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There is a lack of validated predictors on which to decide the timing of discharge in patients already hospitalized for upper nonvariceal bleeding.Identify factors that appear to protect nonvariceal bleeders from the development of negative outcome (rebleeding, surgery, death).Secondary analysis of two prospective multicenter studies. Multivariate analyses for each investigated outcome were performed; a single model was developed including all factors that were statistically significant in each sub-model. A final score was developed to predict favourable outcomes. Prognostic accuracy was tested with ROC curve analysis.Out of 2398 patients, 211 (8.8%) developed one or more adverse outcomes: 87 (3.63%) had rebleeding, 46 (1.92%) needed surgery and 107 (4.46%) died. Predictors of favourable prognosis were: ASA score 1 or 2, absence of neoplasia, outpatient bleeding, use of low-dose aspirin, no need for transfusions, clean-based ulcer, age70 years, no haemodynamic instability successful endoscopic diagnosis/therapy, no Dieulafoy's lesion at endoscopy, no hematemesis on presentation and no need for endoscopic treatment. Overall prognostic accuracy of the model was 83%. The final score accurately identified 20-30% of patients that eventually do not develop any negative outcome.The "good luck score" may be a useful tool in deciding when to discharge a patient already hospitalized for acute non-variceal bleeding.

From an Italian Registry of patients with upper gastrointestinal hemorrhage (UGIH), we assessed the clinical outcomes and explored the roles of clinical, endoscopic, and therapeutic factors on 30-day mortality in a real life setting.Prospective analysis of consecutive patients endoscoped for UGIH at 23 community and tertiary care institutions from 2003 to 2004. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression analysis identified predictors of mortality.One thousand and twenty patients were included. A total of 46 patients died for an overall 4.5% mortality rate. In all, 85% of deaths were associated with one or more major comorbidity. Sixteen of 46 patients (35%) died within the first 24 h of the onset of bleeding. Of these, eight had been categorized as ASA class 1 or 2 and none of them was operated upon, despite a failure of endoscopic intention to treatment in four. Regression analysis showed advanced age, presence of severe comorbidity, low hemoglobin levels at presentation, and worsening health status as the only independent predictors of 30-day mortality (P0.001). The acute use of a PPI exerted a protective effect (OR 0.23, 95% CI 0.09-0.73). Recurrent bleeding was low (3.2%). Rebleeders accounted for only 11% of the total patients deceased (OR 3.27, 95% CI 1.5-11.2).These results indicate that 30-day mortality for nonvariceal bleeding is low. Deaths occurred predominantly in elderly patients with severe comorbidities or those with failure of endoscopic intention to treatment.

Lean body mass wastage in active Crohn's disease is not only related to malnutrition, but also to local and systemic inflammation. Altered bowel permeability can represent a source of pro-inflammatory cytokines, that have been shown to produce muscle wastage by several mechanisms such as apoptosis. In our study we have evaluated the body composition and the pathological changes of skeletal muscle in patients with Crohn's disease to see whether a relationships between altered gut permeability, proinflammatory cytokines production and muscle wastage existed.Thirteen consecutive steroid-free patients with active Crohn's disease underwent evaluation of body composition, sugar test for intestinal permeability, determination of serum levels of TNF-alpha, sphingosine, bacterial lipopolysaccaride, and biopsy of gastrocnemius. In bioptic samples we determined fibres cross sectional area, distribution of myosin heavy chains and apoptosis. Twenty healthy subjects formed the control group.In patients lean body mass was reduced and intestinal permeability increased (p0.01 for both). TNFalpha, sphingosine and lipopolysaccaride were increased (p0.01). Fibres size was reduced (p0.01), with shift of Myosin Heavy Chains from the slow to the fast type. Apoptosis was found in 5 patients' biopsies, never in controls.Crohn's patients have a myopathy characterized by myocyte apoptosis, modifications of myosin and muscle atrophy. TNF-alpha and sphingosine, that are increased because of the enhanced lipopolysaccaride concentration due to altered gut permeability, may play a pathophysiological role in the development of this myopathy.

Aims: To determine whether the functional A49G polymorphism of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a T-cell surface molecule that modulates T-lymphocyte activation and influences the risk of developing alcohol-induced autoantibodies, p lays a role in susceptibility to alcoholic liver disease (ALD) and influences disease severity in Italian alcohol abusers. Methods: One hundred and eighty-three patients with chronic ALD (61 cirrhosis), 115 end-stage HCV cirrhosis, 102 non-alcoholic fatty live r disease (NAFLD), 93 healthy subjects and 43 heavy drinkers without liver disease were studied. CTLA-4 gene polymorphism was analysed by restriction analysis. Results: The frequency of the CTLA-4 polymorphism was higher in patients with ALD than in patients with HCV chronic hepatitis and NAFLD, healthy subjects ( P < 0.0001), and heavy drinkers without liver disease ( P = 0.02). In patients with ALD, homozygosity for the CTLA-4 polymorphic allele (G/G genotype) was more represented in subjects with cirrhosis (P = 0.047), and independently associated with the risk of cirrhosis (OR 3.5; P = 0.03). Conclusions: The CTLA-4 polymorphic G allele, probably by interfering with the immune response, may confer susceptibility to ALD and, in homozygous sta te, to alcoholic cirrhosis.

We compared the efficacy and safety of apheresisand reinfusion of concentrated ascites (ARCA) versustotal paracentesis plus intravenous albumin (PARA) in aprospective trial on cirrhotic patients with tense ascites. Twenty-four patients wererandomized to either ARCA (N = 12) or PARA (N = 12), andfollowed for two years. Sex, age, Child's class, andrenal and liver function were similar in the two groups. The times of the procedures were 2.7 ±1.0 (ARCA) vs 2.2 ± 1.1 (PARA) hr, with removalof 8.8 ± 3.5 (ARCA) and 6.9 ± 3.4 (PARA)liters of ascites and intravenous infusion of 59.8± 35.2 (ARCA) and 42.5 ± 20.5 (PARA) g of albumin. Both procedures were safe.Biochemical signs of coagulative disturbances having noclinical relevance were observed after ARCA, with anincrease in prothrombin time (P = 0.005) and serum FSP (P = 0.02). No significant changes in renalfunction, serum albumin, or plasma and urinaryelectrolytes were shown. Plasma renin activity increasedafter PARA (P = 0.02) and plasma atrial natriureticfactor increased after ARCA (P = 0.008), although nodifferences were observed in diuresis in the immediatefollow-up. During the long-term follow-up, patientsurvival and recurrence of tense ascites were the same in both groups. We conclude that apheresis andreinfusion of concentrated ascites are as safe andeffective as total paracentesis with albumin infusionfor the treatment of tense ascites in cirrhoticpatients.

Aim: Adherence to and the applicability of practice guidelines for the management of hepatocellular carcinoma (HCC) in field practice have not been fully addressed. We designed a multicenter field practice prospective study to evaluate the adherence to the 2005 American Association for the Study of Liver Diseases guidelines in Italy. Materials & methods: The study began in September 2008 and consecutively enrolled cirrhotic patients with newly diagnosed HCC from 30 local, nonreference centers in Italy. Patients were stratified according to Child–Pugh, the model for end-stage liver disease, tumor-node metastasis, performance status and the Barcelona Clinic Liver Cancer (BCLC) classifications. The diagnostic and therapeutic strategies adopted in each individual patient were recorded. Statistical analysis was carried out on 536 patients using all of the valuable data. Results: A total of 286 (54.5%) patients were ≥70 years old. Comorbidities, recorded in 397 (74%) patients, were classified as moderate to severe in 170 patients (43%). Overall, 174 (59%) patients with early-stage BCLC were ≥70 years; 104 (35%) of these had moderate-to-severe comorbidities and 54% were under a regular US surveillance program. Diagnosis was performed by computed tomography in 93% of patients, contrast-enhanced ultrasound in 62% and MRI in 17%. In patients with nodules of ≤2 cm, adherence to noninvasive diagnostic criteria was 56%. Adherence to the BCLC classification was shown to be suboptimal overall, particularly regarding allocation to surgical procedures, and a total of 119 patients (40%) with BCLC stage A did not receive curative therapies. Conclusions: This multicenter survey showed that, in the ‘real world’, adherence to the both the diagnostic and therapeutic American Association for the Study of Liver Diseases 2005 algorithms was low, particularly in patients with early-stage HCC. Difficulties in applying the algorithms in routine clinical practice and the high prevalence of older patients with relevant comorbidities may account for our findings. Strategies to help improve adherence to international guidelines for HCC in field practice are required.

Risk stratification systems that accurately identify patients with a high risk for bleeding through the use of clinical predictors of mortality before endoscopic examination are needed. Computerized (artificial) neural networks (ANNs) are adaptive tools that may improve prognostication.To assess the capability of an ANN to predict mortality in patients with nonvariceal upper GI bleeding and compare the predictive performance of the ANN with that of the Rockall score.Prospective, multicenter study.Academic and community hospitals.This study involved 2380 patients with nonvariceal upper GI bleeding.Upper GI endoscopy.The primary outcome variable was 30-day mortality, defined as any death occurring within 30 days of the index bleeding episode. Other outcome variables were recurrent bleeding and need for surgery.We performed analysis of certified outcomes of 2380 patients with nonvariceal upper GI bleeding. The Rockall score was compared with a supervised ANN (TWIST system, Semeion), adopting the same result validation protocol with random allocation of the sample in training and testing subsets and subsequent crossover. Overall, death occurred in 112 cases (4.70%). Of 68 pre-endoscopic input variables, 17 were selected and used by the ANN versus 16 included in the Rockall score. The sensitivity of the ANN-based model was 83.8% (76.7-90.8) versus 71.4% (62.8-80.0) for the Rockall score. Specificity was 97.5 (96.8-98.2) and 52.0 (49.8 4.2), respectively. Accuracy was 96.8% (96.0-97.5) versus 52.9% (50.8-55.0) (P.001). The predictive performance of the ANN-based model for prediction of mortality was significantly superior to that of the complete Rockall score (area under the curve 0.95 [0.92-0.98] vs 0.67 [0.65-0.69]; P.001).External validation on a subsequent independent population is needed, patients with variceal bleeding and obscure GI hemorrhage are excluded.In patients with nonvariceal upper GI bleeding, ANNs are significantly superior to the Rockall score in predicting the risk of death.

Chronic ethanol consumption causes a DNA repair deficiency. This was demonstrated in Sprague-Dawley rats injected with 14C-labeled dimethylnitrosamine after being pair-fed isocaloric, ethanol, or carbohydrate control diets for 4 weeks. Hepatic DNA was isolated from rats killed at intervals over a 36 hour period after administration of the nitrosamine and concentrations of alkylated guanine derivatives were measured. While N7-methylguanine was lost at equivalent rates from the DNA of both diet groups, 06methylguanine, a promutagenic lesion, persisted at higher levels for longer periods of time in the DNA from the alcohol-fed animals.