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1.
Medicine (Baltimore) ; 100(3): e24058, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546007

RESUMO

ABSTRACT: Mucosal healing (MH) has become a major target in the management of ulcerative colitis (UC). Because repeat endoscopy is expensive and invasive, we aimed to evaluate fecal calprotectin (FC) as an alternative marker to predict MH in UC.Eighty patients with UC in clinical remission were consecutively included in a prospective observational study. FC was measured using a quantitative enzyme-linked immunosorbent assay. The colonic mucosa was assessed for endoscopic and histological measures of inflammatory status. Endoscopic and histological remission were defined according to the Mayo endoscopic subscore (MES) and Geboes score (GS), respectively. Deep remission was defined as a combination of the MES and GS. FC performance and cutoff values for identifying MH and deep remission were determined using contingency tables and receiver operator characteristic (ROC) and area under the curve (AUC) analysis.The median FC concentration in patients who met the criteria for deep remission (MES ≤1 and GS < 3.1) was 65.5 µg/g, while that in patients with disease activity was 389.6 µg/g (P = .025). A FC cutoff value of 100 µg/g, determined by the ROC analysis, resulted in sensitivity and specificity of 91.7% and 57.1%, respectively, for histological remission, and 82.4% and 60.9%, respectively, for deep mucosal remission. Positive correlations were detected between FC concentrations with the histologic (CC: 0.435; P < .001) and the combined endoscopic and histologic (CC: 0.413; P < .001) scores.FC can be used confidently as a noninvasive biomarker to predict deep remission in patients with UC in clinical remission when concentrations are below 100 µg/g.


Assuntos
Colite Ulcerativa/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Adulto , Biomarcadores/metabolismo , Colite Ulcerativa/patologia , Estudos Transversais , Fezes/química , Feminino , Humanos , Mucosa Intestinal/patologia , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão
2.
Medicine (Baltimore) ; 100(1): e24059, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429768

RESUMO

ABSTRACT: Microbiota plays an important role in many diseases including inflammatory bowel diseases. Inflammatory bowel disease patients can have concurrent irritable bowel syndrome symptoms similar to those associated with a flare. The potential role of gut dysbiosis in the pathogenesis of inflammatory bowel disease provides a rationale for treating such patients with rifaximin. This study aimed to assess the efficacy of rifaximin in the management of irritable bowel syndrome-like symptoms (bloating, abdominal pain, stool consistency) and quality of life in patients with Crohn's disease in remission.The present study included 86 patients with Crohn's disease in remission (fecal calprotectin <50 µg/g, C-reactive protein <0.5 mg/dL, simple endoscopic score for Crohn's disease <2) and associated irritable bowel syndrome-like symptoms (bloating, abdominal pain, diarrhea). These patients were randomly assigned to rifaximin treatment group (44 patients) and the control group (42 patients). Besides the baseline inflammatory bowel disease treatment and antispasmodics (as needed), patients in the rifaximin treatment group received 3 repeated courses of treatment, each course being represented by 1200 mg/d of rifaximin for 10 days and 20 days free of treatment (3 months consecutively); patients in the control group also received antispamodics as needed and were observed for 3 months.Monthly analyses of bloating score, abdominal pain score, stool consistency score, and quality of life score showed significant improvement after treatment in the rifaximin group in contrast with control group. Significantly more patients in the rifaximin group than in the control group met the criteria for adequate improvement of bloating score after 3 months of treatment (59.09% vs 19.04%, P = .01), adequate improvement of abdominal pain score (54.5% vs 21.4%, P = .04), stool consistency score (34.09% vs 14.2%, P = .03), and quality of life score (70.4% vs 21.4%, P < .001).Rifaximin in a dose of 1200 mg/d, 10 d/mo, 3 months consecutively is an effective medication for concurrent irritable bowel syndrome-like symptoms in patients with Crohn's disease in remission.


Assuntos
Doença de Crohn/tratamento farmacológico , Rifaximina/normas , Dor Abdominal/tratamento farmacológico , Adulto , Proteína C-Reativa/análise , Doença de Crohn/complicações , Endoscopia/métodos , Fezes , Feminino , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/normas , Fármacos Gastrointestinais/uso terapêutico , Humanos , Complexo Antígeno L1 Leucocitário/análise , Masculino , Microbiota/efeitos dos fármacos , Pessoa de Meia-Idade , Remissão Espontânea , Rifaximina/farmacologia , Rifaximina/uso terapêutico
3.
Sci Rep ; 11(1): 1580, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452298

RESUMO

Patients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis. Further study of tPA as a biomarker is warranted.


Assuntos
/diagnóstico , Inibidor 1 de Ativador de Plasminogênio/sangue , Ativador de Plasminogênio Tecidual/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , /virologia , Estudos de Casos e Controles , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinólise , Hospitalização , Humanos , Contagem de Leucócitos , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Índice de Gravidade de Doença
4.
Am J Gastroenterol ; 116(1): 17-44, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315591

RESUMO

Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder that significantly reduces patients' quality of life. Advances in diagnostic testing and in therapeutic options for patients with IBS led to the development of this first-ever American College of Gastroenterology clinical guideline for the management of IBS using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Twenty-five clinically important questions were assessed after a comprehensive literature search; 9 questions focused on diagnostic testing; 16 questions focused on therapeutic options. Consensus was obtained using a modified Delphi approach, and based on GRADE methodology, we endorse the following: We suggest that a positive diagnostic strategy as compared to a diagnostic strategy of exclusion be used to improve time to initiating appropriate therapy. We suggest that serologic testing be performed to rule out celiac disease in patients with IBS and diarrhea symptoms. We suggest that fecal calprotectin be checked in patients with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease. We recommend a limited trial of a low fermentable oligosaccharides, disacchardies, monosaccharides, polyols (FODMAP) diet in patients with IBS to improve global symptoms. We recommend the use of chloride channel activators and guanylate cyclase activators to treat global IBS with constipation symptoms. We recommend the use of rifaximin to treat global IBS with diarrhea symptoms. We suggest that gut-directed psychotherapy be used to treat global IBS symptoms. Additional statements and information regarding diagnostic strategies, specific drugs, doses, and duration of therapy can be found in the guideline.


Assuntos
Agonistas dos Canais de Cloreto/uso terapêutico , Terapia Cognitivo-Comportamental , Constipação Intestinal/terapia , Diarreia/terapia , Dietoterapia , Fármacos Gastrointestinais/uso terapêutico , Agonistas da Guanilil Ciclase C/uso terapêutico , Síndrome do Intestino Irritável/terapia , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Constipação Intestinal/fisiopatologia , Técnica Delfos , Diagnóstico Diferencial , Diarreia/fisiopatologia , Gerenciamento Clínico , Fezes/química , Gastroenterologia , Humanos , Hipnose , Doenças Inflamatórias Intestinais/diagnóstico , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/fisiopatologia , Complexo Antígeno L1 Leucocitário/análise , Rifaximina/uso terapêutico , Testes Sorológicos , Sociedades Médicas
6.
Am J Trop Med Hyg ; 103(4): 1416-1426, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32618258

RESUMO

The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6-23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups (P = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations (P = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.


Assuntos
Biomarcadores/análise , Diarreia/tratamento farmacológico , Fezes/química , Zinco/administração & dosagem , Desenvolvimento Infantil/efeitos dos fármacos , Saúde da Criança , Diarreia/epidemiologia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Lactente , Laos/epidemiologia , Complexo Antígeno L1 Leucocitário/análise , Masculino , Micronutrientes/administração & dosagem , Micronutrientes/efeitos adversos , Micronutrientes/uso terapêutico , Neopterina/análise , Peroxidase/análise , Zinco/efeitos adversos , Zinco/uso terapêutico
7.
Br J Radiol ; 93(1112): 20200167, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32579403

RESUMO

OBJECTIVE: To compare the diagnostic performance of fecal biomarkers and 18F-fludeoxyglucose (18F-FDG) positron emmision tomography-MR (PET-MR) in the assessment of disease activity in patients with ulcerative colitis. METHODS: This study was conducted under the framework of a single-center clinical trial (clinicaltrials.gov [NCT03781284]). N = 50 participants were enrolled. Fecal samples were collected before bowel preparation. All patients underwent whole-body 18F-FDG PET-MR followed by ileocolonoscopy within 24 h. Diagnostic performance of five fecal biomarkers (calprotectin, lactoferrin, polymorphonuclear leukocyte elastase, S100A12 and eosinophil-derived neurotoxin), MR morphological parameters (MRmorph), diffusion-weighted imaging and PET in detecting active disease determined by Rachmilewitz endoscopic activity index (EAI) were evaluated and compared with each other. Correlations between fecal biomarkers, PET and endoscopy were calculated. RESULTS: According to EAI, n = 38 patients presented with endoscopically active disease (16 mild, 19 moderate and 3 severe). All five biomarkers, PET and MRmorph could differentiate endoscopically active disease from endoscopic remission without significant difference regarding their operating characteristics (accuracies between 0.673 for calprotectin and 0.898 for lactoferrin). In predicting endoscopically moderate to severe disease, PET showed the highest diagnostic performance (accuracy = 0.857) compared to calprotectin and lactoferrin (accuracy = 0.633 and 0.735). PET had also the strongest correlation with endoscopy (ρ = 0.685, p < 0.001), while within fecal biomarkers the levels of lactoferrin and eosinophil-derived neurotoxin correlated significantly with EAI (ρ = 0.423 and 0.528, both p < 0.05). CONCLUSION: Both fecal biomarkers and PET-MR were excellent non-invasive diagnostic tools in the assessment of disease activity in ulcerative colitis. ADVANCES IN KNOWLEDGE: Both fecal biomarkers and PET-MR parameters are able to predict endoscopically active disease with comparable diagnostic performance. PET had the highest correlation with endoscopy and outperformed fecal biomarkers in differentiating moderate to severe from mild disease.


Assuntos
Colite Ulcerativa/diagnóstico , Fezes/química , Imagem por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Biomarcadores/análise , Colite Ulcerativa/diagnóstico por imagem , Colonoscopia , Neurotoxina Derivada de Eosinófilo/análise , Feminino , Fluordesoxiglucose F18 , Humanos , Lactoferrina/análise , Elastase de Leucócito/análise , Complexo Antígeno L1 Leucocitário/análise , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Proteína S100A12/análise , Adulto Jovem
8.
Aliment Pharmacol Ther ; 52(2): 284-291, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32506635

RESUMO

BACKGROUND: Oncostatin M is upregulated in Crohn's disease inflamed intestinal mucosa, and has been suggested as a promising biomarker to predict responsiveness to anti-TNF therapy in patients with inflammatory bowel diseases. AIM: To evaluate the suitability of serum oncostatin M as a predictive marker of response to infliximab in Crohn's disease. METHODS: We included patients treated with infliximab monotherapy. All patients underwent colonoscopy at week 54 to evaluate mucosal healing. Serum oncostatin M and faecal calprotectin were measured at baseline and after 14 weeks of treatment. Mann-Whitney test was used to evaluate correlation of oncostatin M and faecal calprotectin at baseline and week 14 with mucosal healing at week 54. Their accuracy in predicting mucosal healing was assessed by area under the curve (AUC). RESULTS: In a cohort of 45 included patients, 27 displayed mucosal healing. At both baseline and week 14, oncostatin M levels were significantly lower in patients with mucosal healing than in patients not achieving this endpoint (P < 0.001). Faecal calprotectin levels at week 14 were lower also in responders than nonresponders (P < 0.001). Oncostatin M values at baseline and week 14 were significantly associated (Spearman correlation = 0.92, P < 0.001). The diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing (AUC = 0.91) was greater than faecal calprotectin (AUC = 0.51, P < 0.001). CONCLUSION: These results suggest that oncostatin M can predict the outcome of infliximab treatment. Compared with faecal calprotectin, the predictive capability of oncostatin M was appreciable at baseline, thus indicating oncostatin M as a promising biomarker for driving therapeutic choices in Crohn's disease.


Assuntos
Antirreumáticos/uso terapêutico , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Oncostatina M/sangue , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Colonoscopia , Doença de Crohn/patologia , Fezes/química , Feminino , Humanos , Doenças Inflamatórias Intestinais , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/uso terapêutico , Adulto Jovem
9.
Sci Rep ; 10(1): 6071, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269278

RESUMO

Mindfulness-based interventions have shown some efficacy in decreasing stress levels and improving quality of life. However, so far, only a few studies have studied this type of intervention among patients with inflammatory bowel disease and none of them have studied their effects on inflammatory biomarkers. This current study was a two-armed, single-centre, randomised (2:1 ratio) controlled trial used to evaluate the effects of a mindfulness-based intervention (n = 37) compared to standard medical therapy (n = 20) in patients with Crohn's disease or ulcerative colitis. The mindfulness intervention blended four internet-based therapy modules with four face-to-face support sessions. The outcomes we assessed were faecal calprotectin (primary outcome), C-reactive protein, and cortisol levels measured in hair samples at several timepoints. The between-group analysis highlighted significant decreases in faecal calprotectin and in C-reactive protein levels in the mindfulness-based intervention group compared to the standard medical therapy group at the six-month follow-up (faecal calprotectin: -367, [95% CI: -705, -29], P = 0.03; C-reactive protein: -2.82, [95% CI: -5.70, 0.08], P = 0.05), with moderate to large effect sizes (faecal calprotectin: ηp2 = 0.085; C-reactive protein: ηp2 = 0.066). We concluded that mindfulness-based therapy administered as part of standard clinical practice effectively improves inflammatory biomarkers in patients diagnosed with inflammatory bowel disease.


Assuntos
Colite Ulcerativa/terapia , Doença de Crohn/terapia , Atenção Plena/métodos , Adulto , Biomarcadores/análise , Proteína C-Reativa/análise , Feminino , Humanos , Hidrocortisona/sangue , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade
10.
Sci Rep ; 10(1): 5679, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32231227

RESUMO

Discriminating between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains difficult. Thus, novel and efficient biomarkers are required for the diagnosis of pleural effusion (PE). The aim of this study was to validate calprotectin as a diagnostic biomarker of PE in clinical settings. A total of 425 patients were recruited, and the pleural fluid samples collected had BPE in 223 cases (53.7%) or MPE in 137 patients (33%). The samples were all analysed following the same previously validated clinical laboratory protocols and methodology. Calprotectin levels ranged from 772.48 to 3,163.8 ng/mL (median: 1,939 ng/mL) in MPE, and 3,216-24,000 ng/mL in BPE (median: 9,209 ng/mL; p < 0.01), with an area under the curve of 0.848 [95% CI: 0.810-0.886]. For a cut-off value of ≤ 6,233.2 ng/mL, we found 96% sensitivity and 60% specificity, with a negative and positive predictive value, and negative and positive likelihood ratios of 96%, 57%, 0.06, and 2.4, respectively. Multivariate analysis showed that low calprotectin levels was a better discriminator of PE than any other variable [OR 28.76 (p < 0.0001)]. Our results confirm that calprotectin is a new and useful diagnostic biomarker in patients with PE of uncertain aetiology which has potential applications in clinical practice because it may be a good complement to cytological methods.


Assuntos
Complexo Antígeno L1 Leucocitário/análise , Derrame Pleural Maligno/diagnóstico , Derrame Pleural/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Pessoa de Meia-Idade , Pleura/patologia , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espanha/epidemiologia
11.
Aliment Pharmacol Ther ; 51(7): 689-698, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32048751

RESUMO

BACKGROUND: Histologic healing is emerging as a new therapeutic goal in both routine practice and clinical trials in ulcerative colitis (UC). However, it requires repeated endoscopies and biopsies. Faecal calprotectin is a non-invasive marker of mucosal healing (endoscopic and histologic healing). AIM: To conduct a systematic review to clarify the correlation between faecal calprotectin levels and histologic activity in UC patients. METHODS: We searched PubMed/MEDLINE, EMBASE and Web of Science through September 2019 to identify studies in patients with confirmed diagnosis of UC, reporting the correlation between faecal calprotectin levels and histologic analysis. RESULTS: Twelve studies enrolling 1168 patients were included in the final review. Histologic remission was defined according to nonvalidated scores in five articles and using partially validated scores in seven articles. Faecal calprotectin values were measured in 6 of 12 studies (50%) with the same kit, while the remaining six studies adopted individually different kits. A clear correlation between faecal calprotectin levels and histology was showed in all included studies. Eleven different faecal calprotectin cut-off points were identified to distinguish histological remission from histological activity, ranging from 40.5 to 250 µg/g. CONCLUSIONS: Faecal calprotectin can be used to predict histologic remission in patients with UC, but the cut-off level varies across studies, according to the test used to measure this biomarker and according to the definition of histologic remission. Larger prospective studies using validated histologic indexes are needed to identify a globally accepted faecal calprotectin cut-off level to discriminate between histologic remission and histologically active disease.


Assuntos
Colite Ulcerativa/patologia , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Adulto , Biomarcadores/análise , Biópsia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Cicatrização/fisiologia
12.
BMC Gastroenterol ; 20(1): 35, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054445

RESUMO

BACKGROUND: Effective control of the inflammatory process in Crohn's disease (CD) is reflected in intestinal mucosal healing. The performances of faecal calprotectin (fcal), clinical and serologic parameters in the inflammatory activity evaluation and their correlation to the simple endoscopic score (SES-CD) are the goals of this study. METHODS: Patients with CD referred for ileocolonoscopy were prospectively included and distributed according to the degree of endoscopic inflammatory activity into remission, mild activity, and moderate to severe activity groups. The different degrees of endoscopic activity were correlated with the following indexes: Crohn's disease activity index (CDAI), fCal, serum C-reactive protein (CRP), and haemogram. The control group comprised individuals without known intestinal disease who were referred for colorectal cancer screening. RESULTS: Eighty colonoscopies were performed in patients with CD and 21 in the control group. The control group had a lower median fCal (59.7 mcg/g) than patients with CD (683 mcg/g, p < 0.001). A moderate Spearman correlation occurred between SES-CD and CRP (r = 0.525), fCal (r = 0.450), and CDAI (r = 0.407), while a weak correlation was found with the platelet count (r = 0.257). Only fCal distinguished patients in remission from those with mild activity (236.6 mcg/g × 654.9 mcg/g, p = 0.014) or moderate to severe activity (236.6 mcg/g × 1128 mcg/g, p < 0.001). An fCal cut-off of 155 mcg/g was sensitive (96%) and accurate (78%) for the diagnosis of endoscopic activity. CONCLUSIONS: fCal provides greater diagnostic accuracy than the other activity markers for endoscopic activity of patients with CD, moderate correlation to SES-CD, and a capacity to discriminate patients in remission from those with mild or moderate to severe activity.


Assuntos
Doença de Crohn/patologia , Fezes/química , Mucosa Intestinal/patologia , Complexo Antígeno L1 Leucocitário/análise , Adulto , Idoso , Biomarcadores/análise , Proteína C-Reativa/análise , Colonoscopia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
Cochrane Database Syst Rev ; 1: CD012949, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31962375

RESUMO

BACKGROUND: Cystic fibrosis (CF) is a multisystem disease and the importance of growth and nutrition has been well established, given its implications for lung function and overall survival. It has been established that intestinal dysbiosis (i.e. microbial imbalance) and inflammation is present in people with CF. Probiotics are commercially available (over-the-counter) and may improve both intestinal and overall health. OBJECTIVES: To assess the efficacy and safety of probiotics for improving health outcomes in children and adults with CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last register search: 20 January 2020. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 29 January 2019. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials (RCTs) assessing efficacies and safety of probiotics in children and adults with CF. Cross-over RCTs with a washout phase were included and for those without a washout period, only the first phase of each trial was analysed. DATA COLLECTION AND ANALYSIS: We independently extracted data and assessed the risk of bias of the included trials; we used GRADE to assess the certainty of the evidence. We contacted trial authors for additional data. Meta-analyses were undertaken on outcomes at several time points. MAIN RESULTS: We identified 17 trials and included 12 RCTs (11 completed and one trial protocol - this trial was terminated early) (464 participants). Eight trials included only children, whilst four trials included both children and adults. Trial duration ranged from one to 12 months. Nine trials compared a probiotic (seven single strain and three multistrain preparations) with a placebo preparation, two trials compared a synbiotic (multistrain) with a placebo preparation and one trial compared two probiotic preparations. Overall we judged the risk of bias in the 12 trials to be low. Three trials had a high risk of performance bias, two trials a high risk of attrition bias and six trials a high risk of reporting bias. Only two trials were judged to have low or unclear risk of bias for all domains. Four trials were sponsored by grants only, two trials by industry only, two trials by both grants and industry and three trials had an unknown funding source. Combined data from four trials (225 participants) suggested probiotics may reduce the number of pulmonary exacerbations during a four to 12 month time-frame, mean difference (MD) -0.32 episodes per participant (95% confidence interval (CI) -0.68 to 0.03; P = 0.07) (low-certainty evidence); however, the 95% CI includes the possibility of both an increased and a reduced number of exacerbations. Additionally, two trials (127 participants) found no evidence of an effect on the duration of antibiotic therapy during the same time period. Combined data from four trials (177 participants) demonstrated probiotics may reduce faecal calprotectin, MD -47.4 µg/g (95% CI -93.28 to -1.54; P = 0.04) (low-certainty evidence), but the results for other biomarkers mainly did not show any difference between probiotics and placebo. Two trials (91 participants) found no evidence of effect on height, weight or body mass index (low-certainty evidence). Combined data from five trials (284 participants) suggested there was no difference in lung function (forced expiratory volume at one second (FEV1) % predicted) during a three- to 12-month time frame, MD 1.36% (95% CI -1.20 to 3.91; P = 0.30) (low-certainty evidence). Combined data from two trials (115 participants) suggested there was no difference in hospitalisation rates during a three- to 12-month time frame, MD -0.44 admissions per participant (95% CI -1.41 to 0.54; P = 0.38) (low-certainty evidence). One trial (37 participants) reported health-related quality of life and while the parent report favoured probiotics, SMD 0.87 (95% CI 0.19 to 1.55) the child self-report did not identify any effect, SMD 0.59 (95% CI -0.07 to 1.26) (low-certainty evidence). There were limited results for gastrointestinal symptoms and intestinal microbial profile which were not analysable. Only four trials and one trial protocol (298 participants) reported adverse events as a priori hypotheses. No trials reported any deaths. One terminated trial (12 participants and available as a protocol only) reported a severe allergic reaction (severe urticaria) for one participant in the probiotic group. Two trials reported a single adverse event each (vomiting in one child and diarrhoea in one child). The estimated number needed to harm for any adverse reaction (serious or not) is 52 people (low-certainty evidence). AUTHORS' CONCLUSIONS: Probiotics significantly reduce faecal calprotectin (a marker of intestinal inflammation) in children and adults with CF, however the clinical implications of this require further investigation. Probiotics may make little or no difference to pulmonary exacerbation rates, however, further evidence is required before firm conclusions can be made. Probiotics are associated with a small number of adverse events including vomiting, diarrhoea and allergic reactions. In children and adults with CF, probiotics may be considered by patients and their healthcare providers. Given the variability of probiotic composition and dosage, further adequately-powered multicentre RCTs of at least 12 months duration are required to best assess the efficacy and safety of probiotics for children and adults with CF.


Assuntos
Fibrose Cística/microbiologia , Fibrose Cística/terapia , Complexo Antígeno L1 Leucocitário/análise , Probióticos/uso terapêutico , Fibrose Cística/complicações , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
J Gastroenterol Hepatol ; 35(8): 1340-1346, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31999379

RESUMO

BACKGROUND AND AIMS: Small intestinal lesions in patients with Behçet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions. METHODS: This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls. RESULTS: Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P = 0.034 and P = 0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value = 119 µg/g) and FL (cutoff value = 17 µg/g) were biomarkers for small intestinal lesions in patients with BD. CONCLUSION: The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.


Assuntos
Síndrome de Behçet/complicações , Endoscopia por Cápsula , Fezes/química , Enteropatias/diagnóstico , Enteropatias/etiologia , Intestino Delgado , Lactoferrina/análise , Complexo Antígeno L1 Leucocitário/análise , Adolescente , Adulto , Biomarcadores/análise , Feminino , Humanos , Enteropatias/diagnóstico por imagem , Enteropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Adulto Jovem
15.
J Pediatr ; 219: 76-82.e3, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31987658

RESUMO

OBJECTIVE: To investigate the additional value of blood parameters (hemoglobin, C-reactive protein, erythrocyte sedimentation rate) to anti-tissue transglutaminase (anti-tTG), fecal calprotectin, and Giardia lamblia when discriminating a functional from an organic cause in the clinical evaluation of children with chronic abdominal pain. STUDY DESIGN: This retrospective cohort study included patients (4-18 years of age) with abdominal pain for >2 months. Data on hemoglobin, C-reactive protein, erythrocyte sedimentation rate, anti-tTG, fecal calprotectin, alarm symptoms, and diagnosis were collected. RESULTS: We identified 853 patients, of whom 102 (12%) had an organic disorder. Sensitivity and the area under the curve of strategy 1 (fecal calprotectin, anti-tTG, G lamblia, blood parameters) were 90% (95% CI, 83-95) and 0.87 (95% CI, 0.81-0.93), respectively, compared with 88% (95% CI, 81-93) and 0.85 (95% CI, 0.79-0.91), respectively, for strategy 2 (fecal calprotectin, anti-tTG, G lamblia) (P = NS). In the presence of ≥1 alarm symptoms, the sensitivity of strategies 1 and 2 was 92% (95% CI, 83-96) and 92% (95% CI, 83-96), and the areas under the curve were 0.93 (95% CI, 0.89-0.98) and 0.90 (95% CI, 0.84-0.97) (P = NS). CONCLUSIONS: To distinguish between a functional and an organic cause for chronic abdominal pain, hemoglobin, C-reactive protein, and erythrocyte sedimentation rate can be left out from the clinical evaluation as they might have no additional diagnostic yield. However, caution should be taken not to miss extraintestinal infections (2%).


Assuntos
Dor Abdominal/sangue , Gastroenteropatias/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Dor Abdominal/etiologia , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Fezes/química , Feminino , Giardia lamblia/isolamento & purificação , Humanos , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade
16.
J Gastroenterol Hepatol ; 35(3): 390-400, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31795013

RESUMO

Although lacking validated cutoff values, fecal calprotectin (FC), besides C-reactive protein, is considered the standard test for assessing disease activity in Crohn's disease (CD). The aim of the present review is to provide a general overview of the literature addressing the role of FC in the clinical and endoscopic assessment of disease activity in CD, seeking correlations with capsule endoscopy, response to therapy, prediction of relapse, and postoperative recurrence. A systematic search of the literature up to September 2019 was performed using Medline, Embase, and the Cochrane Library. Only papers written in English concerning FC in adult patients affected by CD were included. Pediatric studies, in vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC in ulcerative colitis or in both CD and ulcerative colitis were excluded. Out of 713 citations, 65 eligible studies were identified. FC showed high accuracy in the assessment of intestinal inflammation and response to therapy, in particular in colonic disease, thus proving a good surrogate marker for these aims. FC is useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence, for optimizing or downstage therapy. Unfortunately, FC performs less well in small bowel CD. FC is an effective fecal marker in the management of CD patients, optimizing the use of endoscopic procedures. Owing to its diagnostic accuracy, FC may represent a cornerstone of the "treat-to-target" management strategy of CD patients.


Assuntos
Endoscopia por Cápsula , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Biomarcadores/análise , Humanos
17.
Oral Dis ; 26(3): 558-565, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31845422

RESUMO

OBJECTIVE: We investigated whether patients with geographic tongue have increased salivary levels of calprotectin and whether there is a correlation between the salivary levels of calprotectin and interleukin 8 (IL-8), which is another marker of inflammation. METHODS: Twenty-three patients diagnosed with geographic tongue and 32 control subjects without oral mucosal lesions were included in the study. The patients with geographic tongue were classified based on clinical appearance and number of oral lesions. ELISAs were used to determine the levels of calprotectin and IL-8 in whole saliva samples. RESULTS: There was a statistically significant increase in the salivary output of calprotectin in patients with geographic tongue compared with the healthy controls (62 ± 9,1 vs. 37,5 ± 4,7 µg/min; p = .0134). Furthermore, the levels of calprotectin correlated positively with the number of oral lesions in patients with geographic tongue. There was also a significant and positive correlation between the salivary levels of calprotectin and IL-8, both for the patients with geographic tongue and the controls. CONCLUSION: This study supports the notion that GT is an inflammatory disease, in which the activation of neutrophils and production of calprotectin in the saliva may play roles in its pathogenesis.


Assuntos
Glossite Migratória Benigna/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Saliva/química , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Glossite Migratória Benigna/patologia , Humanos , Inflamação , Interleucina-8/análise
18.
Am J Physiol Gastrointest Liver Physiol ; 318(2): G361-G369, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31869241

RESUMO

Longer colonic transit time and hard stools are associated with increased gut microbiota diversity. Here, we investigate to what extent quantitative measures of (segmental) colonic transit time were related to gut microbiota composition, microbial metabolites, and gut-related parameters in a human cross-sectional study. Using radiopaque markers, (segmental) colonic transit time (CTT) was measured in 48 lean/overweight participants with long colonic transit but without constipation. Fecal microbiota composition was determined using 16S rRNA gene amplicon sequencing. Associations between gastrointestinal transit (segmental CTT and stool frequency and consistency), microbiota diversity and composition, microbial metabolites [short-chain fatty acids (SCFA), branched-chain fatty acids, and breath hydrogen], habitual diet, and gut-related host parameters [lipopolysaccharide-binding protein (LBP) and fecal calprotectin] were investigated using univariate and multivariate approaches. Long descending (i.e., distal) colonic transit was associated with increased microbial α-diversity but not with stool consistency. Using unweighted and weighted UniFrac distance, microbiota variation was not related to (segmental) CTT but to demographics, diet, plasma LBP, and fecal calprotectin. Bray-Curtis dissimilarity related only to stool consistency. Rectosigmoid and descending colonic transit were negatively associated with fecal SCFA and plasma acetate, respectively. This study suggests that the distal colon transit may affect not only microbiota diversity but also microbial metabolism.NEW & NOTEWORTHY We extend previous findings showing that long distal colonic transit time influences microbial diversification and fermentation, whereas stool consistency is related to microbiota composition in humans with a long colonic transit. This study puts the importance of the (distal) colonic site in microbiota ecology forward, which should be considered in future therapeutic studies targeting, for instance, short-chain fatty acid production to improve metabolic health.


Assuntos
Colo/fisiopatologia , Microbioma Gastrointestinal , Trânsito Gastrointestinal , Adulto , Envelhecimento/fisiologia , Colo/microbiologia , Estudos Transversais , Dieta , Ácidos Graxos Voláteis/análise , Fezes/microbiologia , Feminino , Fermentação , Motilidade Gastrointestinal , Humanos , Complexo Antígeno L1 Leucocitário/análise , Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Sobrepeso/fisiopatologia , RNA Ribossômico 16S/análise , Caracteres Sexuais , Adulto Jovem
19.
Gastroenterology ; 158(3): 515-526.e10, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31711925

RESUMO

BACKGROUND & AIMS: Noninvasive tests to measure endoscopic activity in patients with Crohn's disease (CD) have limitations. We aimed to develop a test to identify patients in remission, based on endoscopic analysis, and monitor CD activity based on serum levels of proteins. METHODS: We developed a test to measure 13 proteins in blood (ANG1, ANG2, CRP, SAA1, IL7, EMMPRIN, MMP1, MMP2, MMP3, MMP9, TGFA, CEACAM1, and VCAM1), called the endoscopic healing index [EHI], using samples from 278 patients with CD from a multinational training cohort. We validated the test using 2 independent cohorts of patients with CD: 116 biologic-naive patients with early-stage CD (validation cohort 1) and 195 biologic-exposed patients with chronic CD (validation cohort 2). The ability of the test to identify patients with active disease vs patients in remission (defined as a simple endoscopic score for CD of ≤2 and ≤1 in each segment, or a total CD endoscopic index of severity score <3) was assessed by using area under receiver operating characteristic curve (AUROC) analysis. The diagnostic accuracy of the test was compared with that of measurement of serum C-reactive protein (CRP) and fecal calprotectin. RESULTS: The EHI scores range from 0 to 100 units; higher scores indicate more severe CD activity, based on endoscopy findings. The EHI identified patients in remission with an AUROC of 0.962 in validation cohort 1 (95% confidence interval, 0.942-0.982) and an AUROC of 0.693 in validation cohort 2 (95% confidence interval, 0.619-0.767), regardless of CD location or phenotype. A cutoff value of 20 points identified patients in remission with the highest level of sensitivity (97.1% in validation cohort 1 and 83.2% in validation cohort 2), with specificity values of 69.0% and 36.6%, respectively. A cutoff value of 50 points identified patients in remission with the highest level of specificity (100% in validation cohort 1 and 87.8% in validation cohort 2), with sensitivity values of 37.3% and 30.0%, respectively. The EHI identified patients in remission with a significantly higher AUROC value than the test for CRP (0.876, P < .001 in validation cohort 1 and 0.624, P = .109 in validation cohort 2). In analysis of patients with available FC measurements, the AUROC value for the EHI did not differ significantly from that of measurement of FC (AUROC, 0.950 for EHI vs AUROC, 0.923 for FC; P = .147 in validation cohort 1 and AUROC, 0.803 for EHI vs AUROC, 0.854 for FC; P = .298 in validation cohort 2). CONCLUSIONS: We developed an index called the EHI to identify patients with CD in endoscopic remission based on blood levels of 13 proteins. The EHI identified patients with resolution of endoscopic disease activity, with good overall accuracy, although with variation between the 2 cohorts assessed. The EHI AUROC values were comparable to measurement of FC and higher than measurement of serum CRP. The test might be used in practice to assess endoscopic activity in patients with CD.


Assuntos
Colonoscopia , Doença de Crohn/diagnóstico , Fármacos Gastrointestinais/administração & dosagem , Infliximab/administração & dosagem , Índice de Gravidade de Doença , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Fezes/química , Feminino , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Recidiva , Indução de Remissão/métodos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Gastroenterol Hepatol ; 43(1): 57-61, 2020 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31733888

RESUMO

INTRODUCTION: Colonoscopy is currently considered to be the gold standard for evaluation of colonic mucosa inflammation in patients with ulcerative colitis (UC), but the procedure is invasive and cannot be repeated frequently, especially in the paediatric population. The aim of this study was to assess the role of faecal calprotectin (FC) as a predictor of endoscopic disease activity in paediatric patients with UC in clinical remission. MATERIAL AND METHODS: Single-centre prospective study. Clinical remission was defined as Paediatric Ulcerative Colitis Activity Index <10. Endoscopic findings were assessed according to the Mayo Endoscopic Subscore (MES). MES≤1 was defined as endoscopic remission. All participants provided fresh faecal samples for measurement of FC. RESULTS: A total of 34 visits of 24 children with UC were included in the study. There was a strong positive correlation between FC levels and endoscopic disease activity (n=34, r=0.83, p<0.001). The median FC levels in the subgroup with endoscopic activity (MES 2-3) were significantly higher than the median FC levels in the subgroup without endoscopic activity (MES≤1) (1000µg/g, IQR 575-1800µg/g vs. 100µg/g, IQR 80-223µg/g, p<0.001). At a cut-off of 298.5µg/g, FC had 92.3% sensitivity, 95.2% specificity and an AUROC 0.974 (SE 0.023, 95% CI 0.93-1, p<0.001) to predict endoscopic activity. DISCUSSION: FC is an accurate surrogate marker of endoscopic activity in children with clinically quiescent UC.


Assuntos
Colite Ulcerativa/diagnóstico , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Adolescente , Biomarcadores/análise , Criança , Pré-Escolar , Colite Ulcerativa/diagnóstico por imagem , Colonoscopia , Feminino , Humanos , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade
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