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OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5â years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4â years, colectomy-free survival rates (95% CI) at 1 and 5â years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5â years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.
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Colite Ulcerativa/tratamento farmacológico , Ciclosporina/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Adulto , Colectomia , Colite Ulcerativa/cirurgia , Intervalo Livre de Doença , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esteroides/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of this study was to determine whether the degree of purity achieved in conventional vaccines against the foot and mouth disease virus in Argentina interferes with the interpretation of seroepidemiological surveys for confirming the absence of viral activity, which are performed to support the recognition of free zones practising vaccination. The evaluation of 168 vaccine series due to be marketed in Argentina (2006-2012) and subjected to official control testing in cattle, as well as repeated vaccination of cattle and other species using vaccines with high antigen concentrations, demonstrated that they did not induce antibodies to non-structural proteins (NSPs). The results show clearly that vaccines with satisfactory potency do not induce a response to NSPs, even by forcing the immune response through more concentrated doses with multiple valences and revaccination protocols at shorter irtervals than in vaccination campaigns. These results confirm that the vaccines used in routine vaccination programmes have a degree of antigen purification consistent with the needs observed on the basis of sampling for serological surveillance. Moreover, serological surveys conducted in 2006-2011 by Argentina's official Veterinary Services--the National Health and Agrifood Quality Service (SENASA)--on more than 23,000 sera per year from cattle included in the vaccination programme, in order to confirm the absence of virus circulation, revealed an average 0.05% of reactive results, consistent with the specificity of the tests. In conclusion, the vaccines produced by conventional methods and with proven potencythat are available in Argentina are sufficiently purified to ensure thatthey do not interfere with the interpretation of sampling for serological surveillance performed to support the recognition of FMD-free zones practising vaccination.
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Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais , Argentina/epidemiologia , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/virologia , Febre Aftosa/epidemiologia , Esquemas de Imunização , Estudos Soroepidemiológicos , Ovinos , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/prevenção & controle , Doenças dos Ovinos/virologia , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/virologia , Vacinação , Potência de Vacina , Vacinas de Produtos Inativados , Proteínas Estruturais Virais/imunologia , Vacinas Virais/normasRESUMO
OBJECTIVE: To determine the role of colonic barrier defects and low-grade inflammation in irritable bowel syndrome (IBS)-like symptoms in quiescent inflammatory bowel disease (IBD). DESIGN: Caecal biopsies were collected from 51 IBS, 49 quiescent IBD (31 Crohn's disease (CD) and 18 ulcerative colitis (UC)) patients and 27 controls. IBS was assessed using the Rome III criteria and the IBS severity score. Epithelial barrier integrity was evaluated by determining the paracellular permeability of biopsies mounted in Ussing chambers and the mRNA expression of tight junction proteins (ZO-1, α-catenin and occludin). Low-grade inflammation was evaluated by counting cells, including intraepithelial lymphocytes (IELs), eosinophils and mast cells, and by determining the mRNA and protein expression of tumour necrosis factor (TNF)-α in biopsies and culture supernatants. RESULTS: IBS-like symptoms were present in 35.4 and 38% of CD and UC patients, respectively. Paracellular permeability was significantly increased in both quiescent IBD with IBS-like symptoms and IBS compared with quiescent IBD without IBS-like symptoms (p<0.01, respectively) or controls (p<0.01, respectively). Significantly lower expression of ZO-1 and α-catenin was detected in IBS and quiescent IBD with IBS-like symptoms. IELs and TNF-α were significantly increased in quiescent IBD with IBS-like symptoms, but not in IBS. CONCLUSIONS: In quiescent IBD, IBS-like symptoms related to persistent subclinical inflammation associated with increased colonic paracellular permeability. A persistent increase in TNF-α in colonic mucosa may contribute to the epithelial barrier defects associated with abdominal pain in quiescent IBD, but not in IBS. Optimisation of anti-inflammatory therapy may be considered in quiescent IBD with IBS-like symptoms.
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Colite Ulcerativa/complicações , Colo/metabolismo , Doença de Crohn/complicações , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/etiologia , Adulto , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Colo/imunologia , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Mucosa Intestinal/imunologia , Síndrome do Intestino Irritável/imunologia , Síndrome do Intestino Irritável/metabolismo , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Permeabilidade , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
One of the major problems in bioimaging, often highly underestimated, is whether features extracted for a discrimination or regression task will remain valid for a broader set of similar experiments or in the presence of unpredictable perturbations during the image acquisition process. Such an issue is even more important when it is addressed in the context of deep learning features due to the lack of a priori known relationship between the black-box descriptors (deep features) and the phenotypic properties of the biological entities under study. In this regard, the widespread use of descriptors, such as those coming from pre-trained Convolutional Neural Networks (CNNs), is hindered by the fact that they are devoid of apparent physical meaning and strongly subjected to unspecific biases, i.e., features that do not depend on the cell phenotypes, but rather on acquisition artifacts, such as brightness or texture changes, focus shifts, autofluorescence or photobleaching. The proposed Deep-Manager software platform offers the possibility to efficiently select those features having lower sensitivity to unspecific disturbances and, at the same time, a high discriminating power. Deep-Manager can be used in the context of both handcrafted and deep features. The unprecedented performances of the method are proven using five different case studies, ranging from selecting handcrafted green fluorescence protein intensity features in chemotherapy-related breast cancer cell death investigation to addressing problems related to the context of Deep Transfer Learning. Deep-Manager, freely available at https://github.com/BEEuniroma2/Deep-Manager , is suitable for use in many fields of bioimaging and is conceived to be constantly upgraded with novel image acquisition perturbations and modalities.
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Artefatos , Processamento de Imagem Assistida por Computador , Proteínas de Fluorescência Verde , Redes Neurais de Computação , SoftwareRESUMO
High-throughput phenotyping is becoming increasingly available thanks to analytical and bioinformatics approaches that enable the use of very high-dimensional data and to the availability of dynamic models that link phenomena across levels: from genes to cells, from cells to organs, and through the whole organism. The combination of phenomics, deep learning, and machine learning represents a strong potential for the phenotypical investigation, leading the way to a more embracing approach, called machine learning phenomics (MLP). In particular, in this work we present a novel MLP platform for phenomics investigation of cancer-cells response to therapy, exploiting and combining the potential of time-lapse microscopy for cell behavior data acquisition and robust deep learning software architectures for the latent phenotypes extraction. A two-step proof of concepts is designed. First, we demonstrate a strict correlation among gene expression and cell phenotype with the aim to identify new biomarkers and targets for tailored therapy in human colorectal cancer onset and progression. Experiments were conducted on human colorectal adenocarcinoma cells (DLD-1) and their profile was compared with an isogenic line in which the expression of LOX-1 transcript was knocked down. In addition, we also evaluate the phenotypic impact of the administration of different doses of an antineoplastic drug over DLD-1 cells. Under the omics paradigm, proteomics results are used to confirm the findings of the experiments.
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Adenocarcinoma , Neoplasias Colorretais , Aprendizado Profundo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Expressão Gênica , Humanos , Aprendizado de Máquina , Microscopia , Fenômica , Fenótipo , Imagem com Lapso de TempoRESUMO
BACKGROUND AND AIMS: Defining and assessing the reproducibility of Crohn's disease [CD] endoscopic lesions is essential in assessing endoscopic healing. METHODS: Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as 'moderate' [0.4-0.6], 'substantial' [0.6-0.8], or 'almost perfect' [0.8-1.0]. RESULTS: Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing 'substantial' agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from 'moderate' to 'almost perfect' agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [pâ =â 0.001], 0.607 [±0.043] [pâ =â 0.001], and 0.782 [±0.064][pâ =â 0.001] for DU, AE, and any ulceration, respectively. CONCLUSIONS: Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided 'substantial' inter-observer agreements, especially in case of high-quality videos.
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Doença de Crohn/diagnóstico , Endoscopia Gastrointestinal , Intestinos , Técnica Delphi , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/normas , Endoscopia Gastrointestinal/estatística & dados numéricos , Humanos , Intestinos/diagnóstico por imagem , Intestinos/patologia , Microscopia de Vídeo/métodos , Variações Dependentes do Observador , Melhoria de Qualidade , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Terminologia como AssuntoRESUMO
The incremented uptake provided by time-lapse microscopy in Organ-on-a-Chip (OoC) devices allowed increased attention to the dynamics of the co-cultured systems. However, the amount of information stored in long-time experiments may constitute a serious bottleneck of the experimental pipeline. Forward long-term prediction of cell trajectories may reduce the spatial-temporal burden of video sequences storage. Cell trajectory prediction becomes crucial especially to increase the trustworthiness in software tools designed to conduct a massive analysis of cell behavior under chemical stimuli. To address this task, we transpose here the exploitation of the presence of "social forces" from the human to the cellular level for motion prediction at microscale by adapting the potential of Social Generative Adversarial Network predictors to cell motility. To demonstrate the effectiveness of the approach, we consider here two case studies: one related to PC-3 prostate cancer cells cultured in 2D Petri dishes under control and treated conditions and one related to an OoC experiment of tumor-immune interaction in fibrosarcoma cells. The goodness of the proposed strategy has been verified by successfully comparing the distributions of common descriptors (kinematic descriptors and mean interaction time for the two scenarios respectively) from the trajectories obtained by video analysis and the predicted counterparts.
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Algoritmos , Células/citologia , Biologia Computacional/métodosRESUMO
75% of hospital patients with Crohn's disease (CD) suffer from malnutrition and one third of CD patients have a body mass index below 20. Inflammatory bowel diseases (IBD) patients have many vitamin and nutrient deficiencies which can lead to important consequences such as hyperhomocysteinemia which is associated with a higher risk of thromboembolic disease. Nutritional deficiencies in IBD patients are the result of insufficient intake, malabsorption and protein-losing enteropathy as well as the metabolic distubances directly induced by the chronic disease and its treatments, in particular corticosteroids. Screening for nutritional deficiencies in chronic disease patients is warranted. Managing the deficiencies involves simple nutritional guidelines, vitamin supplements, and nutritional support in the worst cases, in particular in children in order to limit the impact of IBD on growth. In active CD, enteral nutrition is the first line therapy in children and should be used as sole therapy in adults mainly when treatment with corticosteroids is not feasible.
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Doença de Crohn/complicações , Doença de Crohn/dietoterapia , Apoio Nutricional/métodos , Adulto , Composição Corporal , Índice de Massa Corporal , Criança , Doença de Crohn/terapia , Humanos , Síndromes de Malabsorção/etiologia , Desnutrição/etiologia , Guias de Prática Clínica como Assunto , Enteropatias Perdedoras de Proteínas/etiologia , Qualidade de Vida , Resultado do Tratamento , Vitaminas/uso terapêuticoRESUMO
BACKGROUND: A subset of patients with irritable bowel syndrome (IBS) have an increased number of mast cells (MCs) in the colonic mucosa. Psychological factors are believed to contribute to the course of IBS. AIMS: To examine associations between fatigue, depression and MCs of the colonic mucosa in IBS. METHODS: Colonic biopsies were taken from 50 Rome II IBS patients, 21 healthy controls and 11 depressed/fatigued patients without IBS. The cellularity of the lamina propria was determined as the number of inflammatory cells per high power field (hpf) through a 400x microscope. The Fatigue Impact Scale (FIS) and the short form Beck Depression Inventory (BDI) evaluated the severity of fatigue and depression. RESULTS: IBS patients had a significant increase in the cellularity of the lamina propria compared with controls or with depressed patients (mean (SD) 94.5 (48-110) vs 68 (58-82) and 78 (87-90) cells per hpf, p = 0.005 and p = 0.05, respectively), in particular of MCs (9.3 (5.6-11.7) vs 4.0 (2.7-6.8) and 4.3 (2.8-7.8) cells per hpf, p = 0.001 and p = 0.005, respectively). Both the FIS and BDI scores were significantly higher in IBS or in depressed patients than in controls (p<0.001). In IBS, the FIS score correlated significantly with the cellularity of the lamina propria (r = 0.51, p<0.0001) and MCs (r = 0.64, p<0.0001). In IBS, the BDI score correlated significantly with MCs (r = 0.29, p = 0.03). CONCLUSIONS: Elevated MCs counts are a key feature of the low-grade inflammatory infiltrate in the caecal mucosa of IBS. Fatigue and depression are associated with mucosal cell counts, in particular MCs, suggesting that psychological factors are associated with the low-grade inflammatory infiltrate in IBS.
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Colo/patologia , Depressão/patologia , Fadiga/patologia , Síndrome do Intestino Irritável/patologia , Mastócitos/patologia , Adulto , Idoso , Biópsia , Depressão/etiologia , Fadiga/etiologia , Feminino , Humanos , Mucosa Intestinal/patologia , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/psicologia , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
INTRODUCTION: Acute Esophageal Necrosis Syndrome (AENS) is a rare and unknown clinical entity, defined as a diffuse circumferential black-appearing friable esophageal mucosa going from the distal esophageal mucosa to the gastroesophageal (GE) junction. Esophagogastroduodenoscopy (EGD) remains the gold standard in making diagnosis. PRESENTATION OF CASE: We report here the case of a 45-year-old man with necrosis of the esophagus treated conservatively. Regression of the lesion but persistence of ulcerations were seen on the endoscopic follow-up. Distal esophageal stenosis was then diagnosed and treated by endoscopic dilation. DISCUSSION: Diagnosis of AENS must be considered when an old patient, with multiple comorbidities, presents an upper digestive hemorrhage. Upper endoscopy is mandatory. Treatment is in most of the cases conservative. Esophageal stenosis is a frequent complication. CONCLUSION: Although AENS is a rare clinical entity, it should not be dismissed by doctors, avoiding useless surgical management. This pathology remains nevertheless associated with a considerable mortality rate.
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doi:10.1093/ecco-jcc/jjy222 Abstract P528 from the 'Poster presentations' section of the main abstract book has been withdrawn and re-inserted as DOP63 in the 'Late-breaking abstracts' section.
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BACKGROUND: Standard high-volume polyethylene glycol [PEG] bowel preparations [PEG-4L] are recommended for patients with inflammatory bowel disease [IBD] undergoing colonoscopy. However, low-volume preparations [≤2 L of active volume] are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations. METHODS: We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18-75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients' characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires. RESULTS: Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate [Pico], 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston's score efficacy outcome in the PEG-4L group in 51.2% of the patients [p = 0.0011]. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group [p < 0.0001]. Tolerability, as assessed by the patients' VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L [p = 0.008; p = 0.0003]. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients. CONCLUSIONS: Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.
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Catárticos , Colonoscopia/métodos , Doenças Inflamatórias Intestinais/diagnóstico , Polietilenoglicóis , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Catárticos/administração & dosagem , Catárticos/efeitos adversos , Citratos/administração & dosagem , Citratos/efeitos adversos , Colite Ulcerativa/diagnóstico , Colonoscopia/efeitos adversos , Doença de Crohn/diagnóstico , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversos , Picolinas/administração & dosagem , Picolinas/efeitos adversos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Long-term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated. AIM: To evaluate the long-term efficacy and safety of ustekinumab and identify the predictive factors of ustekinumab failure-free persistence in a cohort of anti-TNF refractory CD patients. METHODS: We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD-related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery. RESULTS: Eighty-eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4-34.4) months. Forty-seven patients (54%) continued ustekinumab with a clinical response and 38 (43%) stopped treatment (32 for failure, five for remission and one for pregnancy). Endoscopic response was observed in 82% of patients with endoscopic evaluation and mucosal healing in 39%. Ustekinumab failure-free persistence rates were 78% at 12 months, 66% at 24 months and 55% at 36 months. No predictive factor of ustekinumab failure-free persistence was identified. One severe adverse event was observed (anal adenocarcinoma). CONCLUSION: In this cohort of refractory CD patients receiving long-term ustekinumab therapy, more than 50% of patients continued ustekinumab treatment with no loss of response, intolerance or surgery and with a good safety profile.
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Doença de Crohn/tratamento farmacológico , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos , Adulto , Estudos de Coortes , Doença de Crohn/epidemiologia , Resistência a Medicamentos/efeitos dos fármacos , Endoscopia , Feminino , Seguimentos , Humanos , Masculino , Gravidez , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêuticoRESUMO
BACKGROUND: The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut-specificity. AIM: To assess effectiveness of vedolizumab for EIM in patients with inflammatory bowel disease (IBD) in a large real-life experience cohort. METHODS: Between June and December 2014, 173 patients with Crohn's disease and 121 with ulcerative colitis were treated with vedolizumab. Patients were followed until week 54. EIM activity was assessed at weeks 0, 6, 14, 22, 30 and 54 by using a 3-step scale: complete remission, partial response and no response. RESULTS: At baseline, 49 (16.7%) patients had EIMs of which 47 had inflammatory arthralgia/arthritis, four had cutaneous lesions and two had both rheumatologic and skin EIM. At week 54, 21 (44.7%) patients had complete remission for inflammatory arthralgia/arthritis and three (75%) for cutaneous EIM. In multivariate analysis, complete remission of inflammatory arthralgia/arthritis was associated with clinical remission of IBD (OR = 1.89, IC95% [1.05-3.41], P = .03) and recent onset of inflammatory arthralgia/arthritis (OR = 1.99, IC95% [1.12-3.52], P = .02). During the follow-up period, 34 (13.8%) patients without any EIM at baseline, developed incident cases of inflammatory arthralgia/arthritis consisting mostly of peripheral arthralgia without evidence of arthritis and 14 (4.8%) incident cases of paradoxical skin manifestation. CONCLUSION: Vedolizumab therapy is commonly associated with improvement in EIM. This was associated with quiescent IBD and recent EIM. However, paradoxical skin manifestation and inflammatory arthralgia/arthritis may occur upon vedolizumab therapy.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite/tratamento farmacológico , Inflamação/tratamento farmacológico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Adolescente , Adulto , Artrite/epidemiologia , Artrite/etiologia , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Feminino , França/epidemiologia , Humanos , Inflamação/epidemiologia , Inflamação/etiologia , Doenças Inflamatórias Intestinais/epidemiologia , Pessoa de Meia-Idade , Dermatopatias/epidemiologia , Dermatopatias/etiologia , Adulto JovemRESUMO
OBJECTIVE: To present a case report of bilateral posterior tarsal tunnel syndrome (PTTS) caused by an accessory flexor digitorum longus (AFDL), including the surgical technique and a review of the literature. MATERIALS AND METHODS: Twenty-nine year old male diagnosed with bilateral PTTS, refractory to conservative management, with 53 points on the preoperative AOFAS score. MR of both ankles showed an AFDL within the tarsal tunnel, in close relationship to the posterior tibial nerve. Bilateral tarsal tunnel decompression and AFDL resection was performed. RESULTS: There were no post-operative complications. At 6 months after surgery, the patient had no pain and had 87 points on the AOFAS score. DISCUSSION: The PTTS is an entrapment neuropathy of the posterior tibial nerve or one of its terminal branches. A rare cause is the presence of an AFDL, and its resection is associated with good clinical results. Careful scar tissue resection and neurolysis is recommended. Knowing the normal pathway and anatomical variability of the posterior tibial nerve and its branches is essential to avoid iatrogenic injury. In our case report, MR and intraoperative findings identified a bilateral FDLA in close relationship to the common flexor digitorum, an unusual finding, with few reports in current literature. CONCLUSIONS: Careful tarsal tunnel decompression and AFDL resection in our patient with bilateral symptomatic PTTS has good clinical results and no complications, particularly when diagnosed and treated early.
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Descompressão Cirúrgica/métodos , Procedimentos Ortopédicos/métodos , Síndrome do Túnel do Tarso/cirurgia , Adulto , Humanos , Masculino , Músculo Esquelético/cirurgia , Síndrome do Túnel do Tarso/diagnóstico , Síndrome do Túnel do Tarso/etiologiaRESUMO
BACKGROUND AND AIMS: Crohn's disease [CD] is associated with an increased risk of small bowel adenocarcinoma [SBA]. There are no recommendations on endoscopic screening of SBA in CD patients. The aim of this study was to evaluate the feasibility and value of endoscopic screening for SBA in CD patients at high-risk of SBA. METHODS: We performed an exploratory multi-centre study in a prospective cohort of CD patients at high-risk of SBA defined as long-term small bowel disease without bowel resection for the past 10 years. Depending on the location of the disease, baseline upper and/or lower enteroscopies were performed. Random and targeted biopsies using chromoendoscopy were taken. Patients were followed-up for at least 1 year after inclusion. RESULTS: In total, 101 patients [62 men; median age: 48 years; median duration of disease: 19 years] were recruited in ten centres. The endoscopic procedure was incomplete in 47 cases because of impassable strictures and dilation was performed in four patients. Indeterminate small bowel dysplasia was identified in two patients at endoscopic screening; SBA was confirmed in one after surgical resection. With an at least 1-year follow-up duration, two additional cases of SBA were identified in patients who underwent surgery for obstruction, resulting in a 33% sensitivity rate for SBA endoscopic screening. CONCLUSION: In a cohort of high-risk patients, the prevalence of dysplasia and SBA on CD was 4%. Because of its low sensitivity, endoscopic screening cannot be recommended for surveillance in CD patients at high-risk of SBA.
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Adenocarcinoma/diagnóstico , Doença de Crohn/complicações , Endoscopia Gastrointestinal , Neoplasias Intestinais/diagnóstico , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Adulto , Doença de Crohn/patologia , Feminino , Humanos , Neoplasias Intestinais/etiologia , Neoplasias Intestinais/patologia , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab. AIMS: To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD. METHODS: Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 with UC). Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid-free clinical remission at week 54. RESULTS: At week 54, steroid-free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid-free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation. CONCLUSION: Vedolizumab is able to maintain steroid-free clinical remission in up to one-third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND AND AIMS: Long-term benefits of combination therapy (combotherapy) with infliximab (IFX) and azathioprine (AZA) have been less studied in ulcerative colitis (UC) than in Crohn's disease. The aim of the present study was to determine UC disease activity in patients who received at least 6 months of combotherapy, and whether cotreatment for more than 6 months was useful in these patients. METHODS: A retrospective multicenter study was conducted in seven French academic centers from January 2010 to September 2012, including all UC patients having received at least 6 months of combotherapy in prolonged remission off steroids. During the follow-up period, which was divided into trimesters, scheduled IFX was continued as maintenance and AZA could be withdrawn. Assessment of UC activity by trimester was based on the following events: disease relapse defined by clinical relapse requiring a change of treatment, IFX failure, and colectomy. RESULTS: Eighty-two patients were included (mean age 38 years; male:female ratio 1:1) and followed up for a median of 22.3±14.0 months. Comparing 393 trimesters of combotherapy with 282 trimesters of IFX alone, fewer clinical relapses were observed with combotherapy (p = 0.049). Similar results were observed for IFX failure (p = 0.048). No difference was observed for colectomy. Duration of combotherapy longer than 9 months was inversely associated with clinical relapse (hazard ratio = 0.32 [95% confidence interval 0.15-0.70]). CONCLUSIONS: UC patients treated with combotherapy should maintain IFX and AZA for at least 9 months. Further studies are required to determine the optimal duration of combotherapy before stopping AZA in this situation.
Assuntos
Azatioprina/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Imunossupressores/administração & dosagem , Infliximab/administração & dosagem , Adulto , Azatioprina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , França , Humanos , Imunossupressores/uso terapêutico , Quimioterapia de Indução , Infliximab/uso terapêutico , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 19-year-old woman is presented with high-spiking fever, pericardial tamponade and respiratory failure. A diagnosis of adult onset Still's disease was made. This is a rare inflammatory disease with an unknown aetiology. The diagnosis is made by exclusion and with the help of diagnostic criteria. Treatment with corticosteroids met with a good response.
Assuntos
Febre/diagnóstico , Derrame Pericárdico/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Diagnóstico Diferencial , Feminino , Febre/tratamento farmacológico , Humanos , Derrame Pericárdico/tratamento farmacológico , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/tratamento farmacológico , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológicoRESUMO
The process of dental identification for a mass fatality incident has unique aspects in comparison with that of a routine dental identification, outside of the obvious increase in the number of victims and responders. The dental team is a small part of a large effort to resolve the incident. Incident command structure applies to the dental team as a unit as well as to the entire organization of the response. Teamwork and planning are essential on all levels. Discussing the casework is limited to the public information officer; only the public information officer is authorized to talk to anyone outside the medical examiner's office. For the team, communication is essential between the team members and between the team and other morgue sections. Daily meetings not only update progress, but also identify and solve problems as they arise. Redundancy and cross-checking occur each step in each section. A core team of trained individuals provides a framework for the use of less experienced members. Use of a dental identification computer program is extremely beneficial, especially as the amount of fragmentation or number of victims increases. Because of the magnitude of the response, the physical and mental stresses require critical incident stress debriefing for all responders, regardless of their experience. The past and future service of the dental profession to the victims of mass fatality incidents and their families is an excellent example of the ideal of service on which the profession is based.