Clinical characteristics and outcomes of pediatric patients with autoimmune gastritis.

OBJECTIVES: Autoimmune gastritis (AIG) is a rare chronic inflammatory disorder with potential long-term sequelae including gastric neoplasia. There is limited data on the natural history of pediatric AIG. We aimed to characterize the clinical course and outcomes of children with AIG. METHODS: This was a multicenter retrospective study that included pediatric patients diagnosed with AIG between January 1, 2000 and December 31, 2021. Diagnosis of AIG was based on the demonstration of histological corpus-predominant atrophic gastritis, with or without positive antiparietal cell (APCA) or anti-intrinsic factor (IF) antibodies. Demographic, clinical, laboratory, endoscopic, and histologic data were retrieved, along with follow-up data. RESULTS: Thirty-three patients, (23 females, [69.7%], median age 12.0 [interquartile range 7.0-15.0] years at diagnosis) were identified. Twenty-two patients (66.7%) had positive APCA and/or anti-IF serology. The most common presenting manifestation was iron deficiency anemia (75%), and accompanying autoimmune disorders were significantly more common in patients with positive serology (62% vs. 18%, p < 0.05). Pseudo-pyloric or intestinal-type metaplasia was present at diagnosis in eight patients (24%), and 11 additional patients (33%) developed metaplasia during a median follow-up time of 27 (17.5-48.3) months. One patient developed a type 1 gastric neuroendocrine tumor. Helicobacter pylori was identified in only one patient, while two patients had prior eradication. Endoscopic and histologic improvements weren't identified in any patients. CONCLUSIONS: AIG should be considered in patients with autoimmunity and resistant iron-deficiency anemia. H. pylori infection may not be associated with pediatric AIG. The development of neuroendocrine tumor in one patient, and the high rates of metaplasia, highlight the importance of surveillance.

Infantile and Very Early Onset Inflammatory Bowel Disease: A Multicenter Study.

OBJECTIVES: This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years). METHODS: Cases from 21 centers worldwide diagnosed with VEOIBD (2008-2018), with minimum 2 years of follow-up, were retrospectively reviewed. RESULTS: The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2-18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all). CONCLUSIONS: Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course.

Effectiveness and Safety of Ustekinumab in Pediatric Ulcerative Colitis: A Multi-center Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND OBJECTIVES: Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. METHODS: This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. RESULTS: Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin < 150 µg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p = 0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p = 0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. CONCLUSION: Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.

Baseline Peripheral Blood Mononuclear Cell Transcriptomics Before Ustekinumab Treatment Is Linked With Crohn's Disease Clinical Response at 1 Year.

INTRODUCTION: Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin (IL)-12 and IL-23, is used for Crohn's disease (CD), and the documented clinical remission rate after 1 year was observed in approximately 50% of patients. We aimed to identify predictors for a clinical response using peripheral blood obtained from patients with CD just before ustekinumab treatment initiation. METHODS: RNA extraction from peripheral blood mononuclear cells was followed by mRNA paired-end sequencing. Differential gene expression was performed using DESeq2. RESULTS: We processed samples from 36 adults with CD (13 men, 36%) obtained at baseline before starting ustekinumab treatment. Twenty-two of 36 (61%) were defined as responders and 14/36 (39%) as nonresponders after 1 year based on Physician Global Assessment. Differential gene expression between responders (n = 22) and nonresponders (n = 14) did not show a gene expression signature that passed false discovery rate (FDR) correction. However, the analyses identified 68 genes, including CXCL1/2/3, which were induced in nonresponders vs responders with P < 0.05 and fold change above 1.5. Functional annotation enrichments of these 68 genes using ToppGene indicated enrichment for cytokine activity (FDR = 1.98E-05), CXCR chemokine receptor binding (FDR = 2.11E-05), IL-10 signaling (FDR = 5.03E-07), genes encoding secreted soluble factors (FDR = 1.73E-05), and myeloid dendritic cells (FDR = 1.80E-08). DISCUSSION: No substantial differences were found in peripheral blood mononuclear cell transcriptomics between responders and nonresponders. However, among the nonresponders, we noted an increased inflammatory response enriched for pathways linked with cytokine activity and chemokine receptor binding and innate myeloid signature. A larger cohort is required to validate and further explore these findings.

Psychological distress of college students during the COVID-19 pandemic.

Objectives To assess levels of psychological distress among a group of US undergraduate college students during the initial phases of the novel coronavirus (SARS-CoV-2) pandemic. Methods: All undergraduates at Kent State University were surveyed in three randomly selected cohorts on March 18, March 25, and April 1, yielding 3924 valid responses for the weighted dataset (73.8% female, 88.9% White). Distress was assessed using the Kessler Psychological Distress Scale (K6). Data were weighted using known population counts. Results: K6 scores averaged 8.19 ± 5.9, with 44.3% in the moderately elevated range and 23.8% above the cutoff for severe psychological distress.Conclusions: A high proportion of undergraduate university students reported elevated psychological distress as the COVID-19 pandemic unfolded. K6 scores appeared higher than averages from comparison samples. Targeted surveillance can inform public health in mitigating threats to mental health conferred by pandemics. Colleges and universities should anticipate sharply elevated psychological distress during and after the COVID-19 pandemic.

Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (the Speed-up Study): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN.

OBJECTIVES: Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD. METHODS: This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up. RESULTS: Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation ( P = 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1-20.5) mg/L ( P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) µg/g ( P = 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported. CONCLUSIONS: Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation.

Practice Variations in the Management of Infants With Non-IgE-Mediated Cow's Milk Protein Allergy.

OBJECTIVES: Infants with non-IgE-mediated food allergies are often referred to gastroenterologists or immunologists. We hypothesized that there are practice variations between these disciplines in the diagnosis and management of such infants. METHODS: A computerized questionnaire was distributed between pediatric gastroenterologists and immunologists. The questions addressed diagnosis, management, and follow-up in 3 scenarios of infants with concern for food protein-induced allergic proctocolitis (FPIAP) due to non-IgE-mediated responses to cow's milk. RESULTS: Three cases of infants with suspected FPIAP were presented: milk-based formula-fed (case 1) or breast-fed (case 2) infants that are well appearing and thriving, and a breast-fed infant who is not growing appropriately along with a personal and family history of atopy (case 3). Fifty-eight pediatric gastroenterologists and 32 immunologists completed the questionnaire. Significant differences between gastroenterologists and immunologists were noted regarding the recommended dietary changes in these scenarios. Moreover, despite available guidelines generated by both societies, most physicians confirm the diagnosis based on resolution of symptoms after the dietary change, without re-exposure to the the suspected trigger. In addition, time for recommended re-exposure in infants with FPIAP was also different; most gastroenterologists recommended waiting until 12 months of age, while immunologists suggested reintroduction earlier, up to 6 months of age. CONCLUSIONS: We identified significant practice variations in diagnosis and management of FPIAP between pediatric gastroenterologists and immunologists, with lack of adherence to society guidelines. Joint task forces of primary care pediatricians, gastroenterologists, and immunologists should provide uniform guidelines to standardize care.

Glycogen Storage Disease type IA refractory to cornstarch: Can next generation sequencing offer a solution?

Avoidance of fasting and regular ingestion of uncooked-cornstarch have long been the mainstay dietary treatment of Glycogen Storage Disease type Ia (GSD-Ia). However, GSD-Ia patients who despite optimal dietary treatment show poor glycemic control and are intolerant to cornstarch, present a complex clinical challenge. We pursued Whole Exome Sequencing (WES) in three such unrelated patients, to both confirm a molecular diagnosis of GSD-Ia, and seek additional variants in other genes (e.g. genes associated with amylase production) which may explain their persistent symptoms. WES confirmed the GSD-Ia diagnosis, with all three probands harboring the homozygous p.R83C variant in G6PC. While no other significant variants were identified for patients A and B, a homozygous p.G276V variant in the SI gene was detected in patient C, establishing the dual-diagnosis of GSD-Ia and Sucrase-Isomaltase Deficiency. To conclude, we suggest that WES should be considered in GSD-Ia patients who show persistent symptoms despite optimal dietary management.

Mucosal healing with methotrexate versus azathioprine treatment in pediatric Crohn's disease as reflected by fecal calprotectin.

BACKGROUND/OBJECTIVES: The current treatment goal for inflammatory bowel disease (IBD) is achievement of mucosal healing (MH). While established with biologic or azathioprine (AZA) therapies, the data on MH with methotrexate (MTX( treatment is scarce. We aimed to compare MH rate as reflected by FC in children with Crohn's disease (CD) treated with either MTX or thiopurines monotherapy. METHODS: A cross-sectional multicenter study including children with CD (<18 years), with documented mucosal ulcerations/erosions on their first endoscopy, who were in clinical and biochemical remission for at least 6 months on MTX or AZA/6-MP monotherapy and had fecal calprotectin (FC) measurements during remission. Clinical remission was defined as PCDAI<10 and normal C-reactive-protein (CRP) level. FC < 100 µg/gr was used as a marker of MH. Demographic, clinical and laboratory data were retrieved from the medical charts. RESULTS: 64 patients (41 males, age 16.6±4.2 years) were included; 36 with MTX, 26 with AZA and 2 with 6-MP treatment. The mean treatment dose was 14.0±1.8 mg/m2 for MTX, and 1.8±0.66 mg/kg for AZA, and mean therapy duration was 22 ±17.1 months. MH (FC < 100 µg/gr) was demonstrated in 14/36 (39%) and 18/28 (64%) of patients on MTX and AZA/6-MP therapy, respectively (p=0.04). Rates of FC < 300 µg/gr were comparable [27/36 (75%) MTX, 24/28 (86%) AZA/6-MP, p=0.29]. MH was associated with longer treatment duration (p=0.03). CONCLUSIONS: MH as reflected by FC < 100 µg/gr, was higher with AZA/6-MP compared to MTX treatment in pediatric CD.

"Golden Hour" quality improvement intervention and short-term outcome among preterm infants.

OBJECTIVE: To evaluate the impact of a quality improvement intervention during the first hour of life ("Golden Hour") on short-term preterm neonatal outcome. STUDY DESIGN: A comprehensive protocol designed for initial stabilization and treatment of preterm infants that included cord blood sampling, use of a dedicated resuscitation room and improved team communication using Crew Resource Management tools. The infants admitted before and after implementation of the protocol were retrospectively compared in a matched case-control design. RESULTS: There were 194 infants in the intervention group and 194 controls. Admission temperatures improved significantly from a mean of 35.26 °C to 36.26 °C (P < 0.001), and late-onset sepsis and bronchopulmonary dysplasia rates lowered significantly (P = 0.035 and P = 0.028, respectively) in the intervention group. There was trend towards reduction in early blood transfusion and ventilation duration. CONCLUSIONS: A "Golden Hour" quality improvement intervention was of significant benefit for preterm neonates. Further follow-up to assess long-term effects is warranted.