Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in the Indomethacin Era – A Prospective Study

Background and Aims: Although endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure used to treat conditions affecting the biliopancreatic system, it can lead to several complications. Post-ERCP pancreatitis (PEP) is the most frequent one, with an incidence ranging from 3 to 14%. Our aim was to assess the potential risk factors associated with PEP occurrence in patients undergoing ERCP with indomethacin prophylaxis. Methods: Prospective, single-center, real-world observational study (January to December 2015) with inclusion of patients submitted to ERCP, where relevant patient-related and procedure-related data had been collected. Patients had to have been admitted for a minimum of 24 h in order to establish the presence of early complications. All patients were submitted to PEP prophylaxis with 1 or 2 methods: rectal indomethacin and pancreatic duct (PD) stenting. Results: A total of 188 patients who had undergone ERCP were included (52.7% women; mean age 69.2 ± 16.0 years) and PEP was diagnosed in 13 (6.9%). PEP prophylaxis consisted of indomethacin in all cases (100%) and PD stenting in 7.4%. The pancreatitis was mild in 11 patients (84.6%) and severe in the other 2. One of them died (0.5%). None of the patient-related risk factors were associated with changes in PEP probability. Of all patients, 33.0% had 2 or more procedure-related risk factors. A higher number of synchronous procedure-related risk factors showed a statistically significant correlation with PEP occurrence, p = 0.040. Conclusions: The 6.9% PEP rate is considered acceptable since 33.0% patients had a medium-high risk for PEP due to challenging biliary cannulation. The total number of procedure-related risk factors seems to play a critical role in the development of PEP despite indomethacin prophylaxis

Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes.

β cells may participate and contribute to their own demise during Type 1 diabetes (T1D). Here we report a role of their expression of Tet2 in regulating immune killing. Tet2 is induced in murine and human β cells with inflammation but its expression is reduced in surviving β cells. Tet2-KO mice that receive WT bone marrow transplants develop insulitis but not diabetes and islet infiltrates do not eliminate β cells even though immune cells from the mice can transfer diabetes to NOD/scid recipients. Tet2-KO recipients are protected from transfer of disease by diabetogenic immune cells.Tet2-KO β cells show reduced expression of IFNγ-induced inflammatory genes that are needed to activate diabetogenic T cells. Here we show that Tet2 regulates pathologic interactions between β cells and immune cells and controls damaging inflammatory pathways. Our data suggests that eliminating TET2 in β cells may reduce activating pathologic immune cells and killing of β cells

Comparative RNAi screening identifies a conserved core metazoan actinome by phenotype

RNAi Screens in Drosophila and human cells for novel actin regulators revealed conserved roles for proteins involved in nuclear actin export, RNA splicing, and ubiquitination

Meld, ukled e imeld no prognóstico dos portadores de hepatopatias crónicas

Trabalho final de mestrado integrado em Medicina área científica de Gastroenterologia, apresentada à Faculdade de Medicina da Universidade de CoimbraIntrodução: o conhecimento da sobrevida antecipada em doentes com hepatopatias crónicas é fundamental para que se possam oferecer as melhores opções terapêuticas, como por exemplo o transplante hepático, aos doentes mais indicados. Neste contexto, têm sido utilizados vários scores prognósticos. Ao bastante divulgado MELD recentemente se juntaram UKELD e iMELD entre outros. Objectivo: o objectivo deste trabalho consistiu em estudar 100 doentes portadores de hepatopatias crónicas internados no serviço de Gastroenterologia dos Hospitais da Universidade de Coimbra em 2005. Os scores MELD, UKELD e iMELD foram calculados para a admissão inicial. A evolução dos doentes foi estudada para avaliar a relação do valor inicial do score com a respectiva sobrevida. Metodologia: recorreu-se à análise retrospectiva dos processos dos 100 doentes. Foram registados os dados clínicos essenciais. Foi realizado o tratamento estatístico dos dados recorrendo ao programa Statistical Package for the Social Sciences - SPSS versão 18 para Windows (SPSS Inc. Chicago). Foram utilizados os testes de Chi-Square, Kaplan-Meier e Cox Regression e foram calculadas as curvas Receiver Operating Characeristic Curve (ROC) para os três scores. Resultados: a sobrevida a três meses foi de 87,2%, 71,1% e 50% em doentes com valores de MELD de < 15, 15-25 e > 25 respectivamente. A sobrevida a um ano foi de 78,7%, 60% e 25% em doentes com valores de MELD de < 15, 15-25 e > 25 respectivamente. Nos doentes com score UKELD superior a 49 a mortalidade a um ano foi de 42,0 % e apenas de 16,1% para valores de UKELD iguais ou inferiores a 49. Valores mais altos de iMELD corresponderam a sobrevidas mais baixas, tanto a três meses como a um ano. As áreas abaixo da curva ROC para os scores MELD, UKELD e iMELD para a mortalidade a três meses foram respectivamente 0,700; 0,704 e 0,706. Para a mortalidade a um ano as áreas abaixo da curva ROC para MELD, UKELD e iMELD foram respectivamente de 0,692; 0,725 e 0,747. Conclusões: os doentes com valores de MELD mais alto apresentam sobrevida mais baixa. Os doentes com valor de UKELD superior a 49 apresentam mortalidade a um ano superior a 9%. Os doentes com valor de iMELD mais altos apresentam menor sobrevida. Os scores MELD, UKELD e iMELD são bons métodos para determinar a mortalidade a três meses e a um ano em doentes com hepatopatias crónicas.Introduction: the ability to predict early survival in patients with chronic liver diseases is crucial for offering the best therapeutic options, such as liver transplantation, to the patients most suitable. With this objective, several prognostic scores are used. In addition to the most frequently used MELD, new scores like UKELD and iMELD are now being used. Objective: The aim of this work was to study 100 patients with chronic liver disease, who had all been admitted to the Gastroenterology Service of the Hospitais da Universidade de Coimbra during 2005. The MELD, UKELD and iMELD scores were calculated for the initial admission. The outcome of the patients was studied to determine the correlation between the initial value for each of the three scores and the survival of the patient. Methodology: we retrospectively analyzed the cases of the 100 patients. The relevant clinical data was recorded. The statistical analysis was performed using the statistical program “Statistical Package for Social Sciences – SPSS” version 18 for Windows (SPSS Inc. Chicago). We used the following tests: Chi-square, Kaplan-Meier and Cox regression and we calculated the Receiver Characteristic Operating Curves (ROC) for the three scores included in the study: MELD, UKELD and iMELD. Results: The three months survival was 87.2%, 71.1% and 50% in patients with MELD values of <15, 15-25 and > 25 respectively. The one year survival was 78.7%, 60% and 25% in patients with MELD values of <15, 15-25 and > 25 respectively. In patients with UKELD score greater than 49 the one year mortality was 42.0% and 16.1% for values of UKELD equal or minor than 49. Higher values of iMELD corresponded to lower survival, both at three months and one year follow-up. The areas under the curve (AUC) for the MELD, UKELD and iMELD scores as predictors of three months mortality were respectively 0.700, 0.704 and 0.706. The AUC for the MELD, UKELD and iMELD scores as predictors of one year mortality were respectively 0.692, 0.725 and 0.747. Conclusions: patients with higher MELD values have lower survival rates. Patients with UKELD value greater than 49 have a one year mortality greater than 9%. Patients with higher iMELD values have lower survival rates. The MELD, UKELD and iMELD scores are good predictors of three months and one year mortality in patients with chronic liver disease

The Role of the CLIF-C OF and the 2016 MELD in Prognosis of Cirrhosis with and without Acute-on-Chronic Liver Failure

Introduction and aim. Acute-on-chronic liver failure (ACLF) is defined by the development of acute deterioration of liver function associated with failure of other organs and high short-term mortality in patients with chronic liver disease (CLD). There is no consensus on the diagnostic criteria, and its independence from ordinary decompensation of CLD has frequently been questioned. This study aimed to identify and characterize this condition and to test the CLIF-C OF score comparing it to the 2016-MELD (with sodium) and the Child-Pugh.Material and methods. 18-month prospective observational study with systematic inclusion of admitted patients with CLD decompensation.Results. 39 patients had ACLF (33.1%). These patients experienced higher 28-day and 90-day mortality, when compared to patients without ACLF (43.6% and 64.1% vs. 2.5% and 7.6% respectively, p < 0.0001). ACLF was linked with a higher acute infection rate (74.4%). For all patients (N = 118), the scores 2016-MELD, CLIF-C OF and Child-Pugh showed an area under the curve (AUC) for 28-day mortality of 0.908, 0.844, 0.753 and for 90-day of 0.902, 0.814, 0.724 respectively, p < 0.0001 for all scores. The 90-day mortality 2016-MELD AUC was greater than the CLIF-C OF AUC, p = 0.021. Within ACLF patients, the 2016-MELD, CLIF-C ACLF and Child-Pugh scores showed an AUC of 0.774, 0.734, 0.584 (28-day) and 0.880, 0.771, 0.603 (90-day); for 2016-MELD p = 0.004 (28-day) and p < 0.0001 (90-day).Conclusion. ACLF is a frequent and relevant condition, associated with high mortality. The CLIF-C OF score revealed good accuracy and diagnoses ACLF when it is present. However, the 2016-MELD performed better for 90-day mortality prediction

Transvenous Obliteration Procedure in the Management of Parastomal Variceal Bleeding: A Case Report

Introduction: Parastomal variceal bleeding (PVB) is a recognized complication of ostomized patients in the presence of portal hypertension. However, since there are few reported cases, a therapeutic algorithm has not yet been established. Case Presentation: A 63-year-old man, who had undergone a definitive colostomy, recurrently presented to the emergency department hemorrhage of bright red blood from his colostomy bag, initially assumed to be caused by stoma trauma. Accordingly, temporary success on local approaches such as direct compression, silver nitrate application and suture ligation was achieved. However, bleeding recurred, requiring transfusion of red blood cell concentrate and hospitalization. The patient's evaluation showed chronic liver disease with massive collateral circulation, particularly at the colostomy site. After a PVB with associated hypovolemic shock, the patient was submitted to a balloon-occluded retrograde transvenous obliteration (BRTO) procedure which stopped the bleeding successfully. The patient was subsequently proposed for a transjugular intrahepatic portosystemic shunt (TIPS) conjugated with percutaneous transhepatic obliteration (PTO). After an initial refusal by the patient, a new episode of self-limited PVB resulted in execution of the procedure. Four months later, in a routine consultation, the patient presented with grade II hepatic encephalopathy, successfully treated with medical therapy. After a 9-month follow-up, he remained clinically well and without further episodes of PVB or other adverse effects. Discussion: This report highlights the importance of a high index of suspicion when dealing with significant stomal hemorrhage. Portal hypertension as an etiology of this entity may compel to a specific approach to prevent recurrence of bleeding, including conjugation of endovascular procedures. The authors pre-sent a case of PVB, initially submitted to a variety of treatment options including BRTO, which was successfully addressed with conjugated treatment of TIPS and PTO

Endoscopic Management of Colonic Perforation due to Ventriculoperitoneal Shunt: Case Report and Literature Review

The authors report the case of a 41-year-old woman with a colonic perforation due to a ventriculoperitoneal shunt (VPS) catheter. Left-sided colonic perforation was diagnosed by abdominal computed tomography 28 years after shunt placement, following acute meningitis caused by Escherichia coli. The proximal end of the VPS was exteriorized and it was decided to remove the distal end by colonoscopy. After pulling out the catheter with a polypectomy snare, it broke at the site where it was entering the colon, leaving a small perforation in the colonic wall which was closed with 2 endoclips. The endoluminal fragment of the catheter, being 20 cm in length, was removed through the rectum. The patient is asymptomatic at the 12-month follow-up. A review of the literature regarding 9 endoscopically managed cases of digestive tract perforation caused by VPS is presented