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1.
Wien Klin Wochenschr ; 132(1-2): 12-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31915925

RESUMO

BACKGROUND: The rate of restoration of intestinal continuity after colonic resection and stoma creation in patients with Crohn's disease has not been well-documented in the era of biologics. Thus, the incidence of restoration of intestinal continuity since the introduction of biological drugs was assessed. METHODS: Consecutive patients (n = 43) who underwent colonic resection with ileostomy or colostomy formation for Crohn's disease at a single tertiary referral center between 2002 and 2014 were identified. Data from individual chart review were analyzed retrospectively. Patients were personally contacted for follow-up. RESULTS: Of the 43 patients 8 (18.4%) had a proctectomy leaving 35 patients (81.4%) with the rectum preserved. Of the 30 patients qualifying for final analysis restoration of bowel continuity was finally achieved in 10 patients (33.3%). Permanent stoma rates were comparable in the group of patients with and without biological therapy after surgery (64.3% vs. 60%). The median follow-up period was 7 years (range 3-15 years). Of the patients 20 suffered from perianal disease involvement (66.7%), which was associated with a higher rate of permanent stoma (n = 16/20, 80%) in contrast to patients without perianal disease (n = 4/10, 40%, p = 0.045). CONCLUSION: The overall incidence of stoma formation was low for patients with Crohn's disease; however, once a stoma is created the chance of ending up with a permanent stoma is high even in the era of biologics. Despite the use of new therapeutic agents perianal disease increases the risk of a permanent stoma.


Assuntos
Terapia Biológica , Doença de Crohn , Colostomia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Feminino , Humanos , Ileostomia , Masculino , Estudos Retrospectivos
2.
Postepy Biochem ; 65(4): 313-317, 2020 Jan 04.
Artigo em Polonês | MEDLINE | ID: mdl-31945286

RESUMO

Inflammatory bowel diseases (IBD) are chronic conditions that lead to serious complications and act to the detriment of quality of patients' lives. Etiology of IBD has not been precisely determined but it is assumed that IBD is caused by genetic, immune and environmental factors. The main target in current IBD treatment is the induction and maintenance of remission. The most common strategy in IBD therapy is called "step-up" that is based on gradual introduction of stronger drugs. However, the latest research shows that "top down" strategy is more promising and can change the natural course of the disease. The aim of this article is to discuss both strategies and compare their effectiveness.


Assuntos
Doença de Crohn/terapia , Doença de Crohn/genética , Doença de Crohn/imunologia , Humanos
6.
Gut ; 69(2): 274-282, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31196874

RESUMO

OBJECTIVES: To better understand the real-world impact of biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC), we evaluated the effect of marketplace introduction of infliximab on the population rates of hospitalisations and surgeries and public payer drug costs. DESIGN: We used health administrative data to study adult persons with CD and UC living in Ontario, Canada between 1995 and 2012. We used an interrupted time series design with segmented regression analysis to evaluate the impact of infliximab introduction on the rates of IBD-related hospitalisations, intestinal resections and public payer drug costs over 10 years among patients with CD and 5 years among patients with UC, allowing for a 1-year transition. RESULTS: Relative to what would have been expected in the absence of infliximab, marketplace introduction of infliximab did not produce significant declines in the rates of CD-related hospitalisations (OR at the last observation quarter 1.06, 95% CI 0.811 to 1.39) or intestinal resections (OR 1.10, 95% CI 0.810 to 1.50), or in the rates of UC-related hospitalisations (OR 1.22, 95% CI 1.07 to 1.39) or colectomies (OR 0.933, 95% CI 0.54 to 1.61). The findings were similar among infliximab users, except that hospitalisation rates declined substantially among UC patients following marketplace introduction of infliximab (OR 0.515, 95% CI 0.342 to 0.777). There was a threefold rise over expected trends in public payer drug cost among patients with CD following infliximab introduction (OR 2.98,95% CI 2.29 to 3.86), suggesting robust market penetration in this group, but no significant change among patients with UC (OR 1.06, 95% CI 0.955 to 1.18). CONCLUSIONS: Marketplace introduction of infliximab has not yielded anticipated reductions in the population rates of IBD-related hospitalisations or intestinal resections, despite robust market penetration among patients with CD. Misguided use of infliximab in CD patients and underuse of infliximab in UC patients may largely explain our study findings.


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Hospitalização/estatística & dados numéricos , Doenças Inflamatórias Intestinais/tratamento farmacológico , /uso terapêutico , Adulto , Colectomia/estatística & dados numéricos , Colectomia/tendências , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/cirurgia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Doença de Crohn/cirurgia , Custos de Medicamentos/estatística & dados numéricos , Custos de Medicamentos/tendências , Feminino , Hospitalização/tendências , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/cirurgia , Análise de Séries Temporais Interrompida , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Fatores Socioeconômicos
8.
Gastroenterology ; 158(1): 137-150.e1, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31476299

RESUMO

BACKGROUND & AIMS: Stenosis is a common complication of Crohn's disease (CD) that has no effective medical therapy. Development of antifibrotic agents will require testing in randomized controlled trials. Computed tomography enterography- and magnetic resonance enterography-based technologies might be used to measure outcomes in these trials. These approaches have been validated in studies of patients with symptomatic strictures who underwent imaging evaluations followed by resection with histopathologic grading of the intestinal tissue for inflammation and/or fibrosis (the reference standard). Imaging findings have correlated with findings from quantitative or semiquantitative histologic evaluation of the degree of fibromuscular stenosis and/or inflammation on the resection specimen. However, it is not clear whether histologic findings are an accurate reference standard. We performed a systematic review of all published histologic scoring systems used to assess stenosing CD. METHODS: We performed a comprehensive search of Embase and MEDLINE of studies through March 13, 2019, that used a histologic scoring system to characterize small bowel CD and assessed inflammatory and fibrotic alterations within the same adult individual. All scores fitting the criteria were included in our analysis, independent of the presence of stricturing disease, as long as inflammation and fibrosis were evaluated separately but in the same scoring system. RESULTS: We observed substantial heterogeneity among the scoring systems, which were not derived from modern principles for evaluative index development. None had undergone formal validity or reliability testing. None of the existing indices had been constructed according to accepted methods for the development of evaluative indices. Basic knowledge regarding their operating properties were lacking. Specific indices for evaluating the important pathologic component of myofibroblast hypertrophy or hyperplasia have not been proposed. CONCLUSIONS: In a systematic review of publications, we found a lack of validated histopathologic scoring systems for assessment of fibromuscular stenosis. Data that describe the operating properties of existing cross-sectional imaging techniques for stenosing CD should be questioned. Development and validation of a histopathology index is an important research priority.


Assuntos
Constrição Patológica/diagnóstico , Doença de Crohn/complicações , Íleo/patologia , Índice de Gravidade de Doença , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Fibrose , Humanos , Íleo/diagnóstico por imagem , Íleo/cirurgia , Imagem por Ressonância Magnética , Padrões de Referência , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X
10.
Gastroenterology ; 158(1): 189-199, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600487

RESUMO

BACKGROUND & AIMS: Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies. METHODS: We performed a genome-wide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn's disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer ≥10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease. RESULTS: The HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60-2.25; P = 5.88 × 10-13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35-2.98; P = 6.60 × 10-4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33), and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator (HR, 2.01; 95% CI, 1.57-2.58). CONCLUSIONS: In an observational study, we found a genome-wide significant association between HLA-DQA1*05 and the development of antibodies against anti-TNF agents. A randomized controlled biomarker trial is required to determine whether pretreatment testing for HLA-DQA1*05 improves patient outcomes by helping physicians select anti-TNF and combination therapies. ClinicalTrials.gov ID: NCT03088449.


Assuntos
Adalimumab/imunologia , Doença de Crohn/terapia , Cadeias alfa de HLA-DQ/genética , Infliximab/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adulto , Alelos , Doença de Crohn/sangue , Feminino , Estudo de Associação Genômica Ampla , Heterozigoto , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
14.
Medicine (Baltimore) ; 98(50): e18304, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852111

RESUMO

The differential diagnosis of Crohn disease (CD) from intestinal tuberculosis (ITB) and primary intestinal lymphoma (PIL) is challenging in patients who exhibit atypical clinical characteristics. The aim of the present study was to explore the serum proteome profiles of CD, PIL and ITB and to identify their differentiations.Treatment-naïve patients with CD (n = 10), PIL (n = 10) and ITB (n = 10) were enrolled in the present study. Differentially expressed proteins (DEPs) in patient serum samples were compared between groups using tandem mass tag labeled proteomic technology. A principal component analysis (PCA) plot and volcano maps were also visualized. Functional pathway analysis was performed using Reactome. The Area under the Curve (AUC) was calculated for each DEP.A total of 818 proteins were identified through proteomic quantification. Among them, 108 DEPs were identified to be differentiated between CD and ITB, 105 proteins between CD and PIL and 55 proteins between ITB and PIL. The proteome from the three groups was distinguishable in the PCA plot. The results revealed that 19, 12, and 10 proteins (AUC ≥ 0.95) were differentially expressed between CD and PIL, CD and ITB, and PIL and ITB, respectively. Among these DEPs, tumor necrosis factor ligand superfamily member 13 was higher in CD than in ITB and PIL. Peroxiredoxin-5, T-complex protein 1 subunit Gamma, CutA, and Fibulin-5 were increased in CD and PIL when compared with ITB. The levels of fibrinogen chains were also significantly higher in patients with PIL compared with CD.The current study demonstrated that serum proteome was distinguishable among patients with CD, PIL, and ITB. The identified proteins may assist in the clinical differentiation among them.


Assuntos
Doença de Crohn/diagnóstico , Neoplasias Intestinais/sangue , Linfoma/sangue , Proteoma/análise , Proteômica/métodos , Tuberculose Gastrointestinal/sangue , Adulto , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/diagnóstico , Linfoma/diagnóstico , Masculino , Espectrometria de Massas , Projetos Piloto , Estudos Retrospectivos , Tuberculose Gastrointestinal/diagnóstico
15.
Bratisl Lek Listy ; 120(12): 924-928, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31855052

RESUMO

OBJECTIVES: The aim of this study was to investigate the relationship between thromboxane levels and oxidative stress in children with Crohn´s disease (CD), and examine the effect of natural polyphenolic compounds on thromboxane levels. METHODS: This study involved 14 children suffering from CD and 15 healthy controls. Patients were receiving the polyphenolic extract Pycnogenol for 10 weeks. Plasma levels of the static and dynamic forms of thromboxane B2 as well as their metabolite 11-dehydro thromboxane B2 in urine were determined. RESULTS: In comparison to controls, CD patients had significantly higher levels of the static and dynamic forms of thromboxane B2. Pycnogenol decreased the level of the dynamic form of thromboxane B2 after 10 weeks of administration. CONCLUSIONS: Paediatric Crohn's disease is associated with higher thromboxane levels. Our results indicate that Pycnogenol administration reduces thromboxane levels, which may positively influence some clinical symptoms of CD such as thromboembolic episodes (Tab. 3, Ref. 49).


Assuntos
Doença de Crohn/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Tromboxanos/sangue , Adolescente , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Feminino , Flavonoides/administração & dosagem , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem
18.
Harefuah ; 158(11): 752-754, 2019 Nov.
Artigo em Hebraico | MEDLINE | ID: mdl-31721521

RESUMO

INTRODUCTION: TNFα antagonists, such as infliximab and adalimumab, are widely used for induction and maintenance of remission in pediatric patients with inflammatory bowel disease (IBD). Numerous studies in adult and pediatric patients have demonstrated that monitoring of anti-TNFα drug level improves various outcomes, especially in cases of primary non-response or loss-of-response. In this article we present the recommendations of the Israeli Pediatric Gastroenterology Association regarding measuring anti-TNFα drug and anti-drug levels in pediatric IBD patients. The recommendation to perform these studies will be provided only by a pediatric gastroenterologist based on clinical, laboratory, endoscopic or radiologic signs of active inflammation. We also recommend performing these studies once a year in patients with clinical and biochemical remission. We believe that implementing these recommendations will improve the care provided for pediatric patients with IBD.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Fator de Necrose Tumoral alfa , Criança , Doença de Crohn/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Pacientes , Fator de Necrose Tumoral alfa/antagonistas & inibidores
19.
Medicine (Baltimore) ; 98(44): e17722, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689810

RESUMO

BACKGROUND: Ulcerative colitis (UC) and Crohn disease (CD) are the 2 main types of inflammatory bowel diseases (IBDs). Several studies have been conducted to investigate the association of Glutathione S-Transferase M1 (GSTM1) null genotype with UC and CD, but the results are inconsistent. Here, we performed a meta-analysis to clarify this controversy based on relative large sample size. METHODS: A systematic article searching was conducted in the PubMed, EMBASE, SCOPUS, WOS, ProQuest, Chinese National Knowledge Infrastructure (CNKI), and Chinese Wanfang databases up to August 31, 2019. Meta-analysis results were synthesized by using crude odds ratio (OR) with its 95% confidence interval (CI). Heterogeneity, sensitivity analysis, subgroup analysis, and publication bias were assessed by using STATA 11.0 software. RESULTS: A total of 15 relevant studies including 4353 IBDs patients (1848 CD cases, 2505 UC cases) and 5413 controls were included in this meta-analysis. Totally, we found a significant association between GSTM1 null genotype and risk to IBDs in the overall populations (OR = 1.37, 95%CI = 1.13-1.65, P = .001). Stratified by ethnicity, we found a significant association between GSTM1 null genotype and risk to IBDs in the Asian population (OR = 2.54, 95%CI = 2.15-3.00, P = .001), but not in the Caucasian population. Stratified by disease type, we found a significant association between GSTM1 null genotype with CD in the Asian population (OR = 2.37, 95%CI = 1.11-5.06, P = .026), and with UC in the Asian (OR = 2.48, 95%CI = 1.93-3.20, P = .001) population. In addition, funnel plot and Egger linear regression test suggests no publication bias in all genetic models. CONCLUSION: GSTM1 null genotype is associated with susceptibility to IBD, UC, and CD in the Asian population. Further well-designed studies are still needed to confirm these findings.


Assuntos
Colite Ulcerativa/genética , Doença de Crohn/genética , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Humanos , Masculino , Razão de Chances
20.
Medicine (Baltimore) ; 98(46): e17510, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725605

RESUMO

Due to the complexity of Crohn's disease (CD), it is difficult to predict disease course with a single stratification factor or biomarker. A logistic regression (LR) model has been proposed by Guizzetti et al to stratify patients with CD-related surgical risk, which could help decision-making on disease treatment. However, there are no reports on relevant studies on Chinese population. The aim of the study is to present and validate a novel surgical predictive model to facilitate therapeutic decision-making for Chinese CD patients. Data was extracted from retrospective full-mode electronic medical records, which contained 239 CD patients and 1524 instances. Two sub-datasets were generated according to different attribute selection strategies, both of which were split into training and testing sets randomly. The imbalanced data in the training sets was addressed by synthetic minority over-sampling technique (SMOTE) algorithm before model development. Seven predictive models were employed using 5 popular machine learning algorithms: random forest (RF), LR, support vector machine (SVM), decision tree (DT) and artificial neural networks (ANN). The performance of each model was evaluated by accuracy, precision, F1-score, true negative (TN) rate, and the area under the receiver operating characteristic curve (AuROC). The result revealed that RF outperformed all other baseline models on both sub-datasets. The 10 leading risk factors for CD-related surgery returned from RF for attribute ranking were changes of radiology, presence of a fistula, presence of an abscess, no infliximab use, enteroscopy findings, C-reactive protein, abdominal pain, white blood cells, erythrocyte sedimentation rate and platelet count. The proposed machine learning model can accurately predict the risk of surgical intervention in Chinese CD patients, which could be used to tailor and modify the treatment strategies for CD patients in clinical practice.


Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Técnicas de Apoio para a Decisão , Endoscopia do Sistema Digestório/estatística & dados numéricos , Modelos Anatômicos , Adulto , Algoritmos , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , China , Árvores de Decisões , Feminino , Humanos , Modelos Logísticos , Aprendizado de Máquina/estatística & dados numéricos , Masculino , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Máquina de Vetores de Suporte
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