Massimiliano Copetti

IRCCS Ospedale Casa Sollievo della Sofferenza, Giovanni Rotondo, Apulia, Italy

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Publications (124)573.95 Total impact

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    ABSTRACT: Forced vital capacity (FVC) shows limitations in detecting respiratory failure in the early phase of amyotrophic lateral sclerosis (ALS). In fact, mild-to-moderate respiratory muscle weakness may be present even when FVC is normal, and ALS patients with bulbar involvement might not be able to perform correctly the spirometry test. Sniff nasal inspiratory pressure (SNIP) is correlated with transdiaphragmatic strength. We evaluated SNIP at baseline as a prognostic factor of tracheostomy or death in patients with ALS. In a multidisciplinary tertiary care center for motorneuron disease, we enrolled 100 patients with ALS diagnosed with El Escorial criteria in the period between January 2006 and December 2010. Main outcome measures were tracheostomy or death. RECursive Partitioning and AMalgamation (RECPAM) analysis was also used to identify subgroups at different risks for the tracheostomy or death. Twenty-nine patients with ALS reached the outcome (12 died and 17 had tracheostomy). Using a multivariate model SNIP correctly classified the risk of the composite event within 1 year of follow-up with a continuous Net Reclassification Improvement cNRI of 0.58 (p = 0.03). Sex, Amyotrophic Lateral Sclerosis Functional Rating Scale revisited, site of onset, and FVC did not improve the classification of prognostic classes. SNIP ≤18 cmH2O identified the RECPAM class with the highest risk (Class 1, hazard ratio = 9.85, 95 % confidence interval: 2.67-36.29, p < 0.001). SNIP measured at baseline identified patients with ALS with initial respiratory failure. Finally, using only ALS patients with spinal onset of the disease, our findings were mostly overlapping with those reported in the models including the whole sample. At baseline, SNIP appeared to be the best predictor of death or tracheostomy within 1 year of follow-up. The measurement of SNIP in the early phase of the disease may contribute to identify patients with high risk of mortality or intubation. SNIP may also provide an additional tool for baseline stratification of patients with ALS in clinical trials.
    Journal of Neurology 12/2014; · 3.58 Impact Factor
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    ABSTRACT: We investigated the contribution of cortical lesions to cognitive impairment in 41 paediatric MS patients. Thirteen (32%) paediatric MS patients were considered as cognitively impaired. T2-hyperintense and T1-hypointense white matter lesion volumes did not differ between cognitively impaired and cognitively preserved MS patients. Cortical lesions number, cortical lesions volume and grey matter volume did not differ between cognitively impaired and cognitively preserved patients, whereas white matter volume was significantly lower in cognitively impaired versus cognitively preserved MS patients (p=0.01). Contrary to adult MS, cortical lesions do not seem to contribute to cognitive impairment in paediatric MS patients, which is likely driven by white matter damage.
    Multiple sclerosis (Houndmills, Basingstoke, England). 11/2014;
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    ABSTRACT: Objective: We have previously reported the combined effect of SNPs perturbing insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular events. We here investigated whether such a combined effect affects also all-cause mortality in a sample of 1851 Whites of European ancestry. Methods: We investigated a first sample of 721 patients, 232 deaths, 3389 person-years (py). Replication was assessed in two samples of patients with T2D: the Gargano Mortality Study (GMS) of 714 patients, 127 deaths, 5426 py and the Joslin Kidney Study (JKS) comprising 416 patients, 214 deaths, 5325 py. Results: In the first sample, individuals carrying 1 or ≥2 risk alleles had 33% (p = 0.06) and 51% (p = 0.02) increased risk of mortality, as compared with individuals with no risk alleles. A similar, though not significant, trend was obtained in the two replication samples only for subject carrying ≥ 2 risk alleles. In a pooled analysis, individuals carrying ≥2 risk alleles had higher mortality rate as compared to those carrying 0 risk alleles (HR = 1.34, 95%CI = 1.08-1.67; p = 0.008), and as compared to those carrying only one risk allele (HR = 1.41, 95%CI = 1.13-1.75; p = 0.002). This association was independent from several possible confounders including sex, age, BMI, hypertension and diabetes status. Conclusion: Our data suggest that variants affecting insulin signaling exert a joint effect on all-cause mortality and is consistent with a role of abnormal insulin signaling on mortality risk. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 10/2014; 237(2):639-644. · 3.71 Impact Factor
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    ABSTRACT: Gliomas represent a disparate group of tumours for which there are to date no cure. Thus, there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA (miRNA) profile of 8 WHO grade II gliomas and 24 higher grade tumours (2 WHO grade III and 22 glioblastomas) by using the Affymetrix GeneChip miRNA Array v. 1.0. A relative quantification method (RT-qPCR) with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas (TCGA) datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade tumours. RT-qPCR confirmed the differential expression in the two patients' groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme (GBM) and Lower Grade Glioma (LGG) datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. Moreover, in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses (HR 1.19, p = 0.04, and HR 1.18, p = 0.029 respectively). Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas. Copyright: ß 2014 Barbano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. The array data have been deposited at the ArrayExpress archive, accession number E-MTAB-1840. Funding: Ricerca Corrente 2013 funding was granted by the Italian Ministry of Health. This work was also supported by ''561000'' voluntary contributions, ''Progetto Operativo Nazionale,'' PON 2011-2014 VIRTUALAB (PON01_01297). S.V. is supported by Associazione Italiana per la Ricerca sul Cancro (AIRC – IG13585) and Ministero dell'Istruzione, dell'Università e della Ricerca Progetti di Ricerca di Interesse Nazionale (PRIN 2010) and The National Council of Research of Italy CNR EPIGEN grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
    PLoS ONE 10/2014; 9. · 3.53 Impact Factor
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    ABSTRACT: Background The pathogenesis of cardiovascular (CV) mortality, whose rate is increased in type 2 diabetes, is poorly understood.While high serum adiponectin is associated with increased CV mortality in the general population, no data are available in type 2 diabetes.We here investigated whether this counterintuitive association was observable also in diabetic patients and whether it was sex-specific.Methods Three prospective cohorts were analyzed: 1) Gargano Heart Study (GHS; 359 patients, 58 events/1,934 person-years; py); 2) Health Professional Follow-up Study (HPFS; 833 men, 146 events/10,024 py); 3) Nurses¿ Health Study (NHS; 902 women, 144 events/15,074 py).ResultsIn GHS serum adiponectin predicted CV mortality in men (hazard ratio, HR, and 95% CI per standard deviation, SD, increment¿=¿1.54, 1.19-2.01), but not women (HR¿=¿0.98, 0.48-2.01).Circulating adiponectin predicted CV mortality in men from HPFS (HR¿=¿1.44, 1.21-1.72), but not in women from NHS (HR¿=¿1.08, 0.86-1.35), used as replication samples. In a pooled analysis, HRs were 1.47 (1.27-1.70) in 1,075 men and 1.07 (0.86-1.33) in 1,019 women (p for HRs heterogeneity across sexes¿=¿0.018).Conclusions This is the first report showing that high circulating adiponectin predicts increased CV mortality in men, but not in women with type 2 diabetes. Further studies are necessary to unravel the mechanisms through which adiponectin influences CV mortality in a sex-specific manner.
    Cardiovascular Diabetology 09/2014; 13(1):130. · 4.21 Impact Factor
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    ABSTRACT: Background Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by largely unsatisfactory responses to the currently available therapeutic strategies. In this study we evaluated the expression of genes involved in gemcitabine uptake in a selected cohort of patients with PDAC, with well-defined clinical-pathological features.MethodsmRNA levels of hENT1, CHOP, MRP1 and DCK were evaluated by means of qRT-PCR in matched pairs of tumor and adjacent normal tissue samples collected from PDAC patients treated with gemcitabine after surgical tumor resection. To detect possible interaction between gene expression levels and to identify subgroups of patients at different mortality/progression risk, the RECursive Partitioning and Amalgamation (RECPAM) method was used.ResultsRECPAM analysis showed that DCK and CHOP were most relevant variables for the identification of patients with different mortality risk, while hENT1 and CHOP were able to identify subgroups of patients with different disease progression risk. Conclusion: hENT1, CHOP, MRP1 and DCK appear correlated to PDAC, and this interaction might influence disease behavior.
    Journal of translational medicine. 09/2014; 12(1):248.
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    ABSTRACT: In seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log) threshold of 1.4 and a cut-off of p,0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre-and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to ''healthy'' condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), hydrogen voltage-gated channel 1 (HVCN1), and b-arrestin 1 (ARRB1). The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post-vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils, both before and after therapy. These results indicate more specific targets for future interventions in CF patients involving respiratory burst, apoptosis, and granule exocytosis.
    PLoS ONE 08/2014; · 3.53 Impact Factor
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    ABSTRACT: This study tried to replicate in a large sample of white patients with type 2 diabetes (T2D) from Italy a previously reported association of the IRS1 G972R polymorphism with failure to oral antidiabetes drugs (OAD). A total of 2,409 patients from four independent studies were investigated. Case subjects (n = 1,193) were patients in whom, because of uncontrolled diabetes (i.e., HbA1c >8%), insulin therapy had been added either on, or instead of, maximal or near-maximal doses of OAD, mostly metformin and sulfonylureas; control subjects (n = 1,216) were patients with HbA1c <8% in the absence of insulin therapy. The IRS1 G972R polymorphism was typed by TaqMan allele discrimination. In all samples, individuals carrying the IRS1 R972 risk variant tended to be more frequent among case than control subjects, though reaching statistical significance only in one case. As no IRS1 G972R-by-study sample interaction was observed, data from the four samples were analyzed together; a significant association was observed (allelic odds ratio [OR] 1.30, 95% CI 1.03-1.63). When our present data were meta-analyzed with those obtained in a previous study, an overall R972 allelic OR of 1.37 (1.12-1.69) was observed. This study confirms in a large and ethnically homogeneous sample that IRS1 G972R polymorphism is associated with failure to OAD among patients with T2D.
    Diabetes 06/2014; · 7.90 Impact Factor
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    ABSTRACT: Purpose To use magnetic resonance (MR) imaging and advanced analysis to assess the role of lesions in normal-appearing white matter (NAWM) and gray matter (GM) damage, global versus regional damage, and atrophy versus microstructural abnormalities in the pathogenesis of fatigue in multiple sclerosis (MS). Materials and Methods Local ethics committee approval and written informed consent were obtained. Dual-echo, double inversion-recovery, high-resolution T1-weighted and diffusion-tensor (DT) MR was performed in 31 fatigued patients, 32 nonfatigued patients, and 35 control subjects. Global and regional atrophy and DT MR measures of damage to lesions, NAWM, and GM were compared (analysis of variance). Results Lesional, atrophy, and DT MR measures of global damage to brain, white matter (WM), and GM did not differ between fatigued and nonfatigued patients. Compared with nonfatigued patients and control subjects, fatigued patients experienced atrophy of the right side of the accumbens (mean volume ± standard deviation, 0.37 mL ± 0.09 in control subjects; 0.39 mL ± 0.1 in nonfatigued patients; and 0.33 mL ± 0.09 in fatigued patients), right inferior temporal gyrus (ITG) (Montreal Neurological Institute [MNI] coordinates: 51, -51, -11; t value, 4.83), left superior frontal gyrus (MNI coordinates: -10, 49, 24; t value, 3.40), and forceps major (MNI coordinates: 11, -91, 18; t value, 3.37). They also had lower fractional anisotropy (FA) of forceps major (MNI coordinates: -17, -78, 6), left inferior fronto-occipital fasciculus (MNI coordinates: -25, 2, -11), and right anterior thalamic radiation (ATR) (MNI coordinates: 11, 2, -6) (P < .05, corrected). More lesions were found at T2-weighted imaging in fatigued patients. Multivariable model was used to identify right ITG atrophy (odds ratio, 0.83; 95% confidence interval [CI]: 0.82, 0.97; P = .009) and right ATR FA (odds ratio, 0.74; 95% CI: 0.61, 0.90; P = .003) as covariates independently associated with fatigue (C statistic, 0.85). Conclusion Damage to strategic brain WM and GM regions, in terms of microstructural abnormalities and atrophy, contributes to pathogenesis of fatigue in MS, whereas global lesional, WM, and GM damage does not seem to have a role. © RSNA, 2014 Online supplemental material is available for this article.
    Radiology 06/2014; · 6.34 Impact Factor
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    ABSTRACT: MicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types.
    Molecular cancer. 06/2014; 13(1):142.
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    ABSTRACT: Using diffusion tensor magnetic resonance imaging (DT MRI), we analyzed the architectural integrity of the brain white matter (WM) from a large cohort of MS patients to identify the structural substrates of the concomitant presence of depression and fatigue. Brain dual-echo, 3D T1-weighted and DT MRI scans were acquired from 147 MS patients and 90 gender- and age-matched healthy controls (HCs). Patients were stratified by the presence of depression (92 depressed (D), 55 not depressed (nD)) and fatigue (81 fatigued (F), 66 not fatigued (nF)). Sixty-five patients had co-occurrence of depression and fatigue (DF). Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). Tract-specific analyses were run in brain WM tracts using standard-space templates. Whole-brain voxel-wise analysis yielded no significant differences between patient subgroups. At tract-specific analysis, DF patients had reduced fractional anisotropy (FA) of the forceps minor. Reduced FA of the right anterior thalamic radiation and right uncinate fasciculus was found in F-MS vs not F-MS patients after correcting for depression. No significant differences were found between D vs not D-MS patients, after correcting for fatigue. This study provides evidence for partially overlapping damage to frontal and fronto-temporal pathways underlying depression and fatigue in MS.
    Multiple Sclerosis 04/2014; · 4.47 Impact Factor
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    ABSTRACT: Background and purposeTo evaluate whether cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels could predict the time to generalization (TTG) in amyotrophic lateral sclerosis (ALS).Methods Cerebrospinal fluid NFL levels of 37 cases of sporadic ALS were measured and the time of symptom spreading from spinal or bulbar localization to both (TTG) was evaluated in all patients.ResultsKaplan−Meier analysis showed a short TTG in patients with high NFL levels (log-rank test chi-squared = 19.4, P < 0.0001). In a multivariate regression model patients with NFL levels above the median had an eight-fold higher risk of generalization (adjusted hazard ratio 7.9, 95% confidence interval 2.9–21.4, P < 0.0001) compared with those with NFL levels below the median.Conclusions This study shows that in sporadic ALS NFL, a marker of neurodegeneration, is correlated with TTG, a clinical intermediate parameter of survivorship.
    European Journal of Neurology 04/2014; · 4.16 Impact Factor
  • Journal of diabetes science and technology 03/2014; 8(3):621-622.
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    ABSTRACT: White matter (WM) tract alterations were assessed in patients with progressive supranuclear palsy (PSP) relative to healthy controls and patients with idiopathic Parkinson's disease (PD) to explore the relationship of WM tract damage with clinical disease severity, performance on cognitive tests, and apathy. 37 PSP patients, 41 PD patients, and 34 healthy controls underwent an MRI scan and clinical testing to evaluate physical disability, cognitive impairment, and apathy. In PSP, the contribution of WM tract damage to global disease severity and cognitive and behavioural disturbances was assessed using Random Forest analysis. Relative to controls, PSP patients showed diffusion tensor (DT) MRI abnormalities of the corpus callosum, superior cerebellar peduncle (SCP), cingulum and uncinate fasciculus bilaterally, and right inferior longitudinal fasciculus. Corpus callosum and SCP DT MRI measures distinguished PSP from PD patients with high accuracy (area under the curve ranging from 0.89 to 0.72). In PSP, DT MRI metrics of the corpus callosum and superior cerebellar peduncles were the best predictors of global disease severity scale scores. DT MRI metrics of the corpus callosum, right superior longitudinal and inferior longitudinal fasciculus, and left uncinate were the best predictors of executive dysfunction. In PSP, apathy severity was related to the damage to the corpus callosum, right superior longitudinal, and uncinate fasciculi. In conclusion, WM tract damage contributes to the motor, cognitive, and behavioural deficits in PSP. DT MRI offers markers for PSP diagnosis, assessment, and monitoring.
    Journal of Neurology 03/2014; · 3.58 Impact Factor
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    ABSTRACT: Purpose To assess whether a structural disconnection between the cerebellum and the cerebral hemispheres contributes to cerebellar and brainstem symptoms in multiple sclerosis (MS). Materials and Methods This study was approved by the local ethics committee, and written informed consent was obtained from each participant. Brain T2 lesion load, cerebellar white matter and gray matter volumes, and tract-specific measures of the middle and superior cerebellar peduncles were derived from 172 patients with MS and 46 control subjects. Predictors of clinical impairment, which was determined at ambulation and with cerebellar and brainstem functional system scores, were identified by using random forest analysis. Results Of the 172 patients, 112 (65%) had middle cerebellar peduncle T2 lesions and 74 (43%) had superior cerebellar peduncle T2 lesions. T2 lesions in the middle and superior cerebellar peduncles were more common in clinically impaired patients than in unimpaired patients (P = .05 to <.0001). Most conventional magnetic resonance imaging metrics were more abnormal in impaired patients than in unimpaired patients (P = .03 to <.0001). Except for axial diffusivity, diffusivity abnormalities of the middle and superior cerebellar peduncles were more severe in clinically impaired patients than in unimpaired patients (P = .04 to <.0001). A minimal overlap was found between diffusivity abnormalities and T2 lesions. Compared with volumetric measures of T2 lesions or cerebellar atrophy, diffusivity measures of middle or superior cerebellar peduncle damage enabled better differentiation between clinically impaired and unimpaired patients (C statistics: 61%-70%). Conclusion The assessment of middle and superior cerebellar peduncle damage contributes to the explanation of cerebellar and/or brainstem symptoms and ambulatory impairment in MS. © RSNA, 2014 Online supplemental material is available for this article.
    Radiology 02/2014; · 6.34 Impact Factor
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    ABSTRACT: Primary palmar hyperhidrosis is a distressing and disabling condition that can produce social, psychological and occupational problems. Although the use of botulinum toxin type A (BoNT-A) has been reported as an efficacious and safe intervention to improve palmar hyperhidrosis, only one study concerned botulinum toxin type B (BoNT-B) in this disorder. The aim of study was to evaluate the efficacy and safety of BoNT-B in treating primary palmar hyperhidrosis. Participants were injected with 5,000 IU of BoNT-B in each palm. Visual analogue test (VAS) to evaluate the intensity of decrease in sweat production, Minor's iodine starch test and measurement of paper towels' weight were used to ascertain palmar sweating at baseline, 4, 12 and 24 weeks after BoNT-B injections by a blind examiner. Thirty-two subjects (12 males, 20 females, mean age 31 ± 11) were enrolled. Significant reduction of palmar sweating was detected after BoNT-B injection: 2.9 ± 1.4, 0.3 ± 0.4, 0.9 ± 0.8, and 2.1 ± 1.5 g (p < 0.001) of paper towels' weight for the right palm at baseline, 4, 12 and 24 weeks; and 2.8 ± 1.7, 0.5 ± 0.6, 0.8 ± 0.7, and 1.8 ± 1.25 g (p < 0.001) at same time, respectively for the left palm. Significant reduction of mean VAS values were also detected after BoNT-B injections: 8.6 ± 1.1, 0.6 ± 0.8, 3.5 ± 2.5, and 7.1 ± 2.4 (p < 0.0001) at baseline, 4, 12 and 24 weeks, respectively. Mild side effects consisting in local pain and hand weakness were observed in 4 (12.5 %) subjects. The findings indicated that the use of 5,000 IU BoNT-B injection in each palm was safe and significantly improved the severity of palmar hyperhidrosis.
    Archives for Dermatological Research 02/2014; · 2.71 Impact Factor
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    ABSTRACT: Objective: We review the state of the art in meta-analysis and data pooling following the evolution of the statistical models employed. Methods: Starting from a classic definition of meta-analysis of published data, a set of apparent antinomies which characterized the development of the meta-analytic tools are reconciled in dichotomies where the second term represents a possible generalization of the first one. Particular attention is given to the generalized linear mixed models as an overall framework for meta-analysis. Bayesian meta-analysis is discussed as a further possibility of generalization for sensitivity analysis and the use of priors as a data augmentation approach. Results: We provide relevant examples to underline how the need for adequate methods to solve practical issues in specific areas of research have guided the development of advanced methods in meta-analysis. Conclusions: We show how all the advances in meta-analysis naturally merge into the unified framework of generalized linear mixed models and reconcile apparently conflicting approaches. All these complex models can be easily implemented with the standard commercial software available. © 2013 S. Karger AG, Basel.
    Neuroepidemiology 01/2014; 42(1):59-67. · 2.37 Impact Factor
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    ABSTRACT: Aims Age is one of the most important determinants of cardiovascular health, therefore the management of cardiovascular diseases (CVD) in elderly people entails great challenge. A possible explanation of vascular senescence process is the mitochondrial damage and dysfunction. We hypothesized that metabolomic profiling would identify biomarkers predicting major cardiovascular events (MACEs) in elderly people, improving the clinical standard cardiovascular risk factors. Methods and results Targeted-mass-spectrometry-based profiling of 49 metabolites was performed in a group of very old participants (n = 67, mean age = 85 ± 3 years) with a high rate of previous CVD (68%). Principal Component Analysis, Random Survival Forest analysis and Cox proportional hazards regression modeling were used to evaluate the relation between the metabolite factors and recurring MACEs. We tested discrimination ability and reclassification of clinical and metabolomic models. At follow-up (median = 3.5 years), 17 MACEs occurred (5 cardiovascular deaths, 1 nonfatal myocardial infarction, 7 nonfatal strokes and 4 peripheral artery surgeries) (incidence = 7.3% person-years). Metabolite factor 1, composed by medium- and long-chain acylcarnitines, and factor 7 (alanine) were independently associated with MACEs, after adjustment for clinical CV covariates [HR = 1.77 (95%CI = 1.11–2.81, p = 0.016) and HR = 2.18 (95%CI = 1.17–4.07, p = 0.014), respectively]. However, only factor 1 significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement = 7%, p = 0.01) and correctly reclassifying 41% of events and 37% of non-events resulting in a cNRI = 0.79 (p = 0.005). Conclusions Aging mitochondrial dysfunction evaluated by metabolomic profiling is associated with MACEs, independently of standard predictors.
    Atherosclerosis 01/2014; 232(2):260–264. · 3.71 Impact Factor
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    ABSTRACT: To investigate grey (GM) and white matter (WM) abnormalities and their effects on cognitive and behavioral deficits in a large, phenotypically and genotypically well-characterized cohort of classic adult (aDM1, age at onset ≥20 years) or juvenile (jDM1, age at onset <20 years) patients with myotonic dystrophy type 1 (DM1).
    PLoS ONE 01/2014; 9(8):e104697. · 3.53 Impact Factor
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    ABSTRACT: The FRAX algorithm is a diffused tool to assess fracture risk, but it has not been clinically applied in European patients with diabetes. We investigated FRAX-estimated fracture risk in patients with type 2 diabetes mellitus (DM), compared to concomitantly enrolled control subjects (CS). In our multi-centric cross-sectional study we assessed the FRAX scores of 974 DM and 777 CS from three Italian Diabetes outpatient Clinics, and in DM we tested the association between parameters and complications of the disease and FRAX scores. DM had significantly lower FRAX-estimated probability of both major osteoporotic fracture (MOF) and hip fracture (HF) than CS (6.35 ± 5.07% vs 7.75 ± 6.93%, p < 0.001, and 2.17 ± 3.07% vs 2.91 ± 4.56%, p = 0.023, respectively). When grouping by gender, such differences were found only in men. In DM, the frequency of previous fracture was higher than in CS (29.88% vs 20.46%, p < 0.001). In diabetics, age, sex, BMI, HbA1c and hypoglycemia significantly associated with FRAX-scores; gender-specific regression models differed. Among DM, the tree-based regression (CART) analysis identified groups of patients with different mean FRAX scores. In female DM aged >65 with or without obesity, MOF > 20% was found in 5.66% and 13.53%, and HF > 3% in 40.57% and 63.91% of patients, respectively. DM had mean FRAX scores lower than CS, despite the higher number of previous fractures. Some features and complications of DM did associate with FRAX scores. Among DM patients, the CART analysis identified subgroups with higher FRAX scores. However, despite its potential utility, concerns still remain for using FRAX in DM patients. This article is protected by copyright. All rights reserved.
    Diabetes/Metabolism Research and Reviews 12/2013; · 2.97 Impact Factor

Publication Stats

797 Citations
573.95 Total Impact Points


  • 2008–2014
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      • Research Laboratory of Gastroenterology
      Giovanni Rotondo, Apulia, Italy
  • 2013
    • Università degli Studi di Salerno
      Fisciano, Campania, Italy
  • 2012–2013
    • University-Hospital of Padova
      Padua, Veneto, Italy
    • Sapienza University of Rome
      • Department of Internal and Specialized Medicine
      Roma, Latium, Italy
  • 2011–2013
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
  • 2011–2012
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
  • 2010–2012
    • Università degli Studi di Bari Aldo Moro
      Bari, Apulia, Italy
  • 2009
    • Johns Hopkins University
      • Department of Otolaryngology - Head and Neck Surgery
      Baltimore, MD, United States