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Background and purpose: The presence of a continuum between physiological déjà vu (DV) and epileptic DV is still not known as well as epidemiological data in the Italian population. The aim was to identify the epidemiological distribution of DV in Italy, and secondly to look for specific features of DV able to discriminate between epileptic and non‐epileptic DV. Methods: In all, 1000 individuals, 543 healthy controls (C) (313 women; age 40 ± 15 years) and 457 patients with epilepsy (E) (260 women; age 39 ± 14 years), were prospectively recruited from 10 outpatient neurological clinics throughout Italy. All populations were screened using the Italian Inventory for Déjà Vu Experiences Assessment (I‐IDEA) test and E and pairwise C underwent a comprehensive epilepsy interview. Results: Of E, 69% stated that they experienced 'recognition' and 13.2% reported that this feeling occurred from a few times a month to at least weekly (versus 7.7% of the control group). Furthermore, a greater percentage of E (6.8% vs. 2.2%) reported that from a few times a month to at least weekly they felt that it seemed as though everything around was not real. In E, the feeling of recognition raised fright (22.3% vs. 13.2%) and a sense of oppression (19.4% vs. 9.4%). A fifth of E felt recognition during epileptic seizures. Conclusion: Only E regardless of aetiology firmly answered that they had the feeling of recognition during an epileptic seizure; thus question 14 of the I‐IDEA test part 2 discriminated E from C. Paranormal activity, remembering dreams and travel frequency were mostly correlated to DV in E suggesting that the visual–memory network might be involved in epileptic DV. [ABSTRACT FROM AUTHOR]

Background: Older adults dialysis patients represent the frailest subgroup of the End Stage Renal Disease (ESRD) population and physical exercise program may mitigate the age-related decline in muscle mass and function., Methods: Dialysis patients of the EXCITE trial aged > 65 years (n = 115, active arm, n = 53; control arm, n = 62) were submitted in random order to a home based, low intensity physical exercise program. At baseline and 6 months after exercise training 6-min walking distance (6MWD) and 5-time sit-to-stand test (5STS) were performed, and quality of life (QoL) was tested., Results: The training program improved both the 6MWD (6-months: 327 ± 86 m versus baseline: 294 ± 74 m; P < 0.001) and the 5STS time (6-months: 19.8 ± 5.6 s versus baseline: 22.5 ± 5.1 s; P < 0.001) in the exercise group whereas they did not change in the control group (P = 0.98 and 0.25, respectively). The between-arms differences (6 months-baseline) in the 6MWD (+ 34.0 m, 95% CI: 14.4 to 53.5 m) and in the 5STS time changes (- 1.9 s, 95% CI: -3.6 to - 0.3 s) were both statistically significant (P = 0.001 and P = 0.024, respectively). The cognitive function dimension of QoL significantly reduced in the control arm (P = 0.04) while it remained unchanged in the active arm (P = 0.78) (between groups difference P = 0.05). No patient died during the trial and the training program was well tolerated., Conclusions: This secondary analysis of the EXCITE trial shows that a home-based, exercise program improves physical performance and is well tolerated in elderly ESRD patients., Trial Registration: The trial was registered in ClinicalTrials.Gov ( Clinicaltrials.gov identifier: NCT01255969) on December 8, 2010.

Background: Hyperuricemia is associated with incident cardiovascular events in different settings of patients. We tested whether the inclusion of uric acid (UA) in Cox models including standard risk factors allows to better stratify cardiovascular risk in a cohort of 1522 naïve hypertensives with preserved renal function., Methods: We used multiple Cox regression models to assess the independent effect of UA on cardiovascular outcomes, and Harrell'C index, Net Reclassification Index (NRI), and Integrated Discrimination Improvement (IDI) as indicators of the additional prognostic value of UA beyond and above that provided by standard risk factors and estimated glomerular filtration rate (e-GFR). Study outcomes were fatal and nonfatal cardiovascular events and fatal and nonfatal coronary outcomes/death due to other cardiovascular events., Results: UA resulted strongly related to both outcomes in unadjusted Cox regression analyses (P<0.001). Inclusion of UA into multiple Cox regression models including Framingham risk factors and e-GFR did not affect the association between UA and outcomes (fatal and nonfatal cardiovascular events, HR=1.44, 95% CI=1.36-1.55, P<0.001; fatal and nonfatal coronary outcomes/death due to other cardiovascular events, HR=1.48, 95% CI=1.36-1.61, P<0.001). Inclusion of UA into basic Cox models provided an increase in all indexes of prognostic accuracy for both outcomes: Harrell'C index: +5%; NRI: +24.9%; IDI: +7.6%, all P<0.001; and Harrell'C index: +5%; NRI: +25%; IDI: +6.3%, all P<0.001, respectively., Conclusions: UA is an independent predictor of cardiovascular outcomes and increases prognostic accuracy of Cox models, including Framingham risk factors and e-GFR, in hypertensives with normal renal function, allowing a risk reclassification., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The Inventory Déjà Vu Experiences Assessment (IDEA) is the only screening instrument proposed to evaluate the Déjà vu (DV) experience. Here, we intended to validate the Italian version of IDEA (I-IDEA) and at the same time to investigate the incidence and subjective qualities of the DV phenomenon in healthy Italian adult individuals on basis of an Italian multicentre observational study. In this study, we report normative data on the I-IDEA, collected on a sample of 542 Italian healthy subjects aging between 18-70 years (average age: 40) with a formal educational from 1-19 years. From September 2013 to March 2016, we recruited 542 healthy volunteers from 10 outpatient neurological clinics in Italy. All participants (i.e., family members of neurological patients enrolled, medical students, physicians) had no neurological or psychiatric illness and gave their informed consent to participate in the study. All subjects enrolled self-administered the questionnaire and they were able to complete I-IDEA test without any support. In total, 396 (73%) of the 542 healthy controls experienced the DV phenomenon. The frequency of DV was inversely related to age as well as to derealisation, jamais vu, precognitive dreams, depersonalization, paranormal activity, remembering dreams, travel frequency, and daydreams (all p < 0.012). The Italian version of IDEA maintains good properties, thus confirming that this instrument is reliable for detecting and characterising the DV phenomenon., Competing Interests: The authors declare no conflict of interest.

Background: Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD). We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression., Study Design: Systematic review and meta-analysis., Population: Adults with DKD (either secondary to type 1 or 2 diabetes mellitus)., Search Strategy and Sources: Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs) or quasi-RCTs without language or follow-up restriction., Intervention: Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone) alone or in combination., Outcomes: Primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function., Results: From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants) met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16) but had apparently no tangible effects on renal function (GFR) (3 studies, 85 participants; MD -0.12 ml/min/1.73m2; 95% CI -0.06, 0.01). Evidence of benefits on the other outcomes of interest was inconclusive or lacking., Limitations: Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD). High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy., Conclusions: In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression.

Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n =145) or walking exercise ( n =151); 227 patients (exercise n =104; control n =123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P <0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P =0.001 between groups). The cognitive function score ( P =0.04) and quality of social interaction score ( P =0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis., (Copyright © 2017 by the American Society of Nephrology.)

Introduction: Accruing evidence suggests that vitamin E-coated membranes (ViE-m) might improve the clinical management of chronic hemodialysis (HD) patients., Methods: We conducted a systematic review and meta-analysis of RCTs comparing ViE-m to conventional HD. Endpoints of interest were a series of biomarkers pertaining to anemia status, inflammation, oxidative stress and dialysis efficacy/status., Results: Sixty studies were included. ViE-m significantly improved the Erythropoietin Resistance Index but had no impact on other anemia parameters. As for oxidative stress and inflammation, ViE-m produced a significant decrease in interleukin-6 levels, thiobarbituric acid reactive substances, plasma and red blood cell (RBC) malonylaldehyde and a significant increase in blood and RBC vitamin E. Conversely, ViE-m use had no impact on lipid profile, dialysis adequacy, blood pressure, albumin and uric acid., Conclusions: ViE-m might ameliorate anemia management by reducing oxidative stress and inflammation. Benefits of these bio-membranes on harder clinical outcomes are uncertain and need to be investigated by future, targeted trials., (© 2016 S. Karger AG, Basel.)

Objective: To identify clinical and imaging features at presentation that might predict long-term outcome in patients with mild mesial temporal lobe epilepsy (mMTLE), which is defined by at least 24 seizure-free months with or without antiepileptic medication., Methods: In the setting of a prospective, population-based, longitudinal cohort study, we followed up 101 patients, all with mMTLE at enrolment. By protocol, patients underwent clinical evaluation every 3-12 months. Independent t test, Mann-Whitney test, or χ(2) test was used for comparing 2 groups. The incidence rate of refractory MTLE (rMTLE) was expressed as number of cases every 100 person-years., Results: After a mean follow-up of 12.2 ± 3.7 years, 16 patients dropped out and 85/101 (mean age 46.5 ± 13.3 years) were available for the present analysis. Of these, 64/85 (75%) patients remained seizure-free and 21/85 (25%) became refractory (rMTLE), the latter corresponding to 2.0 cases per 100 persons per year. Patients with rMTLE showed a longer duration of epilepsy (p < 0.001), earlier age at epilepsy onset (p = 0.006), more frequent febrile convulsions (p = 0.02), and hippocampal sclerosis (HS) at MRI (p = 0.004) as compared to those with mMTLE., Conclusions: mMTLE is a syndrome representing the mildest form of the wide spectrum of MTLE. Earlier age at onset, history of febrile convulsions, longer duration of epilepsy, and the presence of HS on MRI predict a worse outcome., (© 2016 American Academy of Neurology.)

Background/aims: In this corollary analysis of the EXCITE study, we looked at possible differences in baseline risk factors and mortality between subjects excluded from the trial because non-eligible (n=216) or because eligible but refusing to participate (n=116)., Methods: Baseline characteristics and mortality data were recorded. Survival and independent predictors of mortality were assessed by Kaplan-Meier and Cox regression analyses., Results: The incidence rate of mortality was higher in non-eligible vs. eligible non-randomized patients (21.0 vs. 10.9 deaths/100 persons-year; P<0.001). The crude excess risk of death in non-eligible patients (HR 1.96; 95% CI 1.36 to 2.77; P<0.001) was reduced after adjustment for risk factors which differed in the two cohorts including age, blood pressure, phosphate, CRP, smoking, diabetes, triglycerides, cardiovascular comorbidities and history of neoplasia (HR 1.60; 95% CI 1.10 to 2.35; P=0.017) and almost nullified after including in the same model also information on deambulation impairment (HR 1.16; 95% CI 0.75 to 1.80; P=0.513)., Conclusions: Deambulation ability mostly explains the difference in survival rate in non-eligible and eligible non-randomized patients in the EXCITE trial. Extending data analyses and outcome reporting also to subjects not taking part in a trial may be helpful to assess the representability of the study population., (© 2014 S. Karger AG, Basel.)

Background/aims: Scarce physical activity predicts shorter survival in dialysis patients. However, the relationship between physical (motor) fitness and clinical outcomes has never been tested in these patients., Methods: We tested the predictive power of an established metric of motor fitness, the Six-Minute Walking Test (6MWT), for death, cardiovascular events and hospitalization in 296 dialysis patients who took part in the trial EXCITE (ClinicalTrials.gov Identifier: NCT01255969)., Results: During follow up 69 patients died, 90 had fatal and non-fatal cardiovascular events, 159 were hospitalized and 182 patients had the composite outcome. In multivariate Cox models - including the study allocation arm and classical and non-classical risk factors - an increase of 20 walked metres during the 6MWT was associated to a 6% reduction of the risk for the composite end-point (P=0.001) and a similar relationship existed between the 6MWT, mortality (P<0.001) and hospitalizations (P=0.03). A similar trend was observed for cardiovascular events but this relationship did not reach statistical significance (P=0.09)., Conclusions: Poor physical performance predicts a high risk of mortality, cardiovascular events and hospitalizations in dialysis patients. Future studies, including phase-2 EXCITE, will assess whether improving motor fitness may translate into better clinical outcomes in this high risk population., (© 2014 S. Karger AG, Basel.)

The human interferon (IFN)-inducible IFI16 protein is a member of the 200-amino acid repeat family encoded by the HIN-200 genes. Forced IFI16 expression in normal human endothelial cells (ECs) inhibits cell growth and tube morphogenesis of ECs through the triggering of apoptosis by caspase-2 and caspase-3 via nuclear factor-κB (NF-κB) complex activation. Accumulating evidence suggests that tumor-derived ECs (TECs) possess a distinct and unique phenotype compared with normal ECs, and they may be able to acquire resistance to antiangiogenic agents such as IFNs. However, few functional studies are available on cultured TEC. In the present study, we have demonstrated that TEC obtained from tumors of various histological origin, namely kidney (Eck25), breast (B-TEC), and head and neck (HN4), continued to proliferate and generate microtubules on Matrigel following IFI16 overexpression. In contrast to normal ECs, they were resistant to apoptosis triggered by caspase-2 and caspase-3 activation via the NF-κB complex. At the molecular level, when overexpressed in TEC, IFI16 appeared unable to regulate NF-κB activity and lead to caspase activation. Altogether, these results indicate that TECs display abnormal responses, in terms of survival and angiogenic properties, to an antiproliferative and antiangiogenic IFN-inducible gene such as IFI16.

The IFN-inducible human IFI16 gene is highly expressed in endothelial cells as well as epithelial and hematopoietic tissues. Previous gene array analysis of human umbilical vein endothelial cells overexpressing IFI16 has revealed an increased expression of genes involved in inflammation and apoptosis. In this study, protein array analysis of the IFI16 secretome showed an increased production of chemokines, cytokines and adhesion molecules responsible for leukocyte chemotaxis. Functional analysis of the promoter for CCL20, the chemokine responsible for leukocyte recruitment in the early steps of inflammation, by site-specific mutation demonstrated that NF-κB is the main mediator of CCL20 induction at the transcriptional level. Finally, both Langerhans DC and B-lymphocyte migration triggered by supernatants from IFI16-overexpressing endothelial cells was partially inhibited by Ab inactivating CCL4, CCL5 and CCL20 chemokines. Altogether, these results demonstrate that the IFI16 gene, through its secretome, regulates proinflammatory activity of endothelial cells, thus corroborating its role in the early steps of inflammation.