Abstract: Aim of this study is to assess the effect of smoothing, based on the assumption that hospitalization rates may be influenced by the neighboring municipalities, the health service organization (HSO) and environmental risk factors. To smooth rates two different Multilevel Multimembership Models are fitted: in the first the random effects where the municipality heterogeneity, the spatial dependence of the municipalities and the local HSO; in the second we replaced the local HSO effect with the environmental risk effect. The models were applied to spatially represent the rates of hospitalization for lung cancer in Apulia in the year 2006. Maps shaded with the rates obtained at the end of the smoothing procedure seem to express a geographical distribution pattern in specific areas of the region. The effect of smoothing was greater in municipalities with a more unstable Risk Adjusted Rate.

Plaque rupture is more frequent in symptomatic than asymptomatic patients and in symptomatic patients in which the fibrous cap is thinner with greater inflammatory infiltrate. The aim of this study was to evaluate the role of major cardiovascular risk factors and histomorphological characteristics, in particular of macrophages and mast cells and of microvascular density, in atherosclerotic plaques collected from 33 consecutive symptomatic and asymptomatic patients undergoing carotid endoarterectomy for carotid disease. Patients were divided in two groups: symptomatic patients [defined according to the North American Symptomatic Carotid Endoarterectomy Trial Classification presenting with cerebrovascular TIAs or stroke within the last three months, and asymptomatic patients, exhibiting progressive ipsilateral internal carotid artery stenosis. Morphological analysis revealed an higher neovascularization in plaques from symptomatic patients, as compared to asymptomatic patients. New-formed blood vessels were located in the intima, interfacing the necrotic core, and at the shoulder area. In parallel, we found a significant increased number of CD68-positive macrophages and tryptase-positive mast cells in plaques from symptomatic patients, as compared to asymptomatic patients. Morphological evidence concerning microvascular density, CD68-positive macrophages and tryptase-postive mast cells have been confirmed by morphometric analysis. Increased plaque vascularity may contribute to lesion progression; being a source of nutrient, inflammatory cell recruitment, and intraplaque hemorrhage, which tends to weaken the plaque and predispose to plaque rupture with ensuing clinical sequelae, such as stroke.

TGF-β1 was inversely correlated with E-cadherin but significantly correlated with VEGF. VEGF and AFP had a low coefficient value but statistically significant. A significant correlation was found between E-cadherin and MMP2. In conclusion, TGF-β and E-cadherin are inversely correlated in HCC patients’ sera and not related to the BCLC classification nor survival but rather to the biological properties of the tumor

Abstract OBJECTIVE: to compare ultrasound (US) and autopsy findings of fetal malformations in second trimester terminations of pregnancy to evaluate the degree of agreement between US and fetal autopsy. METHODS: in this study, all second trimester termination of pregnancy between 2003-2010 were considered. US and autopsy findings were compared and all cases were classified into five categories according to the degree of agreement between US and pathology (A1: full agreement between US and autopsy; A2: autopsy confirmed all US findings but revealed additional anomalies 'rarely detectable' prenatally; B: autopsy demonstrated all US findings but revealed additional anomalies 'detectable' prenatally; C: US findings were only partially demonstrated at fetal autopsy; D: total disagreement between US and autopsy). RESULTS: 144 cases were selected. In 49% of cases there was total agreement between US and autopsy diagnosis (A1). In 22% of cases additional information were about anomalies 'not detectable' by US (A2). In 12% of cases autopsy provided additional information about anomalies not observed but 'detectable' by US (B). In 13% of cases some anomalies revealed at US, such as valve insufficiencies, pericardial and pleural effusions, were not verified at autopsy (C). Total lack of agreement was noted only in 4% of cases (D). Main areas of disagreement concerned cardiovascular, CNS and complex malformations. The degree of agreement was higher if malformations were diagnosed in a tertiary center. CONCLUSIONS: this study shows an overall high degree of agreement between definitive US and autopsy findings in second trimester termination of pregnancy for fetal malformations. Autopsy reveals to be the best tool to diagnose malformations and often showed other abnormalities of clinical importance not detected by US, but sometimes also US could provide additional information about functional anomalies because US is a dynamic examination.

Abstract Background Hypertension and metabolic disorders, attended by impaired microcirculation, represent major risk factors for cerebrovascular impairment, as well as being individual components of the metabolic syndrome (MetS). Aim of the study was to establish whether mild hypertensives, aged ≤ 65 years, may be affected by progressive microvascular damage impairing cerebrovascular perfusion, related to a progressive clustering of MetS components. Methods Twenty-two normotensives with no MetS component (NTN-0), 29 hypertensives with no (HTN-0), 30 with one (HTN-1), 29 with two (HTN-2), 27 with three (HTN-3), 25 with all four (HTN-4) MetS components, were recruited. The study required office and twenty-four hour ambulatory blood pressure monitoring and video capillaroscopy. Functional (fCD), anatomical (aCD) and recruited (RECR) phalangeal skin capillarity were assessed. Cerebral vasodilatory reserve was measured by the breath-holding index (BHI), using transcranial Doppler, in HTN-1 and HTN-2 with MetS. Results The fCD and aCD were reduced in hypertensives and progressively reduced in those with MetS, while RECR was also impaired. BHI was lower in HTN-2 than in HTN-1 (p < 0.001). BHI was correlated with fCD in HTN-1 (.396, p: .046), HNT-2 (.497, p: .011), and with aCD in HTN-2 (.494, p: .012), by partial Pearson test. Discussion The findings show that hypertensives exhibit an increasing microvascular rarefaction with MetS progression and that an impaired cerebral perfusion occurs when the MetS is established. The data underline the importance of preventing MetS in mild hypertensives, as it causes microvascular damage and impairs cerebral arterial perfusion.

Aims: To evaluate the use of the Wilms’ tumour gene (WT1) marker and histomorphological parameters as indicators of prognosis in malignant peritoneal mesothelioma (MPM). Methods and results: Histological samples of 31 MPM were stained immunohistochemically for the WT1 protein. The results were quantified by recording the number of stained nuclei, and then correlated with patient survival. Statistical correlation was evaluated for tumour histotype, mitotic count (MC), nuclear grade (NG), necrosis, lymphoid response (grade of inflammation) and desmoplasia with regard to survival. Highgrade histology (solid epithelioid, pure sarcomatoid or biphasic tumours), high NG, MC more than five per 10 per high-power field (HPF), necrosis and desmoplasia were associated with a significantly worse prognosis. Patients with MPM with low WT1 expression (£25% of positive cells) survived for a significantly shorter time compared to those with high WT1 expression (>25% of positive cells) (P = 0.0001). The 50% survival time of subjects with low WT1 expression was 2.9 months [95% confidence interval (CI): 2.05–3.71] versus 31.5 months (95% CI: 20.4–42.5) for those with high WT1 expression. On multivariate analysis, WT1 and MC were found to be associated independently with survival (P = 0.002; P = 0.005, respectively). Conclusions: Our study suggests that low WT1 expression and high MC may be indicative of an unfavourable prognosis in patients with advanced malignant peritoneal mesothelioma.

BACKGROUND: It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis. PATIENTS AND METHODS: Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry. RESULTS: ROS and interleukin (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs under basal conditions. IL-8 levels further increased after therapy. Early apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and this pattern did not change after antibiotic treatment. CONCLUSIONS: Circulating PMNs are primed in CF acute patients. Further studies are needed to consider PMN-produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF patients.

Background: Refractive laser surgery induces substantial changes in corneal structure, causing inaccurate intraocular pressure (IOP) readings. Pascal dynamic contour tonometry (PDCT) and Icare rebound tonometer (RBT) are two novel devices that do not depend on applanation to measure IOP. Purpose of this prospective study was to compare PDCT and rebound tonometry versus Goldmann tonometry (GAT) in a group of patients who underwent photorefractive keratectomy (PRK). Methods: Central corneal thickness and IOP were measured in 54 eyes before and after PRK. All IOP measurements were taken by the same examiner, using PDCT, RBT and GAT in a randomised, masked fashion. Results: After excimer laser surgery, PDCT measurements were higher than GAT (p<0.0001) and RBT (p=0.0012). Multiple linear regression analysis indicated that size of contact area was significant (b=-0.504; p<0.0001) while corneal thickness was not (b=0.003; p=0.169). Bland-Altman test showed that there was good agreement between RBT and PDCT (p=0.454), whereas GAT gave lower IOP values than both RBT (p=0.0103) and PDCT (p=0.0031). Conclusion: PDCT and RBT are less dependent on iatrogenic corneal changes than GAT and this might be related to their small contact area. In order to minimise IOP underestimation after excimer laser surgery, the clinician should consider adopting non-applanation tonometers like RBT and PDCT as an alternative to GAT.

Abstract This procedure is aimed at solving the chromatic quantification problem in histological images, as well as other fields. On digital images, this is possible using colorimetric software applications. Our solution was to adopt a pre-processing step of the analog signal coming from a video-source (cabling a suitable, dedicated unit to the video-line before signal grabbing). The unit is a hardware device that processes the voltage values of the video signal image section, line by line in the raster image exploiting the vertical interval. The output is a luminance-free video signal compatible with real-time needs (1/25 second), that is in turn compatible with the normal exploration speed of a histological slide. Some experimental results are presented.

The aim of this study was to evaluate the role of macrophages and mast cells and of microvascular density in atherosclerotic plaques collected from 63 consecutive symptomatic and asymptomatic patients undergoing carotid endarterectomy for carotid disease. Results have shown no statistically significant differences between the two groups as concerns: (i) the degree of stenosis; (ii) the extention of the lipidic core; (iii) the thickness of the fibrous cup; (iv) the inflammatory infiltrate; (v) the degree of calcification; (vi) the intraplaque hemorrhage. Otherwise, statistically significant difference was found in microvascular density, in the number of CD68-positive macrophages and tryptase-positive mast cells in plaques from symptomatic patients, as compared to asymptomatic patients. Overall, this study indicate that although advanced symptomatic and asymptomatic carotid plaques present similar histomorphological characteristics, the degree of macrophage and mast cell infiltration and differences in microvascular density could help to discriminate between symptomatic and asymptomatic patients.

Background: The aim of this study was to determine both prognostic clinical-morphological and predictive biomolecular factors affecting course of disease and survival in malignant pleural mesothelioma (MPM). Methods: We retrospectively analyzed (2004-2014) clinical and pathological data of 108 consecutive patients with diagnosis of MPM. Age, stage (WHO 2015), chemotherapy, histotype, nuclear atypia, mitotic count (1/mm2), Ki-67 percentage and 9p21 (p16/CDKN2A) deletion (43 cases) were analyzed and correlated to survival. Survival was evaluated with Kaplan-Meier method and statistical significance with Log-Rank test (SPSS software, 18.0). Results: There were 83 (76.9%) males, 25 (23.1%) females (ratio 3.3/1); median age at diagnosis was 68 (mean 67.2±9.8; range 42-90) years; 94 (87%) patients had asbestos exposure. Overall median survival was 13.3 (mean 19.15±22.4; range 1-136) months. Mean survival (months) was: 30.2±4.6 and 12.4±1.6 in age ≤ 65 and > 65 years (p=0.0001); 24±4.3 in stage I, 21.3±4.5 in II, 21.1±5.8 in III, 9.7±1.7 in IV (p=0.005); 25.9±2.8 and 5±1.3 in patients receiving complete (n=73) and palliative (n=35) chemotherapy (p=0.0001); 21.4±2.5, 11.6±2.7 and 8.5±2.3 in epithelioid, biphasic and sarcomatoid histotypes (p=0.0001); 26.3±3.3 and 12.4±2.5 in moderate and severe nuclear atypia (p=0.0001); 26±3.4 and 9.9±1,3 in low (≤ 5 mm2) and high (> 5 mm2) mitotic count (p=0.0001); 27.2±3.4 and 9.1±1.1 in low (≤ 25%) and high (> 25%) Ki-67 expression (p=0.0001); 35.8±7.7 in absence of p16/CDKN2A deletion, 17.4±3.4 in heterozygous and 8.9±1.9 in homozygous deletion (p=0.0001). Mean survival (months) in patients receiving complete chemotherapy compared to those receiving palliative one was: stage I 30.7±5.4 and 8.2±4.4 (p=0.0001), stage II 25.8±5.3 and 4.2±1.0 (p=0.0001), stage III 25.2±6.8 and 3.0±0.4 (p=0.0001), stage IV 17.7±2.5 and 3.8±0.7 (p=0.0001). Conclusion: Age, stage, chemotherapy, histotype, nuclear atypias, mitoses, proliferating index and loss of 9p21 gene are predictors of survival in MPM and strongly influence the therapeutic strategy. Chemotherapy significantly affects survival in different stages of MPM.

Background: Health service databases of administrative type can be a useful tool for the study of progression of a disease, but the data reported in such sources could be affected by misclassifications of some patients’ real disease states at the time. Aim of this work was to estimate the transition probabilities through the different degenerative phases of liver cirrhosis using health service databases. Methods: We employed a hidden Markov model to determine the transition probabilities between two states, and of misclassification. The covariates inserted in the model were sex, age, the presence of comorbidities correlated with alcohol abuse, the presence of diagnosis codes indicating hepatitis C virus infection, and the Charlson Index. The analysis was conducted in patients presumed to have suffered the onset of cirrhosis in 2000, observing the disease evolution and, if applicable, death up to the end of the year 2006. Results: The incidence of hepatocellular carcinoma (HCC) in cirrhotic patients was 1.5% per year. The probability of developing HCC is higher in males (OR = 2.217) and patients over 65 (OR = 1.547); over 65-year-olds have a greater probability of death both while still suffering from cirrhosis (OR = 2.379) and if they have developed HCC (OR = 1.410). A more severe casemix affects the transition from HCC to death (OR = 1.714). The probability of misclassifying subjects with HCC as exclusively affected by liver cirrhosis is 14.08%. Conclusions: The hidden Markov model allowing for misclassification is well suited to analyses of health service databases, since it is able to capture bias due to the fact that the quality and accuracy of the available information are not always optimal. The probability of evolution of a cirrhotic subject to HCC depends on sex and age class, while hepatitis C virus infection and comorbidities correlated with alcohol abuse do not seem to have an influence.

Computed tomography (CT) does not represent the primary method for the evaluation of breast lesions; however, it can detect breast abnormalities, even when performed for other reasons related to thoracic structures. The aim of this study is to evaluate the potential benefits of 320-row multidetector CT (MDCT) in evaluating and differentiating incidentally detected breast lesions by using vessel probe and 3D analysis software with net enhancement value.

Nanotubular structures, denoted tunneling nanotubes (TNTs) have been described in recent times as involved in cell-to-cell communication between distant cells. Nevertheless, TNT-like, long filopodial processes had already been described in the last century as connecting facing, growing microvessels during the process of cerebral cortex vascularization and collateralization. Here we have investigated the possible presence and the cellular origin of TNTs during normal brain vascularization and also in highly vascularized brain tumors.