| 1. |
- Kvedaraite, Egle, et al.
(författare)
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Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA+CD142−/low fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRA+CD142−/low fibroblasts foster monocyte transition to CCR2+CD206+ macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2+CD206+ cells from co-cultures have a phenotype similar to intestinal CCR2+CD206+ macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation.
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| 2. |
- Malmborg, Petter, et al.
(författare)
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Effects of Childhood-onset Inflammatory Bowel Disease on School Performance : A Nationwide Population-based Cohort Study Using Swedish Health and Educational Registers
- 2019
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 25:10, s. 1663-1673
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Childhood-onset inflammatory bowel disease (IBD) might negatively impact academic school performance. We conducted a nationwide study to examine the association between childhood-onset IBD and school results. METHODS: Our study population was selected from Swedish health registers. In the National Patient Register (1990 to 2013), we identified 2827 children with IBD: Crohn's disease (CD), n = 1207, and ulcerative colitis (UC), n = 1370. Patients were matched with 10 reference individuals by age, sex, birth year, and place of residence (n = 28,235). Final compulsory school grades (0 to 320 grade points) and qualification for high school (yes or no) were obtained through the National School Register. Regression models controlling for socioeconomic factors were used to analyze the association of IBD with school performance. RESULTS: Children with IBD had a lower final grade point average (adjusted mean grade difference [AMGD] -4.9, 95% confidence interval [CI] -7.1 to -2.6) but not a significantly higher risk to not qualify for high school (odds ratio [OR] 1.14, CI 0.99-1.31). The results were similar in children with UC (AMGD -5.5, CI -8.7 to -2.3) and CD (AMGD -4.7, CI -8.2 to -1.2). Underperformance was more common in subsets of IBD children characterized by markers associated with long-standing active disease (eg, >30 inpatient days [AMGD-18.1, CI -25.8 to -10.4]). CONCLUSION: Most children with IBD achieve comparable results in the final year of compulsory school as their healthy peers. Care should be improved for the subgroup of children for which IBD has a stronger negative impact on school performance.
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| 3. |
- Miguel-Berges, María L, et al.
(författare)
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Associations between food and beverage consumption and different types of sedentary behaviours in European preschoolers : the ToyBox-study.
- 2017
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 56:5, s. 1939-1951
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the association between food and beverage consumption and time spent in different sedentary behaviours such as watching TV and DVDs, playing computer/video games and quiet play/activities in preschoolers.METHODS: A sample of 6431 (51.8 % males) European preschoolers aged 3.5-5.5 years from six survey centres was included in the data analyses. Data on dietary habits and sedentary behaviours [watching TV, playing computer and quiet play (both during weekdays and weekend days)] were collected via standardized proxy-administered questionnaires. One-way analysis of covariance and general linear model (adjusted for sex, maternal education, body mass index and centre) were conducted.RESULTS: The results of the generalized linear model showed that the more strong associations in both males and females who were watching TV for > 1 h/day during weekdays were positively associated with increased consumption of fizzy drinks (β = 0.136 for males and β = 0.156 for females), fresh and packed juices (β = 0.069, β = 0.089), sweetened milk (β = 0.119, β = 0.078), cakes and biscuits (β = 0.116, β = 0.145), chocolate (β = 0.052, β = 0.090), sugar-based desserts and pastries (β = 0.234, β = 0.250), salty snacks (β = 0.067, β = 0.056), meat/poultry/processed meat (β = 0.067, β = 0.090) and potatoes (β = 0.071, β = 0.067), and negative associations were observed for the consumption of fruits (β = -0.057, β = -0.099), vegetables (β = -0.056, β = -0.082) and fish (β = -0.013, β = -0.013). During weekend days, results were comparable.CONCLUSIONS: In European preschoolers, sedentary behaviours were associated with consumption of energy-dense foods and fizzy drinks. The present findings will contribute to improve the strategies to prevent overweight, obesity and nutrition-related chronic diseases from early childhood.
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| 4. |
- Mouratidou, Natalia, et al.
(författare)
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Adult height in patients with childhood-onset inflammatory bowel disease : a nationwide population-based cohort study
- 2020
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 51:8, s. 789-800
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Tidskriftsartikel (refereegranskat)abstract
- Background: Growth retardation is well described in childhood-onset inflammatory bowel disease (IBD).Aims: To study if childhood-onset IBD is associated with reduced final adult height.Methods: We identified 4201 individuals diagnosed with childhood-onset IBD 1990-2014 (Crohn's disease: n = 1640; ulcerative colitis: n = 2201 and IBD-unclassified = 360) in the Swedish National Patient Register.Results: Patients with IBD attained a lower adult height compared to reference individuals (adjusted mean height difference [AMHD] -0.9 cm [95% CI -1.1 to -0.7]) and to their healthy siblings (AMHD -0.8 cm [-1.0 to -0.6]). Patients with Crohn's disease (CD) were slightly shorter than patients with ulcerative colitis (UC; -1.3 cm vs -0.6 cm). Lower adult height was more often seen in patients with pre-pubertal disease onset (AMHD -1.6 cm [-2.0 to -1.2]), and in patients with a more severe disease course (AMHD -1.9 cm, [-2.4 to -1.4]). Some 5.0% of CD and 4.3% of UC patients were classified as growth retarded vs 2.5% of matched reference individuals (OR 2.42 [95% CI 1.85-3.17] and 1.74 [1.36-2.22] respectively).Conclusion: Patients with childhood-onset IBD on average attain a slightly lower adult height than their healthy peers. Adult height was more reduced in patients with pre-pubertal onset of disease and in those with a more severe disease course.
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| 5. |
- Mouratidou, Natalia
(författare)
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Childhood-onset inflammatory bowel disease-health care use, impact on growth and school achievements
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to explore the Impact of Inflammatory bowel disease (IBD) on growth and school achievements. We also assessed the Incidence and health care use of patients with very early-onset IBD (VEO-IBD). Furthermore, we examined the validity of register-based definitions of IBD and its subtypes in children. In study 1, we investigated whether patients with childhood-onset IBD are at an increased risk of poorer final grade point average (GPA) at the end of compulsory school (ninth grade) and not qualifying for high school. We identified 2827 children with IBD in National Patient Register (NPR) between 1990 -2014 and compared their final grades obtained from School Register with matched reference individuals and IBD-free siblings. We adjusted for potential confounders, such as parental psychosocial problems and education. We found a statistically significantly lower GPA (adjusted mean grade difference [AMGD] −4.9, 95% CI −7.1 to −2.6, standardised mean difference [SMD] −0.08, 95% CI −0.11 to −0.04) compared to reference individuals though the difference was minimal. Children with IBD did not have an increased risk of not qualifying for high school compared to their siblings or reference individuals (OR 1.14, 95% CI 0.99 to 1.31). In addition, we found that IBD children with markers of longstanding and severe disease underperformed more commonly compared to reference individuals and IBD-free siblings. In study 2, we studied the attained final height and growth retardation in patients with childhood-onset IBD compared to matched reference individuals and their IBD-free full biological siblings using information from the National Patient Register and Pass Register.Analyses were adjusted for potential confounders, including birth order, number of siblings, parental height, parental mental health problems, and education. The adjusted analysis demonstrated that patients with IBD attained a statistically significant shorter final height in adult age (adjusted mean height difference (AMHD) -0.9 cm, 95% CI -1.1 to -0.7) compared to reference individuals and IBD-free full siblings (AMHD-0,8 CM, 95% CI -1.0 to-0.6). Differences in adult mean heights were more prominent in patients with IBD onset before puberty (AMHD -1.6 cm, 95% CI -2.0 to-1.2) than in patients with onset during or after puberty (AMHD-0.8 cm, 95% CI -0.9 to-0.6) and in the subsets of patients exposed to bowel surgery (AMHD -1.9 cm, 95% CI -2.4 to-1.4), perianal surgery (AMHD -1.5 cm, 95% CI -2.3 to -0.7), or inpatient treatment for >30 days listing IBD as the primary diagnosis (AMHD -1.4 cm, 95% CI -1.8 to -1.0) during childhood. Patients with IBD had an increased risk of growth retardation compared to general population reference individuals (OR 1.99, 95% CI 1.68 to 2.37). In study 3, we analysed the positive predictive value (PPV) of the commonly used register-based algorithm (≥2 diagnostic listings) for childhood-onset IBD in the NPR and its subtypes, both for prevalent and incident definitions. We also studied the PPV of childhood-onset IBD diagnosis using Swibreg and combining IBD listings in the NPR and pathology codes from the ESPRESSO cohort. We found the PPV of a commonly used register-based definition of childhood-onset IBD in the NPR (at least two diagnostic listings of IBD) to be high (PPV=93%) when using the Copenhagen criteria based on medical chart review as the gold standard. The PPV for a definition also using pathology reports suggestive of IBD was even higher (97%) and 100% for patients registered in SWIBREG. Using the revised Porto criteria as the gold standard, the PPV for different IBD subtypes based on ICD codes in the NPR at the start of follow-up (incident definition) was 78% for CD and 74% for UC and somewhat higher at the end of follow-up (prevalent definition: 88% for CD and 71% for UC). In study 4, we identified 5308 patients with childhood-onset IBD in the NPR and ESPRESSO cohorts from 2006 until 2020 using ICD codes or a combination of ICD codes with pathology codes and further stratified them by age of IBD onset [infantile onset (<2 years), preschool onset (2-<6), very early onset (<6, VEO-IBD), early onset IBD (6-<10) and adolescent onset (10-<18)]. We described the incidence of VEO-IBD patients (<6 years of age) and analysed and compared health care use (medications, hospitalisations, outpatient visits, surgeries) in VEO-IBD patients compared to older groups. We analysed all these outcomes separately in infantile and toddler groups. The incidences of all childhood-onset IBD age groups (including VEO-IBD) were stable. VEOIBD patients were equally exposed to steroids but significantly less exposed to 5ASA, immunomodulators and targeted therapies (mostly driven by the infantile-onset group) than older-onset children. Time to first hospitalization was shorter in the infantile group while yearly rate of hospitalizations after the second year and of outpatient visits after the year of diagnosis was similar across age groups. The number of surgeries were low and there were no significant differences between VEO-IBD and older onset IBD patients.
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| 6. |
- Mouratidou, Natalia, et al.
(författare)
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Identification of Childhood-Onset Inflammatory Bowel Disease in Swedish Healthcare Registers : A Validation Study
- 2022
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Ingår i: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 14, s. 591-600
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Swedish National Patient Register (NPR) is often used in observational studies of childhood-onset inflammatory bowel disease (IBD) (<18 years of age) and its subtypes, but the validity of previously used register-based algorithms for capturing childhood-onset IBD has never been examined.Methods: We identified a random sample of 233 individuals with at least two first ever diagnostic listings of IBD in the NPR between 2002 and 2014. We calculated the test characteristics for different register-based definitions of IBD and its subtypes using the Copenhagen criteria and the revised Porto criteria as gold standard, both based on medical chart review. We made assumptions of the occurrence of undiagnosed IBD in the general child population based on available literature.Results: Out of 233 individuals with at least two diagnostic listings of IBD, 216 had true IBD, resulting in a positive predictive value (PPV) = 93% (95% confidence interval (CI) 89-96), sensitivity = 88% (95% CI 83-92), specificity = 100% (95% CI 100-100), and negative predictive value (NPV) = 100% (95% CI 100-100). The PPV for the NPR-based definitions of IBD subtypes at time of first IBD diagnosis and at end of follow-up were 78% (95% CI 69-86) and 88% (95% CI 80-94), respectively, for Crohn's disease and 74% (95% CI 63-83) and 71% (95% CI 60-80), respectively, for ulcerative colitis.Conclusion: The validity of register-based definitions of childhood-onset IBD in the Swedish NPR is high and can be used to identify patients in observational research.
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