Effect of anti-SARS-CoV-2 BNT162b2 mRNA vaccination on thrombin generation in children with inflammatory bowel disease.

Background: Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), are associated with higher thrombotic risk and enhanced thrombin generation (TG) in adults. Despite encouraging data reporting vaccine safety and low IBD flare rates in adults with IBD, vaccine hesitancy was demonstrated to be high in families of children with IBD. We aimed to find out whether TG is increased in children with IBD as compared to healthy controls and whether TG parameters show significant changes following SARS-CoV-2 mRNA vaccination. Patients and methods: In this observational case-control study, 38 children with IBD (CD:18, UC: 20) aged 12-18 years and 62 healthy age-and sex-matched children were enrolled. Blood was collected before the first dose and 2-6 weeks after the second dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine dose. Blood cell counts, fibrinogen, inflammatory markers (hsCRP, ferritin), anti-SARS-CoV-2 antibody levels were investigated, TG assay was carried-out using platelet-poor plasma. Detailed clinical parameters including disease activity scores (PUCAI, PCDAI) were registered pre-and post- vaccination. A guided questionnaire was used to collect data on adverse reactions (AEs) post- vaccination. Results: Baseline TG parameters did not differ between patients and controls. Endogenous thrombin potential showed a significant positive correlation with markers of inflammation and with PCDAI. Inflammatory parameters and TG did not increase in patients and controls post-vaccination. Vaccination significantly increased antibody levels in all three investigated groups, but post-vaccination anti-SARS-CoV-2 S IgG/IgM levels were below the 5th percentile value of healthy children in more than one third of patients. Those receiving TNFα inhibitor therapy presented significantly lower SARS-CoV-2 S IgG/IgM levels as compared to patients on other immunosuppressive regimens. Systemic AEs did not differ between patients and controls while lower rate of local symptoms was found post-vaccination in children with IBD. Only 2 IBD flares were detected 2-6 weeks after the second dose of vaccination. Conclusion: Our study is the first to support the safety and efficacy of anti-SARS-CoV-2 BNT162b2 vaccination in children with IBD with detailed pre-and post-vaccination laboratory data including TG. Results of this study may further increase confidence and reduce vaccine hesitancy in caretakers of pediatric IBD patients.

Disease Activity Is Associated with Obesity in Newly Diagnosed Pediatric Patients with Ulcerative Colitis.

Malnutrition and inflammatory bowel disease (IBD) are interrelated conditions. Our aim was to assess the prevalence of malnutrition, to compare anthropometric parameters in the evaluation of nutritional status in pediatric IBD, and to investigate the association between anthropometric parameters and disease activity indices (AI). Pediatric patients with newly diagnosed IBD recorded between 2010 and 2016 in the Hungarian Pediatric IBD Registry were included in this cross-sectional study. Body weight, body mass index (BMI), weight-for-height, and ideal body weight percent (IBW%) were analyzed. Pearson linear and non-linear correlations and polynomial regression analyses were performed to assess correlation between nutritional status and AI. p-values < 0.05 were considered significant. Anthropometric data of 1027 children with IBD (Crohn's disease (CD): 699; ulcerative colitis (UC): 328; mean age 13.7 years) were analyzed. IBW% identified more obese patients than BMI both in CD (7.02% vs. 2.28%) and UC (12.17% vs. 5.48%). Significant negative correlation was found among anthropometric parameters and AI in CD. In contrast, polynomial regression analysis revealed a U-shaped correlation curve between IBW% and AI in UC. Our findings show that obesity has a bimodal association with disease activity in pediatric UC. Furthermore, IBW% was more useful to identify obese pediatric patients with IBD.

Prevalence of Undernutrition and Effect of Body Weight Loss on Survival among Pediatric Cancer Patients in Northeastern Hungary.

Undernutrition is a prevalent condition in pediatric malignancy patients leading to unfavorable outcomes. The aim of this retrospective study was to determine the nutritional status and rate of undernutrition in 174 Hungarian pediatric patients with malignancies and the impact on 5-year survival based on anthropometric measurements. At the time of diagnosis, 5.0%, 4.6%, and 4.0% of patients were undernourished as determined by body weight (BW), weight-for-height (WFH), and body mass index (BMI) Z-score, respectively. The rate of undernutrition was 30.5% using ideal body weight percent (IBW%). Undernutrition at the time of diagnosis worsened the five-year overall survival only in solid tumor patients as defined by BMI Z-score and IBW%. Furthermore, 26.5% of patients became undernourished based on IBW% during the treatment period. Deterioration of nutritional status during treatment unfavorably influenced overall survival in both hematological and solid tumor subsets. Abnormal BW, WFH, and BMI Z-score were associated with poor prognosis in the hematologic group. The mortality risk was higher among hematologic patients with weight loss exceeding 20%. In conclusion, IBW% seems to be the most sensitive parameter to estimate undernutrition. Furthermore, BMI Z-score in both groups and severe weight loss in the hematological group may influence clinical outcome and play a role in prognosis assessment.

Adherence to the Porto Criteria Based on the Hungarian Nationwide Pediatric Inflammatory Bowel Disease Registry (HUPIR).

Objectives: According to the Porto criteria, upper endoscopy and ileocolonoscopy with histology for patients with pediatric inflammatory bowel disease (pIBD) are recommended with small bowel imaging (SBI). We aimed to evaluate the adherence to the Porto criteria and biopsy sampling practice and to evaluate the diagnostic yield of magnetic resonance enterography (MRE) first time in a nationwide pIBD inception cohort. Methods: Newly diagnosed pIBD cases (ages 0-18 years) are registered in the prospective, nationwide Hungarian Paediatric IBD Registry (HUPIR). We analyzed the diagnostic workup of patients recorded between the 1st of January 2007 and the 31st of December 2016. Results: Data for diagnostic workup was available in 1,523 cases. Forty percent of the cases had complied with the Porto criteria. Adherence to the Porto criteria increased significantly from 20 to 57% (p < 0.0001) between 2007 and 2016. The most frequent reason for the incomplete diagnostic work-up was the lack of small bowel imaging (59%). In 2007, 8% of cases had a biopsy from all segments, and this rate reached 51% by 2016 (p < 0.0001). We analyzed the diagnostic yield of MRE in 113 patients (10.1%), who did not have any characteristic lesion for Crohn's disease. The MRE was positive for the small bowel in 44 cases (39%). Conclusions: Adherence to the Porto criteria increased significantly during the 10-year period. This is the first study that reports multiple biopsy sampling as the less accepted recommendation. The diagnostic yield of MRE in patients without characteristic lesion for Crohn's disease is 39%.

Characteristics of biological therapy in pediatric patients with Crohn's disease.

INTRODUCTION: At present, there is a significant amount of data related to biologics used in pediatric patients with Crohn's disease. This review characterizes the different biological drugs administered in this population. AREAS COVERED: Biological therapy of CD, focusing on children, is summarized in this review. After mechanism of action and pharmacokinetics are described, mucosal healing on anti-TNF therapy, aspects of early therapy, long-term outcome and combination therapy are discussed. Moreover, loss of response and treatment optimization, as well as drug withdrawal are summarized. Subsequently, perianal disease and surgical aspects are discussed followed by safety issues. In addition, new drugs (vedolizumab, ustekinumab), cost-effectiveness and administration of biosimilars were also included. EXPERT COMMENTARY: There are significant data to characterize biological drugs administered in pediatric patients with Crohn's disease. However, head-to-head comparative studies using different biologics are missing.