Sacro Cuore Hospital of Negrar

Negrar, Italy

Sacro Cuore Hospital of Negrar

Negrar, Italy
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Giani A.,G B Bietti Eye Foundation | Cigada M.,University of Milan | Esmaili D.D.,Massachusetts Eye and Ear Infirmary | Salvetti P.,University of Milan | And 7 more authors.
Retina | Year: 2010

Purpose: The purpose of this study was to compare and evaluate artifact errors in automatic inner and outer retinal boundary detection produced by different time-domain and spectral-domain optical coherence tomography (OCT) instruments. Methods: Normal and pathologic eyes were imaged by six different OCT devices. For each instrument, standard analysis protocols were used for macular thickness evaluation. Error frequencies, defined as the percentage of examinations affected by at least one error in retinal segmentation (EF-exam) and the percentage of total errors per total B-scans, were assessed for each instrument. In addition, inner versus outer retinal boundary delimitation and central (1,000 μm) versus noncentral location of errors were studied. Results: The study population of the EF-exam for all instruments was 25.8%. The EF-exam of normal eyes was 6.9%, whereas in all pathologic eyes, it was 32.7% (P < 0.0001). The EF-exam was highest in eyes with macular holes, 83.3%, followed by epiretinal membrane with cystoid macular edema, 66.6%, and neovascular age-related macular degeneration, 50.3%. The different OCT instruments produced different EF-exam values (P < 0.0001). The Zeiss Stratus produced the highest percentage of total errors per total B-scans compared with the other OCT systems, and this was statistically significant for all devices (P ≤ 0.005) except the Optovue RTvue-100 (P = 0.165). Conclusion: Spectral-domain OCT instruments reduce, but do not eliminate, errors in retinal segmentation. Moreover, accurate segmentation is lower in pathologic eyes compared with normal eyes for all instruments. The important differences in EF among the instruments studied are probably attributable to analysis algorithms used to set retinal inner and outer boundaries. Manual adjustments of retinal segmentations could reduce errors, but it will be important to evaluate interoperator variability. Copyright © by Ophthalmic Communications Society, Inc.


Targher G.,University of Verona | Bertolini L.,Sacro Cuore Hospital of Negrar | Rodella S.,Sacro Cuore Hospital of Negrar | Lippi G.,University of Parma | And 2 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2010

Background and objectives: We assessed whether nonalcoholic steatohepatitis (NASH) diagnosed by liver biopsy is associated with decreased kidney function and whether such association is independent of insulin resistance and features of the metabolic syndrome. Design, settings, participants, & measurements: We enrolled 80 consecutive overweight patients with biopsy-proven NASH and 80 nonsteatotic control subjects who were matched for age, gender, and body mass index. Chronic kidney disease (CKD) was defined as the presence of estimated GFR (eGFR) of ≤60 ml/min per 1.73 m 2 and/or abnormal albuminuria (i.e., urinary albumin/creatinine ratio ≥30 mg/g). Results: NASH patients had significantly (P < 0.001) lower eGFR (75.3 ± 12 versus 87.5 ± 6 ml/min per 1.73 m 2) and a greater frequency of abnormal albuminuria (14 versus 2.5%) and CKD (25 versus 3.7%) than control subjects. The significant differences in eGFR, albuminuria, and CKD that were observed between the two groups were only slightly weakened after adjustment for age, gender, body mass index, smoking status, insulin resistance (by homeostasis model assessment), and components of the metabolic syndrome. Notably, histologic severity of NASH (i.e., fibrosis stage) was strongly associated with either decreasing eGFR or increasing albuminuria (P < 0.01 or less), independently of potential confounding factors. Conclusions: Our findings suggest that patients with biopsy-proven NASH have moderately decreased eGFR and a higher frequency of abnormal albuminuria and CKD than matched control subjects and that the severity of NASH histology is associated with decreased kidney function, independently of traditional risk factors, insulin resistance, and components of the metabolic syndrome. Copyright © 2010 by the American Society of Nephrology.


PubMed | University Hospital of Tuebingen, Heinrich Heine University Düsseldorf, Sacro Cuore Hospital of Negrar, Friedrich - Alexander - University, Erlangen - Nuremberg and 2 more.
Type: | Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | Year: 2017

Somatostatin receptor 2A expression is a feature of well-differentiated neuroendocrine neoplasms and is important for their diagnosis and therapy. Little is known about somatostatin receptor 2A expression in poorly differentiated neuroendocrine neoplasms in relation to TP53 and RB1 status and how these features may contribute to the separation of well from poorly differentiated neuroendocrine neoplasms with a proliferation index above 20%. This study investigates the expression of somatostatin receptors, p53 and Rb1, and TP53 alterations in pancreatic and extrapancreatic well and poorly differentiated neuroendocrine neoplasms (Ki67-index >20%). Thirty-seven poorly differentiated neuroendocrine neoplasms of pancreatic (n=12) and extrapancreatic origin (n=25) as well as 10 well-differentiated neuroendocrine neoplasms of the pancreas (n=9) and rectum (n=1) with a Ki67-index >20% were immunostained for synaptophysin, chromogranin A, Ki67, CD56, p53, Rb1, ATRX, DAXX, progesterone receptor, somatostatin receptor 2A, somatostatin receptor 5, and cytokeratin 20, and sequenced for TP53, exons 5-9. Somatostatin receptor 2A was positive in 6/37 of poorly differentiated and in 8/10 of well-differentiated neuroendocrine neoplasms. One well-differentiated and two poorly differentiated neuroendocrine neoplasms expressed somatostatin receptor 5. Abnormal nuclear p53 and Rb1 staining was found in 29/37 and 22/37 poorly differentiated neuroendocrine neoplasms, respectively, whereas all well-differentiated neuroendocrine neoplasms showed normal p53 and Rb1 expression. TP53 gene alterations were restricted to poorly differentiated neuroendocrine neoplasms (24/34) and correlated well with p53 expression. All cases were progesterone receptor negative. Somatostatin receptor 2A expression is not limited to well-differentiated neuroendocrine neoplasms but also occurs in 16% of poorly differentiated neuroendocrine neoplasms from various sites. Most poorly differentiated neuroendocrine neoplasms are characterized by TP53 alterations and Rb1 loss, usually in the absence of somatostatin receptor 2A expression. In the pancreas, these criteria contribute to separate well-differentiated neuroendocrine neoplasms with a Ki67-index above 20% from poorly differentiated neuroendocrine neoplasms.Modern Pathology advance online publication, 6 January 2017; doi:10.1038/modpathol.2016.217.


Migliarini S.,University of Pisa | Pacini G.,University of Pisa | Pelosi B.,University of Pisa | Lunardi G.,Sacro Cuore Hospital of Negrar | Pasqualetti M.,University of Pisa
Molecular Psychiatry | Year: 2013

Despite increasing evidence suggests that serotonin (5-HT) can influence neurogenesis, neuronal migration and circuitry formation, the precise role of 5-HT on central nervous system (CNS) development is only beginning to be elucidated. Moreover, how changes in serotonin homeostasis during critical developmental periods may have etiological relevance to human mental disorders, remains an unsolved question. In this study we address the consequences of 5-HT synthesis abrogation on CNS development using a knock-in mouse line in which the tryptophan hydroxylase 2 (Tph2) gene is replaced by the eGFP reporter. We report that lack of brain 5-HT results in a dramatic reduction of body growth rate and in 60% lethality within the first 3 weeks after birth, with no gross anatomical changes in the brain. Thanks to the specific expression of the eGFP, we could highlight the serotonergic system independently of 5-HT immunoreactivity. We found that lack of central serotonin produces severe abnormalities in the serotonergic circuitry formation with a brain region-and time-specific effect. Indeed, we observed a striking reduction of serotonergic innervation to the suprachiasmatic and thalamic paraventricular nuclei, while a marked serotonergic hyperinnervation was found in the nucleus accumbens and hippocampus of Tph2eGFP mutants. Finally, we demonstrated that BDNF expression is significantly up-regulated in the hippocampus of mice lacking brain 5-HT, mirroring the timing of the appearance of hyperinnervation and thus unmasking a possible regulatory feedback mechanism tuning the serotonergic neuronal circuitry formation. On the whole, these findings reveal that alterations of serotonin levels during CNS development affect the proper wiring of the brain that may produce long-lasting changes leading to neurodevelopmental disorders. © 2013 Macmillan Publishers Limited All rights reserved.


Targher G.,University of Verona | Valbusa F.,Sacro Cuore Hospital of Negrar | Bonapace S.,Sacro Cuore Hospital of Negrar | Bertolini L.,Sacro Cuore Hospital of Negrar | And 7 more authors.
PLoS ONE | Year: 2013

Background: The relationship between non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) in type 2 diabetes is currently unknown. We examined the relationship between NAFLD and risk of incident AF in people with type 2 diabetes. Methods and Results: We prospectively followed for 10 years a random sample of 400 patients with type 2 diabetes, who were free from AF at baseline. A standard 12-lead electrocardiogram was undertaken annually and a diagnosis of incident AF was confirmed in affected participants by a single cardiologist. At baseline, NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other liver diseases. During the 10 years of follow-up, there were 42 (10.5%) incident AF cases. NAFLD was associated with an increased risk of incident AF (odds ratio [OR] 4.49, 95% CI 1.6-12.9, p<0.005). Adjustments for age, sex, hypertension and electrocardiographic features (left ventricular hypertrophy and PR interval) did not attenuate the association between NAFLD and incident AF (adjusted-OR 6.38, 95% CI 1.7-24.2, p = 0.005). Further adjustment for variables that were included in the 10-year Framingham Heart Study-derived AF risk score did not appreciably weaken this association. Other independent predictors of AF were older age, longer PR interval and left ventricular hypertrophy. Conclusions: Our results indicate that ultrasound-diagnosed NAFLD is strongly associated with an increased incidence of AF in patients with type 2 diabetes even after adjustment for important clinical risk factors for AF. © 2013 Targher et al.


Agaimy A.,University Hospital | Erlenbach-Wunsch K.,University Hospital | Konukiewitz B.,TU Munich | Schmitt A.M.,University of Bern | And 7 more authors.
Modern Pathology | Year: 2013

The human insulin gene enhancer-binding protein islet-1 (ISL1) is a transcription factor involved in the differentiation of the neuroendocrine pancreatic cells. Recent studies identified ISL1 as a marker for pancreatic well-differentiated neuroendocrine neoplasms. However, little is known about ISL1 expression in pancreatic poorly differentiated and in extrapancreatic well and poorly differentiated neuroendocrine neoplasms. We studied the immunohistochemical expression of ISL1 in 124 neuroendocrine neoplasms. Among pancreatic neuroendocrine neoplasms, 12/13 with poor differentiation were negative, whereas 5/7 with good differentiation but a Ki67 >20% were positive. In extrapancreatic neuroendocrine neoplasms, strong positivity was found in Merkel cell carcinomas (25/25), pulmonary small cell neuroendocrine carcinomas (21/23), medullary thyroid carcinomas (9/9), paragangliomas/ pheochromocytomas (6/6), adrenal neuroblastomas (8/8) and head and neck neuroendocrine carcinomas (4/5), whereas no or only weak staining was recorded in pulmonary carcinoids (3/15), olfactory neuroblastomas (1/4) and basaloid head and neck squamous cell carcinomas (0/15). ISL1 stained the neuroendocrine carcinoma component of 5/8 composite carcinomas and also normal neuroendocrine cells in the thyroid, adrenal medulla, stomach and colorectum. Poorly differentiated neuroendocrine neoplasms, regardless of their ISL1 expression, were usually TP53 positive. Our results show the almost ubiquitous expression of ISL1 in extrapancreatic poorly differentiated neuroendocrine neoplasms and neuroblastic malignancies and its common loss in pancreatic poorly differentiated neuroendocrine neoplasms. These findings modify the role of ISL1 as a marker for pancreatic neuroendocrine neoplasms and suggest that ISL1 has a broader involvement in differentiation and growth of neuroendocrine neoplasms than has so far been assumed. © 2013 USCAP, Inc.


Valbusa F.,Sacro Cuore Hospital of Negrar | Labat C.,University of Lorraine | Salvi P.,University of Bologna | Salvi P.,University of Lorraine | And 3 more authors.
Journal of Hypertension | Year: 2012

Objective: Orthostatic hypotension has a prognostic role in determining cardiovascular and all-cause mortality. The aim of this study was to assess the prevalence of orthostatic hypotension and its association with blood pressure (BP) levels, arterial stiffness, cardiovascular and metabolic disorders and medication in individuals aged 80 years and over living in nursing home. Methods: In 994 individuals (77% women, mean age 88±5 years), the presence of orthostatic hypotension was tested according to American Autonomic Society and American Academy of Neurology guidelines. Arterial stiffness was evaluated with carotid-femoral pulse wave velocity (cf-PWV), peripheral to central pulse pressure amplification (PPA) and augmentation index. Cardiovascular and metabolic disorders as well as medications were recorded from patients' medical records. Results: The prevalence of orthostatic hypotension was 18%. Treated hypertensive patients with SBP 140 mmHg or less had a lower prevalence of orthostatic hypotension than patients with SBP more than 140 mmHg (respectively, 13 vs. 23%; P < 0.001). Individuals with orthostatic hypotension exhibited higher brachial and central PP than individuals without orthostatic hypotension (respectively, 69±18 vs. 65±16 mmHg and 57±17 vs. 54±15 mmHg; P < 0.01). In these same individuals, a significant increase in augmentation index (31.1±14.0 vs. 27.2±13.6%; P < 0.01), but not in cf-PWV or in PPA, was observed. Individuals with orthostatic hypotension were treated more frequently with β-blockers and less frequently with angiotensin receptor blockers or nitrates than individuals without orthostatic hypotension (P < 0.05 for both). Conclusion: Contrary to the general belief, elderly individuals with well controlled BP (SBP < 140 mmHg) show lower orthostatic hypotension, thus constituting a complementary argument for efficaciously treating hypertension in these individuals. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Valbusa F.,Sacro Cuore Hospital of Negrar | Bertolini L.,Sacro Cuore Hospital of Negrar | Bonapace S.,Sacro Cuore Hospital of Negrar | Zenari L.,Sacro Cuore Hospital of Negrar | And 4 more authors.
American Journal of Cardiology | Year: 2013

The association between serum uric acid (SUA) levels and atrial fibrillation (AF) is currently poorly known. We examined the association between SUA levels and risk of incident AF in patients with type 2 diabetes mellitus. We followed for 10 years a random sample of 400 type 2 diabetic outpatients, who were free from AF at baseline. A standard 12-lead electrocardiography was undertaken annually and a diagnosis of incident AF was confirmed in affected participants by a single cardiologist. Over 10 years, there were 42 incident AF cases (cumulative incidence of 10.5%). Elevated SUA level was associated with an increased risk of incident AF (odds ratio 2.43, 95% confidence interval 1.8 to 3.4, p <0.0001 for each 1-SD increase in SUA level). Adjustments for age, gender, body mass index, hypertension, chronic kidney disease, electrocardiographic features (left ventricular hypertrophy and PR interval), and use of diuretics and allopurinol did not attenuate the association between SUA and incident AF (adjusted odds ratio 2.44, 95% confidence interval 1.6 to 3.9, p <0.0001). Further adjustment for variables that were included in the 10-year Framingham Heart Study-derived AF risk score did not appreciably weaken this association. Results remained unchanged even when SUA was modeled as a categorical variable (stratifying by either SUA median or hyperuricemia), and when patients with previous coronary heart disease or heart failure were excluded from analysis. In conclusion, our findings suggest that elevated SUA levels are strongly associated with an increased incidence of AF in patients with type 2 diabetes mellitus even after adjustment for multiple clinical risk factors for AF. © 2013 Elsevier Inc. All rights reserved.


Targher G.,University of Verona | Valbusa F.,Sacro Cuore Hospital of Negrar | Bonapace S.,Sacro Cuore Hospital of Negrar | Bertolini L.,Sacro Cuore Hospital of Negrar | And 7 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2014

Background and aims: The relationship between nonalcoholic fatty liver disease (NAFLD) and prolonged heart rate-corrected QT (QTc) interval, a risk factor for ventricular arrhythmias and sudden cardiac death, is currently unknown. We therefore examined the relationship between NAFLD and QTc interval in patients with type 2 diabetes. Methods and results: We studied a random sample of 400 outpatients with type 2 diabetes. Computerized electrocardiograms were performed for analysis and quantification of QTc interval. NAFLD was diagnosed by ultrasonographic detection of hepatic steatosis in the absence of other liver diseases. Mean QTc interval and the proportion of those with increased QTc interval (defined as either QTc interval above the median, i.e. ≥416ms, or QTc interval >440ms) increased steadily with the presence and ultrasonographic severity of NAFLD. NAFLD was associated with increased QTc interval (odds ratio [OR] 2.16, 95% CI 1.4-3.4, p<0.001). Adjustments for age, sex, smoking, alcohol consumption, BMI, hypertension, electrocardiographic left ventricular hypertrophy, diabetes-related variables and comorbid conditions did not attenuate the association between NAFLD and increased QTc interval (adjusted-OR 2.26, 95% CI 1.4-3.7, p<0.001). Of note, the exclusion of those with established coronary heart disease or peripheral artery disease from analysis did not appreciably weaken this association. Conclusion: This is the first study to demonstrate that the presence and severity of NAFLD on ultrasound is strongly associated with increased QTc interval in patients with type 2 diabetes even after adjusting for multiple established risk factors and potential confounders. © 2014 Elsevier B.V.


Valbusa F.,Sacro Cuore Hospital of Negrar | Bonapace S.,Sacro Cuore Hospital of Negrar | Bertolini L.,Sacro Cuore Hospital of Negrar | Zenari L.,Sacro Cuore Hospital of Negrar | And 2 more authors.
Diabetes Care | Year: 2012

OBJECTIVE - To examine whether baseline pulse pressure (PP), a marker of arterial stiffness, is associated with subsequent development of atrial fibrillation (AF) in type 2 diabetes. RESEARCH DESIGN AND METHODS - A total of 350 type 2 diabetic patients, who were free from AF at baseline, were followed for 10 years. A standard electrocardiogram was performed annually and a diagnosis of incident AF was con fi rmed in affected participants by a single cardiologist. RESULTS - During the follow-up, 32 patients (9.1% of total) developed incident AF. After adjustments for age, sex, BMI, diabetes duration, presence of left ventricular hypertrophy, hypertension treatment, kidney dysfunction, and pre-existing history of coronary heart disease, heart failure, and mild valvular disease, baseline PP was associated with an increased incidence of AF (adjusted odds ratio 1.76 for each SD increment [95% CI 1.1-2.8]; P < 0.01). CONCLUSIONS - Our findings suggest that increased PP independently predicts incident AF in patients with type 2 diabetes. © 2012 by the American Diabetes Association.

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