OBJECTIVEIn liver cirrhosis, a complex coagulopathy does exist. The aim was to investigate whether a possible chronic consumption coagulopathy is the underlying phenomenon of the disease.PATIENTS AND METHODSWe measured endogenous thrombin generation with and without thrombomodulin (ETP ratio) along with D-Dimer in a group of consecutive 282 cirrhotic patients. Fibrinogen, Platelet count and the Hemorrhagic score were previously computed in the same patients. The ETP ratio represents the resistance to the anticoagulant activity of TM and should be considered as an index of a procoagulant imbalance.RESULTSETP ratio and D-Dimer showed higher values in the cirrhotic patients when compared to controls thus showing a hypercoagulable state. When the patients were divided based on the Hemorrhagic score >7, we found that Fibrinogen, ETP ratio, D-Dimer and the platelet count were significantly different between the two groups. Again, when we considered ETP ratio >0.88, the median value of the cirrhotic patients, all parameters, were statistically different between the two groups. D-Dimer were higher while fibrinogen and platelet count were statistically lower in cirrhotic patients with higher ETP ratio values. Even when the same patients were divided based on their platelet count ( 100 x 109/L) the results showed a similar behavior. ROC curves showed significant AUCs when the hemorrhagic score was challenged against Fibrinogen, D-Dimer, Platelet count and ETP ratio.CONCLUSIONSIn liver cirrhosis hypercoagulable state is associated with an increase in D-Dimer levels along with a decrease in fibrinogen and platelet count thus indicating a low-grade intravascular coagulation which predicts a high hemorrhagic risk.

Endometriosis is a chronic inflammatory disease of women of reproductive age. Small bowel (SB) permeability and lipopolysaccharides (LPS) could play a role in the perduration of low grade inflammation status and the pathogenesis of endometriosis. To clarify this hypothesis, we measured SB permeability through plasma values of LPS and urinary secretion of lactulose (La), mannitol (Ma) and their ratio (L/M) in patients with endometriosis compared with healthy controls (HC). Eight patients and 14 HC entered the study. SB permeability was evaluated by high-performance liquid chromatography of urine concentrations of La and Ma. Plasma levels of LPS were measured in the blood. Moreover, a nutritional, gastroenterological, quality of life evaluation was performed through validates questionnaires and complete gynaecological evaluations. The statistical analysis of the obtained data did not show differences in anthropometric and nutritional characteristics and gastrointestinal functional disease in the two groups. Patients reported higher levels of pelvic chronic pain (3.87 +/- 2.99 vs 0.15 +/- 0.55; pe = 0.001) and significantly higher LPS plasma levels (0.529 +/- 0.11 vs 0.427 +/- 0.08; p value = .027) than HC. Our results indicate that intestinal permeability is abnormal in endometriosis patients, and it might play a role in the pathogenesis of this chronic disease.

There are few data on epidemiological and clinical features of adult ulcerative colitis (UC) patients in Sardinia (Italy), mainly derived from administrative sources such as Hospital Discharge Register. The aim of this study was to assess the main clinical and epidemiological features of adult patients diagnosed with ulcerative colitis (UC) in Sardinia, Italy. We evaluated the main clinical features of UC patients followed-up in 7 Gastroenterology/Endoscopy Units in Sardinia, Italy. Data were obtained from medical patients’ records and from a questionnaire administered at inclusion visit. 374 patients with UC were included: 52.9% were female, with a female-to-male ratio of 1.125. Eleven per cent of patients were active smokers and 36.4% were former smokers. Mean age at diagnosis was 39.2 years (SD 15.4). Only 4.3% of patients were < 16 years old at diagnosis; 53.2% were diagnosed at age ranging from 17 to 40 and 42.5% at age >40. About three quarters of patients were diagnosed between 17 and 49 years old (23.7% between 17 and 29, 25.8% between 30 and 39 and 22.8% between 40 and 49). Disease extent at diagnosis was proctitis in 18.2% of patients, left-sided colitis in 38.8% and extensive colitis in 41.2% (missing data in 1.9% of patients). After a median disease duration of 9 years (IQR 13.8), proximal extension of proctitis or left-sided colitis (from E1 to E2/E3 or from E2 to E3) occurred in 12% of patients. 17.9% of patients developed extraintestinal manifestations, the most frequent being articular (11.8%). There were six patients (1.6%) with concomitant primary sclerosing cholangitis. Two patients developed colorectal cancer. This multi-centre study provides important preliminary clinical data on UC in Sardinia.

Background: An increased risk for small bowel carcinoma (SBC) has been reported in Crohn's disease (CrD). We aimed to explore clinical, histopathologic, molecular and prognostic features of CrD-associated SBC (CrD-SBC) in comparison to both coeliac disease (CD)-associated SBC (CD-SBC) and sporadic SBC (spo-SBC). Methods: Seventy-six patients, who underwent surgical resection for non-familial SBC (25 CrD-SBC26, CD-SBC and 25 spo-SBC), were retrospectively recorded to investigate survival together with histological and molecular features detected by immunohistochemistry, multiplex PCR and sequencing. Results: CD-SBC showed a significantly (p=0.004) better sex-, age- and stage-adjusted overall and cancer-specific survival in comparison to CrD-SBC, while no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly (p=0.001) higher rate of microsatellite instability (MSI, 65%) compared to both CrD-SBC (16%) and Spo-SBC (16%). The median number of tumor-infiltrating lymphocytes (TIL) correlated with MSI status and was significantly higher in CD-SBC than in both CrD-SBC (p<0.001) and spo-SBC (p=0.002). Among CD-SBC, MSI allowed to separate two subgroups with different outcome, stage and TP53 mutation rate. MSI was the result of MLH1 methylation in all cases (with the exception of one case of CrD-SBC). No BRAF mutation was observed in any SBC. Mutations in KRAS, NRAS, and PIK3CA were detected in 30%, 4% and 13% of cases, respectively. HER2 gene amplification was identified in two CD-SBC, two CrD-SBC and one spo-SBC. Conclusions: In comparison to CrD-SBC, CD-SBC harbor much more frequently MSI and show a more favorable prognosis, likely related to their high density of TILs, which have independent prognostic value in SBC. MSI status, KRAS/NRAS mutations and HER2 amplifications might contribute to stratify patients for targeted anti-cancer therapy.