Sibylle Koletzko

Background: Reference values of the validated German Perceived Stress Questionnaire (PSQ) were published in 2005 for healthy adults and individuals with different clinical conditions. We compared historical values with PSQ from the large German cohort participating in “Risk Factors for COVID-19 Vaccine Failure study (RisCoin). Methods: In late 2021, we enrolled 4115 adults: hospital employees or patients with inflammatory bowel disease (IBD) or psychiatric disorders with ≥ 2 COVID-19 vaccinations. Participants completed extensive questionnaires including PSQ. Healthcare workers (HCW) were categorized as HCW-healthy or HCW-plus (any chronic medical condition). PSQ total and domain scores (worries, tension, joy, demands) were compared to reference values. Multivariable logistic regression identified factors associated with cohort-specific high scores (mean + 1SD). Results: HCW-healthy (N = 1998, mean age ± SD: 38 ± 12 years) reached higher mean total PSQ scores than historical healthy individuals (36 ± 18 vs. 33 ± 17, respectively, p<0.001), but lower scores (40 ± 19, p < 0.001) than HCW-plus (N = 1717, 43 ± 13 years). Female HCW-healthy perceived higher stress than males, especially at younger age. Participants with IBD (N = 161, 45 ± 15 years) exhibited lower scores than historical IBD patients (38 ± 19 vs. 43 ± 17, p < 0.001); psychiatric patients (N = 100, 41 ± 15 years) showed the highest scores (60 ± 19). Among HCW, female gender, frequent consumption of ready-to-eat meals/foods, and living with children were associated with higher, whereas regular physical activity and healthy dietary habits with lower PSQ scores. Conclusion: Assuming representativeness of our cohort, these PSQ data could serve as updated benchmark for future research.

Background: According to current guidelines, disease activity in eosinophilic esophagitis (EoE) is measured based on eosinophil infiltration in the esophageal tissue. To investigate the functional role of non‐eosinophilic immune cells, we examined immune cell infiltrate over the disease course in pediatric patients with EoE and performed single‐cell molecular analysis of the T‐cell infiltrate. Methods: We collected clinical data and biopsies from pediatric patients with EoE ( N = 50, baseline, up to six follow‐up endoscopies), gastroesophageal reflux disease (GERD, N = 33), or functional disorders (FD, N = 67). Multiparametric immunofluorescence staining (mIF; n = 114 biopsies) and single‐cell RNA sequencing of CD45 ⁺ CD3 ⁺ T‐cells ( n = 82 biopsies; 35,112 cells) with T cell receptor repertoire analysis were performed. Results: Immune cell infiltration was significantly higher in active EoE than in inactive EoE, GERD, and FD (inactive: EPX p = 0.0156, MCT p = 0.0312, CD3 p = 0.0078). During remission, CD8 ⁺ T‐cell infiltration was significantly greater with PPI treatment compared to TS ( p = 0.0092). GNLY‐positive activated CD8 ⁺ T‐cells ( R = 0.33, p = 0.038), and T _H 2 cells ( R = 0.36, p = 0.036) positively correlated with esophageal eosinophilia in the single‐cell analysis, whereas IL17‐positive CD4 ⁺ T‐cells showed a negative correlation ( R = −0.43, p = 0.016 ) . During active EoE, T _H 2 cells were enriched ( p = 0.002). Absolute clone size was higher in active EoE than in inactive EoE and controls, while mean clone size only differed for CD4 clones between active EoE and controls. Diversity and the ratio of expanded clonotypes did not differ. Conclusion: Distinct immunophenotypic profiles are associated with treatment response and disease activity in pediatric EoE. TS were associated with lower residual T cell infiltration than PPI. The evaluation of therapy‐induced phenotypic changes by single‐cell analysis was limited by low T cell yields in biopsies after TS treatment.

Background: Allergic diseases often develop jointly during early childhood. Potential disease trajectories and relevant early‐life factors have been described, yet existing prediction approaches mostly focus on single allergic diseases cross‐sectionally. Models addressing allergic multimorbidity and disease trajectories are lacking. We aim to predict allergic disease trajectories from birth up to adolescence using early‐life factors. Methods: Preceding research using data from 4646 adolescents of the German birth cohorts GINIplus and LISA identified seven allergic disease trajectories up to the age of 15 years. A set of predictors comprising parental and perinatal factors, early allergic or respiratory symptoms, lifestyle and environmental factors was used with an XGBoost machine learning approach to perform multiclass classification. In a subsample ( N = 2109), polygenic risk scores (PRS) for asthma, allergic rhinitis, atopic dermatitis, and any allergy were added to the predictor set. Results: Our approach revealed moderate classification success (multiclass area under the curve (AUC) = 0.69). A macro‐averaged sensitivity of 0.26 and specificity of 0.89 were obtained. The most important predictors were early‐life skin rash, respiratory symptoms, and air pollution. In the sub‐analysis, the PRS were among the factors with high importance, but the prediction performance in external test data was not improved. Conclusions: Our prediction success was comparable to established prediction scores while accounting for multiple allergic disease trajectories and using solely early‐life factors. This study cannot yet provide reliable individual‐level prediction in a clinical setting but can inform development of future work on this.

Objectives: Monitoring for Helicobacter pylori (H. pylori) ‐eradication is important, since symptom improvement does not indicate treatment success. Using EuroPedHp Registry data, we investigated characteristics of children missing monitoring visits after prescribed therapy, compliance effect on eradication, and factors associated with loss to follow‐up and low compliance. Methods: Between 2017 and 2020, 30 paediatric hospitals from 17 European countries reported 1605 children with biopsy‐proven H. pylori ‐infection. Children with prescribed therapy were analysed. Risk factors for loss to follow‐up or low compliance (taking ≤90% of prescribed medications) were identified applying multivariable logistic regression. Results: Of 1263 infected children with prescribed therapy, 390 (31%) were lost to follow‐up. Risk factors for loss to follow‐up included nausea/dyspepsia ( p = 0.004) or gastrointestinal bleeding ( p = 0.03) as indication for endoscopy, living in Israel or Türkiye ( p = 0.0002), and having no antibiotic susceptibility result ( p = 0.004). Risk decreased with living in Southern Europe ( p = 0.002), migration background ( p = 0.052), and probiotic use during therapy ( p = 0.02). Low compliance, reported in 69/831 (8%) children with follow‐up data, was associated with vomiting ( p = 0.003), peptic ulcers or erosions ( p = 0.03), living in EasternEurope ( p = 0.009), Israel or Türkiye ( p = 0.0008), and any adverse event during therapy ( p = 0.0009). First‐line tailored triple therapy (TTT) for 14 days ( N = 480) was successful in 92% with excellent versus 61% with low compliance ( p < 0.0001). After ≥1 failed therapies ( N = 60), TTT was successful in 71% with high versus 13% with low compliance ( p = 0.003). Conclusion: The registry data identified several factors associated with non‐adherence to medication and monitoring visits. Improving information to patient/caregiver may increase adherence, care and treatment success.

Introduction: European and National Celiac Disease (CeD) guidelines offer an easy pathway to diagnose CeD. The German CeD Registry aimed to assess symptoms and clinical findings before diagnosis, diagnostic delay, care during the diagnostic process, and factors associated with persistence of symptoms. Methods: Individuals with CeD provided demographic, clinical, and healthcare-related information. Participants were divided into four subgroups according to age at diagnosis (>18 or <18 years) and year of diagnosis (before and since 2012). Factors associated with symptoms after at least 1 year on a gluten-free diet (GFD) were assessed using multivariate logistic regression. Results: From 11/2019 to 10/2021, 2,333 participants were enrolled. After exclusion of 169 (7.2%), 2,164 remained for analysis, thereof 796 (36.8%) were diagnosed <18 years, and 1,283 (59.3%) since 2012. Most common symptoms before diagnosis included abdominal pain (83%), bloating (82%), fatigue (78%), and diarrhoea (71%). Diagnostic delay after 2012 was longer in adults than children (median 4.4 years [interquartile range; IQR: 1.2–13.0] versus 1.1 [IQR: 0.5–2.2], respectively) (p < 0.001). Guideline-conform diagnoses increased over time. After diagnosis, only 60% received professional dietary counselling. Factors associated with symptoms despite GFD included female gender (odds ratio [OR]: 1.79 [95% confidence interval: 1.34; 2.40], p < 0.001), same symptom before diagnosis (OR: 3.45 [2.45; 4.96], p < 0.001), insufficient information provided at diagnosis (OR: 1.25 [1.00; 1.57], p = 0.046), and age at diagnosis (per decade) (OR: 1.11 [1.04; 1.18], p < 0.001) but not time since diagnosis. Conclusions: Our findings revealed deficits in awareness, the diagnostic process, and post-diagnostic care that are linked to decreased clinical improvement over time.

Objectives: STRIDE (selecting therapeutic targets in inflammatory bowel disease) established evidence‐based targets for treat‐to‐target strategies in inflammatory bowel disease (IBD). STRIDE‐II designates clinical remission, C‐reactive protein (CRP) normalization, and fecal calprotectin (FC) reduction as short‐ to intermediate‐term targets, and mucosal healing as a long‐term target. This study evaluated STRIDE‐II application and disease control in a real‐world pediatric cohort. Methods: We retrospectively analyzed newly diagnosed pediatric IBD patients (ages 3–18 years) treated according to guidelines between June 2017 and January 2023. Time‐to‐reach STRIDE‐II targets and time‐to‐first flare were assessed over 52 weeks using disease activity indices, inflammatory biomarkers (CRP, FC), and endoscopy. Results: Seventy‐four patients were included (37 Crohn's disease [CD], 37 ulcerative colitis [UC]). All CD patients received primary maintenance therapy with immunomodulators or biologics, versus 51% UC patients. Clinical remission and CRP normalization occurred within 5–10 weeks; FC normalization within 12–19 weeks. By 6 months, combined targets (clinical remission plus CRP and FC normalization) were achieved by 54% of CD patients and 43% of UC patients. Clinical relapse after remission occurred more frequently in UC than in CD (67% vs. 43%, p = 0.0334). Follow‐up endoscopy at a median of 41 weeks (CD) and 52 weeks (UC) showed endoscopic healing in 7/18 (39%) CD and 13/22 (59%) UC patients. Conclusions: Most pediatric IBD patients achieved clinical remission and CRP normalization within STRIDE‐II timeframes, whereas FC normalization occurred later, and relapses—particularly in UC—remained common. The notable proportion of patients with suboptimal disease control underscores the need for continuous monitoring in pediatric IBD.

Objectives: Celiac disease (CeD) is a life‐long systemic immune‐mediated disorder. Data on burden and cost of CeD in children are scarce. We assessed healthcare resource utilization (HCRU) and cost of healthcare services of newly diagnosed children in Germany. Methods: This retrospective case‐control study covered a period from 2014 to 2021, using German Statutory Health Insurance claims data from the “Institute for Applied Health Research Berlin” (InGef). The HCRU (hospitalizations, outpatient contacts, outpatient drug prescriptions) and cost of CeD patients aged p < 0.001). Conclusions: These findings underscore the substantial burden of CeD on patients and healthcare systems, highlighting the need for targeted interventions and effective management strategies to mitigate this impact.