Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with -acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that mouse models displaying a deficiency in the branched N-glycosylation pathway (, ) exhibited increased susceptibility to severe forms of colitis and early-onset disease. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.
Background and objective: To assess clinical outcomes after foreign body ingestion and food impaction; to identify predictors of foreign body presence at the time of endoscopy. Methods: A prospective study including consecutive adult patients with foreign body ingestion or suspected food impaction between May 2014 and August 2016. Results: In total, 521 patients were included, 320 with foreign body ingestion and 201 with suspected food impaction. Food impaction patients were significantly older and more frequently had a history of oesophageal disease. The foreign body was encountered in the upper digestive tract in 43% of the patients with foreign body ingestion, and food impaction was confirmed in 87%. Older age (odds ratio (OR) year 1.04, 95% confidence interval (CI) 1.02-1.06) and early presentation (OR first six hours 4.41, 95% CI 2.24-8.66) were independent predictors of foreign body presence, while a history of psychiatric disease was an independent predictor of food impaction (OR 6.69, 95% CI 1.66-26.9). Successful endoscopic treatment was achieved in more than 90% of the cases, with adverse events occurring in fewer than 5%. Foreign body forceps was the preferred device in foreign body ingestion, while retrieval basket and mobilisation were preferred in food impaction. The need to use more than one instrument was significantly higher in food impaction. Conclusion: Foreign bodies are encountered at endoscopy in almost half of the cases. Older age and earlier presentation are independent predictors of its presence. Given the high proportion of patients with foreign body at endoscopy and the low risk of complications, endoscopic evaluation is probably justified in the majority of cases.
SUMMARY BackgroundFirst-degree relatives (FDRs) of early-onset gastric carcinoma (EOGC) patients are at increased risk of cancer development. OLGA/OLGIM (Operative Link on Gastritis/Intestinal Metaplasia Assessment) classifications have been proposed for the identification of individuals at high risk of gastric cancer development.
BACKGROUND: Rubber band ligation and sclerotherapy are considered the office-based procedures of choice in hemorrhoidal disease. However, there are no studies comparing rubber band ligation and polidocanol foam sclerotherapy. OBJECTIVE:We aimed to evaluate the efficacy and safety of polidocanol foam sclerotherapy compared with rubber band ligation. DESIGN:This study was a randomized open-label study with 1-year follow-up. SETTINGS:The study was conducted in the colorectal unit of a tertiary hospital. PATIENTS:One hundred twenty patients with hemorrhoidal disease grades I to III were included. INTERVENTIONS:Patients were stratified by hemorrhoidal disease grade and randomly assigned (1:1) to treatment with either rubber band ligation (n = 60) or polidocanol foam sclerotherapy (n = 60). MAIN OUTCOME MEASURES:Efficacy outcomes included therapeutic success and recurrence. Safety outcomes included the occurrence of complications related to the procedures. RESULTS: Therapeutic success was not significantly different between the groups (polidocanol foam sclerotherapy 93.3% vs rubber band ligation 85.0%, p = 0.14). However, complete success rate was higher in the polidocanol foam sclerotherapy group (88.3% vs 66.7%, p = 0.009) with fewer office-based sessions (mean ± SD: 1.32 ± 0.60 vs 1.62 ± 0.76, p = 0.02). Recurrence rates were lower in the polidocanol foam sclerotherapy group (16.1% vs 41.2%, p = 0.004). Most recurrences were mild (83.3%). Complications were more frequent in the rubber band ligation group (30.0% vs 10.0%, p = 0.01) and were mostly minor (91.7%). No severe complications were observed in either group. LIMITATIONS: This study was performed in a single center, and both patients and investigators were not blinded to the treatment group. CONCLUSIONS: Both procedures are effective in the treatment of hemorrhoidal disease grades I to III. Polidocanol foam sclerotherapy was more effective than rubber band ligation when considering complete success. Patients in the polidocanol foam sclerotherapy group needed fewer treatment sessions, had lower recurrence rates, and were less likely to have complications. See
Immune checkpoint inhibitors have shown anti-tumour activity in cancers such as melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma, colorectal cancer, and Hodgkin’s lymphoma. Though immune checkpoint inhibitors have revolutionized the treatment and prognosis of some advanced malignancies, they are also associated with a significant risk of immune-related adverse events. These adverse events can occur in any organ system, but gastrointestinal side effects are among the most commonly reported, with manifestations ranging from mild diarrhoea to severe colitis, sharing some features with inflammatory bowel disease. Anticipating a greater use of these drugs in the future, gastroenterologists should expect to be increasingly faced with gastrointestinal immune-related adverse events. Knowledge of these toxicities, as well as effective management algorithms, is essential to enable early diagnosis and treatment, decreasing morbidity and mortality. We reviewed the currently available literature on gastrointestinal toxicity induced by immune checkpoint inhibitors, namely the clinical features, diagnosis, and management.
Background: Direct-acting antivirals (DAA) have revolutionized hepatitis C treatment, with high sustained virological response (SVR) rates reported, even in historically difficultto-treat groups. SVR is associated with a decreased risk of hepatocellular carcinoma (HCC), need for transplantation, and overall and liver-related mortality. Data from real-life cohorts on the medium-to long-term outcomes of patients with advanced liver disease and DAA-induced SVR are still missing. Objectives: To report and analyze the long-term Seguimento a longo prazo da doença hepática avançada após cura do vírus C com antivíricos de ação direta: dados de uma coorte Portuguesa Palavras ChaveAgentes antivirais · Carcinoma hepatocelular · Cirrose hepática · Hepatite C · Resposta virológica sustentada Resumo Introdução: Os antivíricos de ação direta (AAD) revolucionaram o tratamento da hepatite C ao atingirem elevadas taxas de resposta virológica sustentada (RVS), mesmo em grupos historicamente difíceis de tratar. A RVS associa-se a uma diminuição do risco de carcinoma hepatocelular (CHC), necessidade de transplantação e mortalidade, global e de causa hepática. São ainda insuficientes de coortes reais na literatura dados que permitam avaliar a extensão dos benefícios clínicos a médio-longo prazo do atingimento de uma RVS com os AAD. Objetivos: Reportar e analisar o impacto a longo prazo da RVS numa coorte real de doentes com doença hepática avançada, tratados com AAD. Métodos: Estudo unicêntrico, retrospetivo, longitudinal com inclusão de doentes com hepatite C crónica com cirrose ou fibrose avançada, que iniciaram tratamento com AAD de fevereiro de 2015 a janeiro de 2017. Resultados: Foram incluídos 237 doentes. Verificou-se uma taxa de retenção no tratamento de 98.7% com uma taxa de RVS de 97.8% (intention to treat: 96.6%). Dos 229 doentes curados, 67.2% eram cirróticos (64.2% Child-Pugh A, 3.1% Child-Pugh B) e 32.8% F3, com um seguimento médio de 28 meses. A taxa de mortalidade global foi de 19/1,000 pessoas-ano e de mortalidade associada à doença hepática de 9.5/1,000 pessoasano. A incidência de eventos de descompensação hepática foi de 25/1,000 pessoas-ano e a de CHC foi de 11.6/1,000 pessoas-ano. Verificou-se um aumento sustentado dos valores séricos de plaquetas até 2 anos de seguimento. A história de eventos de descompensação hepática, concentração de plaquetas e albumina prétratamento encontrou-se significativamente associada a eventos adversos hepáticos durante o seguimento. Conclusões: A cura virológica após tratamento com AAD é sustentada no tempo, encontrando-se associada a um excelente prognóstico clínico em doentes com doença hepática avançada compensada, e a uma melhoria ou estabilização da doença em doentes descompensados. O atingimento de RVS associa-se a um baixo risco de CHC, não o eliminando, e de progressão da doença, sobretudo perante a presença de outros cofatores de agressão hepática, recomendando-se a manutenção do seguimento destes doentes.
The incidence of neuroendocrine tumors of the rectum has been increasing in the last decades, partly due to improved investigation. They are mostly well-differentiated small tumors with a rather good overall prognosis. In the last few years, some aspects of neuroendocrine tumors have been evolving. In 2010, the World Health Organization proposed a new classification, indicating that these tumors, as a category, should be considered malignant. Afterwards the European Neuroendocrine Tumor Society published their guidelines for the management of colorectal neoplasms. Treatment algorithm is mainly based on tumor size and grading and, in general, well-differentiated rectal tumors <2 cm can be endoscopically resected. Endorectal ultrasound plays a particularly important role by accurately assessing tumor size and depth of invasion prior to resection. There are no specific recommendations on the optimal endoscopic resection method, but data from recent studies suggests that modified endoscopic mucosal resection techniques and endoscopic submucosal dissection have superior complete resection rates.
Background: Angiodysplasias are one of the most frequent causes of gastrointestinal bleeding. Pharmacological options, such as octreotide Long-Acting Release (LAR), do not yet have a defined role and are currently used for patients who are not candidates for or are refractory to endoscopic treatment. Aims: (1) To evaluate the efficacy of octreotide LAR by considering transfusion requirements (units of packed erythrocytes (UPE)/month) and number of hospitalizations/month before and during therapy; (2) to verify whether the characteristics of patients and/or concurrent medication influenced response to therapy; and (3) to evaluate the safety of therapy by registering adverse effects. Methods: A retrospective cohort of 16 patients with angiodysplasias treated with octreotide LAR was reviewed. Results: (1) There was a significant decrease (follow up before vs. follow up during) in the median number of UPE/month (1.84 vs. 0.42, p = 0.008) and the number of admissions/month (0.21 vs. 0.00, p = 0.015). (2) Of the characteristics analyzed, only the presence of aortic stenosis (vs. other comorbidities) positively influenced the response to therapy in relation to the variation in transfusion requirements (−2.39 UPE/month vs. −0.61 UPE/month; p = 0.009). (3) Adverse effects: splenic infarction (1 patient) and gallstones (1 patient).Conclusions: Octreotide LAR is effective as prophylaxis for gastrointestinal bleeding angiodysplasia by decreasing transfusion requirements and the need for hospitalizations. Patients with Octreotide LAR prevents angiodysplasia bleeding 177 aortic stenosis were those who most benefited from the therapy. A dose of 20 mg/month did not prove more effective than a dose of 10 mg/month. O octreótido Long-Acting Release é eficaz na prevenção de hemorragia por angiodisplasias gastrointestinais ResumoIntrodução: As angiodisplasias são uma das causas mais frequentes de hemorragia com ponto de partida no intestino delgado. As opções farmacológicas como o octreótido LAR não têm ainda um papel definido destinando-se a doentes não candidatos ou refratários à terapêutica endoscópica. Objetivos: (1) Avaliar a eficácia terapêutica comparando: necessidades transfusionais (unidades de concentrado eritrocitário/mês) e número de internamentos/mês antes e durante a terapêu-tica;(2) Verificar se as características dos doentes e/ou da medicação tiveram influência na resposta à terapêutica; (3) Avaliar a segurança da terapêutica (registo de efeitos adversos). Métodos: Efetuado estudo retrospetivo de coorte de 16 doentes com AD tratados com octreótido LAR. Resultados: (1) Observou-se diminuição significativa (follow up before vs follow up during) do número mediano de UCE/mês [1.84 UCE/mês vs 0,42 UCE/mês; p=0.008] e do número de internamentos/mês [0,21 internamentos/mês vs 0,00 internamentos/mês; p=0.015].(2) Das características analisadas, apenas a presença de estenose aórtica (vs outras comorbilidades) influenciou positivamente a resposta à terapêutica no que concerne à variação das necessidades transfusionais (---2,39 ...
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