BACKGROUND: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking. AIMS: To examine the usability of darvadstrocel therapy in managing perianal CD. METHODS: We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression. RESULTS: Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported. CONCLUSION: Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.
- MeSH
- Crohnova nemoc * terapie komplikace MeSH
- dospělí MeSH
- indukce remise MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- rektální píštěl * terapie etiologie MeSH
- retrospektivní studie MeSH
- spokojenost pacientů MeSH
- transplantace mezenchymálních kmenových buněk * metody škodlivé účinky 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
Stratified and precision nutrition refers to disease management or prevention of disease onset, based on dietary interventions tailored to a person's characteristics, biology, gut microbiome, and environmental exposures. Such treatment models may lead to more effective management of inflammatory bowel disease (IBD) and reduce risk of disease development. This societal position paper aimed to report advances made in stratified and precision nutritional therapy in IBD. Following a structured literature search, limited to human studies, we identified four relevant themes: (a) nutritional epidemiology for risk prediction of IBD development, (b) food-based dietary interventions in IBD, (c) exclusive enteral nutrition (EEN) for Crohn's disease (CD) management, and (d) pre- and probiotics for IBD management. There is scarce literature upon which we can make recommendations for precision or stratified dietary therapy for IBD, both for risk of disease development and disease management. Certain single-nucleotide polymorphisms related to polyunsaturated fatty acid (PUFA) metabolism may modify the effect dietary PUFA have in increasing the risk of IBD development. Non-colonic CD, mild-to-moderate CD, and high microbiota richness may predict success of EEN and may be used both for prediction of treatment continuation, but also for early cessation in nonresponders. There is currently insufficient evidence to make recommendations for precision or stratified dietary therapy for patients with established IBD. Despite the great interest in stratified and precision nutrition, we currently lack data to support conclusive recommendations. Replication of early findings by independent research groups and within structured clinical interventions is required.
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
Crohnova choroba (CD – Crohn’s disease) je chronické nešpecifické zápalové ochorenie tráviacej trubice v celej jej dĺžke, vznikajúce z neznámych príčin. Ochorenie je celoživotné a striedajú sa pri ňom fázy remisií a relapsov. Svojimi pestrými symptómami, zdĺhavým priebehom a rozvíjajúcimi sa komplikáciami patrí k náročným ochoreniam, a to nielen na diagnostiku ochorenia, ale aj na medicínsku, ošetrovateľskú a následnú starostlivosť v domácom prostredí. Cieľom článku je charakterizovať a popísať CD s možnými príčinami jej vzniku a príznaky spolu s možnými komplikáciami. Venovali sme sa aj diagnostickým metódam a najnovším poznatkom v terapii tohto ochorenia. Medzi najdôležitejšie problémy sme zaradili starostlivosť o vyprázdňovanie, výživu a príjem tekutín, manažment bolesti, edukáciu, prípravu pacienta na zmenu životného štýlu a vhodnú psychologickú pomoc.
Crohn’s disease (CD) is a chronic nonspecific inflammatory disease of the digestive tract along the whole of its length resulting from unknown causes. The disease is lifelong with changing phases of remissions and relapses. Due to its various symptoms as well as lengthy and developing complications, it belongs to difficult diseases, not only in the means of its diagnosing, but also for medical and nursing care and for aftercare at home. The aim of this work was to characterize and describe CD with potential underlying causes and symptoms with possible complications. We were also interested in diagnostic methods and the latest findings in the treatment of this disease. The most important problems included the care of emptying, nutrition and fluid intake, pain management, education, preparation of the patient to the changes in his/her lifestyle and appropriate psychological support.
Crohnova choroba (CD – Crohn’s disease) je chronické nešpecifické zápalové ochorenie tráviacej trubice v celej jej dĺžke, vznikajúce z neznámych príčin. Ochorenie je celoživotné a striedajú sa pri ňom fázy remisií a relapsov. Svojimi pestrými symptómami, zdĺhavým priebehom a rozvíjajúcimi sa komplikáciami patrí k náročným ochoreniam, a to nielen na diagnostiku ochorenia, ale aj na medicínsku, ošetrovateľskú a následnú starostlivosť v domácom prostredí. Cieľom článku je charakterizovať a popísať CD s možnými príčinami jej vzniku a príznaky spolu s možnými komplikáciami. Venovali sme sa aj diagnostickým metódam a najnovším poznatkom v terapii tohto ochorenia. Medzi najdôležitejšie problémy sme zaradili starostlivosť o vyprázdňovanie, výživu a príjem tekutín, manažment bolesti, edukáciu, prípravu pacienta na zmenu životného štýlu a vhodnú psychologickú pomoc.
Crohn’s disease (CD) is a chronic nonspecific inflammatory disease of the digestive tract along the whole of its length resulting from unknown causes. The disease is lifelong with changing phases of remissions and relapses. Due to its various symptoms as well as lengthy and developing complications, it belongs to difficult diseases, not only in the means of its diagnosing, but also for medical and nursing care and for aftercare at home. The aim of this work was to characterize and describe CD with potential underlying causes and symptoms with possible complications. We were also interested in diagnostic methods and the latest findings in the treatment of this disease. The most important problems included the care of emptying, nutrition and fluid intake, pain management, education, preparation of the patient to the changes in his/her lifestyle and appropriate psychological support.
- MeSH
- Crohnova nemoc * diagnóza ošetřování patologie terapie MeSH
- lidé MeSH
- ošetřovatelská péče MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Mucosal healing (MH) has become a perspective treatment target in patients with Crohn's disease (CD). Data about the impact of MH on long-term outcome in pediatric patients are still scarce. METHODS: Seventy-six pediatric patients with CD were evaluated retrospectively (2000-2015) in a tertiary care center. Based on MH achievement, they were divided into two groups (MH, N.=17; and No MH, N.=59). The primary endpoint was to assess the association of MH and the need for CD-related hospitalizations or surgery in pediatric patients with CD. RESULTS: The number of hospitalized patients was 24% in the MH group and 42% in the No MH group (P=0.26). The total number of CD-related hospitalizations was not significant between the MH group and the No MH group (5 vs. 41, P=0.15). The time to the first hospitalization was 24 months in MH and 21 months in No MH (P>0.99). About 24% of the patients in the MH group and 39% patients in the No MH group underwent CD-related operation (P=0.39). Time to the first operation was 43 months for MH and 19 months for the No MH group (P=0.13). The follow-up period was 91 months in the MH group and 80 months in the No MH group (P=0.74). The use of infliximab was positively associated with MH (P=0.002). CONCLUSIONS: MH was not associated with fewer CD-related hospitalizations or operations in pediatric patients with CD during seven years of follow-up.
- MeSH
- časové faktory MeSH
- centra terciární péče MeSH
- Crohnova nemoc * terapie MeSH
- dítě MeSH
- hojení ran MeSH
- hospitalizace * statistika a číselné údaje MeSH
- infliximab terapeutické užití MeSH
- lidé MeSH
- mladiství MeSH
- následné studie MeSH
- retrospektivní studie MeSH
- střevní sliznice * patologie MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization. OBJECTIVES: This study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD. METHODS: In children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR). RESULTS: Of 37 patients recruited, 15 responded (FCal < 250 μg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (μmol/g) butyrate [responders: 13.2 (8.63-18.4) compared with nonresponders: 22.3 (12.0-32.0); P = 0.03], acetate [responders: 49.9 (46.4-68.4) compared with nonresponders: 70.4 (57.0-95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013-0.611) compared with nonresponders: 0.943 (0.438-1.35); P = 0.021], and a higher microbiota richness [315 (269-347) compared with nonresponders: 243 (205-297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38-0.72) compared with nonresponders: 0.19 (0.01-0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN. CONCLUSIONS: We identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.
- MeSH
- acetáty MeSH
- butyráty MeSH
- Crohnova nemoc * terapie metabolismus MeSH
- dítě MeSH
- enterální výživa MeSH
- fenylacetáty MeSH
- indukce remise MeSH
- lidé MeSH
- metabolom MeSH
- mikrobiota * MeSH
- prospektivní studie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Ustekinumab, is a new therapy for patients with IBD, especially for patients suffering from Crohn's disease (CD) who did not respond to anti-TNF treatment. To shed light on the longitudinal effect of ustekinumab on the immune system, we investigated the effect on skin and gut microbiota composition, specific immune response to commensals, and various serum biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 11 patients with IBD who were monitored over 40 weeks of ustekinumab therapy and 39 healthy controls (HC). We found differences in the concentrations of serum levels of osteoprotegerin, TGF-β1, IL-33, and serum IgM antibodies against Lactobacillus plantarum between patients with IBD and HC. The levels of these biomarkers did not change in response to ustekinumab treatment or with disease improvement during the 40 weeks of observation. Additionally, we identified differences in stool abundance of uncultured Subdoligranulum, Faecalibacterium, and Bacteroides between patients with IBD and HC. CONCLUSION/SIGNIFICANCE: In this preliminary study, we provide a unique overview of the longitudinal monitoring of fecal and skin microbial profiles as well as various serum biomarkers and humoral and cellular response to gut commensals in a small cohort of patients with IBD on ustekinumab therapy.
- MeSH
- biologické markery MeSH
- Crohnova nemoc * terapie MeSH
- inhibitory TNF MeSH
- lidé MeSH
- mikrobiota * MeSH
- pilotní projekty MeSH
- ustekinumab terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Crohnova choroba (CD) je multifaktoriálně podmíněné onemocnění, které společně s ulcerózní kolitidou řadíme mezi idiopatické střevní záněty (IBD). CD má progresivní charakter a je spojena s rozvojem četných komplikací, které vedou k často závažným strukturálním změnám střevní stěny (BD). Časná fáze Crohnovy choroby (eCD) se vyznačuje charakteristickou imunitní odpovědí a představuje atraktivní cíl pro specifickou agresivní terapii. Použití biologické léčby (BL) u eCD může vést k prevenci BD a umožnit časnou redukci dávky, či dokonce vysazení BL. Obsáhlá literární evidence podporuje význam BL u eCD na základě studií s anti-TNF preparáty (jelikož jsou součástí klinické praxe už relativně dlouho). Slibná data však existují i u modernějších preparátů BL (vedolizumab a ustekinumab), jejichž užití je spojeno s nižším výskytem nežádoucích účinků. Definování rizikových skupin a relevantních biomarkerů v budoucnu napomůže identifikaci těch pacientů s eCD, kteří by mohli z časného nasazení BL nejvíce profitovat.
Crohn's disease (CD) is a multifactorial disease that (along with ulcerative colitis) represents a phenotype of inflammatory bowel disease (IBD). CD has progressive character and is associated with the development of various complications leading to potentially serious bowel damage (BD). Early stage of Crohn's disease (eCD) is characterized by a specific immune response and represents an attractive target for specific agressive therapy. The use of biologics (BL) in eCD may help to prevent BD and allow early dose reduction or even discontinuation of BL. Wide scientific evidence supports the importance of BL in eCD based on studies with anti-TNF biologics (being part of clinical practice for relatively long time now). However, studies on novel biologics with low rate of the adverse events (vedolizumab, ustekinumab) also show promising results. Defining high-risk groups and suitable biomarkers would help to select those eCD patients who would benefit the most from early biological therapy.
- MeSH
- biologická terapie MeSH
- Crohnova nemoc terapie MeSH
- idiopatické střevní záněty * terapie MeSH
- lidé MeSH
- sekundární prevence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
