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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.
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COVID-19 , Traumatología , Humanos , Intento de Suicidio , Pandemias , Hungría/epidemiología , Violencia , COVID-19/epidemiologíaRESUMEN
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.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Desnutrición , Humanos , Masculino , Niño , Adolescente , Estudios de Seguimiento , Inhibidores del Factor de Necrosis Tumoral , Calidad de Vida , Estudios Prospectivos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/complicaciones , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/complicaciones , Composición Corporal , Desnutrición/complicacionesRESUMEN
Background: Patients with phenylketonuria (PKU) must maintain a lifelong natural protein-restricted diet to prevent neuro-cognitive damage. Early diagnosis is established with newborn screening, with diet subsequently controlled by regular phenylalanine (Phe) monitoring. During the COVID-19 pandemic, significant lockdown measures were introduced that may have influenced the above. Aim of our study: To establish whether the diagnosis was delayed in neonates during the pandemic. In addition, metabolic control was further assessed during the COVID-19 pandemic era (CE) compared to the same period a year prior (non-COVID-19 era, NCE). The lockdown periods (LD) were also compared with unrestricted periods (URP). Patients methods: Six neonates born during the CE and eight neonates born during NCE were included in the newborn screening analysis. Seventy-two classical PKU patients aged 2-18 years and categorized as children (2-12 years; 51 patients) and adolescents (>13 years; 21 patients) were included in the metabolic control analysis. The frequency of dried blood spot (DBS) sampling and Phe levels were assessed according to the different periods. Results: There was no diagnostic or therapeutic delay in reaching the recommended Phe range in neonates born during CE compared to those born in NCE (median [interquartile range, IQR]: 23.5 [22.5-24] vs. 22 [18.0-27] days, p = NS). The cumulative DBS sampling frequency in children increased by 9.9% in the CE while no change was noted in the adolescent group. The median Phe level increased significantly in both age groups in the CE, but remained within the recommended target range. During CE, changes in Phe levels differed in the two age groups: children had the highest median Phe in the second lockdown period (LD2), while the adolescents had an increased Phe in URP.There were significant negative correlations between DBS sampling frequencies and Phe levels in both age groups in NCE (children: r - 0.43, p = 0.002; adolescents r = -0.37, p = 0.012), and in adolescents in CE (r = -0.62, p = 0.006). Conclusion: The pandemic did not impact newborn metabolic screening. The increased frequency of DBS sampling in CE and good target Phe levels suggest a better compliance in a very sensitive period. Since many factors may impact metabolic control in the different age groups, further studies are needed to analyse their respective role.
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BACKGROUND: Phenylketonuria (PKU) is an inherited error of metabolism, screened at 48-72 h of life since 1975 in Hungary. The patients have to keep a strict lifelong protein-restricted diet, resulting in PKU and its treatment can lead to social and financial burdens. The current study aimed to evaluate the health-related quality of life (HRQoL) of children living with PKU. PATIENTS AND METHODS: A single-centre, cross-sectional, observational study was conducted at the Center of Newborn Screening and Inherited Metabolic Disorders of Budapest, Hungary, using the PKU-quality of life (PKU-QoL) questionnaire. Responses of 59 parents and 11 teenagers were collected. Numerous aspects regarding HRQoL were analysed according to clinical compliance and severity. The patients were classified into groups with good or suboptimal adherence based on regular phenylalanine (Phe) values. The online officially translated versions of the adolescent or parental PKU-QoL questionnaire were used and analysed anonymously. Differences in HRQoL were compared - PKU vs. Hyperphenylalaninaemia (HPA) and good vs. suboptimal adherence. RESULTS: Twenty-five of 32 examined parameters had no or little impact on HRQoL. The most frequently reported symptom was irritability. Food enjoyment was the most impacted domain, with a major severity score in the adolescent group (median 62,5, IQR: 25-75). The emotional impact was scored at moderate severity by both the adolescents and parents. Classical PKU patients with good metabolic control were more frequently tired than HPA patients (0,0027). The group with poor metabolic adherence showed more frequent tiredness (p = 0,03), slow thinking (p = 0,018) and anxiety (p = 0,015). CONCLUSION: Overall, our patients showed an excellent HRQoL; most domains (29/36) were reported as little/no impacted. Worse QoL was found in patients with suboptimal metabolic control. Particular attention should be paid to the emotional health of PKU patients.
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Összefoglaló. A glutén, alimentáris környezeti antigénként, különbözo szervrendszereket érinto autoimmun betegségeket tud kiváltani. A kórképek hátterében a gluténtolerancia veleszületett hiánya vagy az élet során bekövetkezo elvesztése áll. A gluténindukált autoimmun betegségek között a leggyakoribb a coeliakia, melyet különbözo súlyosságú enteropátia jellemez, és melynek a szöveti, 2-es típusú transzglutamináz az autoantigénje. A coeliakia extraintestinalis tünetei között azonban néha olyan bor- és idegrendszeri kórképek jellegzetességei is megtalálhatók, melyek hátterében további transzglutamináz-autoimmunitás kialakulása áll. Idesorolható a hevesen viszketo, polimorf autoimmun borbetegség, a dermatitis herpetiformis (transzglutamináz-3-autoimmunitás) és a centrális és/vagy perifériás neurológiai károsodások egy jellegzetes csoportja (transzglutamináz-6-autoimmunitás). Az indukált autoimmunitás reverzibilis, a szigorúan tartott gluténmentes diéta mellett a coeliakia és a bortünetek elmúlnak, de az idegrendszeri tünetek egy része maradandó. Az elmúlt évtizedben beszámoltak gluténérzékeny, transzglutamináz-6-pozitív, nem coeliakiás (transzglutamináz-2-negatív) betegekrol is. A gluténszenzitivitás sokféle megjelenését ma is erosen kutatják. Fontos a korai felismerés és a kórképek interdiszciplináris szemléletu kezelése. A coeliakia családi szurovizsgálatokkal való korai felismerése és a tünetmentes egyének diétás kezelése is nagy jelentoségu a gluténérzékenység által kiváltott hiányállapotok és a társuló egyéb betegségek kialakulásának megelozésében. Orv Hetil. 2021; 162(28): 1107-1118. Summary. Autoimmune diseases induced by digestion of gluten, an environmental antigen, can affect different organ systems. The diseases develop in individuals with congenital or acquired loss of gluten tolerance for life. Amongst the gluten-induced autoimmune diseases, celiac disease is the most common one, characterized by an enteropathy of varying severity. Here the target autoantigen is tissue (type 2) transglutaminase. While the extraintestinal manifestations of celiac disease are complex, they may include characteristics of certain skin and nervous system disorders that develop due to additional transglutaminase autoimmunities. Such diseases are the severely pruritic, polymorphic autoimmune skin disease, dermatitis herpetiformis due to epidermal (type 3) transglutaminase autoimmunity, and a distinctive group of gluten-sensitive neuropathies with central and/or peripheral neurological involvement caused by type 6 transglutaminase autoimmunity. While the celiac and skin autoimmune diseases gradually get into remission under a strict gluten-free diet, some neurological symptoms may persist. In the last decade, gluten-induced transglutaminase 6 positive but non-celiac (transglutaminase 2 negative) patients were reported. Today, various manifestations of gluten sensitivity are under extensive research. Early detection and interdisciplinary treatment of these disorders are important. Family screenings are of particular relevance in early recognition and dietary treatment of latent disease forms in order to prevent enteropathy-induced, malabsorption-related and other associated co-morbidities. Orv Hetil. 2021; 162(28): 1107-1118.
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Autoinmunidad , Glútenes , Glútenes/efectos adversos , HumanosRESUMEN
Eosinophilic colitis (EC) is a common cause of haematochezia in infants and young children. The exact pathomechanism is not understood, and the diagnosis is challenging. The role of microRNAs as key class of regulators of mRNA expression and translation in patients with EC has not been explored. Therefore, the aim of the present study was to explore the miRNA profile in EC with respect to eosinophilic inflammation. Patients enrolled in the study (n = 10) had persistent rectal bleeding, and did not respond to elimination dietary treatment. High-throughput microRNA sequencing was carried out on colonic biopsy specimens of children with EC (EC: n = 4) and controls (C: n = 4) as a preliminary screening of the miRNA profile. Based on the next-generation sequencing (NGS) results and literature data, a potentially relevant panel of miRNAs were selected for further measurements by real-time reverse transcription (RT)-PCR (EC: n = 14, C: n = 10). Validation by RT-PCR resulted in significantly altered expression of miR-21, -31, -99b, -125a, -146a, -184, -221, -223, and -559 compared to controls (p ≤ 0.05). Elevation in miR-21, -99b, -146a, -221, and -223 showed statistically significant correlation to the extent of tissue eosinophilia. Based on our results, we conclude that the dysregulated miRNAs have a potential role in the regulation of apoptosis by targeting Protein kinase B/Mechanistic target of rapamycin (AKT/mTOR)-related pathways in inflammation by modulating Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related signalling and eosinophil cell recruitment and activation, mainly by regulating the expression of the chemoattractant eotaxin and the adhesion molecule CD44. Our results could serve as a basis for further extended research exploring the pathomechanism of EC.
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Colitis/metabolismo , Colon/metabolismo , Eosinofilia/metabolismo , MicroARNs/genética , Apoptosis , Niño , Preescolar , Colitis/genética , Colitis/patología , Colon/patología , Eosinofilia/genética , Eosinofilia/patología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , MicroARNs/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , TranscriptomaRESUMEN
AIM: Although Crohn's disease (CD) is an extensively investigated autoimmune condition, knowledge on early phase activation of lymphocytes, especially CD8+ Tc cells is scarce. Our aim was to investigate the calcium influx characteristics of CD8+ cells upon activation as well as the expression and function of Kv1.3 and IKCa1 lymphocyte potassium channels. METHODS: We took peripheral blood from 12 healthy controls, 23 CD children on conventional therapy and 6 severe CD children before and after infliximab therapy. Intracellular calcium levels were monitored in CD8+ lymphocytes using flow cytometry. RESULTS: In CD treated with standard therapy calcium response during activation was elevated. This was not affected by the inhibition of Kv1.3 or IKCa1 potassium channels. After the switch to infliximab potassium channel function and expression of CD8+ lymphocytes were comparable to healthy controls in severe CD. CONCLUSION: Calcium handling of CD8+ lymphocytes is altered in pediatric CD, which is normalized by infliximab therapy.
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Linfocitos T CD8-positivos/inmunología , Enfermedad de Crohn/inmunología , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/metabolismo , Canal de Potasio Kv1.3/metabolismo , Activación de Linfocitos , Adolescente , Antirreumáticos/uso terapéutico , Circulación Sanguínea , Señalización del Calcio , Niño , Enfermedad de Crohn/tratamiento farmacológico , Femenino , Humanos , Infliximab/uso terapéutico , Masculino , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
INTRODUCTION: MicroRNAs (miRs) came recently into focus as promising novel research targets offering new insights into the pathogenesis of inflammatory bowel diseases (IBD). AIMS: The aim of our study was to identify a pediatric IBD (pIBD) characteristic miR profile serving as potential Crohn's disease (CD) and ulcerative colitis (UC) specific diagnostic pattern and to further analyze the related target genes. METHODS: Small RNA sequencing was performed on inflamed and intact colonic biopsies of CD, and control patients. Selected miRs were further investigated by RT-PCR, complemented with an UC group, in order to address the differential diagnostic potential of miRs in the two IBD subtypes. To analyze network connection of differentially expressed miRs and their target genes MiRTarBase database and previous transcriptome sequencing data from pediatric patient groups were used. RESULTS: Sequencing analysis identified 170 miRs with altered expression. RT-PCR analysis revealed altered expression of miR-31, -125a, -142-3p, and -146a discriminating between the inflamed mucosa of CD and UC. In the intact mucosa of CD patients the expression of miR-18a, -20a, -21, -31, -99a, -99b, -100, -125a, -126, -142-5p, -146a, -185, -204, -221, and -223 was elevated compared to the controls. The expression of miR-20a, -204 and -221 was elevated exclusively in the intact region of CD patients compared to the controls. Enrichment analysis identified main IBD-related functional groups. CONCLUSIONS: We demonstrated a characteristic colonic miR pattern in pIBD that could facilitate deeper understanding of the pathomechanism of IBD and may serve as a diagnostic tool.
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Colon/patología , Regulación de la Expresión Génica , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/genética , MicroARNs/genética , Adolescente , Niño , Femenino , Perfilación de la Expresión Génica , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Hungría , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/patología , Masculino , MicroARNs/metabolismo , PediatríaRESUMEN
AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn's disease (CD) and the effect of transforming growth factor-ß (TGF-ß) on these miRs in duodenal epithelial and fibroblast cells. METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-ß (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well. RESULTS: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 ± 0.50 vs CD intact: 0.62 ± 0.26, P ≤ 0.01) and to the control group (CD inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, P ≤ 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 ± 1.02 vs CONTROL: 1.00 ± 0.40, P ≤ 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-ß treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-ß: 0.7 ± 0.083 vs CONTROL: 1 ± 0.09, P ≤ 0.05) and also the expression of miR-146a (TGF-ß: 0.67 ± 0.04 vs CONTROL: 1 ± 0.15, P ≤ 0.01) and miR-155 (TGF-ß: 0.72 ± 0.09 vs CONTROL: 1 ± 0.06, P ≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-ß treatment did not influence the expression of miR-122. CONCLUSION: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-ß plays an important role in the regulation of the expression of these miRs.
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Enfermedad de Crohn/genética , Duodeno/metabolismo , Mucosa Intestinal/metabolismo , MicroARNs/genética , Adolescente , Niño , Enfermedad de Crohn/metabolismo , Duodeno/citología , Duodeno/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Técnicas In Vitro , Mucosa Intestinal/citología , Mucosa Intestinal/efectos de los fármacos , Masculino , MicroARNs/efectos de los fármacos , MicroARNs/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
OBJECTIVE: Crohn's disease is a chronic inflammation of the gastrointestinal tract with an abnormal immune phenotype. We investigated how intracellular calcium kinetics of Th1 and Th2 lymphocytes alter upon specific inhibition of Kv1.3 and IKCa1 channels in pediatric Crohn's disease. STUDY DESIGN: Blood was taken from 12 healthy and 29 Crohn's disease children. Of those, 6 were switched to infliximab and re-sampled after the 4th infliximab treatment. Intracellular calcium levels were monitored using flow cytometry in the presence or absence of specific inhibitors of Kv1.3 and IKCa1 potassium channels. RESULTS: In Crohn's disease treated with standard therapy, calcium response during activation was higher than normal in Th2 cells. This was normalized in vitro by inhibition of Kv1.3 or IKCa1 potassium channels. After the switch to infliximab, potassium channel function and expression in Th2 lymphocytes were comparable to those in Th1 cells. CONCLUSION: These results may indicate that potassium channels are potential immune modulatory targets in Crohn's disease.
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Calcio/metabolismo , Enfermedad de Crohn/metabolismo , Fármacos Gastrointestinales/uso terapéutico , Infliximab/uso terapéutico , Células Th2/metabolismo , Adolescente , Niño , Enfermedad de Crohn/tratamiento farmacológico , Femenino , Humanos , Activación de Linfocitos/efectos de los fármacos , Masculino , Canales de Potasio/efectos de los fármacos , Células Th2/efectos de los fármacosRESUMEN
BACKGROUND: Evidence suggests the central role of tumor necrosis factor (TNF)-α in the pathomechanism of inflammatory bowel disease (IBD); however, its effect on epigenetic factors, including small non-coding microRNAs (miRs), is less known. Our present aim was the comparative investigation of the expression of TNF-α and immune response-related miRs in children with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Fresh-frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) biopsies were used to analyze the expression of miR-146a, -155, -122, and TNF-α by real-time reverse transcription polymerase chain reaction in macroscopically inflamed (CD: 12 FFPE and 24 FF; UC: 10 FF) and intact (CD: 12 FFPE; 14 FF) colonic biopsies of children with IBD and controls (16 FFPE; 23 FF). The expression of miR-146a, -155, and -122 was also determined in TNF-α-treated HT-29 colonic epithelial cells. RESULTS: Increased expression of TNF-α was observed in the colonic mucosa of children with CD and UC in comparison with controls. Expression of miR-146a and -155 was higher in the inflamed mucosa of children with CD and UC than in the intact mucosa. Expression of miR-122 elevated in the macroscopically intact colonic regions of CD compared with controls and patients with UC. In HT-29 cells, TNF-α treatment increased the expression of miR-146a and -155, but not that of miR-122. CONCLUSIONS: Our results showed altered expression of miR-146a, -155, and -122 in the colonic mucosa of children with IBD and in TNF-α-treated colonic epithelial cells. Our data suggest the TNF-α-related involvement of these miRs in the pathogenesis of IBD.
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Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , MicroARNs/genética , Adolescente , Estudios de Casos y Controles , Niño , Colitis Ulcerosa/patología , Enfermedad de Crohn/patología , Femenino , Estudios de Seguimiento , Células HT29 , Humanos , Masculino , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
OBJECTIVES: Predicting short-term relapses and long-term prognosis is of utmost importance in paediatric inflammatory bowel disease (IBD). Our aim was to investigate the short-term disease outcome and medication during the first year in a paediatric incident cohort from Hungary. In addition, association laboratory markers and disease activity indices with short-term disease outcome and medication were analysed. METHODS: From January 1, 2008 to December 31, 2010, demographic data and clinical characteristics of newly diagnosed paediatric patients with IBD < 18 years of age were prospectively recorded. RESULTS: A total of 420 patients were identified (Crohn disease [CD] 266 and ulcerative colitis [UC] 124). Initially, 48% (124/256) of the patients with CD had moderate-to-severe disease (Pediatric Crohn's Disease Activity Index [PCDAI] > 31), and this rate decreased to 2.1% at 1-year follow-up. Proportion of patients with UC with moderate-to-severe disease (Pediatric Ulcerative Colitis Activity Index > 35) at diagnosis declined from 57.5% (69/120) to 6.8% at 1-year follow-up. Terminal ileal involvement correlated with higher initial C-reactive protein (CRP) (P = 0.021) and initial PCDAI (P = 0.026). In UC, elevated CRP (P = 0.002) was associated with disease extension. CRP and PCDAI at diagnosis were associated with the need for immunomodulators at 1 year in children with CD. Initial CRP was also associated with the need for immunomodulators in patients with UC at 1-year follow-up. CONCLUSIONS: At diagnosis, half of the patients with IBD had moderate-to-severe disease, and this rate decreased to <10% after 1 year. Initial CRP and PCDAI were related to the need for aggressive therapy in CD.
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Colitis Ulcerosa/patología , Enfermedad de Crohn/patología , Progresión de la Enfermedad , Fenotipo , Adolescente , Proteína C-Reactiva/análisis , Niño , Colitis Ulcerosa/sangre , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/sangre , Enfermedad de Crohn/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Íleon/patología , Factores Inmunológicos/uso terapéutico , Masculino , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Paediatric Crohn's disease patients suffer from several complications, including low bone mineral density and inadequate serum levels of 25-hydroxy vitamin D. AIMS: The aim of this prospective study was to address the effect of infliximab therapy on bone metabolism, bone mineral density and vitamin D homeostasis. The seasonal variability of serum vitamin D levels in relation to infliximab treatment was also analysed. METHODS: Serum osteocalcin and beta-crosslaps (markers of bone metabolism), seasonal variability of vitamin D, and bone mineral density were assessed and followed throughout the yearlong treatment regimen of infliximab in 50 consecutive paediatric patients with moderate to severe Crohn's disease. RESULTS: Bone forming osteocalcin levels were significantly (p<0.001) increased during infliximab therapy. In contrast, no significant changes in beta-crosslaps and vitamin D levels were observed. Vitamin D levels were significantly different when the summer and winter periods were compared at week 0 (p=0.039); however, this difference was not detected after one year of infliximab therapy. Despite the beneficial clinical effect of infliximab, there was no significant change in bone mineral density Z-scores after one year of treatment. CONCLUSION: Infliximab may beneficially affect bone homeostasis. Moreover, seasonal variability in vitamin D levels observed prior to initiation of infliximab treatment was diminished after one year of treatment.
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Enfermedad de Crohn/sangre , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/farmacología , Infliximab/farmacología , Vitamina D/análogos & derivados , Adolescente , Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/metabolismo , Niño , Femenino , Homeostasis/efectos de los fármacos , Humanos , Masculino , Osteocalcina/sangre , Estudios Prospectivos , Estaciones del Año , Índice de Severidad de la Enfermedad , Vitamina D/sangreRESUMEN
Celiac disease (CD) is a chronic autoimmune enteropathy caused by exposure to dietary gluten in genetically predisposed individuals. The transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) was shown to exert protective effects in several immune-mediated disorders. Activation of PPARγ suppressed the expression of thymic stromal lymphopoietin (TSLP), an inducer of proinflammatory cytokines. Since the role of TSLP in gluten-sensitive enteropathy is completely unknown, we investigated the involvement of TSLP and its regulator PPARγ in childhood CD. We collected duodenal biopsy specimens from 19 children with newly diagnosed CD, 6 children with treated CD (gluten-free diet, GFD), and 10 controls. Expression of mRNA and protein levels of PPARγ, TSLP, and TSLP receptor were determined by real-time RT-PCR and Western blot, respectively. Duodenal localization of PPARγ and TSLP was studied by immunohistochemistry. In duodenal mucosa of children with CD, the amount of PPARγ was significantly lower and simultaneously that of TSLP significantly higher compared to controls (p < 0.05). In GFD-treated patients, the levels of PPARγ mRNA and protein were significantly higher while that of TSLP markedly lower compared to newly diagnosed CD (p < 0.05). Immunohistochemistry revealed PPARγ and TSLP expression in lamina propria immune cells and in enterocytes. Low expression of PPARγ and high expression of TSLP in the duodenal mucosa of children with newly diagnosed CD suggest that they are involved in the pathophysiology of CD. We hypothesize that PPARγ may be an inhibitory regulator of TSLP-stimulated inflammatory processes in CD.
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Enfermedad Celíaca/metabolismo , Citocinas/metabolismo , PPAR gamma/metabolismo , Adolescente , Western Blotting , Enfermedad Celíaca/dietoterapia , Niño , Preescolar , Dieta Sin Gluten , Duodeno/patología , Femenino , Humanos , Inmunohistoquímica , Mucosa Intestinal/patología , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfopoyetina del Estroma TímicoRESUMEN
The biological therapy of Crohn's disease, such as infliximab is a powerful approach in the therapy of inflammatory bowel diseases. However, in some patients with aggressive disease course, even a combined immunosuppressive therapy will not result in permanent remission. Hematopoietic stem cell transplantation has emerged as a new potential therapeutic tool for inflammatory bowel diseases. The authors report the case of a 15-year-old boy with severe Crohn's disease resistant to combined immunosuppressive therapy. After a 3-years course of unsuccessful conventional therapy including infliximab, autologous hematopoietic stem cell transplantation was performed which resulted in a complete remission. One year after transplantation the patient has relapsed, but he could be treated effectively with conventional therapy regiments. To the best of knowledge of the authors, this is the first report in Hungary presenting hematopoietic stem cell therapy in patient with severe Crohn's disease.
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Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/cirugía , Resistencia a Medicamentos , Trasplante de Células Madre Hematopoyéticas , Adolescente , Anticuerpos Monoclonales/administración & dosificación , Colonoscopía , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/patología , Fármacos Gastrointestinales/administración & dosificación , Humanos , Hungría , Inmunosupresores/administración & dosificación , Infliximab , Masculino , Índice de Severidad de la Enfermedad , Trasplante Autólogo , Resultado del TratamientoRESUMEN
BACKGROUND: Quality of life (QoL) is an important outcome measure in the evaluation of therapies for inflammatory bowel disease. The primary aim of this study was to determine the effect of one year infliximab treatment on QoL and clinical parameters in pediatric patients with Crohn's diseases (CD). METHODS: Our prospective study involved 51 children with conventional therapy resistant, severe CD (mean age: 15.25years, range: 11-18years). Infliximab was given according to the protocol (5mg/kg, at weeks 0, 2, 6 and every 8weeks). During the infliximab courses QoL of patients was evaluated by IMPACT-III questionnaire at weeks 0, 6, 30 and 53. At the same time, the Pediatric Crohn's Disease Activity Index (PCDAI) score was calculated. Moreover, serum C-reactive protein (CRP), serum platelets and serum albumin were followed up. Auto-regressive, cross-lagged models were used to assess relation between QoL and the clinical parameters. RESULTS: The initial IMPACT-III scores [median, percentile 25-75 (pc 25-75) at week 0: 115, 102.5-130.25] increased significantly (p<0.001) following infliximab therapy at week 54 (median: 141.5, 124.5-153.75). Clinical and laboratory parameters also improved significantly (p<0.001). Auto-regressive regression coefficients (ß value) were significant between each variable over time. The strongest cross-lagged relations were observed between IMPACT-III and serum albumin, IMPACT-III and platelets. Reliability test of IMPACT-III revealed an excellent level of internal consistency (Cronbach's alpha=0.931). CONCLUSION: Infliximab treatment has beneficial clinical effect which is confirmed by decrease of PCDAI and increase of IMPACT-III. Autoregressive regression analysis showed regression relation between IMPACT-III and PCDAI and laboratory parameters.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Calidad de Vida , Adolescente , Niño , Femenino , Humanos , Infliximab , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Genetic background of coeliac disease has been subjects to intensive research since decades. However, only results of HLA phenotyping have been taken over to routine clinical practice. Meanwhile, data on the role of epigenetical factors in the manifestation of diseases have been emerging. In coeliac disease, there are several questions both in the fields of genetics and epigenetics yet to be answered. In this review, a cross section of current knowledge on these issues is presented with special interest regarding the future clinical applications.
Asunto(s)
Enfermedad Celíaca/genética , Epigénesis Genética , Epigenómica , Predisposición Genética a la Enfermedad , HumanosRESUMEN
In the last decades our knowledge has been enormously broadened about the structure and function of the gut associated lymphoid system. It was recognized how intricate and finely tuned connection exists between the gut bacterial flora and the intestinal mucosa. This subtle balance ensures mucosal homeostasis, which has a key role in organ defence against pathogens. However, at the same time this system makes possible the development of oral tolerance toward the commensals and the food antigens. In case of any disturbances in this finely tuned process, immunmediated intestinal disorders may easily develop. The first part of this paper reviews the structure and function of the mucosal immune system, while the second part surveys the pathogenesis, diagnosis and therapy of coeliac disease, inflammatory bowel disease and cow's milk allergy induced enteropathy.
Asunto(s)
Enfermedad Celíaca/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Mucosa Intestinal/inmunología , Hipersensibilidad a la Leche/complicaciones , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/fisiopatología , Enfermedad Celíaca/terapia , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/fisiopatología , Enfermedades Inflamatorias del Intestino/terapia , Enfermedades Intestinales/inmunología , Hipersensibilidad a la Leche/inmunología , Hipersensibilidad a la Leche/fisiopatologíaRESUMEN
AIM: To investigate the characteristics of mucosal lesions and their relation to laboratory data and long-term follow up in breast-fed infants with allergic colitis. METHODS: In this study 31 breast-fed infants were prospectively evaluated (mean age, 17.4 wk) whose rectal bleeding had not ceased after a maternal elimination diet for cow's milk. Thirty-four age-matched and breast-fed infants (mean age, 16.9 wk) with no rectal bleeding were enrolled for laboratory testing as controls. Laboratory findings, colonoscopic and histological characteristics were prospectively evaluated in infants with rectal bleeding. Long-term follow-up with different nutritional regimes (L-amino-acid based formula or breastfeeding) was also included. RESULTS: Iron deficiency, peripheral eosinophilia and thrombocytosis were significantly higher in patients with allergic colitis in comparison to controls (8.4 ± 3.2 µmol/L vs 13.7 ± 4.7 µmol/L, P < 0.001; 0.67 ± 0.49 G/L vs 0.33 ± 0.17 G/L, P < 0.001; 474 ± 123 G/L vs 376 ± 89 G/L, P < 0.001, respectively). At colonoscopy, lymphonodular hyperplasia or aphthous ulceration were present in 83% of patients. Twenty-two patients were given L-amino acid-based formula and 8 continued the previous feeding. Time to cessation of rectal bleeding was shorter in the special formula feeding group (mean, 1.4 wk; range, 0.5-3 wk) when compared with the breast-feeding group (mean, 5.3 wk; range, 2-9 wk). Nevertheless, none of the patients exhibited rectal bleeding at the 3-mo visit irrespective of the type of feeding. Peripheral eosinophilia and cessation of rectal bleeding after administration of elemental formula correlated with a higher density of mucosal eosinophils. CONCLUSION: Infant hematochezia, after cow's milk allergy exclusion, is generally a benign and probably self-limiting disorder despite marked mucosal abnormality. Formula feeding results in shorter time to cessation of rectal bleeding; however, breast-feeding should not be discouraged in long-lasting hematochezia.