Interleukin-24 regulates mucosal remodeling in inflammatory bowel diseases.

BACKGROUND: Recently, increased interleukin (IL)-24 expression has been demonstrated in the colon biopsies of adult patients with inflammatory bowel disease (IBD). However, the role of IL-24 in the pathomechanism of IBD is still largely unknown. METHODS: Presence of IL-24 was determined in the samples of children with IBD and in the colon of dextran sodium sulfate (DSS) treated mice. Effect of inflammatory factors on IL24 expression was determined in peripheral blood (PBMCs) and lamina propria mononuclear cells (LPMCs). Also, the impact of IL-24 was investigated on HT-29 epithelial cells and CCD-18Co colon fibroblasts. Expression of tissue remodeling related genes was investigated in the colon of wild type (WT) mice locally treated with IL-24 and in the colon of DSS treated WT and Il20rb knock out (KO) mice. RESULTS: Increased amount of IL-24 was demonstrated in the serum and colon samples of children with IBD and DSS treated mice compared to that of controls. IL-1ß, LPS or H2O2 treatment increased the expression of IL24 in PBMCs and LPMCs. IL-24 treatment resulted in increased amount of TGF-ß and PDGF-B in HT-29 cells and enhanced the expression of extracellular matrix (ECM)-related genes and the motility of CCD-18Co cells. Similarly, local IL-24 treatment increased the colonic Tgfb1 and Pdgfb expression of WT mice. Moreover, expression of pro-fibrotic Tgfb1 and Pdgfb were lower in the colon of DSS treated Il20rb KO compared to that of WT mice. The disease activity index of colitis was less severe in DSS treated Il20rb KO compared to WT mice. CONCLUSION: Our study suggest that IL-24 may play a significant role in the mucosal remodeling of patients with IBD by promoting pro-fibrotic processes.

Helicobacter pylori Infection in Pediatric Patients Living in Europe: Results of the EuroPedHP Registry 2013 to 2016.

OBJECTIVES: The aim of the study was to assess clinical presentation, endoscopic findings, antibiotic susceptibility and treatment success of Helicobacter pylori (H. pylori) infected pediatric patients. METHODS: Between 2013 and 2016, 23 pediatric hospitals from 17 countries prospectively submitted data on consecutive H. pylori-infected (culture positive) patients to the EuroPedHP-Registry. RESULTS: Of 1333 patients recruited (55.1% girls, median age 12.6 years), 1168 (87.6%) were therapy naïve (group A) and 165 (12.4%) had failed treatment (group B). Patients resided in North/Western (29.6%), Southern (34.1%) and Eastern Europe (23.0%), or Israel/Turkey (13.4%). Main indications for endoscopy were abdominal pain or dyspepsia (81.2%, 1078/1328). Antral nodularity was reported in 77.8% (1031/1326) of patients, gastric or duodenal ulcers and erosions in 5.1% and 12.8%, respectively. Primary resistance to clarithromycin (CLA) and metronidazole (MET) occurred in 25% and 21%, respectively, and increased after failed therapy. Bacterial strains were fully susceptible in 60.5% of group A, but in only 27.4% of group B. Primary CLA resistance was higher in Southern and Eastern Europe (adjusted odds ratio [ORadj] = 3.44, 95% confidence interval [CI] 2.22-5.32, P < 0.001 and 2.62, 95% CI: 1.63-4.22, P < 0.001, respectively) compared with Northern/Western Europe. Children born outside Europe showed higher primary MET resistance (ORadj = 3.81, 95% CI: 2.25-6.45, P < 0.001). Treatment success in group A reached only 79.8% (568/712) with 7 to 14 days triple therapy tailored to antibiotic susceptibility. CONCLUSIONS: Peptic ulcers are rare in dyspeptic H. pylori-infected children. Primary resistance to CLA and MET is markedly dependent on geographical regions of birth and residence. The ongoing survey will show whether implementation of the updated ESPGHAN/NASPGHAN guidelines will improve the eradication success.

Role of microRNA-223 in the regulation of poly(ADP-ribose) polymerase in pediatric patients with Crohn's disease.

OBJECTIVES: Crohn's disease (CD) is a multifactorial disease, characterized by oxidant-induced tissue injury with a possible activation of poly(ADP-ribose) polymerase (PARP)-1. MicroRNAs (miRs) can offer a potential link between the genetic susceptibility, environmental and immunologic factors in the pathogenesis of CD. Previously, PARP-1 was identified as a direct target gene of miR-223 in an epithelial cell line. Our aim was to examine PARP activation and miR-223 expression in colonic biopsies of pediatric CD. To support our in vivo findings, the effect of lipopolysaccharide (LPS) on same parameters was examined in HT-29 colonic epithelial cell line. METHODS: Colonic biopsies were taken from patients with macroscopically inflamed and intact mucosa with CD and controls. LPS treated HT-29 cells served as our in vitro model. To analyze the PARP-1 expression real-time PCR, Western blot and immunohistochemical analyses were used. PARP-1 enzymatic activity was assessed on the basis of poly(ADP-ribosyl)ated proteins. Expression of miR-223 was examined by real-time PCR. RESULTS: PARP-1 mRNA and miR-223 expression was significantly elevated, however, the amount of PARP-1 protein and poly(ADP-ribose) was reduced in pediatric CD compared to controls. LPS incubation did not affect the expression of PARP-1 mRNA, however, decreased miR-223 expression, and enhanced PARP-1 activity. CONCLUSIONS: In our study, we showed that the expression of miR-223 is up-regulated and poly(ADP-ribosyl)ation is reduced in pediatric patients with CD. Moreover, we confirmed their opposite change in LPS treated epithelial cells, too. These data suggest that the hypofunctionality of PARP-1 may play a potential role in the pathomechanism of CD.

Incidence, Paris classification, and follow-up in a nationwide incident cohort of pediatric patients with inflammatory bowel disease.

OBJECTIVES: The aim of the study was to evaluate the incidence, baseline disease characteristics, and disease location based on the Paris classification in pediatric inflammatory bowel disease (IBD) in the Hungarian nationwide inception cohort. In addition, 1-year follow-up with therapy was analyzed. METHODS: From January 1, 2007 to December 31, 2009, newly diagnosed pediatric patients with IBD were prospectively registered. Twenty-seven pediatric gastroenterology centers participated in the data collection ensuring the data from the whole country. Newly diagnosed patients with IBD younger than 18 years were reported. Disease location was classified according to the Paris classification. RESULTS: A total of 420 patients were identified. The incidence rate of pediatric IBD was 7.48/105 (95% confidence interval [CI] 6.34/105-8.83/105). The incidence for Crohn disease (CD) was 4.72/105 (95% CI 3.82-5.79), for ulcerative colitis (UC) 2.32/105 (95% CI 1.71-3.09), and for IBD-unclassified 0.45/105 (95% CI 0.22-0.84). Most common location in CD was L3 (58.7%); typical upper gastrointestinal abnormalities (ulcer, erosion and aphthous lesion) were observed in 29.9%. Extensive colitis in patients with UC (E4, proximal to hepatic flexure) was the most common disease phenotype (57%), whereas only 5% of children had proctitis. A total of 18.6% of patients had ever severe disease (S1). Frequency of azathioprine administration at diagnosis was 29.5% in patients with CD, and this rate increased to 54.6% (130/238) at 1-year follow-up. In UC, only 3.3% received azathioprine initially, and this rate elevated to 22.5% (25/111). Use of corticosteroid decreased from 50% to 15.3% in patients with UC. Rate of bowel resection in patients with CD during the first year of follow-up was 5%. CONCLUSIONS: The incidence of pediatric IBD in Hungary was among the higher range reported. This is the first large, nationwide incident cohort analyzed according to the Paris classification, which is a useful tool to determine the characteristic pediatric CD phenotype.

Lymphocyte subsets in pediatric migraine.

Aseptic inflammation due to activated immune cells has been implicated in the pathomechanism of migraine. We measured the prevalence of regulatory T cells (Tregs), along with that of CD4(+)/CD8(+) lymphocytes and their Th1/Th2 commitment in pediatric migraine. Children and adolescents suffering from migraine without aura, migraine with aura and hemiplegic migraine ictally (n = 53, 27, and 20, respectively), also interictally (n = 33) were recruited and compared to 24 healthy children. Our results indicated comparable prevalence of Tregs, CD4(+) and Th1/Th2 committed cells. CD8(+) prevalence was lower, and CD4(+)/CD8(+) ratio was higher in ictal phase irrespective of the subtype of migraine. No association between CD8(+) prevalence and gender, body weight, disease onset and attack duration in migraine subtypes was found. CD8(+) prevalence was normal in patients in interictal phase. These results suggest the absence of major systemic alteration of adaptive immunity in children and adolescents suffering from migraine; however, a transient decrease of CD8(+) prevalence during the ictal phase was detected irrespective of the subtype of migraine.

[Changes of violent suicide attempts during the first two years of COVID-19 pandemic in Dr. Manninger Jeno National Traumatology Center, Hungary.] / A violens öngyilkossági kísérletek számának változása a COVID­19-járvány elso két évében a Dr. Manninger Jeno Baleseti Központban.

INTRODUCTION: During the pandemic years in Hungary, the completed suicide rates have risen significantly. Violent suicide attempts represent the majority of completed suicides. OBJECTIVE: In our study, we analyzed the change of the number of inpatients treated in Dr. Manninger Jeno National Traumatology Center between 2016 and 2021 due to violent suicide attempts, focusing on the trend in the first two years of the pandemic outbreak. METHOD: We used an interrupted time-series analysis with Prais-Winsten regression, controlling autoagressive and seasonal effects, to estimate the effect of the pandemic on the violent suicide attempt rates in our sample. RESULTS: In the first two pandemic years, the number of inpatients treated in Dr. Manninger Jeno National Traumatology Center due to violent suicide attempts rose significantly, compared to the previous years. After the rapid rise observed in 2020, decreasing numbers were seen in 2021. DISCUSSION AND CONCLUSION: Analyzing the numbers of violent suicide attempts between 2016 and 2021, an increase in the number of attempts was observed during the first two pandemic years. Orv Hetil. 2023; 164(26): 1003-1011.

Body composition, physical activity, and quality of life in pediatric patients with inflammatory bowel disease on anti-TNF therapy-an observational follow-up study.

BACKGROUND: Poor outcome of inflammatory bowel disease (IBD) is associated with malnutrition. Our aim was to compare body composition (BC) and physical activity (PA) between patients with IBD and healthy controls, and to assess the changes in BC, PA and health related quality of life (HRQoL) in children with IBD during anti-TNF therapy. METHODS: 32 children with IBD (21 with Crohn's disease (CD), (age: 15.2 ± 2.6 years, 9 male) and 11 with ulcerative colitis (UC), (age: 16.4 ± 2.2 years, 5 male) participated in this prospective, observational follow up study conducted at Semmelweis University, Hungary. As control population, 307 children (age: 14.3 ± 2.1) (mean ± SD) were included. We assessed BC via bioelectric impedance, PA and HRQoL by questionnaires at initiation of anti-TNF therapy, and at two and six months later. The general linear model and Friedman test were applied to track changes in each variable. RESULTS: During follow-up, the fat-free mass Z score of children with CD increased significantly (-0.3 vs 0.1, p = 0.04), while the BC of patients with UC did not change. PA of CD patients was lower at baseline compared to healthy controls (1.1 vs. 2.4), but by the end of the follow up the difference disappeared. CONCLUSIONS: The fat-free mass as well as PA of CD patients increased during the first six months of anti-TNF treatment. As malnutrition and inactivity affects children with IBD during an important physical and mental developmental period, encouraging them to engage in more physical activity, and monitoring nutritional status should be an important goal in patient care.

Adaptive immunity in ankylosing spondylitis: phenotype and functional alterations of T-cells before and during infliximab therapy.

Our aim was to assess the phenotype of T-cell subsets in patients with ankylosing spondylitis (AS), a chronic inflammatory rheumatic disease. In addition, we also tested short-term T-cell activation characteristics. Measurements were done in 13 AS patients before and during the intravenous therapy with anti-TNF agent infliximab (IFX). Flow cytometry was used to determine T-cell subsets in peripheral blood and their intracellular signaling during activation. The prevalence of Th2 and Th17 cells responsible for the regulation of adaptive immunity was higher in AS than in 9 healthy controls. Although IFX therapy improved patients' condition, immune phenotype did not normalize. Cytoplasmic and mitochondrial calcium responses of CD4+ and CD8+ cells to a specific activation were delayed, while NO generation was increased in AS. NO generation normalized sooner upon IFX than calcium response. These results suggest an abnormal immune phenotype with functional disturbances of CD4+ and CD8+ cells in AS.

Pancreatic autoantibodies and autoantibodies against goblet cells in pediatric patients with inflammatory bowel disease.

BACKGROUND: Significance of pancreatic autoantibodies determined by using exocrine pancreas (PAB) and antibodies against recombinant pancreas antigen (rPAB), as well as the importance of autoantibodies against goblet cells (GAB), is not known in pediatric patients with inflammatory bowel disease (IBD). Our aim was to determine the complex analysis of PAB, rPAB, GAB, antibodies against Saccharomyces cerevisiae, and perinuclear components of neutrophils in pediatric patients with IBD. Moreover, association with NOD2/CARD15 and disease phenotype was determined. METHODS: A total of 152 pediatric patients (median age 13.9 years) with IBD (103 patients with Crohn disease [CD] and 49 patients with ulcerative colitis [UC]) and 104 controls were included. Serum autoantibodies were determined by indirect immunofluorescence assay. NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The presence of PAB and rPAB was significantly higher in CD (34% and 35.9%) and in UC (20.4% and 24.5%) compared with pediatric control cohort (0% and 0%, P<0.0001). In addition, GAB positivity was significantly increased in patients with UC in comparison with CD and controls, respectively (UC, 12.2%; CD, 1.9%; controls, 1.9%; P=0.02). Specificity of PAB and rPAB was 100%; however, sensitivity was low. The combination of PAB and/or antibodies against Saccharomyces cerevisiae/perinuclear components of neutrophils improved the sensitivity of serological markers in CD (87.4%) and in UC (79.6%); specificities were 89.3% and 93.2%, respectively. Pancreatic autoantibodies (PAB, rPAB) and GAB were not related to clinical presentation, medical therapy, or need for surgery in CD or in UC. CONCLUSIONS: Pancreatic autoantibodies and GAB were specific for IBD, but the sensitivity was limited as well because there was lack of correlation with clinical phenotype. Combinations of these antibodies have shown increased sensitivity; therefore, it may be recommended in the diagnostic procedure of IBD.

[The role of intestinal alkaline phosphatase in pediatric inflammatory bowel and celiac diseases]. / Az intestinalis alkalikus foszfatáz szerepe gyermekkori gyulladásos bélbetegségben és coeliakiában.

Intestinal alkaline phosphatase enzyme plays a pivotal role in the maintenance of intestinal mucosal barrier integrity with the detoxification capacity of lipopolysaccharide, the ligand of Toll-like receptor 4. The inappropriate immune responses and the damage of the mucosal barrier may contribute to the initiation of inflammatory bowel and celiac diseases. In the inflamed colonic mucosa of children with inflammatory bowel disease and in the duodenal mucosa of newly diagnosed children with celiac disease, the decreased intestinal alkaline phosphatase and increased Toll-like receptor 4 protein expression may generate enhanced lipopolysaccharide activity, which may strengthen tissue damaging processes. The enhancement of intestinal alkaline phosphatase activity in an animal model of colitis and in therapy resistant, adult patients with ulcerative colitis reduced the symptoms of intestinal inflammation. In accordance with these results, the targeted intestinal administration of the enzyme in the two examined disorders may be a supplemental therapeutic option in the future.

The gastrointestinal effects of COVID­19 infection during childhood and among the children affected with inflammatory bowel disease / A COVID-19-fertozés gastrointestinalis hatásai gyermekkorban és a gyulladásos bélbeteg gyermekekben.

Összefoglaló. A SARS-CoV-2-infekció változatos kórlefolyású, a gyermekpopulációban növekvo incidenciát mutató fertozés. Ebben a korcsoportban a felnottekkel szemben sokkal gyakrabban tapasztalhatók gasztroenterológiai tünetek a betegség során, 18-32%-ban jelentkezik legalább egy szimptóma. Ezek nem specifikusak, gyakran megegyezhetnek a virális enteritisek, a gyulladásos bélbetegségek vagy a vakbélgyulladás tüneteivel. A gyermekkori SARS-CoV-2-infekciónak egy viszonylag ritkán megjeleno, de súlyos, akár életveszélyes szövodménye a gyermekkori sokszervi gyulladásos szindróma (multisystem inflammatory syndrome in children, MIS-C). Ilyenkor a gastrointestinalis tünetek gyakorisága 60-100%-ra no, sok esetben akut has benyomását keltve. A jelenlegi kutatások eredményei alapján a gyulladásos bélbeteg gyerekek az alapbetegségük miatt nincsenek nagyobb veszélynek kitéve az átlagpopulációhoz képest a COVID-19-fertozés szempontjából. A terápiájukban alkalmazott gyógyszereik közül a nagy dózisú szteroidkezelés okoz nagyobb kockázatot a megfertozodésre, illetve ebben az esetben a súlyosabb kórlefolyásra. Az éppen remisszióban lévo gyulladásos bélbetegek fenntartó terápiájának módosítások nélküli folytatása javasolt, kiemelt figyelmet fordítva a biológiai terápiák idoben történo, megszakítás nélküli alkalmazására. Törekedni kell a személyes vizitek számának csökkentésére a pandémia idején, ezek telemedicinával történo helyettesítése javasolt. A halasztható endoszkópos vizsgálatok noninvazív vizsgálómódszerekkel történo átmeneti kiváltása részesítendo elonyben a betegség aktivitásának, a terápia hatékonyságának megítélésére. A gyulladásos bélbetegségben szenvedo gyermekek COVID-19 elleni védooltása javasolt, jelenleg minden elérheto oltóanyag alkalmazható náluk (az élo ágenst tartalmazó vakcinák ellenjavalltak). Immunmoduláns, szteroid- vagy anti-tumornekrózisfaktor (TNF)-alfa-terápia esetén az oltás lehetséges csökkent hatékonyságával kell számolni. Orv Hetil. 2022; 163(6): 214-221. Summary. The SARS-CoV-2 infection is showing high variety in the disease course, with a constantly increasing incidence among the pediatric population. In this age group, at least one gastrointestinal symptom appears in 18-32% of the cases, showing a significant difference compared to the adult population. The gastrointestinal signs of COVID-19 are not specific, can mimic the symptoms of viral enteritis, inflammatory bowel diseases or acute appendicitis. The multisystem inflammatory syndrome in children (MIS-C) is a rather rare, but serious complication of the pediatric COVID-19 disease: in these cases, the incidence of the gastrointestinal symptoms is increased up to 60-100%, often observed as acute abdomen. Based on recent researches, patients with inflammatory bowel diseases (IBD) are shown to have the same risk in developing COVID-19 infection compared to the normal population: in their medications, the high dose steroid treatment is proved to increase the risk of infection or to make the disease course more serious. The treatment of patients with IBD should be continued without any changes (when the disease is in remission). The use of biologics should be done with special care, with more attention keeping the schedule and the continuity. It is advised to minimise the number of personal visits during the pandemic, they should be substituted with telemedicine. The postponable endoscopic examinations should be temporarily redeemed by non-invasive methods for screening the disease activity and the efficacy of the treatment. The vaccination against COVID-19 is advised in the population with IBD. All vaccines currently available are usable in this patient group (the use of vaccines containing live agents are contraindicated). In the case of patients treated with immunmodulators, steroids or anti-tumor necrosis factor (TNF) alpha, a possible lower efficacy can be expected after the vaccination. Orv Hetil. 2022; 163(6): 214-221.

Joint involvement, disease activity and quality of life in pediatric Crohn's disease - a cross-sectional study.

BACKGROUND: Few published data describe how joint involvement, the most prevalent extraintestinal manifestation, affects quality of life (QoL) of children with Crohn's disease (CD). Arthritis and arthralgia rates in pediatric CD patients are reportedly 3-24% and 17-22%, respectively, but studies on pre-emptive and systematic screening of joint involvement with detailed musculoskeletal rheumatological exam are lacking. More detailed data collection on joint involvement improves our understanding of how arthropathy relates to disease activity and QoL measured by the Pediatric CD Activity Index (PCDAI) and IMPACT-III questionnaire. Our study aims were to assess joint involvement in pediatric CD and correlate it with the PCDAI and IMPACT-III. METHODS: In this cross-sectional, observational study, a pediatric gastroenterologist assessed consecutively-seen pediatric CD patients at a tertiary care center. Patients were screened for prevalence of current and previous arthropathy, including arthritis, enthesitis and arthralgia. A single experienced pediatric rheumatologist evaluated detailed musculoskeletal history, joint status, and modified Juvenile Arthritis Multidimensional Assessment Reports (JAMAR). PCDAI, IMPACT-III, sacroiliac MRI, and HLA-B27 genetic testing were also completed. RESULTS: A total of 82 (male:female, 1.2:1; age, 13.7 ± 3.2 years) patients were involved in this study. Mean disease duration at time of study was 21.6 ± 21 months; eight of the patients were newly-diagnosed. Of the 82 patients, 29 (35%) had evidence of arthritis; for 24 of those, this was revealed by physical exam during cross-sectional screening, and by prior documentation for the remaining five patients. Joint examination confirmed active arthritis in 8/24 (33%), active enthesitis in 1/24 (4%), and evidence of previous arthritis in 15/24 (62.5%) patients. Hip (41%) and knee (38%) joints were most commonly affected. Cumulative incidence of arthralgia was 48% (39/82), and 46% (18/39) of those patients had only arthralgia without arthritis, usually affecting the knee. Axial involvement was present in 10/82 (12%) patients. Joint involvement correlated with more severe CD disease activity, specifically higher PCDAI and lower IMPACT-III scores, and increased requirement for infliximab treatment. Sacroiliitis and HLA-B27 positivity were insignificant factors in this cohort. CONCLUSIONS: When a rheumatologist performed the assessment, joint involvement in pediatric CD was more prevalent than previously reported, in this cross-sectional study. Arthritis was associated with more severe CD disease activity and lower QoL.

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.

Immune phenotype of children with newly diagnosed and gluten-free diet-treated celiac disease.

BACKGROUND: Recent data suggest the involvement of both the adaptive and the innate immune system in celiac disease (CD). However, little is known about the immune phenotype of children with CD and its alteration upon dietary intervention. AIMS: We characterized the prevalence of major interacting members of the adaptive and innate immune system in peripheral blood of newly diagnosed children with CD and tested its alteration with the improvement of clinical signs after the introduction of gluten-free diet (GFD). METHODS: Peripheral blood was taken from ten children with biopsy-proven CD at the time of diagnosis and after the resolution of clinical symptoms following GFD. As controls, 15 children with functional abdominal pain were enrolled. The prevalence of the cells of adaptive and innate immunity was measured with labeled antibodies against surface markers and intracellular FoxP3 using a flow cytometer. RESULTS: Patients with CD were found to have lower T helper, Th1 and natural killer (NK), NKT and invariant NKT cell prevalence and with higher prevalence of activated CD4(+) cells, myeloid dendritic cells (DC) and Toll-like receptor (TLR) 2 and TLR-4 positive DCs and monocytes compared to controls. After resolution of symptoms on GFD, the majority of these changes normalized, although the prevalence of NK and NKT cell, DC and TLR-2 expressing DCs and monocytes remained abnormal. CONCLUSIONS: The immune phenotype in childhood CD indicates the implication of both adaptive and innate immune system. The normalization of immune abnormalities occurs on GFD, but the kinetics of this process probably differs among different cell types.

Serum maternal hepcidin levels 3 days after delivery are higher compared to those measured at parturition.

AIM: Our aim was to investigate the levels of hepcidin at parturition and 3 days after delivery and to relate hepcidin levels to parameters of iron homeostasis. MATERIALS AND METHODS: We measured hepcidin levels with mass spectrometry in serum samples of 38 term pregnant women taken just prior to and 3 days after vaginal delivery (n = 23) or cesarean section (CS) (n = 15). Hepcidin levels were related to iron homeostasis parameters and interleukin (IL)-6 levels. Parameters measured before and after delivery were compared with the Wilcoxon test. RESULTS: Serum iron levels (median, interquartile range) decreased (14.3, 9.6-21.1 vs. 8.9, 6.8-11.5 µmol/L, P < 0.01), while hepcidin levels increased (2.73, 2.2-3.45 vs. 10.62, 6.70-15.89 µg/L, P < 0.01) by the third day after parturition compared to those measured before delivery. IL-6 levels were comparable before and after delivery. No direct association between serum hepcidin and iron homeostasis parameters or IL-6 levels was found. CONCLUSIONS: Factors triggering hepcidin synthesis dominate 3 days after delivery. Studies are needed to assess the contribution of hepcidin to iron homeostasis during the periparturition period.

Pregnancy rates with recombinant versus urinary human chorionic gonadotropin in in vitro fertilization: an observational study.

Randomized clinical trials (RCTs) demonstrated the equal efficacy of urinary human chorionic gonadotropin (uhCG) and recombinant hCG (rhCG) products in in vitro fertilisation (IVF). However, limitations inherent with RCTs necessitate the reinforcement of RCT results in real-life. We retrospectively analyzed pregnancies after treatment with rhCG and uhCG products (n = 391, and 96, resp.). We found that laboratory-verified pregnancy occurred more frequently in rhCG patients than in those on uhCG (43% versus 30%, P = 0.02). The association remains significant (P = 0.002) after its adjustment for clinical characteristics. The prevalence of laboratory-verified pregnancies was higher with GnRH agonist use (P = 0.012) and BMI under 30 kg/m(2) (P = 0.053) while decreased the age (P = 0.014) and the number of previous failed attempts (P = 0.08). Similar (but not significant) trends were observed with rates of pregnancy filled the 24th week. These results reinforce RCTs supporting the notion that rhCG is more efficient as uhCG during IVF.

Significance and effects of prenatal and postnatal microbiome in the period of early individual development and options for interventional treatment / A praenatalis és postnatalis mikrobiom jelentosége és hatásai a korai egyedfejlodés idoszakában és az intervenciós kezelés lehetoségei.

Összefoglaló. A humán mikrobiom az emberi szervezetben és az emberi testfelszínen élo mikrobaközösségek összessége, amelyek többsége a gyomor-bél rendszerben él. Ezek a mikrobaközösségek számos és sokféle baktériumot tartalmaznak, gombákat, vírusokat, archeákat és protozoonokat. Ez a mikrobiális közösség, vagy mikrobiota, a gazdaszervezetben nagyrészt egymással kölcsönösségi viszonyban tenyészik, és gondoskodik a bélben a tápanyagok anyagcseréjérol, kalibrálja az anyagcsere-muködést, tanítja az immunrendszert, fenntartja a közösség integritását, és véd a kórokozók ellen. A majdan megszületendo magzat a megfelelo tápanyagellátását az anyai véráramból kapja, és így az anyai szervezetben a mikrobiota indukálta baktériumkomponensek vagy metabolitok hatékonyan átvihetok a magzatba. Az anyai mikrobiális közösségek - ideértve a praenatalis bélrendszeri, hüvelyi, száj- és bormikrobiomot - a terhesség alatt valójában kifejezett változásokon mennek keresztül, amelyek befolyásolhatják az egészség megorzését, és hozzájárulhatnak a közismert betegségek kialakulásához. A magzat nem steril, és immunológiai szempontból sem naiv, hanem az anya révén környezeti ingerek hatásaitól befolyásolva kölcsönhatásba lép az anyai immunrendszerrel. Számos anyai tényezo - beleértve a hormonokat, a citokineket és a mikrobiomot - módosíthatja az intrauterin környezetet, ezáltal befolyásolva a magzati immunrendszer fejlodését. A fokozott stresszben élo anyák csecsemoinél nagyobb az allergia és a gyomor-bél rendszeri rendellenességek aránya. A várandós étrendje is befolyásolja a magzati mikrobiomot a méh közvetítésével. A bélflóránk, vagyis a mikrobiom, a belünkben élo mikrobák összessége és szimbiózisa, amelynek kényes egyensúlya már csecsemokorban kialakul, és döntoen meghatározza az intestinalis barrier és a bélasszociált immunrendszer muködését. A probiotikumok szaporodásához szükséges prebiotikummal is befolyásolható a bélflóra. A pre- és a probiotikum kombinációja a szimbiotikum. Az anyatej a patogénekkel szemben protektív hatású, részben azáltal, hogy emeli a Bifidobacterium-számot az újszülött bélflórájában. A dysbiosis a kommenzális, egészséges bélflóra megváltozása. Ennek szerepét feltételezik funkcionális gastrointestinalis kórképekben, egyre több pszichiátriai és neurológiai kórképben is, mint az autizmus-spektrumzavar. Orv Hetil. 2021; 162(19): 731-740. Summary. The human microbiome is the totality of microbe communities living in the human body and on the human body surface, most of which live in the gastrointestinal tract. These microbe communities contain many and varied bacteria, fungi, viruses, archaea and protozoa. This microbial community or microbiota in the host is largely reciprocal and takes care of nutrient metabolism in the gut, calibrates metabolism, teaches the immune system, maintains community integrity, and protects against pathogens. The fetus to be born is adequately supplied with nutrients from the maternal bloodstream, and thus microbial-induced bacterial components or metabolites can be efficiently transferred to the fetus in the maternal body. Maternal microbial communities, including prenatal intestinal, vaginal, oral, and dermal microbiomes, actually undergo pronounced changes during pregnancy that can affect health maintenance and contribute to the development of well-known diseases. The fetus is not sterile or immunologically naïve, but interacts with the maternal immune system through the effects of environmental stimuli through the mother. Many maternal factors, including hormones, cytokines, and the microbiome, can modify the intrauterine environment, thereby affecting the development of the fetal immune system. Infants of mothers under increased stress have higher rates of allergies and gastrointestinal disorders. The diet of the gravida also affects the fetal microbiome through the uterus. Our intestinal flora, or microbiome, is the totality and symbiosis of the microbes living in them, the delicate balance of which is established in infancy and decisively determines the functioning of the intestinal barrier and the intestinal associated immune system. The prebiotic required for the proliferation of probiotics can also affect the intestinal flora. The combination of pre- and probiotic is symbiotic. Breast milk has a protective effect against pathogens, in part by raising the number of Bifidobacteria in the intestinal flora of the newborn. Dysbiosis is a change in the commensal, healthy gut flora. Its role is hypothesized in functional gastrointestinal disorders, as well as in more and more psychiatric and neurological disorders such as the autism spectrum disorder. Orv Hetil. 2021; 162(19): 731-740.