Papers by Rodolfo Cotichini
Nutrition Metabolism and Cardiovascular Diseases, May 1, 2014
Background and aims: Carotid intima-media thickness (IMT) and arterial stiffness parameters, incl... more Background and aims: Carotid intima-media thickness (IMT) and arterial stiffness parameters, including aortic augmentation index (AIx) and pulse wave velocity (PWV), are independent predictors of stroke and cardiovascular disease. Genetic effects on these traits were never explored in a Mediterranean country. The present study aims to quantify the contribution of genes, environment and age to carotid IMT and aortic Aix and PWV. Methods and results: The twin design was used. A total of 348 adult twins from the Italian Twin Register underwent measurements of carotid IMT and aortic PWV and AIx in three university hospitals located in Rome, Padua and Perugia. Carotid IMT was measured by B-mode ultrasound, aortic PWV and AIx by Arteriograph. Genetic modelling was performed to decompose total variance of traits into genetic, shared and unshared environmental and age components. For each phenotype, the best-fitting model included additive genetic, unshared environmental and age effects. For IMT, heritability was 0.32 (95% confidence interval (CI): 0.25e0.38), unshared environmental component was 0.25 (0.18e0.32) and age contribution was 0.44 (0.39e0.49). For AIx and PWV, heritabilities were 0.42 (0.29e0.55) and 0.49 (0.35e0.62), unshared environmental components were 0.31 (0.22e0.44) and 0.37 (0.26e0.51) and age contributions were 0.27 (0.16 e0.39) and 0.14 (0.06e0.24), respectively. Conclusion: This study shows substantial genetic and unshared environmental influences on carotid intima-media thickness and arterial stiffness and confirms the relevant role of age in the aetiology of these traits. Further support is provided for prevention and health promotion strategies based on modifiable factors.
PubMed, Apr 1, 2006
In this hospital-based, multicenter case-control study we investigated the prevalence of hepatiti... more In this hospital-based, multicenter case-control study we investigated the prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus (HCV) co-infection among B-cell non-Hodgkin's lymphoma (B-NHL) cases and controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other departments of the same hospitals were studied. The prevalence of positivity for hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV co-infection was found in four cases, but in no controls. The finding of a positive association between HBV infection and B-NHL raises the possibility that HBV may play an etiologic role in the induction of B-NHL.
Twin Research and Human Genetics, Jun 1, 2001
Notiziario dell'Istituto Superiore di Sanità, 2009
Journal of Hepatology, Apr 1, 2006
viruses such as HSV, CMV, RSV and measles virus. In this study, we aimed to elucidate whether TLR... more viruses such as HSV, CMV, RSV and measles virus. In this study, we aimed to elucidate whether TLR2 and 4 are involved in HCV antigen recognition and induction of innate immune responses. Methods: TLR activation was assessed in TLR2-and TLR4-transfected HEK and CHO cell lines following the incubation with recombinant HCV structural proteins, insect cell-derived HCV-like particles as well as cell culture-derived infectious recombinant virus derived from the HCV JFH1 strain (HCVcc). Results: Binding of recombinant C-terminally truncated core protein to CHO and HEK cells stably or transiently expressing TLR2 and 4 resulted in specific activation of TLR2 in a dose-dependent manner. By contrast, incubation of transfected target cell lines with cell-culture derived recombinant infectious virions (HCVcc), HCV-LPs or recombinant envelope proteins did not result TLR2 and TLR4 signaling. Conclusions: Our findings suggest that monomeric core protein, but not core as part of the viral nucleocapsid or virion induces TLR2 signaling. Viral disassembly with degradation of nucleocapsids or unassembled core protein released from infected hepatocytes may be required for core protein recognition by TLR2 and the induction of antiviral innate immune responses.
Twin Research and Human Genetics, Jun 1, 2001
Twin Research and Human Genetics, Jun 1, 2001
European Journal of Clinical Microbiology & Infectious Diseases, Apr 3, 2000
In 1996-1997 data was collected and a Mantoux tuberculin test performed in 2882 Italian military ... more In 1996-1997 data was collected and a Mantoux tuberculin test performed in 2882 Italian military recruits aged 18-23 years in order to establish the prevalence of tuberculin reactivity. In addition, the annual risk of infection, defined as the probability that a non-infected individual would be infected during the following year, was calculated. Of the 2882 recruits, 513 had received a BCG vaccination, the remaining 2369 had not. The overall prevalence of subjects with a tuberculin skin reaction size >5 mm (the cut-off point for positivity corresponding to the antimode in the reaction size frequency curve) was 6.1% (144/2369). The prevalence of skin reactivity increased with age but remained similar when related to area of residence, duration of father's school education and family size. The same general trend was observed if the standard pre-established cut-off point of 10 mm was used. In this case the overall prevalence of a positive skin reaction was 4% (95/2369). The annual risk of infection was 0.3% for a prevalence of tuberculin skin reactivity of 6.1% (cut-off point 5 mm) and 0.19% for a prevalence of 4% (cut-off point 10 mm). Analysis of the population sample vaccinated with BCG showed a lack of correlation between the positive reaction after vaccination reported retrospectively by the subject and the current skin reaction observed by the physician in this study (K = 0.254). Moreover, a significant difference was observed between the skin reaction in subjects vaccinated with BCG in 1993-1994 (average size 12.5 mm) and that of subjects vaccinated in 1995-1996 (average size 10.1 mm, P<0.01), probably as a consequence of mycobacteria circulating in the general population which act as a natural booster in people already vaccinated with BCG. A booster effect of tuberculin in Mantoux assays also cannot be excluded.
Twin Research and Human Genetics, 2001
Neuroepidemiology, 2008
Basel · Freiburg · Paris · London · New York · Bangalore · Bangkok · Shanghai · Singapore · Tokyo... more Basel · Freiburg · Paris · London · New York · Bangalore · Bangkok · Shanghai · Singapore · Tokyo · Sydney Neuroepidemiology 2008;31:201–223 Published online: September 19, 2008 DOI: 10.1159/000156450 The abstracts are only available online, free of charge, under www.karger.com/doi/10.1159/000156450 XIIIth National Meeting of the Italian Neuroepidemiology Association Verona, Italy, September 26–28, 2008 Chairperson Adriano Chiò, Torino
Investigative ophthalmology & visual science, 1994
To compare the relationship between logMAR visual acuity (VA) and cataract severity and between c... more To compare the relationship between logMAR visual acuity (VA) and cataract severity and between contrast sensitivity (CS) and cataract severity in pure types of age-related lens opacities. Analysis included patients followed in the ongoing Italian-American Study of the Natural History of Age-Related Cataract. Lens opacities were classified and graded according to the Lens Opacities Classification System II (LOCS II). Visual acuity was measured with the Early Treatment Diabetic Retinopathy Study Chart. Contrast sensitivity was measured with the Pelli-Robson chart. Data from 1,076 eyes were used for the analysis (366 clear lenses; 550, 124, and 36 eyes with cortical, nuclear and posterior subcapsular cataract, respectively). In age-adjusted analyses, increasing severity of all three cataract types was associated with progressively higher logMAR VA, which translates into poorer acuity, and lower CS scores. For both VA and CS, the effect of increasing severity was greatest for nuclear a...
Atherosclerosis Supplements, 2010
Haematologica, 2004
Infection with hepatitis C virus (HCV) is associated with type II mixed cryoglobulinemia (MC), a ... more Infection with hepatitis C virus (HCV) is associated with type II mixed cryoglobulinemia (MC), a lymphoproliferative disorder which, in some patients, evolves into overt B-cell non-Hodgkin's lymphoma (B-NHL). Recently, also the association between HCV infection and B-NHL, which had long been controversial, was confirmed in a large case-control study. Little knowledge is, however, available on possible associations between HCV infection and other lymphoid or myeloid malignancies. The present study was set up in order to investigate this aspect. The study was conducted in hematology departments of ten hospitals in different Italian cities. The cases consisted of consecutive patients with a new diagnosis of T-NHL, Hodgkin's disease (HD), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), multiple myeloma (MM), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). The controls were patients in other departments of the same hospitals. HCV infectio...
Neurology, 2011
Metals are suspected of being involved in the pathogenesis of various neurologic diseases. We pre... more Metals are suspected of being involved in the pathogenesis of various neurologic diseases. We previously found a complex imbalance in serum chemical elements and oxidative status in patients with clinically definite multiple sclerosis (CDMS). To understand whether this imbalance affects people with clinically isolated syndrome (CIS) and, if so, whether it predicts conversion to CDMS. We studied 22 chemical elements and the oxidative status in 49 patients with CIS, 49 patients with CDMS, and 49 healthy donors (HD). Univariate and multivariate approaches were used to identify profiles for each group. A logistic regression analysis was used to identify the predictive potential of baseline data (elements, oxidative status, and MRI findings) for conversion to CDMS over 36 months. Several elements and oxidative status values differed significantly among the 3 groups. Discriminant analysis revealed a major contribution of Ca, Fe, Sn, Zn, serum antioxidant capacity, and serum oxidative status, which resulted in distinct profiles (the prediction of group membership was 96% [cross-validated 92%] for HD, 92% [cross-validated 92%] for CDMS, and 90% [cross-validated 86%] for CIS). A weighted combination of element concentrations and oxidative status values, adjusting for all other predictors, would predict a reduction in the risk of conversion to CDMS within 3 years (odds ratio 0.37; 95% confidence interval 0.18-0.76; p = 0.007), thereby proving more effective than MRI at baseline. The peculiar imbalance in serum elements and oxidative status that characterizes patients with CIS and may predict conversion to CDMS warrants studies on larger sample sizes.
Journal of Pediatric Gastroenterology & Nutrition, 2010
Objectives: Obesity and exposure to cardiovascular risk factors during adolescence may be associa... more Objectives: Obesity and exposure to cardiovascular risk factors during adolescence may be associated with the development of atherosclerosis and cardiovascular diseases later in life. The objective of the study was to investigate whether any excess body weight, including moderate overweight, is associated with a more severe cardiovascular risk profile and signs of early atherosclerosis in a pediatric population. Patients and Methods: A cross-sectional study was conducted among 646 adolescents ages 11 to 13 years from several primary schools of Reggio Calabria, Italy. Body mass index, waist circumference, blood pressure, glucose, insulin, homeostatic model assessment of insulin resistance, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and C-reactive protein (CRP) were determined. All of the subjects underwent carotid ultrasonography for the measurement of intima-media thickness. Complete clinical data were available from 575 subjects. Results: Overweight was similarly frequent in boys and girls (31.2% vs 31.0%), whereas prevalence of obesity was higher in boys (18.4% vs 10.1%). Subjects with lower levels of HDL and higher levels of triglycerides, insulin, and CRP plasma were observed more frequently among overweight and obese subjects than nonoverweight. At multivariate analysis, HDL cholesterol, insulin, and CRP were associated (P < 0.05) with overweight and obesity in girls, whereas in boys, insulin and CRP were associated (P < 0.05) with overweight and obesity, and LDL cholesterol with obesity. The association between overweight or obesity and increased intima-media thickness, a sign of early atherosclerosis, was present in girls (P < 0.05) and was close to statistical significance in obese boys (P ¼ 0.07). Conclusions: Overweight and obese adolescents have a higher prevalence of cardiovascular risk factors and show signs of early atherosclerosis. In girls, in particular, overweight is sufficient to determine a more severe cardiovascular risk profile.
Journal of Hepatology, 2009
Background and Aims: Until now, there was no satisfactory measurement of liver steatosis. Our aim... more Background and Aims: Until now, there was no satisfactory measurement of liver steatosis. Our aim was to implement a quantitative histological measurement through the area of steatosis (AOS) to dispose a reference, and to try to obtain a non invasive diagnosis. Methods and Results: 1st step: implementation of an algorithm for AOS by image analysis with automatic thresholding. 2nd step: qualitative validation of AOS images obtained in liver specimen by 3 independent pathologists according to 6 criteria. The global result was considered as very good or good in 87.3% of 100 images. 3rd step: quantitative validation. The algorithm specificity was checked in 12 patients classified without steatosis by pathologists: mean AOS = 0.84±0.04%. The intra-and inter-operator AOS reproducibility was evaluated by 2 engineers in 20 patients with NAFLD: intraclass correlation coefficient = 1.00. The relationship between AOS and steatosis Kleiner grades was very significant in 204 patients with NAFLD (difference p < 10 -3 by ANOVA and between each grade with Bonferroni weighting, table). The AOS increased from fibrosis stage F0 to F2 then decreased from stage F2 to F4 (cirrhosis) (p < 10 -3 , table ). Thus, in stages F 2, the AOS was negatively correlated with the area of fibrosis (r s = -0.57, p < 10 -3 ) and with the architectural distortion (fractal dimension) of fibrosis (r s = -0.50, p < 10 -3 ). 4th step: non invasive diagnosis. In the population of 204 NAFLD, the AOS was estimated by a score including blood or clinical variables ( a R 2 = 0.34): glycemia, AST, ALT, triglycerides, weight and adjusted on blood fibrosis score. The presence of significant AOS ( 3%) was diagnosed by another score (glycemia, AST, ALT, triglycerides, hyaluronate, haemoglobin, and weight) with AUROC: 0.84. Conclusions: It is possible to measure liver steatosis via the AOS in an objective, precise and very reproducible manner thanks to a near complete automation. The steatosis degree can be non-invasively diagnosed and quantified by clinical and blood scores with a satisfactory accuracy. Table: area of steatosis (%) as a function of Kleiner steatosis grade or fibrosis.
Journal of Hepatology, 2003
Background/Aims: The natural outcome of ultrasound-detected macronodules in cirrhosis is still po... more Background/Aims: The natural outcome of ultrasound-detected macronodules in cirrhosis is still poorly understood. In this study we assessed the incidence and predictors of malignant transformation in a prospective study of 90 consecutive ultrasound-detected macronodules in cirrhosis. Methods: Macronodules classification was based on recently proposed histological criteria. Extranodular large (LCC) and small cell changes were also evaluated. The follow-up included ultrasound and serum alfa-fetoprotein determination every 3 months. Independent predictors of hepatocellular carcinoma were evaluated by Cox proportional hazards regression analysis. Results: During a mean follow-up of 33 months, 28 (31%) nodules transformed into hepatocellular carcinoma. The incidence of hepatocellular carcinoma per 100 person-years of follow-up was 11.3%, with a malignant transformation rate of 3.5, 15.5, 31 and 48.5% at 1, 2, 3, and 5 years respectively. High-grade dysplastic nodules (HGDN) (hazard risk 5 2.4; CI 95% 5 1.1-5.0) and LCC (hazard risk 5 3.1; CI 95% 5 1.2 -7.8) were independent predictors of malignant transformation. Eight additional hepatocellular carcinomas developed outside the original lesions raising the overall malignant transformation rate to 40% while 15 macronodules (17%) became undetectable at ultrasound (US). Conclusions: Macronodules characterize a cirrhotic subpopulation with high risk of hepatocellular carcinoma. HGDN and LCC are strong predictors of malignant transformation; subjects with simultaneous presence of both these two conditions are at highest risk of cancer development. The management of cirrhotics with macronodules should be based on morphologic features detected on liver microsamples.
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Papers by Rodolfo Cotichini