have a high rate of antibiotic-induced diarrhea which can result in dehydration, growth limitations, and failure to thrive. Some infants also experience idiopathic diarrhea. Serum-derived bovine immunoglobulin/protein isolate (SBI) is a specially formulated prescription medical food intended for use in patients with chronic loose and frequent stools under physician supervision. In adult populations with HIV-associated enteropathy and IBS-D, SBI has been shown to improve stool consistency and reduce daily bowel movements. SBI has also been shown to be safe in children as young as 6 months of age with duration of administration of up to 8 months. Two male infants experiencing daily, severe diarrhea for ~1 month were given SBI 5 g/day in an attempt to manage their diarrheal conditions. The first infant (9 months) was initially treated with antibiotics for an ear infection. He subsequently presented with fussiness, multiple episodes of diarrhea, and poor appetite. Stool cultures were positive for Clostridium difficile. The patient was administered metronidazole and a probiotic containing Saccharomyces boulardii lyo for 1-week without resolution of symptoms. Treatment with vancomycin followed by another course of metronidazole was unsuccessful. The infant began to lose weight from the continued diarrhea. So an esophagogastroduodenoscopy (EGD)/colonoscopy was performed with a repeat stool culture evaluation for C. difficile during the colonoscopy. The stool was negative and all biopsies were normal. SBI was added to his Similac® Sensitive formula daily at 5 g/day. On the second day, the patient was having 1-2 formed stools a day. His appetite had increased, he appeared content and the appropriate weight gain resumed. The second infant (18 months) experienced 4-weeks of idiopathic diarrhea with 5 watery stools per day and weight
CDI: Clostridium difficile infection, CA-CDAD: Community associated Clostridium difficile associated disease, HO-HCFA: Healthcare facility-onset healthcare facility-associated, COHCFA: Community-onset healthcare facility-associated, 1 Fisher's exact test; 2 Wilcoxon test Tu2010 Esophageal Aspergilloma in 3-Year-Old With HLH and Massive GI Bleed Khoa Tran, Garrett Zella, Jyoti Ramakrishna Introduction: Aspergillus is a frequent cause of opportunistic infection in immunocompromised patients with high mortality. The gastrointestinal tract is a common location for dissemination and symptoms can include abdominal pain and gastrointestinal bleeding. In particular, esophageal Aspergillus is associated with poor outcomes. Case: A previously healthy 3-year-old female presented with fever of unknown origin and elevated LFTs that quickly progressed to sepsis and multi-system organ failure. She was diagnosed with Hemophagocytic Lymphohistiocytosis (HLH) based on pancytopenia, markedly elevated ferritin, liver dysfunction, and bone marrow biopsy. She was treated with an individualized HLH chemotherapy protocol and broad spectrum antibiotics including fluconazole prophylaxis. Repeat bone
S-959
AGA Abstracts
AGA Abstracts
transplant at less than 1 year of age, 3 are currently listed and 4 did not require transplant. There was no correlation between APRI and early transplantation Conclusion: The progression of fibrosis in BA is unpredictable and varied. Based on our retrospective review we did not find APRI to be a useful surrogate non-invasive marker for fibrosis. Since our sample size was small, further study of a larger cohort is necessary to ascertain the value of APRI or similar markers as a screening tool for fibrosis in this patient group. References: 1. Wai et al Hepatology 2003;38:518. 2. Kim et al JPGN 2010;51: 198.