BACKGROUND: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN. METHODS: Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing. RESULTS: Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi. CONCLUSIONS: This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.

• MeSH
• Crohnova nemoc * terapie   mikrobiologie   imunologie   MeSH
• dítě MeSH
• enterální výživa * metody   MeSH
• feces * mikrobiologie   chemie   MeSH
• leukocytární L1-antigenní komplex * analýza   MeSH
• leukocyty mononukleární imunologie   metabolismus   MeSH
• lidé MeSH
• mladiství MeSH
• střevní mikroflóra * MeSH
• TNF-alfa * metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous (SC) compared to intravenous (IV) IFX. However, it is unknown whether re-exposure to IFX SC after secondary loss of response and immunogenicity to its intravenous formulation is safe and effective. METHODS: In a retrospective cohort study conducted at two medical centers, patients with clinically (Harvey-Bradshaw Index ≥ 5) and/or biochemically (fecal calprotectin > 250 μg/g) active Crohn's disease (CD) and previous immunogenic failure of IFX IV underwent exposure to IFX SC. Harvey-Bradshaw Index, fecal calprotectin, IFX serum concentration, and anti-drug antibodies were assessed until month 12. RESULTS: Twenty CD patients were included. The majority of patients (90%) had previous treatment with three or more biologics. Fifteen (75%) and ten (50%) of 20 patients continued IFX SC treatment until months 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients discontinued IFX SC treatment because of delayed hypersensitivity at week 2 and week 4. IFX serum concentrations increased from baseline to month 12, while anti-drug antibody levels decreased. Combined clinical and biochemical remission at month 12 was observed in seven of 20 patients (35%). CONCLUSION: Subcutaneous infliximab treatment of Crohn's disease patients with previous immunogenic failure of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn's disease.

• MeSH
• Crohnova nemoc * farmakoterapie   imunologie   MeSH
• dospělí MeSH
• feces chemie   MeSH
• infliximab * terapeutické užití   imunologie   aplikace a dávkování   MeSH
• injekce subkutánní MeSH
• intravenózní podání MeSH
• leukocytární L1-antigenní komplex analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• retrospektivní studie MeSH
• terapie neúspěšná MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibrostenosis in CD.

• MeSH
• Crohnova nemoc * metabolismus   patologie   imunologie   MeSH
• dospělí MeSH
• endopeptidasy metabolismus   genetika   MeSH
• extracelulární matrix metabolismus   patologie   MeSH
• fibroblasty * metabolismus   patologie   MeSH
• fibróza * MeSH
• ileum patologie   metabolismus   imunologie   MeSH
• jaderné proteiny metabolismus   genetika   MeSH
• lidé MeSH
• mezibuněčná komunikace MeSH
• monocyty * metabolismus   patologie   imunologie   MeSH
• myši MeSH
• receptory buněčného povrchu metabolismus   genetika   MeSH
• transkripční faktor Twist * metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• alopurinol aplikace a dávkování   škodlivé účinky   MeSH
• azathioprin aplikace a dávkování   škodlivé účinky   MeSH
• Crohnova nemoc * farmakoterapie   imunologie   komplikace   MeSH
• dospělí MeSH
• infliximab * aplikace a dávkování   imunologie   škodlivé účinky   MeSH
• kombinovaná farmakoterapie MeSH
• lékové postižení jater etiologie   MeSH
• leukocytární L1-antigenní komplex analýza   MeSH
• lidé MeSH
• náhrada léků MeSH
• terapie neúspěšná MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Background and Aims: The pathogenesis and risk factors for early postoperative endoscopic recurrence of Crohn's disease (CD) remain unclear. Thus, this study aimed to identify whether histological inflammation at the resection margins after an ileocaecal resection influences endoscopic recurrence. Methods: We have prospectively followed up patients with CD who underwent ileocaecal resection at our hospital between January 2012 and January 2018. The specimens were histologically analysed for inflammation at both of the resection margins (ileal and colonic). We evaluated whether histological results of the resection margins are correlated with endoscopic recurrence of CD based on colonoscopy 6 months after ileocaecal resection. Second, we assessed the influence of known risk factors and preoperative therapy on endoscopic recurrence of CD. Results: A total of 107 patients were included in our study. Six months after ileocaecal resection, 23 patients (21.5%) had an endoscopic recurrence of CD. The histological signs of CD at the resection margins were associated with a higher endoscopic recurrence (56.5% versus 4.8%, p < 0.001). Disease duration from dia­gnosis to surgery (p = 0.006) and the length of the resected bowel (p = 0.019) were significantly longer in patients with endoscopic recurrence. Smoking was also proved to be a risk factor for endoscopic recurrence (p = 0.028). Conclusions: Histological inflammation at the resection margins was significantly associated with a higher risk of early postoperative endoscopic recurrence after an ileocaecal resection for CD.

• MeSH
• anastomóza chirurgická MeSH
• chirurgická rána * imunologie   MeSH
• chirurgie trávicího traktu * metody   škodlivé účinky   MeSH
• Crohnova nemoc * chirurgie   diagnóza   epidemiologie   imunologie   MeSH
• endoskopie trávicího systému metody   statistika a číselné údaje   MeSH
• ileocekální chlopeň chirurgie   patologie   MeSH
• lidé MeSH
• následné studie MeSH
• pooperační komplikace chirurgie   diagnóza   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH

BACKGROUND AND AIMS: Vedolizumab was shown to be safe and effective for the treatment of Crohn's disease [CD] and ulcerative colitis [UC] in the GEMINI Long-Term Safety [LTS] study. The vedolizumab Extended Access Program [XAP] provides patients with continued treatment. This XAP pharmacokinetics [PK] sub-study investigated vedolizumab efficacy, safety, and PK. METHODS: Vedolizumab dosing frequency was reduced from every 4 weeks [Q4W] to every 8 weeks [Q8W] at XAP enrolment, and patients were followed for 56 weeks. Outcomes included: efficacy, loss of clinical benefit, and re-escalation to Q4W dosing; and vedolizumab PK, immunogenicity, and adverse events. RESULTS: Among 167 enrolled patients [CD = 88, UC = 79], 80 [91%] with CD and 73 [92%] with UC completed 56 weeks; 76 [86%] and 71 [90%] with CD and UC, respectively, remained on Q8W dosing for 56 weeks. Clinical remission, corticosteroid-free clinical remission, and C-reactive protein levels were stable among patients remaining on Q8W through Week 56. Four patients with CD and two with UC resumed Q4W dosing [three with CD regained clinical response]. Patients with CD who completed Week 56 on Q8W dosing had median trough vedolizumab concentrations of 43.6 µg/mL at enrolment and 10.4 µg/mL at Week 56; concentrations were 42.4 µg/mL and 13.3 µg/mL, respectively, in patients with UC. Treatment-related adverse events were infrequent; no new or serious adverse events related to vedolizumab were reported. CONCLUSIONS: In the XAP-PK sub-study, adherence to Q8W dosing was high, with no loss of efficacy; very few patients required re-escalation to Q4W. There were no new safety signals.

• MeSH
• Crohnova nemoc * diagnóza   farmakoterapie   imunologie   MeSH
• dospělí MeSH
• gastrointestinální látky aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• imunologická odpověď na dávku MeSH
• integriny antagonisté a inhibitory   MeSH
• intravenózní infuze MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• ulcerózní kolitida * diagnóza   farmakoterapie   imunologie   MeSH
• vysazování léků metody   MeSH
• výsledky a postupy - zhodnocení (zdravotní péče) MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze IV MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH

BACKGROUND: Vaccine-preventable diseases and opportunistic infections in pediatric inflammatory bowel disease (IBD) are increasingly recognized issues. The aims of this study were to evaluate vaccinations, immunization status, and consequent therapeutic management in children with IBD and to analyze the differences among patients diagnosed before (Group 1) and after June 2012 (Group 2). METHODS: This was a multicenter, retrospective cohort investigation. Between July 2016 and July 2017, 430 children with IBD were enrolled in 13 centers. Diagnosis, therapeutic history, vaccinations, and immunization status screening at diagnosis and at immunosuppressant (IM)/biologic initiation and reasons for incomplete immunization were retrieved. RESULTS: Vaccination rates at diagnosis were unsatisfactory for measles, mumps, and rubella (89.3%), Haemophilus influenzae (81.9%), meningococcus C (23.5%), chickenpox (18.4%), pneumococcus (18.6%), papillomavirus (5.9%), and rotavirus (1.9%). Complete immunization was recorded in 38/430 (8.8%) children, but specific vaccines were recommended in 79/430 patients (18.6%), without differences between the 2 groups. At IM start, 22% of children were tested for Epstein-Barr virus (EBV) status, with 96.2% of EBV-naïve patients starting azathioprine, without differences between Groups 1 and 2. Screening for latent tuberculosis (TB) before start of biologics was performed in 175/190 (92.1%), with up to 9 different screening strategies and numerous inconsistencies. CONCLUSIONS: We demonstrated a poor immunization status at diagnosis in children with IBD, which was not followed by proper vaccination catch-up. EBV status before IM initiation and latent TB before biologics were not adequately assessed. Thus, the overall impact of the current guidelines seems unsatisfactory.

• MeSH
• Crohnova nemoc farmakoterapie   imunologie   MeSH
• dítě MeSH
• dodržování směrnic MeSH
• idiopatické střevní záněty farmakoterapie   imunologie   MeSH
• imunosupresiva škodlivé účinky   MeSH
• infekce virem Epsteina-Barrové prevence a kontrola   MeSH
• latentní tuberkulóza prevence a kontrola   MeSH
• lidé MeSH
• Mycobacterium tuberculosis MeSH
• očkovací schéma MeSH
• oportunní infekce imunologie   prevence a kontrola   MeSH
• retrospektivní studie MeSH
• ulcerózní kolitida farmakoterapie   imunologie   MeSH
• vakcinace normy   statistika a číselné údaje   MeSH
• virus Epsteinův-Barrové MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Idiopatické střevní záněty (IBD) jsou skupinou onemocnění, jejichž příčina není zcela jasná a kde předpokládáme, že se na jejich vzniku podílí jak faktory genetické, tak i vnější vlivy. Léčba je tedy komplikovaná, jejím základem jsou aminosalicyláty, kortikoidy, imunosupresiva a v posledních letech také biologická léčba. Probiotika jsou specifické živé mikroorganismy, jež mohou příznivě ovlivňovat či zlepšit zdravotní stav jedince, pokud jsou přijímány v dostatečném množství. Jejich význam v léčbě idiopatických střevních zánětů není dominantní, mají však svůj prokázaný význam v prevenci pouchitidy a v udržovací léčbě ulcerózní kolitidy.

Crohn´s disease and ulcerative colitis are inflammatory bowel diseases, whose cause is not clear. We expected, that genetic and external factors participate in to their origin. The treatment of Crohn´s disease and ulcerative colitis is complicated and aminosalicylates, corticosteroids, immunosuppressants, and recently also biological therapy are the basis of the treatment of inflammatory bowel diseases (IBD). Probiotics are living microorganisms of the human origin, that can influence human health, if they are used in sufficient quantities. Their position in IBD treatment is not dominant, but they are important in the long-term treatment of ulcerative colitis and in prevention of pouchitis.

• MeSH
• Crohnova nemoc imunologie   mikrobiologie   terapie   MeSH
• idiopatické střevní záněty * farmakoterapie   imunologie   mikrobiologie   MeSH
• lidé MeSH
• probiotika aplikace a dávkování   terapeutické užití   MeSH
• ulcerózní kolitida imunologie   mikrobiologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND AND AIMS: Intestinal inflammation in inflammatory bowel diseases [IBD] is thought to be T cell mediated and therefore dependent on the interaction between the T cell receptor [TCR] and human leukocyte antigen [HLA] proteins expressed on antigen presenting cells. The collection of all TCRs in one individual, known as the TCR repertoire, is characterised by enormous diversity and inter-individual variability. It was shown that healthy monozygotic [MZ] twins are more similar in their TCR repertoire than unrelated individuals. Therefore MZ twins, concordant or discordant for IBD, may be useful to identify disease-related and non-genetic factors in the TCR repertoire which could potentially be used as disease biomarkers. METHODS: Employing unique molecular barcoding that can distinguish between polymerase chain reaction [PCR] artefacts and true sequence variation, we performed deep TCRα and TCRβ repertoire profiling of the peripheral blood of 28 MZ twin pairs from Denmark and Germany, 24 of whom were discordant and four concordant for IBD. RESULTS: We observed disease- and smoking-associated traits such as sharing, diversity and abundance of specific clonotypes in the TCR repertoire of IBD patients, and particularly in patients with active disease, compared with their healthy twins. CONCLUSIONS: Our findings identified TCR repertoire features specific for smokers and IBD patients, particularly when signs of disease activity were present. These findings are a first step towards the application of TCR repertoire analyses as a valuable tool to characterise inflammatory bowel diseases and to identify potential biomarkers and true disease causes.

• MeSH
• C-reaktivní protein analýza   MeSH
• Crohnova nemoc * diagnóza   imunologie   patofyziologie   MeSH
• dospělí MeSH
• dvojčata monozygotní MeSH
• feces MeSH
• geny TcR alfa * MeSH
• geny TcR beta * MeSH
• kouření imunologie   MeSH
• leukocytární L1-antigenní komplex analýza   MeSH
• lidé MeSH
• posouzení stavu pacienta MeSH
• receptory antigenů T-buněk alfa-beta krev   MeSH
• sekvenční analýza DNA MeSH
• ulcerózní kolitida * diagnóza   imunologie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• studie na dvojčatech MeSH
• Geografické názvy
• Dánsko MeSH
• Německo MeSH

BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice. AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease. METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists. RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)). CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

• MeSH
• antiflogistika nesteroidní terapeutické užití   MeSH
• biologické faktory terapeutické užití   MeSH
• Crohnova nemoc diagnóza   imunologie   terapie   MeSH
• dospělí MeSH
• hospitalizace statistika a číselné údaje   MeSH
• imunologické faktory terapeutické užití   MeSH
• kolektomie statistika a číselné údaje   MeSH
• kombinovaná farmakoterapie metody   statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mesalamin terapeutické užití   MeSH
• mladý dospělý MeSH
• následné studie MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• udržovací chemoterapie metody   statistika a číselné údaje   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH