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Stine Dydensborg Sander,1,2 Anne Vinkel Hansen,3,4 Ketil Størdal,5,6 Anne-Marie Nybo Andersen,3 Joseph A Murray,7 Steffen Husby1,2 1Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark; 2Institute of Clinical Research, Faculty of Health Science, University of Southern Denmark, Odense, Denmark; 3Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 4Statistics Denmark, Copenhagen, Denmark; 5Department of Child Health, Norwegian Institute of Public Health, Oslo, Norway; 6Department of Pediatrics, Ostfold Hospital Trust, Grålum, Norway; 7Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA Purpose: The purpose of this study was to investigate the association between mode of delivery and the risk of celiac disease in two large population-based birth cohorts with different prevalence of diagnosed celiac disease. Patients and methods: This is an observational register-based cohort study using two independent population cohorts. We used data from administrative registers and health administrative registers from Denmark and Norway and linked the data at the individual level. We included all children who were born in Denmark from January 1, 1995 to December 31, 2010 and all children who were born in Norway from January 1, 2004 to December 31, 2012. Results: We included 1,051,028 children from Denmark. Cesarean sections were registered for 196,512 children (18.9%). Diagnosed celiac disease was registered for 1,395 children (0.13%). We included 537,457 children from Norway. Cesarean sections were registered for 90,128 children (16.8%). Diagnosed celiac disease was registered for 1,919 children (0.35%). We found no association between the mode of delivery and the risk of diagnosed celiac disease. The adjusted odds ratio for celiac disease for children delivered by any type of cesarean section compared to vaginal delivery was 1.11 (95% CI: 0.96–1.29) in the Danish cohort and 0.96 (95% CI: 0.84–1.09) in the Norwegian cohort. The adjusted odds ratio for celiac disease for children delivered by elective cesarean section compared to vaginal delivery was 1.20 (95% CI: 1.00–1.43) in the Danish cohort and 0.96 (95% CI: 0.79–1.17) in the Norwegian cohort. Conclusion: In this large registry-based study, mode of delivery was not associated with an increased risk of diagnosed celiac disease. Keywords: cesarean section, autoimmunity, epidemiology, administrative health register

Stine Dydensborg Sander,1-3 Ketil Størdal,4,5 Tine Plato Hansen,6 Anne-Marie Nybo Andersen,7 Joseph A Murray,8 Søren Thue Lillevang,9 Steffen Husby1,2 1Hans Christian Andersen Children’s Hospital, Odense University Hospital, 2Institute of Clinical Research, University of Southern Denmark, 3Odense Patient Data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark; 4Mental and Physical Health, Norwegian Institute of Public Health, Oslo, 5Department of Pediatrics, Ostfold Hospital Trust, Fredrikstad, Norway; 6Department of Pathology, Hvidovre Hospital, 7Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 8Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 9Department of Clinical Immunology, Odense University Hospital, Odense, Denmark Purpose: The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank) and information on celiac disease-specific antibodies and human leukocyte antigen (HLA) genotypes obtained from patient medical records.Patients and methods: We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG) and HLA genotypes.Results: We identified 2,247 children who were registered in the Danish National Patient Register with celiac disease. Duodenal biopsies for 1,555 of the children (69%) were registered in the Patobank; 1,127 (50%) had a biopsy that was compatible with celiac disease (ie, Marsh 2–3). We accessed the medical records of 95% of the children who were registered in the ­Danish National Patient Register with celiac disease. We found that 1,510 (67%) had one or more positive antibody-test results; 1,120 (50%) had anti-tissue transglutaminase 2, IgA at tenfold or greater the upper limit of the normal range and/or positive endomysial antibody results. The positive predictive value depended on the criteria used for validation and the types and numbers of registrations that were included in the analysis and ranged from 62% (95% confidence interval: 60%–64%) to 86% (95% confidence interval: 84%–87%).Conclusion: Our findings indicate that the Danish National Patient Register is a valuable source to identify patients who have been diagnosed with celiac disease. However, validation of the diagnoses is warranted before data on the patients are used for research purposes. Keywords: administrative health register, national patient register, pathology register, medical record, histology, serology

Especially patients treated with CAR-T cell therapy for B-cell malignancies have poor outcomes after COVID-19, with case mortality rates >40%. B Results: b Of 130 treated patients we identified 43 patients infected with SARS-CoV-2, 5 were infected prior to CD20xCD3 treatment, and 38 were infected during CD20xCD3 treatment or after end-of-treatment. B Introduction: b Patients with hematological malignancies are at an increased risk of morbidity and mortality from COVID-19. [Extracted from the article]

Many modern pesticides have endocrine disrupting abilities and early-life exposure may affect growth and disease risk later in life. Previously, we reported associations between prenatal pesticide exposure and higher childhood body fat content measured by anthropometry. The associations were affected by child PON1 Q192R genotype. We aimed to study whether prenatal pesticide exposure was still associated with body fat content and distribution in the children at puberty and the potential impact of both maternal and child PON1 Q192R genotype. In this prospective cohort study of 247 children born by occupationally exposed or unexposed women (greenhouse workers and controls) two follow-up examinations (age 10-15 and 11-16 years) including simple anthropometry, skinfold measurements, pubertal staging and blood sampling were performed. Total and regional fat% was determined by dual X-ray absorptiometry (DXA) at age 10-15. Prenatal pesticide exposure was associated with increased total, android, and gynoid fat percentage (DXA) at age 10-15 years after adjustment for sex, socioeconomic status, and puberty (all β = 0.5 standard deviation score (SDS) p < 0.05). Stratified by sex, the associations were significant in girls (total fat: β = 0.7 SDS, android-gynoid ratio: β = 0.1, both p < 0.05), but not in boys. Carrying the R-allele (child or mother, separately, or both) augmented the differences between exposed and unexposed children (total fat: β = 1.0 SDS, β = 0.8 SDS, p < 0.05, respectively, and β = 1.2 SDS, p < 0.01). No exposure-related differences were found if either the child or mother had the QQ wild-type. At age 11-16, exposed children tended to have a higher total fat% estimated by skinfolds than unexposed children ( p = 0.06). No significant associations between prenatal exposure and body mass index or waist circumference were found. Prenatal pesticide exposure was associated with higher adolescent body fat content, including android fat deposition, independent of puberty. Girls appeared more susceptible than boys. Furthermore, the association depended on maternal and child PON1 Q192R genotype. [ABSTRACT FROM AUTHOR]

Objective To describe prevalence, prenatal diagnosis and epidemiological data on oesophageal atresia from 23 well-defined European regions and compare the prevalence between these regions. Design Population-based study using data from a large European database for surveillance of congenital anomalies (EUROCAT) for two decades (1987-2006). Settings Twenty-three participating registries based on multiple sources of information including information about live births, fetal deaths with gestational age >=20 weeks and terminations of pregnancy. Patients 1222 cases of oesophageal atresia in a population of 5 019 804 births. Results The overall prevalence was 2.43 cases per 10 000 births (95% CI 2.30 to 2.57). There were regional differences in prevalence ranging from 1.27 to 4.55. Prenatal detection rates varied by registry from >50% of cases to <10% of cases. A total of 546 cases (44.7%) had an isolated oesophageal anomaly, 386 (31.6%) were multiple malformed and 290 (23.7%) had an association or a syndrome. There were 1084 live born cases (88.7%), 43 cases were fetal deaths and 95 cases were terminations of pregnancy. One-week survival for live births was 86.9% and 99.2% if the gestational age was >=38 weeks and isolated oesophageal atresia was present. Males accounted for 57.3% of all cases and 38.5% of live born cases were born with gestational age <37 weeks. Conclusion There were regional differences in prevalence of oesophageal atresia in Europe. Half of all cases had associated anomalies. Prenatal detection rate increased from 26% to 36.5% over the two decades. Survival in infants with isolated oesophageal atresia born at term is high. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study was performed to 1) determine the prevalence of celiac disease in Danish children with type 1 diabetes and 2) estimate the clinical effects of a gluten-free diet (GFD) in patients with diabetes and celiac disease. RESEARCH DESIGN AND METHODS: In a region comprising 24% of the Danish population, all patients <16 years old with type 1 diabetes were identified and 269 (89%) were included in the study. The diagnosis of celiac disease was suspected in patients with endomysium and tissue transglutaminase antibodies in serum and confirmed by intestinal biopsy. Patients with celiac disease were followed for 2 years while consuming a GFD. RESULTS: In 28 of 33 patients with celiac antibodies, an intestinal biopsy showed villous atrophy. In 5 patients, celiac disease had been diagnosed previously, giving an overall prevalence of 12.3% (95% CI 8.6-16.9). Patients with celiac disease had a lower SD score (SDS) for height (P < 0.001) and weight (P = 0.002) than patients without celiac disease and were significantly younger at diabetes onset (P = 0.041). A GFD was obtained in 31 of 33 patients. After 2 years of follow-up, there was an increase in weight SDS (P = 0.006) and in children <14 years old an increase in height SDS (P = 0.036). An increase in hemoglobin (P = 0.002) and serum ferritin (P = 0.020) was found, whereas HbA(1c) remained unchanged (P = 0.311) during follow-up. CONCLUSIONS: This population-based study showed the highest reported prevalence of celiac disease in type 1 diabetes in Europe. Patients with celiac disease showed clinical improvements with a GFD. We recommend screening for celiac disease in all children with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux disease (GERD) and cow milk hypersensitivity are frequent disorders of infancy. A possible causative association between these two entities has been suggested.Objective: The primary aim was to elucidate whether a causative relationship between the two entities could be established in a population of infants and children. A secondary aim was to evaluate whether cow milk challenge during esophageal pH monitoring is useful as an objective method to identify this subgroup of patients.Methods: Upper endoscopy followed by a 48-hour esophageal pH monitoring with cow's milk elimination diet at day 1 and challenge at day 2. Cow milk hypersensitivity was later verified by elimination diet and a second open (in patients < 3 years of age) or double-blind placebo-controlled (in patients > or = 3 years of age) challenge. Skin prick test, specific serum immunoglobulin E and skin patch test were used as supplementary procedures. Follow-up endoscopy and pH monitoring were performed after 3 months of treatment (omeprazole versus elimination diet dependent on evidence of food hypersensitivity).Results: Eighteen of 42 investigated patients had severe GERD, defined as endoscopic esophagitis and/or a reflux index > 10%. Among these patients, a group of 10 patients with GERD and cow milk hypersensitivity was identified. This group had a significantly higher reflux index compared with children with primary GERD. No significant increase was noted in reflux index during simultaneous pH monitoring and milk challenge.Conclusions: An association between GERD and cow milk hypersensitivity was observed in both infants and children with severe GERD. Simultaneous cow milk challenge and pH monitoring had limited value as a method to identify this subgroup. [ABSTRACT FROM AUTHOR]

The association between polymorphisms in the programmed death (PD-1) gene and susceptibility to systemic lupus erythematosus (SLE) was determined using genomic DNA, isolated from a population-based cohort of 95 SLE patients and 155 healthy controls. Polymorphisms in the complete PD-1 gene except the large intron 1 were detected by sequencing. Furthermore, the patients were stratified according to the presence or absence of lupus nephropathy. The influence of the detected single nuclear polymorphisms (SNPs) on this specific clinical disease parameter was determined. In total, we identified 12 single nucleotide polymorphisms, of which six were novel and eight were considered to be rare (the frequency of the minor allele of these was less than 1% in our study populations). We found a significant association of an intronic 6867C/G SNP in the PD-1 gene with the presence of lupus nephropathy. As the 6867C/G SNP is located in a putative binding site for the transcriptional repressor ZEB, the associated allele of this SNP potentially alters the transcriptional regulation of PD-1. This report, for the first time, indicates that a 6867C/G SNP of the PD-1 gene is associated with lupus nephropathy in Caucasian SLE patients. [ABSTRACT FROM AUTHOR]