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1.
Inflamm Bowel Dis ; 25(11): 1862-1870, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31006801

RESUMO

BACKGROUND: Anti-tumor necrosis factor agents (anti-TNFs) are efficacious at preventing the postoperative recurrence (POR) of Crohn disease, as demonstrated in 2 randomized controlled trials. However, real-life data for infliximab or adalimumab in this setting are scarce. Our aim was to assess both the efficiency of anti-TNFs at preventing early POR of Crohn disease in clinical practice and the associated risk factors for POR. METHODS: Patients in whom anti-TNFs were prescribed for the prevention of POR within 3 months after ileocolonic resection and who had an endoscopic assessment within 18 months were identified from the ENEIDA registry. Clinical and endoscopic features were collected within 18 months after surgery. RESULTS: In total, 152 patients were included (55 treated with infliximab, 97 with adalimumab, and 39% with concomitant immunosuppressants). Anti-TNF treatment was started after a median time of 29 days (IQR 13-44) after surgery. Eighty-two percent of patients had at least one risk factor for POR, and 82% had been exposed to anti-TNFs before the index surgery. Overall, 34% had endoscopic POR (as defined using a Rutgeerts endoscopic score > i1); 14% had advanced endoscopic POR (>i2); and 20% had clinical POR, with no differences between infliximab and adalimumab. In the multivariate analysis, only perianal disease (odds ratio 2.73, 95% confidence interval [CI] 1.26-5.91) and rectal involvement (odds ratio 2.79, 95% CI 1.09-7.14) were independent predictors of endoscopic POR. CONCLUSIONS: In clinical practice, anti-TNFs for the prevention of POR of Crohn disease are frequently used in patients experienced with anti-TNFs and with concomitant immunosuppressants. The efficacy of infliximab and adalimumab for POR prevention is similar and in accordance with the results obtained in randomized controlled trials.

2.
Int J Colorectal Dis ; 34(5): 861-865, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30826963

RESUMO

PURPOSE: Nivolumab, a monoclonal antibody-targeting programmed cell death protein-1, is being increasingly used for the treatment of some advanced neoplasms. Several of its adverse effects are a result of the upregulation of T cells, with colitis as one of the most severe, and a challenging differential diagnosis with ulcerative colitis. However, few real-life clinical practice cases have been reported beyond trials. Our aim was to report a series of new cases, reviewing previously communicated endoscopic-proven nivolumab-induced colitis. METHOD: All patients treated with nivolumab in three university centers were identified and those who developed immune-mediated colitis (defined as the presence of diarrhea and evidence of colitis demonstrated by colonoscopy) were described. Additionally, a review of case reports of nivolumab-induced colitis reported in the literature up to March 2018 was performed. RESULTS: Six new cases of nivolumab-induced colitis and 13 previously reported cases out of randomized clinical trials are described. Colonoscopy showed a mucosal pattern mimicking ulcerative colitis in a large proportion of patients. Clostridium difficile superinfection was observed in two out of 19 cases. All but three patients definitively discontinued nivolumab therapy. Most patients were initially managed with oral or intravenous corticosteroids, but five of them required rescue therapy with infliximab. CONCLUSIONS: Nivolumab-induced colitis may mimic ulcerative colitis. Steroid therapy (oral or intravenously) is often efficient, but one-fourth of patients need rescue therapy with anti-TNF. Intestinal superinfection with Clostridium difficile or cytomegalovirus should be ruled out before starting immunosuppressive therapy.


Assuntos
Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Nivolumabe/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa/patologia , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
Dig Liver Dis ; 51(5): 669-674, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30606697

RESUMO

BACKGROUND: Peculiarities of inflammatory bowel disease (IBD) have been explored in ethnic groups, such as Asians, Hispanics, and Afro-Americans, but not in other ethnic minorities, such as Roma/Gypsies. METHODS: In a retrospective, hospital-based study, all adult Roma/Gypsy patients included in the IBD databases of seven Spanish centres were identified as cases. For each Roma/Gypsy patient, a Caucasian patient, matched for several demographic features, was searched as a control. Data on phenotypic features, therapeutic requirements, and familial aggregation were recorded. RESULTS: Sixty-eight Roma/Gypsy patients were identified, 29 of them being women. The mean age at diagnosis of IBD was 24.9±9.5years, and the mean time elapsed since diagnosis was 96.6±72.2months. Roma/Gypsy IBD patients showed a significantly higher rate of familial aggregation (43%) than their Caucasian controls (9%) (p=0.00001). CD in Roma/Gypsies had more often a complicated pattern (mainly penetrating) while UC patients showed a marked trend to more often developing extraintestinal manifestations. In addition, Roma/Gypsy IBD patients had a somewhat greater need for immunosuppressants, biological agents or surgery. CONCLUSIONS: These are the first data on IBD in Roma/Gypsy patients. Familial aggregation is the most prominent feature in these patients, suggesting a predominant role of genetics in its pathogenesis.


Assuntos
Doenças Inflamatórias Intestinais/etnologia , Fenótipo , Roma/estatística & dados numéricos , Adolescente , Adulto , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/terapia , Masculino , Espanha/epidemiologia , Adulto Jovem
4.
J Crohns Colitis ; 13(3): 385-388, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30346606

RESUMO

BACKGROUND: Colonic cytomegalovirus [CMV] reactivation has been involved in steroid refractoriness in patients with active ulcerative colitis [UC]. The benefits of antiviral therapy in this clinical setting are still under debate, but the burden of viral reactivation has been associated with a poorer outcome in some studies. Our aim was to assess whether the burden of CMV reactivation measured by the number of viral inclusions by immunohistochemistry [IHC-CMV] is associated with a risk of colectomy. METHODS: Biopsy sets of UC patients with positive IHC-CMV were identified from the Pathology departments of three university hospitals. All biopsies were reviewed by expert pathologists, and the maximum number of IHC-CMV-positive cells in each biopsy set was re-assessed. Epidemiological and clinical features and clinical outcomes were recorded. RESULTS: Forty-six positive IHC-CMV cases with UC were included. At the time of CMV reactivation, 70% were receiving corticosteroids, 33% azathioprine, and 24% anti-tumour necrosis factor [TNF] agents. Thirty-two patients [70%] were treated with antiviral therapy. The median number of IHC-CMV-positive cells was 2 cells/biopsy [IQR 1-4]. Fourteen patients [30%] underwent colectomy, and 4 of them [29%] showed persistence of CMV in the surgical specimen. In the multivariate analysis, colectomy was only associated with >2 positive cells/biopsy [p = 0.048] and younger age [p = 0.023]. CONCLUSIONS: The burden of CMV colonic reactivation in patients with active UC, as measured by IHC, seems to be related to the risk of colectomy, and more data is needed to understand whether antiviral therapy guided by CMV burden will alter the clinical outcome.


Assuntos
Colectomia , Colite Ulcerativa/cirurgia , Colo/virologia , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/fisiologia , Ativação Viral , Corticosteroides/uso terapêutico , Adulto , Fatores Etários , Antivirais/uso terapêutico , Azatioprina/uso terapêutico , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colo/patologia , Infecções por Citomegalovirus/complicações , Feminino , Humanos , Imuno-Histoquímica , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prognóstico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Valganciclovir/uso terapêutico
5.
Aliment Pharmacol Ther ; 48(8): 807-816, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30178869

RESUMO

BACKGROUND: The convoluted relationship between obesity, bariatric surgery and inflammatory bowel disease (IBD) is of increasing interest. AIM: To analyse evidence regarding the role of bariatric surgery in the development of de novo IBD and its impact on clinical outcomes and safety in patients with established IBD. METHODS: A PubMed/Medline search was performed to identify studies reporting the development of IBD after bariatric surgery and the outcomes of IBD patients after bariatric surgery. RESULTS: Eighty patients were reported to have developed de novo IBD after bariatric surgery (21% ulcerative colitis [UC], 75% Crohn's disease [CD]), mostly females. Roux-en-Y gastric bypass was the most frequent bariatric technique (80%). Symptoms related to IBD occurred within 1 month and 16 years after surgery. Regarding patients with known IBD undergoing bariatric surgery, 60 patients (35 CD, 24 UC, and 1 unclassified colitis) have been reported. Sleeve gastrectomy was the most frequent bariatric procedure, particularly in CD patients. Acute flares after surgery were observed in only four UC patients. In addition, two retrospective population-based studies described perioperative outcomes of bariatric surgery on IBD patients, demonstrating only a significant increase in small bowel obstruction in these patients. CONCLUSIONS: Bariatric surgery in carefully selected patients with established IBD is technically feasible and probably safe. Development of de novo IBD should be taken into account in individuals with previous bariatric surgery who develop diarrhoea, anaemia or excessive weight loss.


Assuntos
Cirurgia Bariátrica/métodos , Colite Ulcerativa/cirurgia , Doença de Crohn/cirurgia , Obesidade/cirurgia , Feminino , Gastrectomia/métodos , Derivação Gástrica/métodos , Humanos , Masculino , Resultado do Tratamento , Perda de Peso
7.
United European Gastroenterol J ; 6(2): 322-330, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29511562

RESUMO

Background: Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. Objective: The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Methods: Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. Results: A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. Conclusions: The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population.

8.
Scand J Gastroenterol ; 53(2): 152-157, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29189092

RESUMO

BACKGROUND: Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (UC), and it is a good predictor of relapse. However, its use in clinical practice is constrained by the need for the patient to deliver stool samples, and for their handling and processing in the laboratory. The availability of hand held devices might spread the use of FC in clinical practice. OBJECTIVES: To evaluate the usefulness of a rapid semi-quantitative test of FC in predicting relapse in patients with UC in remission. MATERIALS AND METHODS: Prospective, multicenter study that included UC patients in clinical remission for ≥6 months on maintenance treatment with mesalamine. Patients were evaluated clinically and semi-quantitative FC was measured using a monoclonal immunochromatography rapid test at baseline and every three months until relapse or 12 months of follow-up. RESULTS: One hundred and ninety-one patients had at least one determination of FC. At the end of follow-up, 33 patients (17%) experienced clinical relapse. Endoscopic activity at baseline (p = .043) and having had at least one FC > 60 µg/g during the study period (p = .03) were associated with a higher risk of relapse during follow-up. We obtained a total of 636 semi-quantitative FC determinations matched with a three-month follow-up clinical assessment. Having undetectable FC was inversely associated with early relapse (within three months), with a negative predictive value of 98.6% and a sensitivity of 93.9%. CONCLUSIONS: Serial, rapid semi-quantitative measurement of FC may be a useful, easy and cheap monitoring tool for patients with UC in remission.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Mesalamina/uso terapêutico , Adulto , Biomarcadores/análise , Colonoscopia , Feminino , Humanos , Mucosa Intestinal/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Indução de Remissão , Índice de Gravidade de Doença , Espanha
10.
Gastroenterol. hepatol. (Ed. impr.) ; 40(10): 663-668, dic. 2017. graf, tab
Artigo em Inglês | IBECS | ID: ibc-169208

RESUMO

Background: Ulcerative proctitis (UP) presents distinctive clinical characteristics, outcomes and therapeutic approaches as compared to left-sided and extensive ulcerative colitis (UC). Aim: To describe the current therapeutic requirements and clinical outcomes in patients with active UP. Methods: Retrospective observational study conducted in a referral IBD centre. Patients with UP in follow-up between 1989 and 2014 were included. The clinical characteristics, as well as the different treatments and drug formulations administered to treat flares, were recorded. Results: Out of 687 UC patients, 101 patients (15%) with UP were included. Median follow-up was 8 years (IQR 3-14) and 49% of patients presented disease activity during the study period. Topical mesalazine monotherapy (90%) was the most commonly administered treatment for disease activity (mostly as suppositories), followed by topical steroids (47%) and oral mesalazine (56%) in monotherapy or combination therapy. Only 14% and 16% of patients required oral prednisone and beclomethasone, respectively. Conclusions: In clinical practice, active UP presents mostly favourable outcomes. Mesalazine suppositories are by far the most used treatment for these patients (AU)


Antecedentes: La proctitis ulcerosa (PU) presenta unas características clínicas, evolutivas y terapéuticas distintas con respecto a la colitis ulcerosa izquierda o extensa. Objetivo: Describir los requerimientos terapéuticos y la evolución clínica en pacientes con PU activa. Métodos: Estudio observacional retrospectivo realizado en un centro de referencia en EII, en el que se incluyeron pacientes en seguimiento entre 1989 y 2014 con PU. Se registraron las características clínicas, así como los diferentes tratamientos y galénicas utilizados para tratar el brote de actividad. Resultados: De un total de 687 pacientes con colitis ulcerosa se incluyeron 101 (15%) con PU. La mediana de seguimiento fue de 8 años (RIC 3-14). El 49% de los pacientes presentó actividad de la enfermedad durante el período a estudio. La monoterapia con mesalazina tópica (90%) fue el tratamiento más utilizado para la actividad de la enfermedad (predominantemente en forma de supositorios), seguida de los esteroides tópicos (47%) y la mesalazina oral (56%) en monoterapia o en terapia combinada. Solo el 14 y el 16% de los pacientes requirieron prednisona oral y beclometasona, respectivamente. Conclusiones: En la práctica clínica, los supositorios de mesalazina son el tratamiento más utilizado en pacientes con PU activa, presentando la mayoría de ellos una evolución clínica favorable (AU)


Assuntos
Humanos , Proctite/terapia , Surtos de Doenças , Prednisona/uso terapêutico , Beclometasona/uso terapêutico , Supositórios/uso terapêutico , Mesalamina/uso terapêutico , Administração Tópica , Estudos Retrospectivos , Proctite/complicações
11.
Dig Liver Dis ; 49(12): 1327-1331, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28958412

RESUMO

BACKGROUND: It has been suggested that acute histological activity has a prognostic value in the outcome of ulcerative colitis (UC) patients in clinical and endoscopic remission. Our aim was to assess the role of histology as a risk factor for clinical relapse (CR) in patients in both clinical and endoscopic remission. METHODS: Patients with left-sided or extensive UC in clinical and endoscopic remission (Mayo endoscopic subscore ≤1) undergoing colonoscopy for dysplasia surveillance with random colonic biopsies between 2005-2015 were included. Basal plasmacytosis, acute (AHA), and the chronic (CHA) histological inflammatory activity of all biopsy sets were evaluated. RESULTS: One hundred and thirteen patients were included. Median time in clinical remission at inclusion was 27 months (IQR 15-56). Eight percent of patients relapsed within the first year and 33% during the whole follow-up period. In the univariate analysis, the presence of AHA, alone (P=0.048) or together with a past flare within the previous 12 months (P=0.01), was associated with CR within the first year of follow-up. In the multivariate analysis, AHA, together with a flare within the previous 12 months, remained the only risk factor for relapse (RR=7.5; IC95%; 1.8-29.9; P=0.005). CONCLUSIONS: In UC patients in clinical and endoscopic remission, the presence of AHA is a risk factor for clinical relapse.


Assuntos
Colite Ulcerativa/patologia , Mucosa Intestinal/patologia , Cicatrização , Adulto , Idoso , Biomarcadores/metabolismo , Colite Ulcerativa/terapia , Colonoscopia , Determinação de Ponto Final , Fezes/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Espanha , Centros de Atenção Terciária
12.
Gastroenterol Hepatol ; 40(10): 663-668, 2017 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28666605

RESUMO

BACKGROUND: Ulcerative proctitis (UP) presents distinctive clinical characteristics, outcomes and therapeutic approaches as compared to left-sided and extensive ulcerative colitis (UC). AIM: To describe the current therapeutic requirements and clinical outcomes in patients with active UP. METHODS: Retrospective observational study conducted in a referral IBD centre. Patients with UP in follow-up between 1989 and 2014 were included. The clinical characteristics, as well as the different treatments and drug formulations administered to treat flares, were recorded. RESULTS: Out of 687 UC patients, 101 patients (15%) with UP were included. Median follow-up was 8 years (IQR 3-14) and 49% of patients presented disease activity during the study period. Topical mesalazine monotherapy (90%) was the most commonly administered treatment for disease activity (mostly as suppositories), followed by topical steroids (47%) and oral mesalazine (56%) in monotherapy or combination therapy. Only 14% and 16% of patients required oral prednisone and beclomethasone, respectively. CONCLUSIONS: In clinical practice, active UP presents mostly favourable outcomes. Mesalazine suppositories are by far the most used treatment for these patients.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Proctite/tratamento farmacológico , Adulto , Colite Ulcerativa/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proctite/complicações , Estudos Retrospectivos , Resultado do Tratamento
13.
Dig Liver Dis ; 49(8): 934-937, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28454852

RESUMO

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a little known entity that can affect the oropharyngeal mucosa, the gastrointestinal tract and the skin. The main risk factor for the development of this lesion is immunosuppression. Because its features are similar to other Epstein-Barr virus-associated lymphoproliferative disorders, a differential diagnosis can sometimes prove challenging. Here, we report the case of a man diagnosed with Crohn's disease and treated with azathioprine and infliximab who developed ulceration at the rectum that was refractory to conventional medical treatment. Although the histological characteristics were suggestive of an EBVMCU, lymphoproliferative disease could not be ruled out. The patient did not improve after discontinuation of the treatment, a proctectomy was performed and the diagnosis of this disease was confirmed. Although very few cases of EBVMCU affecting the colon have been reported, its diagnosis should be always considered in refractory cases of inflammatory bowel disease with patients undergoing immunosuppressive treatment.


Assuntos
Doença de Crohn/tratamento farmacológico , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/isolamento & purificação , Reto/patologia , Úlcera/virologia , Adulto , Colonoscopia , Doença de Crohn/imunologia , Doença de Crohn/virologia , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos , Masculino , Proctoscopia , Reto/cirurgia , Úlcera/diagnóstico , Úlcera/imunologia
14.
Dig Liver Dis ; 49(8): 903-909, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28410915

RESUMO

BACKGROUND & AIMS: The early hospital readmission of patients with decompensated cirrhosis is a current problem. A study is presented on the incidence, the impact on mortality, and the predictive factors of early hospital readmission. PATIENTS AND METHODS: On the study included 112 cirrhotic patients, discharged after some decompensation between January 2013 and May 2014. Multivariate analyses were performed to identify predictors of early readmission and mortality. RESULTS: The early readmission rate was 29.5%. The predictive factors were male gender (OR: 2.81; 95% CI: 1.07-7.35), Model for End-Stage Liver Disease-sodium score ≥15 (OR: 3.79; 95% CI 1.48-9.64), and Charlson index ≥7 (OR: 4.34, 95% CI 1.65-11.4). This model enabled patients to be classified into low or high risk of early readmissions (13.6% vs. 52.2%). The mortality rate was significantly higher among patients with early readmission (73% vs. 35%) (p<.0001). After adjusting for the Model for End-Stage Liver Disease-sodium score, Charlson index, dependence in activities of daily living, educational status, and number of medications on discharge, the early readmission was independently associated with mortality. CONCLUSIONS: Early hospital readmission is common, and is independently associated with mortality. Male gender, MELD-Na ≥15, and Charlson index ≥7 are predictors of early readmission. These results could be used to develop future strategies to reduce early readmission.


Assuntos
Atividades Cotidianas , Escolaridade , Cirrose Hepática/mortalidade , Readmissão do Paciente/estatística & dados numéricos , Idoso , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Espanha/epidemiologia
15.
J Invest Dermatol ; 137(6): 1297-1310, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28188776

RESUMO

The cell cycle-related genes AURKA and FOXM1 are overexpressed in melanoma. We show here that AURKA overexpression is associated with poor prognosis in three independent cohorts of melanoma patients and correlates with the presence of genomic amplification of AURKA locus and BRAFV600E mutation. AURKA overexpression may also be driven by increased promoter activation through elements such as ETS and FOXM1 found within the 5' proximal promoter region. Activated MAPK/ERK signaling pathway mediates robust AURKA promoter activation, thereby knockdown of BRAFV600E and ERK inhibition results in reduced AURKA transcription and expression. We show a positive correlation between FOXM1 and AURKA expression in three independent cohorts of melanoma patients. FOXM1 silencing decreases expression of AURKA and late cell cycle genes in melanoma cells. We further found that FOXM1 expression levels are significantly higher in tumors carrying the BRAFV600E mutation compared with the wild-type BRAF (BRAFwt). Accordingly, the knockdown of BRAFV600E also reduces the expression of FOXM1 in BRAFV600E cells. Moreover, Aurora kinase A and FOXM1 inhibition by either genetic knockdown or pharmacologic inhibitors impair melanoma growth and survival both in culture and in vivo, underscoring their therapeutic value for melanoma patients who fail to benefit from BRAF/MEK signaling inhibition.


Assuntos
Aspartato-tRNA Ligase/genética , Aurora Quinase A/genética , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Mutação , Aminoacil-RNA de Transferência/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Humanos , Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Sensibilidade e Especificidade , Transdução de Sinais , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Probiotics Antimicrob Proteins ; 9(1): 71-80, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27832441

RESUMO

Use of probiotic therapy is an active area of investigation to treat intestinal disorders. The clinical benefits of the I3.1 probiotic formula (Lactobacillus plantarum (CECT7484, CECT7485) and P. acidilactici (CECT7483)) were demonstrated in irritable bowel syndrome (IBS) patients in a randomized, double-blind, placebo-controlled clinical trial. The aim of this study was to evaluate the therapeutic effects of I3.1 in two experimental models of colitis, a dextran sulfate sodium (DSS)-induced colitis model and an interleukin (IL)-10-deficient mice model. Colitis was induced in 32 8-week-old Balb/c mice by administering 3% (w/v) DSS in drinking water for 5 days. Probiotics were administered orally (I3.1 or VSL#3, 1 × 109 CFU daily) for 10 days before the administration of DSS. Also, probiotics (I3.1 or VSL#3, 1 × 109 CFU daily) were administered orally to 36 6-week-old C57B6J IL-10(-/-) mice for 10 weeks. Body weight was recorded daily. Colon samples were harvested for histological examination and cytokine measurements. Body weight after DSS administration did not change in the I3.1 group, whereas the VSL#3 group had weight loss. Also, I3.1 normalized IL-6 to levels similar to that of healthy controls and significantly increased the reparative histologic score. In the IL-10-deficient model, both VSL#3 and I3.1 reduced the severity of colitis compared to untreated controls, and I3.1 significantly reduced the levels of IFN-γ compared to the other two groups. In conclusion, I3.1 displays a protective effect on two murine models of experimental colitis. Results suggest that the mechanism of action could be different from VSL#3.


Assuntos
Colite/tratamento farmacológico , Probióticos/administração & dosagem , Animais , Colite/induzido quimicamente , Colite/microbiologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Interferon gama/imunologia , Interleucina-6/imunologia , Lactobacillus plantarum/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
17.
Inflamm Bowel Dis ; 22(12): 2879-2885, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27824646

RESUMO

BACKGROUND: Fecal calprotectin (FC) is the best noninvasive biomarker of disease activity in inflammatory bowel disease. Its correlation with endoscopic mucosal lesions could save inconvenient, expensive, and repeated endoscopic examinations in particular clinical settings. PATIENTS AND METHODS: To assess the correlation between FC and the existence and severity of endoscopic postoperative recurrence (POR), a group of clinically stable outpatients with Crohn's disease for whom an ileocolonoscopy was routinely planned to assess POR were invited to collect a stool sample before starting bowel cleansing to measure FC. POR was graded by means of Rutgeerts endoscopic score. RESULTS: One hundred nineteen ileocolonoscopies were included, 42% with endoscopic POR. FC was significantly lower in the absence of endoscopic POR and in the absence of any endoscopic lesion. The area under the receiver operating characteristic curve was 0.76 (95% confidence interval, 0.68-0.85) for the diagnosis of the absence of lesions and 0.75 (95% confidence interval, 0.66-0.84) for endoscopic POR. Better sensitivity and negative predictive value were observed when combining FC and serum C-reactive protein (CRP), leading to a sensitivity of 82%, a specificity of 53%, and negative and positive predictive values of 81% and 54%, respectively, for the prediction of endoscopic POR with a combination of FC 100 µg/g and CRP 5 mg/L cutoff values. CONCLUSIONS: FC correlates closely with endoscopic POR in clinically stable postoperative patients with Crohn's disease and, when used in combination with CRP, might save endoscopic examinations and allow for a high-grade suspicion of endoscopic POR in the long-term monitoring of these patients.


Assuntos
Doença de Crohn/patologia , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Adulto , Biomarcadores/análise , Proteína C-Reativa/análise , Colectomia/métodos , Colo/patologia , Colo/cirurgia , Colonoscopia , Doença de Crohn/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Prospectivos , Curva ROC , Recidiva , Sensibilidade e Especificidade
18.
PLoS One ; 11(6): e0156605, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27272720

RESUMO

Efforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. α4ß7 for gut). Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as α4ß1 and α4ß7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes.


Assuntos
Moléculas de Adesão Celular/metabolismo , Infecções por Chlamydia/metabolismo , Chlamydia muridarum/imunologia , Gardnerella vaginalis/imunologia , Linfócitos T/imunologia , Vaginose Bacteriana/metabolismo , Adulto , Animais , Antígeno CD11c/genética , Antígeno CD11c/metabolismo , Moléculas de Adesão Celular/genética , Infecções por Chlamydia/genética , Infecções por Chlamydia/veterinária , Chlamydia muridarum/genética , Modelos Animais de Doenças , Feminino , Células HeLa , Humanos , Integrina alfa4beta1/genética , Integrina alfa4beta1/metabolismo , Camundongos , Receptores CCR2/genética , Receptores CCR2/metabolismo , Receptores CCR5/genética , Receptores CCR5/metabolismo , Receptores CCR6/genética , Receptores CCR6/metabolismo , Vaginose Bacteriana/genética , Adulto Jovem
19.
Dig Liver Dis ; 48(6): 608-12, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27012443

RESUMO

BACKGROUND AND AIM: Intravenous corticosteroids remain the first line therapy for severe attacks of ulcerative colitis although up to 30-40% of patients do not respond to treatment. The availability of alternative therapies to colectomy and the knowledge of early predictors of response to corticosteroids should have improved the clinical outcomes of patients with severe refractory ulcerative colitis. The aim of the study is to describe the current need, way of use, and efficacy of rescue therapies, as well as colectomy rates in patients with severe ulcerative colitis flares. METHODS: Between January 2005 and December 2011, all patients admitted in three referral centres for a severe ulcerative colitis flare who received intravenous corticosteroids were identified and clinical and biological data were accurately collected. Patients were followed-up until colectomy, death, or date of data collection. RESULTS: Sixty-two flares were included. Initial efficacy of intravenous corticosteroids (mild activity or inactive disease without rescue treatment, at day 7 after starting intravenous corticosteroids) was achieved in 50% of flares, and rescue therapies were used in 27 episodes (43%). After a median follow-up of 18 months, the colectomy rate was 6.5%. Failed oral corticosteroids for the index flare were the only baseline feature that predicted the need for rescue therapy and colectomy. CONCLUSIONS: There is a marked reduction in the colectomy rate and an increased use of medical rescue therapies as compared to historical series. Patients worsening while on oral corticosteroids for a moderate flare are at high risk of rescue therapy and colectomy and, therefore, should be directly treated with rescue therapies instead of attempting intravenous corticosteroids.


Assuntos
Corticosteroides/uso terapêutico , Colite Ulcerativa/terapia , Fármacos Gastrointestinais/uso terapêutico , Imunossupressores/uso terapêutico , Administração Intravenosa , Adulto , Colectomia , Ciclosporina/uso terapêutico , Feminino , Seguimentos , Humanos , Infliximab/uso terapêutico , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Espanha , Centros de Atenção Terciária , Falha de Tratamento
20.
J Crohns Colitis ; 9(12): 1063-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26351379

RESUMO

BACKGROUND AND AIMS: Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. METHODS: All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected. RESULTS: A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN. CONCLUSIONS: The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Neoplasias Colorretais/etiologia , Imunossupressores/uso terapêutico , Mercaptopurina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa/complicações , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Espanha
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