Rising Prevalence of Mild Chronic Gastritis in Children: A Single Center Experience.

OBJECTIVES AND METHODS: We analyzed upper endoscopic and histological findings in 3 cohorts of children undergoing upper gastrointestinal endoscopy over a 10-year period. Five hundred seventy-nine patients were identified, with 244 (42%), 199 (35%), and 136 (23%) in the 2011, 2015, and 2019 cohorts, respectively. The most common symptoms and signs were abdominal pain, vomiting, failure to thrive, and diarrhea. RESULTS: The number of patients who had histological evidence of chronic gastritis increased from 2011 (n = 70, 29%) to 2015 (n = 106, 53%) and 2019 (n = 92, 68%; P < .001). The prevalence of "normal" endoscopic gastric findings was higher in controls (n = 247, 90%) compared to cases (n = 201, 76%; P < .001). There was a small but statistically significant difference in endoscopic esophageal grading (P = .008) over time, with lower grades being more prevalent in 2011 compared to 2015 (P = .026) and 2019 (P = .001). Crude comparisons of the predictors (sex, weight percentile, payor type, month of endoscopy, symptom duration, PPI exposure, and endoscopic stomach findings) yielded no difference between cases and controls. CONCLUSIONS: There has been a significant rise in the prevalence of mild chronic gastritis or non-specific gastritis over the last decade in our population.

Plasma Biomarkers and Fractional Exhaled Nitric Oxide in the Diagnosis of Eosinophilic Esophagitis.

OBJECTIVES: Eosinophilic esophagitis (EoE) is a chronic disease which requires endoscopy with biopsies for diagnosis and monitoring. We aimed to identify a panel of non-invasive markers that could help identify patients with active EoE. METHODS: In this prospective cohort study, we enrolled 128 children aged 5-18 years old, scheduled for endoscopy for suspected esophageal or peptic disease. On the day of the endoscopy, fractionated exhaled nitric oxide (FeNO) was measured; and blood was collected for peripheral absolute eosinophil count (AEC), plasma amino acids, and plasma polyamine analysis. Patients were grouped into controls (n = 91), EoE in remission (n = 16), or active EoE (n = 21), based on esophageal eosinophilia and history of EoE. RESULTS: AEC was not statistically significant different among the groups compared ( P = 0.056). Plasma amino acids: citrulline (CIT), ß-alanine (ß-ALA), and cysteine (CYS) were higher in active EoE compared to controls ( P < 0.05). The polyamine spermine was lower in active EoE versus controls ( P < 0.05). Receiver operator characteristic (ROC) curve to assess the predictive capability of a combined score made of FeNO, ß-ALA, CYS, and spermine had an area under curve (AUC) of 0.90 (95% CI: 0.80-0.96) in differentiating active EoE from controls and 0.87 (95% CI: 0.74-1.00) when differentiating active EoE from EoE in remission. CONCLUSION: A panel comprising FeNO, 2 plasma amino acids (ß-ALA, CYS) and the polyamine spermine can be used as a non-invasive tool to differentiate active EoE patients from controls.

Placental Findings in Postpartum Preeclampsia: A Comparative Retrospective Study.

OBJECTIVE: Preeclampsia is a multifactorial placental disease that can occur after delivery. The pathophysiology of postpartum preeclampsia remains unknown. The objective was to describe placental findings in postpartum preeclampsia. STUDY DESIGN: This is a case-control study, comparing the placental histologic findings in four groups of 30 patients with postpartum preeclampsia, early-onset preeclampsia, late-onset preeclampsia, and normotensive controls. RESULTS: Placentas of postpartum preeclampsia had a mean placental weight not different from that of late-onset preeclampsia at a similar gestational age (479.0 ± 152.7 vs. 521.3 ± 144.1 g, p = 0.07); they showed a higher rate of acute deciduitis of 42.4% than early preeclampsia (5.7%, p < 0.01) or in controls (3.2%, p < 0.01); 18.2% had decidual arteriolopathy, with no significant difference with other groups. These placentas had fewer villous infarcts as compared with early preeclampsia (9.1 vs. 62.9%, p < 0.01) and less accelerated maturation of villi (24.2 vs. 74.3%, p < 0.01). CONCLUSION: There were no significant differences for decidual arteriolopathy and villous infarcts among postpartum preeclampsia, late-onset preeclampsia, and the controls. This suggests that postpartum preeclampsia is more of a maternal disease in which the placenta may act as a priming effect in predisposed mothers and becomes clinically apparent after delivery.

LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV.

Transposable elements modify human genome by inserting into new loci or by mediating homology-, microhomology-, or homeology-driven DNA recombination or repair, resulting in genomic structural variation. Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Eighty-five percent of 45 ACDMPV-causative CNV deletions, of which junctions have been sequenced, had at least one of their two breakpoints located in a retrotransposon, with more than half of them being Alu elements. We describe a novel ∼35 kb-large genomic instability hotspot at 16q24.1, involving two evolutionarily young LINE-1 (L1) elements, L1PA2 and L1PA3, flanking AluY, two AluSx, AluSx1, and AluJr elements. The occurrence of L1s at this location coincided with the branching out of the Homo-Pan-Gorilla clade, and was preceded by the insertion of AluSx, AluSx1, and AluJr. Our data show that, in addition to mediating recurrent CNVs, L1 and Alu retrotransposons can predispose the human genome to formation of variably sized CNVs, both of clinical and evolutionary relevance. Nonetheless, epigenetic or other genomic features of this locus might also contribute to its increased instability.

Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia.

Hyperinsulinemic hypoglycemia is the most common cause of severe, persistent neonatal hypoglycemia. The treatment of hyperinsulinemic hypoglycemia that is unresponsive to diazoxide is subtotal pancreatectomy. We examined the effectiveness of the mammalian target of rapamycin (mTOR) inhibitor sirolimus in four infants with severe hyperinsulinemic hypoglycemia that had been unresponsive to maximal doses of diazoxide (20 mg per kilogram of body weight per day) and octreotide (35 µg per kilogram per day). All the patients had a clear glycemic response to sirolimus, although one patient required a small dose of octreotide to maintain normoglycemia. There were no major adverse events during 1 year of follow-up.

Can 3-dimensional power Doppler indices improve the prenatal diagnosis of a potentially morbidly adherent placenta in patients with placenta previa?

BACKGROUND: Traditionally, 2-dimensional ultrasound parameters have been used for the diagnosis of a suspected morbidly adherent placenta previa. More objective techniques have not been well studied yet. OBJECTIVE: The objective of the study was to determine the ability of prenatal 3-dimensional power Doppler analysis of flow and vascular indices to predict the morbidly adherent placenta objectively. STUDY DESIGN: A prospective cohort study was performed in women between 28 and 32 gestational weeks with known placenta previa. Patients underwent a two-dimensional gray-scale ultrasound that determined management decisions. 3-Dimensional power Doppler volumes were obtained during the same examination and vascular, flow, and vascular flow indices were calculated after manual tracing of the viewed placenta in the sweep; data were blinded to obstetricians. Morbidly adherent placenta was confirmed by histology. Severe morbidly adherent placenta was defined as increta/percreta on histology, blood loss >2000 mL, and >2 units of PRBC transfused. Sensitivities, specificities, predictive values, and likelihood ratios were calculated. Student t and χ2 tests, logistic regression, receiver-operating characteristic curves, and intra- and interrater agreements using Kappa statistics were performed. RESULTS: The following results were found: (1) 50 women were studied: 23 had morbidly adherent placenta, of which 12 (52.2%) were severe morbidly adherent placenta; (2) 2-dimensional parameters diagnosed morbidly adherent placenta with a sensitivity of 82.6% (95% confidence interval, 60.4-94.2), a specificity of 88.9% (95% confidence interval, 69.7-97.1), a positive predictive value of 86.3% (95% confidence interval, 64.0-96.4), a negative predictive value of 85.7% (95% confidence interval, 66.4-95.3), a positive likelihood ratio of 7.4 (95% confidence interval, 2.5-21.9), and a negative likelihood ratio of 0.2 (95% confidence interval, 0.08-0.48); (3) mean values of the vascular index (32.8 ± 7.4) and the vascular flow index (14.2 ± 3.8) were higher in morbidly adherent placenta (P < .001); (4) area under the receiver-operating characteristic curve for the vascular and vascular flow indices were 0.99 and 0.97, respectively; (5) the vascular index ≥21 predicted morbidly adherent placenta with a sensitivity and a specificity of 95% (95% confidence interval, 88.2-96.9) and 91%, respectively (95% confidence interval, 87.5-92.4), 92% positive predictive value (95% confidence interval, 85.5-94.3), 90% negative predictive value (95% confidence interval, 79.9-95.3), positive likelihood ratio of 10.55 (95% confidence interval, 7.06-12.75), and negative likelihood ratio of 0.05 (95% confidence interval, 0.03-0.13); and (6) for the severe morbidly adherent placenta, 2-dimensional ultrasound had a sensitivity of 33.3% (95% confidence interval, 11.3-64.6), a specificity of 81.8% (95% confidence interval, 47.8-96.8), a positive predictive value of 66.7% (95% confidence interval, 24.1-94.1), a negative predictive value of 52.9% (95% confidence interval, 28.5-76.1), a positive likelihood ratio of 1.83 (95% confidence interval, 0.41-8.11), and a negative likelihood ratio of 0.81 (95% confidence interval, 0.52-1.26). A vascular index ≥31 predicted the diagnosis of a severe morbidly adherent placenta with a 100% sensitivity (95% confidence interval, 72-100), a 90% specificity (95% confidence interval, 81.7-93.8), an 88% positive predictive value (95% confidence interval, 55.0-91.3), a 100% negative predictive value (95% confidence interval, 90.9-100), a positive likelihood ratio of 10.0 (95% confidence interval, 3.93-16.13), and a negative likelihood ratio of 0 (95% confidence interval, 0-0.34). Intrarater and interrater agreements were 94% (P < .001) and 93% (P < .001), respectively. CONCLUSION: The vascular index accurately predicts the morbidly adherent placenta in patients with placenta previa. In addition, 3-dimensional power Doppler vascular and vascular flow indices were more predictive of severe cases of morbidly adherent placenta compared with 2-dimensional ultrasound. This objective technique may limit the variations in diagnosing morbidly adherent placenta because of the subjectivity of 2-dimensional ultrasound interpretations.

Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis.

Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases (IBDs): Crohn disease (CD) and ulcerative colitis (UC). Dietary n-6 fatty acids have been associated with UC in prospective studies. However, the critical developmental period when (n-6) consumption may induce UC is not known. We examined the effects of transiently increased n-6 consumption during pediatric development on subsequent dextran-sulfate-sodium (DSS)-induced acute murine colitis. The animals transiently became obese then rapidly lost this phenotype. Interestingly, mice were protected against DSS colitis 40 days after n-6 consumption. The transient high n-6-induced protection against colitis was fat type- and dietary reversal-dependent and could be transferred to germ-free mice by fecal microbiota transplantation. We also detected decreased numbers of chemokine receptor (Cxcr)5(+) CD4(+) T cells in the mesenteric lymph nodes (MLNs) of transiently n-6-fed mice. Further experiments revealed that anti-chemokine ligand (Cxcl)13 (the ligand of Cxcr5) antibody treatment decreased DSS colitis severity, implicating the importance of the Cxcr5-Cxcl13 pathway in mammalian colitis. Consecutively, we found elevated CXCL13 concentrations (CD: 1.8-fold, P = 0.0077; UC: 1.9-fold, P = 0.056) in the serum of untreated pediatric IBD patients. The human serologic observations supported the translational relevance of our findings.

Fibrosis of the Intestines in Response to Foreign Objects: A Case Report.

Foreign body ingestion of sharp objects can be a striking feature of psychological dysfunction with high morbidity and mortality. While the phenomenon has been reported on, primarily from a psychiatric perspective, this report will present the effects of this behavior on the intestinal system from a pathology perspective. The report is of a 43-year-old female with a past medical history of foreign object ingestion, borderline personality disorder, depression, anxiety, and prior suicidality who passed away due to bowel obstruction. Review of her history revealed an eighteen-year history of repeated foreign body ingestion with multiple surgical interventions. A particularly remarkable aspect revealed through the surgical history is the nature of the complications. They begin in 2008 with bowel perforation due to a blunt object and continue to present with perforation in the early years but show a gradual change to adhesions and obstruction as the primary concern. Her final presentation to the hospital and cause of death was due to obstruction, not perforation, even though the foreign bodies were six knives. While this case is not the only known report of foreign body ingestion, the extensive timeline and frequency allow for an examination of the gradual progression of fibrosis and adhesions within the intestines and abdominal wall, which led to the obstruction and death despite being a protective factor against further perforation.This case was presented at the annual Association of Clinical Scientists meeting (April 2-4, Jacksonville, FL).

Monotonous diets protect against acute colitis in mice: epidemiologic and therapeutic implications.

OBJECTIVES: Multiple characteristics of industrialization have been proposed to contribute to the global emergence of inflammatory bowel diseases (IBDs: Crohn disease and ulcerative colitis). Major changes in eating habits during the last decades and the effectiveness of exclusive enteral nutrition in the treatment of Crohn disease indicate the etiologic importance of dietary intake in IBDs. A uniform characteristic of nutrition in developing countries (where the incidence of IBD is low) and exclusive enteral nutrition is their consistent nature for prolonged periods; however, the potentially beneficial effect of dietary monotony in respect to mammalian intestinal inflammation has not been examined. METHODS: The association between alternating (2 different complete chows) and persistent regular diets, and dextran sulfate sodium colitis susceptibility in C57BL/6J mice was studied. Colonic mucosal microbiota changes were investigated by high-throughput pyrosequencing of the 16S rRNA gene. RESULTS: The severity of colitis increased upon dietary alternation compared with consistent control feeding. The microbiota of the alternating nutritional group clustered discretely from both control groups. CONCLUSIONS: Our findings highlight that monotonous dietary intake may decrease mammalian vulnerability against colitis in association with microbiota separation. The epidemiologic and therapeutic implications of our results are also discussed.

Epigenetic maturation in colonic mucosa continues beyond infancy in mice.

Monozygotic twin and other epidemiologic studies indicate that epigenetic processes may play an important role in the pathogenesis of inflammatory bowel diseases that commonly affect the colonic mucosa. The peak onset of these disorders in young adulthood suggests that epigenetic changes normally occurring in the colonic mucosa shortly before adulthood could be important etiologic factors. We assessed developmental changes in colitis susceptibility during the physiologically relevant period of childhood in mice [postnatal day 30 (P30) to P90] and concurrent changes in DNA methylation and gene expression in murine colonic mucosa. Susceptibility to colitis was tested in C57BL/6J mice with the dextran sulfate sodium colitis model. Methylation specific amplification microarray (MSAM) was used to screen for changes in DNA methylation, with validation by bisulfite pyrosequencing. Gene expression changes were analyzed by microarray expression profiling and real time RT-PCR. Mice were more susceptible to chemically induced colitis at P90 than at P30. DNA methylation changes, however, were not extensive; of 23 743 genomic intervals interrogated, only 271 underwent significant methylation alteration during this developmental period. We found an excellent correlation between the MSAM and bisulfite pyrosequencing at 11 gene associated intervals validated (R(2) = 0.89). Importantly, at the genes encoding galectin-1 (Lgals1), and mothers against decapentaplegic homolog 3 or Smad3, both previously implicated in murine colitis, developmental changes in DNA methylation from P30 to P90 were inversely correlated with expression. Colonic mucosal epigenetic maturation continues through early adulthood in the mouse, and may contribute to the age-associated increase in colitis susceptibility. Transcript Profiling: Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE18031 (DNA methylation arrays), GSE19506 (gene expression arrays).

Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll-like receptor 2-knockout mice.

The connection between intestinal microbiota and host physiology is increasingly becoming recognized. The details of this dynamic interaction, however, remain to be explored. Toll-like receptor 2 (Tlr2) is important for its role in bacterial recognition, intestinal inflammation, and obesity-related metabolic changes. Therefore, we sought to determine the epigenomic and metagenomic consequences of Tlr2 deficiency in the colonic mucosa of mice to gain insights into biological pathways that shape the interface between the gut microbiota and the mammalian host. Colonic mucosa from wild type (WT) and Tlr2(-/-) C57BL/6 mice was interrogated by microarrays specific for DNA methylation and gene expression. The mucosal microbiome was studied by next-generation pyrosequencing of bacterial 16S rRNA. The expression of genes involved in immune processes was significantly modified by the absence of Tlr2, a number of which correlated with DNA methylation changes. The epigenomic and transcriptomic modifications associated with alteration in mucosal microbial composition. Several bacterial species, including members of the Firmicutes were significantly different in abundance between WT and Tlr2(-/-) animals. This manuscript highlights the intimate interrelationships between expression of immune-related genes and immunity pathways in the host with compositional and functional differences of the mammalian microbiome.

Rapidly Evolving and Fatal Miliary Tuberculosis and COVID-19 Infection in an Infant.

Tuberculosis (TB) and SARS-CoV-2 (COVID-19) are two important infectious diseases causing morbidity and mortality worldwide. Active TB infection can stimulate host immune responses and together with COVID-19, may lead to cytokine storm and immune dysregulation leading to multi-organ failure. We present a rare case of both miliary tuberculosis and SARS-CoV-2 co-infection in an infant who was a 6-month-old previously healthy term boy. He had persistent cough and congestion, became severely ill, and was brought to the emergency department. He was found to be COVID-19 positive by PCR test. Laboratory studies showed pancytopenia, elevated inflammatory markers, and an abnormal coagulation profile with coagulopathy. He developed strokes, severe sepsis, and electrolyte abnormalities, and declined rapidly within 6 days. Autopsy examination showed multifocal micro-abscesses in multiple organs, which on microscopic examination showed necrotic foci teeming with Mycobacteria and were culture positive for M. tuberculosis Neuropathological examination showed infarction in the right middle and posterior cerebral artery territories. This patient helps illuminate some immunological and pathological aspects of two co-occurring infectious diseases and the susceptibility for the development of fatal complications with SARS-CoV-2 infection in the pediatric population.

Chronic Diarrhea in an Infant With Malrotation: A Diagnostic Dilemma.

In children, diarrhea has a global incidence of 2.7 episodes per child-year and contributes to significant disease burden and mortality in children under 5 years of age. Chronic diarrhea, defined as diarrhea lasting for more than 2 weeks, may be particularly challenging to evaluate and manage in children under 2 years of age. While most have infectious enteritis or cow milk protein intolerance, others have conditions such as malnutrition, anatomic abnormalities, or congenital enteropathies that can be challenging to diagnose and treat. We present here a complex case of chronic diarrhea in an infant and highlight such diagnostic and therapeutic challenges.

Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development.

The question of whether DNA methylation contributes to the stabilization of gene expression patterns in differentiated mammalian tissues remains controversial. Using genome-wide methylation profiling, we screened 3757 gene promoters for changes in methylation during postnatal liver development to test the hypothesis that developmental changes in methylation and expression are temporally correlated. We identified 31 genes that gained methylation and 111 that lost methylation from embryonic day 17.5 to postnatal day 21. Promoters undergoing methylation changes in postnatal liver tended not to be associated with CpG islands. At most genes studied, developmental changes in promoter methylation were associated with expression changes, suggesting both that transcriptional inactivity attracts de novo methylation, and that transcriptional activity can override DNA methylation and successively induce developmental hypomethylation. These in vivo data clearly indicate a role for DNA methylation in mammalian differentiation, and provide the novel insight that critical windows in mammalian developmental epigenetics extend well beyond early embryonic development.

Changes in intestinal Toll-like receptors and cytokines precede histological injury in a rat model of necrotizing enterocolitis.

It is unclear whether the broad inflammatory response shown in neonatal necrotizing enterocolitis (NEC) is the cause or the effect of tissue injury. Toll-like receptors (TLRs) on intestinal dendritic, mononuclear, and epithelial cells recognize bacterial ligands and damaged tissues, thus activating the inflammatory response. The present study aimed to determine whether active TLR signaling would precede histological injury in NEC. Newborn rat pups were divided into four groups: dam fed, dam fed-hypoxic, formula fed, and formula fed-hypoxic (NEC). The ileal tissues were evaluated for NEC scores at 24, 48, 72, and 120 h. Quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry were used to measure and localize intestinal TLRs. Cytokines were assessed by a multispot cytokine array. Among the four groups, ileal injury was seen only after 72 h of formula feeding and hypoxia. We found selective induction of mRNA levels in NEC compared with dam-fed controls for TLR2 > TLR4 > TLR1 = TLR3, TLR7, and TLR9 > TLR6 (P < 0.01); TLR5 was downregulated (P < 0.01). All TLR changes started at 48 h, before any histological evidence of NEC. Both Th1-type cytokines (IFN-gamma, IL-1beta, TNF-alpha, and KC/GRO) and Th2-type cytokines (IL-4, IL-5 and IL-13) were significantly increased in NEC but also in nondamaged formula-fed rat ileum. In conclusion, the intestinal expression of TLRs and cytokines precedes histological injury in the experimental NEC.

Antibiotic-modulated microbiome suppresses lethal inflammation and prolongs lifespan in Treg-deficient mice.

BACKGROUND: Regulatory T cell (Treg) deficiency leads to IPEX syndrome, a lethal autoimmune disease, in Human and mice. Dysbiosis of the gut microbiota in Treg-deficient scurfy (SF) mice has been described, but to date, the role of the gut microbiota remains to be determined. RESULTS: To examine how antibiotic-modified microbiota can inhibit Treg deficiency-induced lethal inflammation in SF mice, Treg-deficient SF mice were treated with three different antibiotics. Different antibiotics resulted in distinct microbiota and metabolome changes and led to varied efficacy in prolonging lifespan and reducing inflammation in the liver and lung. Moreover, antibiotics altered plasma levels of several cytokines, especially IL-6. By analyzing gut microbiota and metabolome, we determined the microbial and metabolomic signatures which were associated with the antibiotics. Remarkably, antibiotic treatments restored the levels of several primary and secondary bile acids, which significantly reduced IL-6 expression in RAW macrophages in vitro. IL-6 blockade prolonged lifespan and inhibited inflammation in the liver and lung. By using IL-6 knockout mice, we further identified that IL-6 deletion provided a significant portion of the protection against inflammation induced by Treg dysfunction. CONCLUSION: Our results show that three antibiotics differentially prolong survival and inhibit lethal inflammation in association with a microbiota-IL-6 axis. This pathway presents a potential avenue for treating Treg deficiency-mediated autoimmune disorders.

Bacteroides ovatus ATCC 8483 monotherapy is superior to traditional fecal transplant and multi-strain bacteriotherapy in a murine colitis model.

Background and aims: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined Bacteroides-based bacteriotherapy could be an effective and consistent alternative to fecal microbiota transplantation (FMT) in a murine model of IBD. Methods: We induced experimental colitis in 8- 12-week-old C57BL/6 mice using 2-3% dextran sodium sulfate. Mice were simultaneously treated by oral gavage with a triple-Bacteroides cocktail, individual Bacteroides strains, FMT using stool from healthy donor mice, or their own stool as a control. Survival, weight loss and markers of inflammation (histology, serum amyloid A, cytokine production) were correlated to 16S rRNA gene profiling of fecal and mucosal microbiomes. Results: Triple-Bacteroides combination therapy was more protective against weight loss and mortality than traditional FMT therapy. B. ovatus ATCC8483 was more effective than any individual strain, or a combination of strains, in preventing weight loss, decreasing histological damage, dampening inflammatory response, and stimulating epithelial recovery. Irrespective of the treatment group, overall Bacteroides abundance associated with treatment success and decreased cytokine production while the presence of Akkermansia correlated with treatment failure. However, the therapeutic benefit associated with high Bacteroides abundance was negated in the presence of Streptococcus. Conclusions: Bacteroides ovatus monotherapy was more consistent and effective than traditional FMT at ameliorating colitis and stimulating epithelial recovery in a murine model of IBD. Given the tolerability of Bacteroides ovatus ATCC 8483 in an active, on-going human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.

EBV+ lymphoproliferative disease following prolonged chemotherapy for refractory LCH.

Epstein-Barr virus (EBV) is a herpesvirus for which latent infection in B lymphocytes occurs in most individuals by middle childhood. Clinically significant reactivation of this virus occurs in the context of suppressed cell-mediated immunity, occasionally developing into lymphoproliferative disease (EBV-LPD). EBV reactivation is rarely associated with intensive chemotherapy alone. Here we present the case of a 4-year-old female who developed EBV-LPD as a complication of prolonged immunosuppressive chemotherapy for her multiply-recurrent Langerhans cell histiocytosis (LCH).

Steroid responsive eosinophilic gastric outlet obstruction in a child.

Gastric outlet obstruction is a rare complication of eosinophilic gastroenteritis, most commonly treated surgically. We report a case of eosinophilic gastric outlet obstruction in a child that responded to conservative medical management. A brief review of this clinical entity is also provided.