Behçet’s syndrome as a tool to dissect the mechanisms of thrombo-inflammation: clinical and pathogenetic aspects

Behçet’s syndrome (BS) is a complex disease with different organ involvement. The vascular one is the most intriguing, considering the existence of a specific group of patients suffering from recurrent vascular events involving the venous and, more rarely, the arterial vessels. Several clinical clues suggest the inflammatory nature of thrombosis in BS, especially of the venous involvement, thus BS is considered a model of inflammation-induced thrombosis. Unique among other inflammatory conditions, venous involvement (together with the arterial one) is currently treated with immunosuppressants, rather than with anti-coagulants. Although many in-vitro studies have suggested the different roles of the multiple players involved in clot formation, in-vivo models are crucial to study this process in a physiological context. At present, no clear mechanisms describing the pathophysiology of thrombo-inflammation in BS exist. Recently, we focused our attention on BS patients as a human in-vivo model of inflammation-induced thrombosis to investigate a new mechanism of clot formation. Indeed, fibrinogen displays a critical role not only in inflammatory processes, but also in clot formation, both in the fibrin network and in platelet aggregation. Reactive oxygen species (ROS)-derived modifications represent the main post-translational fibrinogen alterations responsible for structural and functional changes. Recent data have revealed that neutrophils (pivotal in the pathogenetic mechanisms leading to BS damage) promote fibrinogen oxidation and thrombus formation in BS. Altogether, these new findings may help understand the pathogenetic bases of inflammation-induced thrombosis and, more importantly, may suggest potential targets for innovative therapeutic approaches.     

Temperature monitoring and lesion volume estimation during double-applicator laser-induced thermotherapy in ex vivo swine pancreas: a preliminary study

Tissue temperature distribution plays a crucial role in the outcome of laser-induced thermotherapy (LITT), a technique employed for neoplasias removal. Since recent studies proposed LITT for pancreatic tumors treatment, assessment of temperature and of its effects around the laser applicator could be useful to define optimal laser settings. The aims of this work are temperature monitoring and measurement of ablated tissue volume in an ex vivo porcine pancreas undergoing double-applicator LITT. A three-dimensional numerical model is implemented to predict temperature rise and volumes of ablated tissue in treated pancreas. Experiments are performed to validate the model, with two modalities: (1) 12-fiber Bragg grating sensors are adopted to monitor the heating and cooling during LITT at several distances from the applicators tip, and (2) 1.5-T MR imaging is used to estimate the ablated volume. Experimental data agree with theoretical ones: at 2 mm from both applicators tips, the maximum temperature increase is approximately 60 °C downward from the tips, while it increases of about 40 °C and 30 °C, respectively, at the level and upward from the tips. This behavior occurs also at other distances, proving that the tissue downward from the tip is mostly heated. Furthermore, the estimated volume with MRI agrees with theoretical one (i.d., 0.91?±?0.09 vs. 0.95 cm³). The encouraging results indicate that the model could be a suitable tool to choose the optimal laser settings, in order to control the volume of ablated tissue.     

Epidemiological,demographic and clinical data on chronic viral hepatitis C in Tuscany

Background: Recent introduction of direct antiviral agents (DAAs) has completely changed the scenario regarding hepatitis C virus (HCV) treatment. Certain countries’ economic health programs prioritize DAAs according to specific clinical features of HCV-infected patients. The aim of this study was to define epidemiological, demographic and clinical characteristics of HCV-infected patients in the Tuscany region of central Italy.

Methods: We enrolled HCV patients with chronic viral hepatitis who were referred to the outpatient services of 16 hospitals in Tuscany from 1 January 2015 to 31 December 2015. Case report forms contained patient information including main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations (liver biopsy or transient elastometry, liver ultrasound), eligibility for DAAs, and liver transplantation or therapy already in progress.

Results: Of all patients considered, 2919 HCV patients were enrolled (mean age: 57.44?±?15.15; 54% males, 46% females). All routes of transmission were well represented (intravenous drug use in 20.7%; nosocomial/dental care in 20.6%; and coagulation factors/blood transfusions in 13.3%). Diabetes was the highest represented comorbidity (20.8%), followed by metabolic syndrome (15.5%) and ischemic heart disease (6.2%). The most prevalent HCV genotypes were 1b (47.4%) and 2 (16.5%). In the whole cohort of patients, 32.8% were cirrhotic (40 patients were listed for liver transplantation). Signs of portal hypertension were present mostly in the group older than 45 years (92.3%). Extrahepatic HCV-related diseases were present in 13.3% of cases (cryoglobulinemic syndrome in 58.3% and B-cell non-Hodgkin’s lymphoma in 10.5%).

Conclusions: Our study provides evidence of a high prevalence of epidemiological changes in HCV infection with a major prevalence of advanced liver disease, such as portal hypertension, in this elderly cohort of patients.     

急性有机磷杀虫药中毒中间综合征的临床分析

目的探讨急性有机磷杀虫药中毒中间综合征（intermediate syndrome,IMS）的诊断治疗。方法回顾性分析10例IMS患者临床表现和治疗方法。结果有机磷中毒中间综合征的10例患者均出现不同程度呼吸肌麻痹症,及时建立人工气道及机械通气和乙酰胆碱酯酶（AchE）复能剂应用,治愈8例,死亡2例。结论 IMS应早期识别,建立人工气道与机械通气是抢救成功的重要方法。     

Early decrease in nasal eosinophil proportion after nasal allergen challenge correlates with baseline bronchial reactivity to methacholine in children sensitized to house dust mites.

BACKGROUND: Allergic rhinitis is induced by an IgE mediated inflammation after allergen exposure of the membranes lining the nose which, in predisposed individuals, may constitute a risk factor for the occurrence of asthma. OBJECTIVE: To detect early changes in nasal inflammation after allergen exposure, 11 children [9.0 (7, 11) yrs], sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and an age- and gender-matched control group (Ctr) were studied. METHODS: The following parameters were evaluated: i) pulmonary function; ii) bronchial reactivity to methacholine (MCh), expressed as Pd20MCh; iii) nasal brushing (NB) 'at baseline' and, on a separate day, 30 min after nasal allergen challenge (NAC). On NBs, the following markers of inflammation were evaluated: a) neutrophil and eosinophil proportion, b) 'intact to degranulated eosinophil' ratio, and c) expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR by nasal epithelial cells. RESULTS: 'At baseline', allergic children showed elevated nasal eosinophilia and increased ICAM-1 and HLA-DR expression (p<0.05), as compared to Ctr. In allergic children, nasal eosinophilia correlated with Pd20MCh (p=0.002). The significant decrease in nasal eosinophilia observed after NAC (p=0.002) was associated with a significant decrease in the 'intact to degranulated eosinophil' ratio (p=0.001). Interestingly, correlations were still present between Pd20MCh and 'post NAC' eosinophilia (p=0.004) or the NAC-induced decrease in eosinophilia (p=0.010). CONCLUSIONS: In children sensitized to HDM, experimental allergen exposure is followed by an early depletion of nasal eosinophils. The correlation between allergen-induced changes in nasal eosinophilia and bronchial reactivity to MCh further supports the concept of a tight link between upper and lower respiratory tract involvement in respiratory allergy.     

Ectopic expression of rhombotin-2 causes selective expansion of CD4-CD8- lymphocytes in the thymus and T-cell tumors in transgenic mice

Although the proto-oncogene rhombotin-2 (RBTN-2) is widely expressed in most tissues, it is not expressed in T cells. We investigated the potential for overexpression of RBTN-2 to cause tumors in T cells and other tissues by constructing transgenic mice that expressed RBTN-2 under control of the metallothionein-1 promoter. Despite overexpression of RBTN-2 in all tissues, transgenic mice developed T-cell tumors only, thus indicating that tumorigenesis caused by RBTN-2 is T-cell-specific. Thymic tumors were found between 37 and 71 weeks and were invariably associated with metastasis to nonlymphoid organs. Thymuses from apparently healthy transgenic mice were also examined. In some mice there was an 10-fold increase in the CD4-CD8- thymocyte subset, yet the total number of thymocytes was the same as that in wild-type mice. Thymic homeostasis was maintained by a compensatory reduction in the CD4+CD8+ subset. The expansion of CD4-CD8- thymocytes was associated with increased expression of RBTN-2 and with increased cell proliferation. No differences were found in the proportion of thymocytes undergoing apoptosis in transgenic mice. Furthermore, RBTN-2- induced expansion of CD4-CD8- cells did not block differentiation of these cells. Thymuses with 30% CD4-CD8- cells were essentially monoclonal, indicating that all thymic immunophenotypes were derived from a single clone. Overall, our data are consistent with the following scenario: (1) RBTN-2 expression in T cells causes selective and polyclonal proliferation of CD4-CD8- thymocytes accompanied by a compensatory decrease in other thymocyte subsets; (2) a clone with growth advantage and differentiation potential is selected and populates the thymus; and (3) this clone eventually breaches homeostasis of the thymus, accompanied or followed by metastasis to other organs.