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Exposure to metals has been hypothesized as possible cause of chronic kidney disease of unknown cause (CKDu) in Sri Lanka; however, evidence is inconclusive. We measured the concentrations of nephrotoxic metals (As, Pb, and Cd), as well as Se in rice (a staple grain in Sri Lanka) and other grains consumed in CKDu endemic and non-endemic regions using Inductively Coupled Mass Spectrometry (ICP-MS). Our results showed comparable mean concentrations (in µg/kg) of 24.5 ± 18, 7.3 ± 6.4, and 14.2 ± 15 for As, Pb, and Cd, respectively, in rice from endemic regions and 17.7 ± 4.7, 12.7 ± 6.8, and 17.8 ± 16 in rice from non-endemic regions. Selenium concentrations (in mg/kg) were 0.05 ± 0.02 in rice cultivated in both endemic and non-endemic regions. Arsenic and Cd concentrations were significantly higher in rice compared to other grains, which themselves had higher Se than rice. All samples were below the Codex standards established for Cd (400 µg/kg for rice; 100 µg/kg for cereal grains), Pb (200 µg/kg) and inorganic As (200 µg/kg) for white rice. Our findings show that dietary exposure to low levels of As, Pb, Cd, and inadequate Se in staple grains cannot be clearly linked to CKDu, suggesting that the disease could be multifactorial. Additional research is needed to determine the contribution of other risk factors such as lifestyle habits and heat stress to plan preventive strategies for reducing CKDu health cases in Sri Lanka.

Preeclampsia (PE) is a pregnancy-related disorder characterized by hypertension and proteinuria that affects 3-10% of all pregnancies. Although its pathophysiology remains obscure, placental hypoxia-induced oxidative stress and alterations in vascular function, morphology, and endothelial barrier integrity are considered to play a key role in the development of preeclampsia. In this study, placental villous explants of noncomplicated placentae and BeWo cells were subjected to hypoxia. The effect of placental hypoxic-conditioned medium (HCM) on intraluminal-induced contraction and endothelial barrier integrity in chorionic arteries was investigated using pressure myography. The impact of BeWo cell HCM on endothelial cell viability, reactive oxygen species formation and inflammation was also determined. Alterations in arterial morphology and contractile responsiveness to the thromboxane A2 analog (U46619) after exposure to placental HCM were examined immunohistochemically and by wire myography, respectively. Intraluminal administration of placental HCM induced vasoconstriction and increased the endothelial permeability for KCl, which was concentration-dependently prevented by quercetin. Placental and BeWo cell HCMs decreased endothelial cell viability, increased the production of reactive oxygen species and enhanced the secretion of IL-6 and IL-8. The cross-sectional area of the arterial media was increased upon exposure to placental HCM, which was associated with increased vascular proliferation and contractile responsiveness to U46619, and all of these effects were prevented by the antioxidants quercetin and RRR-alpha-tocopherol. This study is the first to comprehensively demonstrate the link between factors secreted by placental cells in response to hypoxia and vascular abnormalities and paves the way for new diagnostic approaches and therapies to better protect the maternal vasculature during and after a preeclampsia-complicated pregnancy.

BACKGROUND:There is an increasing concern about age-related frailty because of the growing number of elderly people in the general population. The Longevity-Associated Variant (LAV) of the human BPIFB4 gene was found to correct endothelial dysfunction, one of the mechanisms underlying frailty, in aging mice whereas the RV-BPIFB4 variant induced opposite effects. Thus, we newly hypothesize that, besides being associated with life expectancy, BPIFB4 polymorphisms can predict frailty.Aim and Results: Here we investigated if the BPIFB4 haplotypes, LAV, wild-type (WT) and RV, differentially associate with frailty in a cohort of 237 elderly subjects from Calabria region in Southern Italy. Moreover, we studied the effect of systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer on the progression of frailty in aging mice. We found an inverse correlation of the homozygous LAV-BPIFB4 haplotype with frailty in elderly subjects. Conversely, carriers of the RV-BPIFB4 haplotype showed an increase in the frailty status and risk of death. Moreover, in old mice, LAV-BPIFB4 gene transfer delayed frailty progression.CONCLUSIONS:These data indicate that specific BPIFB4 haplotypes could represent useful genetic markers of frailty. In addition, horizontal transfer of a healthy gene variant can attenuate frailty in aging organisms.

OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in both adults and children. Along with obesity and metabolic syndrome, genetic predisposition influences the progression of NAFLD. Here, we investigated the effect of lifespan/healthspan-related single nucleotide polymorphisms (SNPs) on metabolically associated fatty liver disease in children. METHODS We evaluated the impact of 10 SNPs involved in both human liver/metabolic diseases and healthspan (interleukin-6 [IL-6] rs1800795, antisense non coding RNA in the INK4 locus (ANRIL) rs1556516, SH2B3/ATXN2 rs7137828, FURIN rs17514846, TP53 rs1042522, APOC3 rs2542052, KL rs9536314, KL rs9527025, SIRT6 rs107251, FOXO3 rs2802292) on NAFLD-related metabolic and liver features in 177 pediatric patients with biopsy-proven NAFLD, by comparing them to 146 healthy controls. We then applied a multidimensional reduction (MDR) case-control analysis of SNP-SNP interactions, to identify the joint effect of analyzed SNPs in predicting NAFLD and associated features. RESULTS Discrete SNPs were significantly associated with individual metabolic NAFLD features, but none of them significantly associated with NAFLD diagnosis. By testing potential synergies using the MDR approach, the best combination to diagnose NAFLD (P = 0.0011) resulted in the one encompassing IL-6 rs1800795 and ANRIL rs1556516. Consistently, the risk combinations suggested by SNP-SNP analysis strongly associated with a higher level of fasting plasma blood glucose level (P = 0.024). CONCLUSION In conclusion, here we demonstrated a synergic interaction between IL-6 rs1800795 and ANRIL rs1556516 in the diagnosis of NAFLD, and NAFLD-associated hyperglycemia in children. Larger studies are required to confirm our findings and to elucidate mechanisms by which the genetic interaction between these two genes influences healthspan in pediatric NAFLD.

Contains fulltext : 244253.pdf (Publisher’s version ) (Open Access) BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated. OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging. METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score. RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (d(max) = -0.20, d(min) = -0.09). The bilateral putamen (d(left) = -0.14, d(right) = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures. CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Several studies reported that genetic variants predisposing to neurodegeneration were at higher frequencies in centenarians than in younger controls, suggesting they might favor also longevity. IP6K3 and IPMK regulate many crucial biological functions by mediating synthesis of inositol poly- and pyrophosphates and by acting non-enzymatically via protein-protein interactions. Our previous studies suggested they affect Late Onset Alzheimer Disease (LOAD) and longevity, respectively. Here, in the same sample groups, we investigated whether variants of IP6K3 also affect longevity, and variants of IPMK also influence LOAD susceptibility. We found that: i) a SNP of IP6K3 previously associated with increased risk of LOAD increased the chance to become long-lived, ii) SNPs of IPMK, previously associated with decreased longevity, were protective factors for LOAD, as previously observed for UCP4. SNP-SNP interaction analysis, including our previous data, highlighted phenotype-specific interactions between sets of alleles. Moreover, linkage disequilibrium and eQTL data associated to analyzed variants suggested mitochondria as crossroad of interconnected pathways crucial for susceptibility to neurodegeneration and/or longevity. Overall, data support the view that in these traits interactions may be more important than single polymorphisms. This phenomenon may contribute to the non-additive heritability of neurodegeneration and longevity and be part of the missing heritability of these traits.

Prolonged exposure to higher concentrations of fluoride (> 1.5 mg/L) is associated with dental and skeletal fluorosis. The effects of fluoride on dental and skeletal system have been studied extensively; however, the neurological consequences of fluoride in population-based studies are limited. The study aims to assess the epidemiology of neurological and other manifestations of fluorosis among rural populations living in the Main Ethiopian Rift valley. In this cross-sectional study, we enrolled 316 individuals from 23 rural communities in the Main Ethiopian Rift valley. Fluoride concentration was measured in drinking water samples collected from 23 community wells. Association between fluoride concentrations and clinical features of fluorosis was assessed using student t test, chi square, multivariable regression using adjusted odds ratio (OR). The mean fluoride concentration in the drinking water was 6.8 ± 4.3 mg/L (range: 0.3–15.5 mg/L). At least one clinical sign of skeletal fluorosis was observed in 54.4% (n = 175) of the study participants. Headache and joint pain reported by 67.1% and 56.3% of the participants as the most common neurological manifestation, and skeletal fluorosis symptom, respectively. The mean fluoride level was higher for those individuals who reported paresthesia compared to those with no-paresthesia. Loss of appetite, constipation, and fatigue were reported by 48.0%, 45.6%, and 56.6% of the participants, respectively. Signs of crippling fluorosis were observed in small proportion (1.6%) of the participants. Individuals who reported headache are most likely exposed to higher fluoride concentrations in drinking water compared to those reported no-headache (p

BackgroundBrain structure abnormalities throughout the course of Parkinson’s disease (PD) have yet to be fully elucidated. Inconsistent findings across studies may be partly due to small sample sizes and heterogeneous analysis methods. Using a multicenter approach and harmonized analysis methods, we aimed to overcome these limitations and shed light on disease stage-specific profiles of PD pathology as suggested by in vivo neuroimaging.MethodsIndividual brain MRI and clinical data from 2,367 PD patients and 1,183 healthy controls were collected from 19 sites, deriving from 20 countries. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effect linear models. Patients were grouped according to the Hoehn & Yahr (HY) disease stages and compared to age- and sex-matched controls. Within the PD sample, we investigated associations between Montreal Cognitive Assessment (MoCA) scores and brain morphology.FindingsThe main analysis showed a thinner cortex in 38 of 68 regions in PD patients compared to controls (dmax = −0·25, dmin = −0·13). The bilateral putamen (left: d = −0·16, right: d = −0·16) and left amygdala (d = −0·15) were smaller in patients, while the left thalamus was larger (d = 0·17). HY staging indicated that a thinner cortex initially presents in the occipital, parietal and temporal cortex, and extends towards caudally located brain regions with increased disease severity. From HY stage 2 and onwards the bilateral putamen and amygdala were consistently smaller with larger effects denoting each increment. Finally, we found that poorer cognitive performance was associated with widespread cortical thinning as well as lower volumes of core limbic structures.InterpretationOur findings offer robust and novel imaging signatures that are specific to the disease severity stages and in line with an ongoing neurodegenerative process, highlighting the importance of such multicenter collaborations.FundingNIH Big Data to Knowledge program, ENIGMA World Aging Center, and ENIGMA Sex Differences Initiative, and other international agencies (listed in full in the Acknowledgments).

[Image: see text] Gold-nanoparticle (AuNP)-conjugated drugs represent a promising and innovative antitumor therapeutic approach. In our study, we describe the design, the synthesis, the preparation, and the characterization of AuNPs conjugated with the pyrazolo[3,4-d]pyrimidine derivative SI306, a c-Src inhibitor. AuNPs–SI306 showed a good loading efficacy (65%), optimal stability in polar media and in human plasma, and a suitable morphological profile: a ζ-potential of −43.9 mV, a nanoparticle diameter of 48.6 nm, and a 0.441 PDI value. The antitumoral activity of AuNPs–SI306 was evaluated in vitro in the glioblastoma model, by the low-density growth assay, and also in combination with radiotherapy (RT). Results demonstrated that AuNPs had a basal radiosensitization ability and that AuNPs–SI306, when used in combination with RT, were more effective in inhibiting tumor cell growth with respect to AuNPs and free SI306.

Parkinson’s disease (PD) is associated with brain mitochondrial dysfunction. High-energy phosphates (HEPs), which rely on mitochondrial functioning, may be considered potential biomarkers for PD. Phosphorus magnetic resonance spectroscopy (31P-MRS) is a suitable tool to explore in vivo cerebral energetics. We considered 10 31P-MRS studies in order to highlight the main findings about brain energetic compounds in patients affected by idiopathic PD and genetic PD. The studies investigated several brain areas such as frontal lobes, occipital lobes, temporoparietal cortex, visual cortex, midbrain, and basal ganglia. Resting-state studies reported contrasting results showing decreased as well as normal or increased HEPs levels in PD patients. Functional studies revealed abnormal PCr + βATP levels in PD subjects during the recovery phase and abnormal values at rest, during activation and recovery in one PD subject with PINK1 gene mutation suggesting that mitochondrial machinery is more impaired in PD patients with PINK1 gene mutation. PD is characterized by energetics impairment both in idiopathic PD as well as in genetic PD, suggesting that mitochondrial dysfunction underlies the disease. Studies are still sparse and sometimes contrasting, maybe due to different methodological approaches. Further studies are needed to better assess the role of mitochondria in the PD development.

Item does not contain fulltext The reduction of childhood obesity through the promotion of a healthy lifestyle is one of the most important public health challenges at the moment. It is known that the unhealthy habits of children can cause unavoidable side effects in their early stage of life, including both physical and mental consequences. This work considers that the physical activity level of children is a behaviour that can be spread throughout the social relations of children in their daily life at school. Therefore, the aim of this work is to define what the best strategy is to find 'targets' (i.e., influential children that can initiate behavioural change) for physical activity (PA) interventions that would affect the average PA of a population of Dutch school classes. We tuned a model based on the influence of the children’s peers in their social network, based on the data set from the MyMovez project - Phase I. Five intervention strategies were implemented, and their efficacy was compared. Once the targets were chosen, an increase of 17% was applied to their initial PA. Then, the diffusion model was run to verify the improvement on the PA of the whole network after one year. We discuss implications of the simulation results on which strategies may be used to make informed choices about the setup of social network interventions and future model improvements. Our results show that targeting more vulnerable children (i.e. in a worse environment) and applying a network optimization algorithm are the best solutions for this data set indicating that future interventions should aim for these two strategies. 8th International Conference on Simulation and Modeling Methodologies, Technologies and Applications (SIMULTECH 2018), Porto, Portugal , 29-31 July 2018

The benefit of statin therapy in patients with advanced chronic kidney disease remains uncertain. Randomized trials have questioned the efficacy of the drug in improving outcomes for on-dialysis populations, and many patients with end-stage renal disease are not currently taking statins. This study aimed to investigate the impact of statin use on survival of patients with vascular access performed at a vascular center for chronic dialysis. Consecutive end-stage renal disease patients admitted for vascular access surgery in 2006 to 2013 were reviewed. Information on therapy was retrieved and patients on statins were compared to those who were not on statins. Primary endpoint was 5-year survival. Independent predictors of mortality were assessed with Cox regression analysis adjusting for covariates (ie, age, sex, hyperlipidemia, hypertension, cardiac disease, cerebrovascular disease, chronic obstructive pulmonary disease, obesity, diabetes, and statins). Three hundred fifty-nine patients (230 males; mean age 68.9 ± 13.7 years) receiving 554 vascular accesses were analyzed: 127 (35.4%) were on statins. Use of statins was more frequent in patients with hypertension (89.8% v 81%; P = .034), hyperlipidemia (52.4% v 6.2%; P < .0001), coronary disease (54.1% v 42.6%; P = .043), diabetes (39.4% v 21.6%; P = .001), and obesity (11.6% v 2.0%; P < .0001). Mean follow-up was 35 months. Kaplan-Meier survival rates at 3 and 5 years were 84.4% and 75.9% for patients taking statins and 77.0% and 65.1% for those not taking statins (P = .18). Cox regression analysis selected statins therapy as the only independent negative predictor (odds ratio = 0.55; 95% confidence interval = 0.32-0.95; P = .032) of mortality, while age was an independent positive predictor (odds ratio = 1.05; 95% confidence interval = 1.03-1.08; P < .0001). Vascular access patency was comparable in statin takers and those not taking statins (P = .60). Use of statins might halve the risk of all-cause mortality at 5 years in adult patients with vascular access for chronic dialysis. Statins therapy should be considered in end-stage renal disease populations requiring dialysis access placement.

The concept of risk assessment and the identification of surgical unfitness for vascular intervention is a particularly controversial issue today as the minimally invasive surgical population has increased not only in volume but also in complexity (comorbidity profile) and age, requiring an improved pre-operative selection and definition of high risk. A practical step by step (three steps, two points for each) approach for surgical risk assessment is suggested in this review. As a general rule, the identification of a "high risk" patient for vascular surgery follows a step by step process where the risk is clearly defined, quantified (when too "high"?), and thereby stratified based on the procedure, the patient, and the hospital, with the aid of predictive risk scores. However, there is no standardized, updated, and objective definition for surgical unfitness today. The major gap in the current literature on the definition of high risk in vascular patients explains the lack of sound validated predictive systems and limited generalizability of risk scores in vascular surgery. In addition, the concept of fitness is an evolving tool and many traditional high risk criteria and definitions are no longer valid. Given the preventive purpose of most vascular procedures performed in elderly asymptomatic patients, the decision to pursue or withhold surgery requires realistic estimates not only regarding individual peri-operative mortality, but also life expectancy, healthcare priorities, and the patient's primary goals, such as prolongation of life versus maintenance of independence or symptom relief. The overall "frailty" and geriatric risk burden, such as cognitive, functional, social, and nutritional status, are variables that should be also included in the analyses for stratification of surgical risk in elderly vascular patients.

Amino acid (AA) availability is a rate-limiting factor in the regulation of muscle protein metabolism and, consequently, a risk factor for age-related decline in muscle performance. AA transporters are emerging as sensors of AA availability and activators of mTORC1 signalling, acting as transceptors. Here, we evaluated the association of 58 single nucleotide polymorphisms (SNPs) in 10 selected AA transporter genes with parameters of physical performance (Hand Grip, Activity of Daily Living, Walking time). By analysing a sample of 475 subjects aged 50-89 years, we found significant associations with SLC7A5/LAT1, SLC7A8/LAT2, SLC36A1/PAT1, SLC38A2/SNAT2, SLC3A2/CD98, SLC38A7/SNAT7 genes. Further investigation of the SNPs in a cross-sectional study including 290 subjects aged 90-107 years revealed associations of SLC3A2/CD98, SLC38A2/SNAT2, SLC38A3/SNAT3, SLC38A9/SNAT9 variability with longevity. Finally, a longitudinal study examining the survival rate over 10 years showed age-dependent complexity due to possible antagonistic pleiotropic effects for a SNP in SLC38A9/SNAT9, conferring a survival advantage before 90 years of age and a disadvantage later, probably due to the remodelling of AA metabolism. On the whole, our findings support the hypothesis that AA transporters may impact on the age-related physical decline and survival at old age in a complex way, likely through a mechanism involving mTORC1 signalling.

Objective The aim of this study was to investigate outcomes of patients treated with endovascular repair (ER) with the use of fenestrated and branched stent grafts or open surgery (OS) for thoracoabdominal aortic aneurysm (TAAA) in a current series of patients. Methods All TAAA patients undergoing repair at three centers between January 2007 and December 2014 were included in a prospective database. Patients were stratified according to treatment by ER or OS, and outcomes were compared using propensity score matching (1:1). Covariates included age, sex, aneurysm extent, hypertension, coronary disease, chronic pulmonary disease, diabetes, and renal function. The primary end points were mortality and paraplegia. Secondary end points included any spinal cord ischemia (SCI), renal and respiratory insufficiency, and a composite of these complications or death at 30 days. All-cause survival and freedom from reintervention were compared in the two groups. Results Of 341 patients, 84 (25%) underwent ER and 257 underwent OS (75%). After propensity score matching (65 patients per group), no significant differences were observed in rates of 30-day mortality (7.7% in ER and 6.2% in OS; P = 1) and paraplegia (9.2% and 10.8%; P = 1). Any SCI, renal insufficiency, and respiratory insufficiency were 12.3% and 20% ( P = .34), 9.2% and 12.3% ( P = .78), and 0% and 12.3% ( P = .006) in ER and OS, respectively. The incidence of the composite end point was significantly lower in ER patients (18.5% in ER vs 36.0% in OS; P =.03). According to Kaplan-Meier estimates, all-cause survival at 24 months was 82.8% in ER and 84.9% in OS, with rates unchanged at 42 months ( P = .9). Rates of freedom from reintervention were 91.0% vs 89.7% at 24 months and 80.0% vs 79.9% at 42 months in ER vs OS, respectively ( P = .3). Conclusions A propensity score analysis in patients with TAAA undergoing repair suggests an early benefit from ER compared with OS with regard to the composite end point because of reduced 30-day respiratory complications. No significant differences were found in SCI and renal insufficiency at 30 days and in survival and reintervention rates at midterm.

Background Decompression sickness (DCS) is a potential danger and risk for both divers and aircrew alike. DCS is also a potential side effect of altitude (hypobaric) chamber training as well and can present long after training occurs. Literature review shows that altitude chamber induced DCS has approximately a 0.25% incidence. Case report A 32-yr-old, active duty military member developed symptoms of DCS 3 h after his hypobaric chamber training. Unfortunately, he did not seek treatment for DCS until 48 h after the exposure. His initial treatment included ground level oxygen therapy for 30 min at 12 L of oxygen per minute using a nonrebreathing mask. He achieved complete symptom resolution and was returned to duty. However, 12 d after his initial Flight Medicine evaluation, the patient returned complaining of a right temporal headache, multijoint pains, and fatigue. He was treated in the hyperbaric chamber and had complete resolution of symptoms. He was returned to flying status and 5 mo later denied any return of symptoms. Discussion Hypobaric chamber familiarity training is a requirement for all military aircrew personnel to allow them assess their ability to identify symptoms of hypoxia. This training method is not only costly to maintain, but it also places aircrew and chamber technicians at risk for potential long-term side effects from failed recompression treatment of DCS. We are presenting a case of recurrent DCS symptoms 12 d after initial ground level oxygen therapy.Gentry J, Rango J, Zhang J, Biedermann S. Latent presentation of decompression sickness after altitude chamber training in an active duty flier. Aerosp Med Hum Perform. 2017; 88(4):427-430.

Background and aims Non-alcoholic fatty liver disease is recognized not only as part of the metabolic syndrome but also as an independent predictor of cardiovascular disease. Methods In this study, NMR spectroscopy method, together with perfusion techniques, was used to detect subclinical brain vascular damage in subjects with NAFLD without overt atherosclerosis risk factors (i.e. hypertension, diabetes, hypercholesterolemia, obesity). Results The results suggest that subjects with histologically proven NAFLD have a reduced cerebral perfusion (CBFr) confined to limited brain areas, i.e., left semioval center and posterior cingulate cortex. No statistically significant differences in CBFr values were found, dividing the NAFLD cohort into subgroups, considering NAS score, presence/absence of NASH/fibrosis, and degree of steatosis. Conclusions Our data suggest that NAFLD per se may be involved in cerebral atherosclerotic disease. It will be interesting to draw longitudinal studies to determine whether these changes could evolve in more serious cerebral injury.

Background/Objective Durability is the main concern of aortic endografting, but it is not clear to what extent trial results are applicable to "real world" patients. The purpose of this study was to assess the durability of a single model of aortic endograft in an unselected population with core lab analysis of morphological changes. Methods Computed tomography (CT) images of patients treated with Talent Unidoc (Medtronic, Santa Rosa, Calif) endografts from 2002 to 2006 in nine European centers with more than 1 year follow-up were centrally reviewed using a dedicated software with multiplanar and volume reconstructions. Images were checked for aneurysm growth ≥5 mm, neck enlargement >3 mm, graft migration ≥10 mm, endoleak, structural integrity. Morphological changes were defined clinically relevant when associated with reintervention or aneurysm-related death. Results A total of 349 patients (mean age 73.8 years, 90% males) were available for analysis; 1187 CT examinations were reviewed. Median abdominal aortic aneurysm (AAA) diameter was 56 mm (interquartile range [IQR] 49-62), neck length 20 mm (IQR 16-30), and neck diameter 25 mm (IQR 23-26). Mean follow-up was 25 months (range 12-60 months). During the study period, 10 late deaths (1 aneurysm-related, 0.3%) with a survival rate of 89.2% at 48 months and 33 reinterventions including 8 conversions (2.2%), 2 AAA ruptures (0.6%) and 1 (0.3%) loss of graft integrity were recorded. Cumulative reintervention rate was 6%, 8%, 13%, and 16% at 1, 2, 3, and 4 years, respectively. According to core lab analysis, 22 AAA grew, 169 were unchanged, and 158 shrunk, with a growing AAA rate of 3.1% patients/year. Five growths required reintervention, one for rupture. Forty-seven (6.5% patients/year) neck enlargements, three clinically relevant, 17 migrations (2.4% patients/year), five clinically relevant, and 70 endoleaks (9.7 % patients/year), 11 clinically relevant, were detected. Conclusion Data from this real world experience monitored with a centralized imaging review show that endovascular repair of abdominal aortic aneurysm with the latest generation of a single model of endograft is associated with low graft thrombosis and graft fatigue, and low late aneurysm rupture and related death risks. Neck enlargement although common after EVAR, is almost always without clinical consequences but a longer follow-up and prospective clinical studies are advisable to confirm the present results.

This cross-sectional study explores the relationships between children's F(-) exposure from drinking groundwater and urinary F(-) concentrations, combined with dental fluorosis (DF) in the Main Ethiopian Rift (MER) Valley. We examined the DF prevalence and severity among 491 children (10 to 15 years old) who are life-long residents of 33 rural communities in which groundwater concentrations of F(-) cover a wide range. A subset of 156 children was selected for urinary F(-) measurements. Our results showed that the mean F(-) concentrations in groundwater were 8.5 ± 4.1 mg/L (range: 1.1-18 mg/L), while those in urine were 12.1±7.3 mg/L (range: 1.1-39.8 mg/L). The prevalence of mild, moderate, and severe DF in children's teeth was 17%, 29%, and 45%, respectively, and the majority (90%; n=140) of the children had urinary F(-) concentrations above 3 mg/L. Below this level most of the teeth showed mild forms of DF. The exposure-response relationship between F(-) and DF was positive and non-linear, with DF severity tending to level off above a F(-) threshold of ~6 mg/L, most likely due to the fact that at ~6 mg/L the enamel is damaged as much as it can be clinically observed in most children. We also observed differential prevalence (and severity) of DF and urinary concentration, across children exposed to similar F(-) concentrations in water, which highlights the importance of individual-specific factors in addition to the F(-) levels in drinking water. Finally, we investigated urinary F(-) in children from communities where defluoridation remediation was taking place. The lower F(-) concentration measured in urine of this population demonstrates the capacity of the urinary F(-) method as an effective monitoring and evaluation tool for assessing the outcome of successful F(-) mitigation strategy in relatively short time (months) in areas affected with severe fluorosis.

Elevated level of fluoride (F(-)) in drinking water is a well-recognized risk factor of dental fluorosis (DF). While considering optimization of region-specific standards for F(-), it is reasonable, however, to consider how local diet, water sourcing practices, and non-F(-) elements in water may be related to health outcomes. In this study, we hypothesized that non-F(-) elements in groundwater and lifestyle and demographic characteristics may be independent predictors or modifiers of the effects of F(-) on teeth. Dental examinations were conducted among 1094 inhabitants from 399 randomly-selected households of 20 rural communities of the Ziway-Shala lake basin of the Main Ethiopian Rift. DF severity was evaluated using the Thylstrup-Fejerskov Index (TFI). Household surveys were performed and water samples were collected from community water sources. To consider interrelations between the teeth within individual (in terms of DF severity) and between F(-) and non-F(-) elements in groundwater, the statistical methods of regression analysis, mixed models, and principal component analysis were used. About 90% of study participants consumed water from wells with F(-) levels above the WHO recommended standard of 1.5mg/l. More than 62% of the study population had DF. F(-) levels were a major factor associated with DF. Age, sex, and milk consumption (both cow's and breastfed) were also statistically significantly (p0.05) associated with DF severity; these associations appear both independently and as modifiers of those identified between F(-) concentration and DF severity. Among 35 examined elements in groundwater, Ca, Al, Cu, and Rb were found to be significantly correlated with dental health outcomes among the residents exposed to water with excessive F(-) concentrations. Quantitative estimates obtained in our study can be used to explore new water treatment strategies, water safety and quality regulations, and lifestyle recommendations which may be more appropriate for this highly populated region.

Epidemiologic evidence suggests that patients with diabetes may have a lower incidence of abdominal aortic aneurysm (AAA); however, the link between diabetes and AAA development and expansion is unclear. The aim of this review is to analyze updated evidence to better understand the impact of diabetes on prevalence, incidence, clinical outcome, and expansion rate of AAA. A systematic review of literature published in the last 20 years using the PubMed and Cochrane databases was undertaken. Studies reporting appropriate data were identified and a meta-analysis performed using the generic inverse variance method. Sixty-four studies were identified. Methodological quality was “fair” in 16 and “good” in 44 studies according to a formal assessment checklist (Newcastle–Ottawa). In 17 large population prevalence studies there was a significant inverse association between diabetes and AAA: pooled odds ratio (OR) 0.80; 95% confidence intervals (CI) 0.70–0.90 (p = .0009). An inverse association was also confirmed by pooled analysis of data from smaller prevalence studies on selected populations (OR 0.59; 95% CI 0.35–0.99; p = .05), while no significant results were provided by case-control studies. A significant lower pooled incidence of new AAA in diabetics was found over six prospective studies: OR 0.54; 95% CI 0.31–0.91; p = .03. Diabetic patients showed increased operative (30-day/in-hospital) mortality after AAA repair: pooled OR 1.26; 95% CI 1.10–1.44; p = .0008. The increased operative risk was more evident in studies with 30-day assessment. In the long-term, diabetics showed lower survival rates at 2–5 years, while there was general evidence of lower growth rates of small AAA in patients with diabetes compared to non-diabetics. There is currently evidence to support an inverse relationship between diabetes and AAA development and enlargement, even though fair methodological quality or unclear risk of bias in many available studies decreases the strength of the finding. At the same time, operative and long-term survival is lower in diabetic patients, suggesting increased cardiovascular burden. The higher mortality in diabetics raises the question as to whether AAA repair should be individualized in selected diabetic populations at higher AAA rupture risk.

ObjectiveCurrent data supporting the effect of anticoagulation drug use on aneurysm sealing and the durability of endovascular abdominal aneurysm repair (EVAR) are conflicting. This study assessed the safety of chronic anticoagulation therapy after EVAR.MethodsRecords of 1409 consecutive patients having elective EVAR during 1997–2011 who were prospectively followed were reviewed. Survival, reintervention, conversion, and endoleak rates were analyzed in patients with and without chronic anticoagulants. Cox proportional hazards models were used to estimate the effect of anticoagulation therapy on outcomes.ResultsOne-hundred and three (7.3%) patients were on chronic anticoagulation drugs (80 on vitamin K antagonists) at the time of EVAR. An additional 46 patients started on anticoagulants after repair were identified. Patients on chronic anticoagulation therapy at repair (mean age 73.6 years; 91 males) had more frequent cardiac disease (74.8% vs. 44.2%; p

BackgroundOperator training is a key factor for the safety of carotid stenting (CAS). Whether institutional practice is associated with improved individual operator outcomes is debated.ObjectiveTo evaluate the effect of the institutional experience on outcomes of new trainees with CAS, a retrospective analysis of a prospectively held database was performed.MethodsThe overall study period, 2004–2012, was divided into two sequential time frames: 2004–April 2006 (leaders-team phase) and May 2006–2012 (expanded team phase). In the first frame, a single leader-operators team that first approached CAS and passed the original institutional learning curve, performed all the procedures; in the following expanded-team phase, five new trainees joined. Institutional CAS training for new trainees was based on a team-working approach including selection of patients, devices and techniques and collegial meetings with critical review and discussion of all procedural steps and imaging.ResultsA total of 431 CAS procedures were performed in the leaders-team phase and 1026 in the sequential expanded-team phase. Periprocedural complication rates in the two time frames were similar: stroke/death (3.0% vs. 2.1%; P = 0.35), stroke (2.8% vs. 2.1%; P = 0.45) major stroke (0.9% vs. 0.6%, P = 0.49), death (0.2% vs. 0%; P = 0.29) during the leaders-team and expanded-team phase, respectively. However, rates of CAS failure requiring surgical conversions (3.7% vs. 0.8%; P

An expert multidisciplinary panel in the treatment of type B aortic dissection reviewed available literature to develop treatment algorithms using a consensus method. Data from 63 studies published from 2006 to 2012 were retrieved for a total of 1,548 patients treated medically, 1,706 patients who underwent open surgery, and 3,457 patients who underwent thoracic endovascular repair (TEVAR). For acute (first 2 weeks) type B aortic dissection, the pooled early mortality rate was 6.4% with medical treatment and increased to 10.2% with TEVAR and 17.5% with open surgery, mostly for complicated cases. Limited data for treatment of subacute (2 to 6 weeks after onset) type B aortic dissection showed an early mortality rate of 2.8% with TEVAR. In chronic (after 6 weeks) type B aortic dissection, 5-year survival of 60% to 80% was expected with medical therapy because complications were likely. If interventional treatment was applied, the pooled early mortality rate was 6.6% with TEVAR and 8.0% with open surgery. Medical treatment of uncomplicated acute, subacute, and chronic type B aortic dissection is managed with close image monitoring. Hemodynamic instability, organ malperfusion, increasing periaortic hematoma, and hemorrhagic pleural effusion on imaging identify patients with complicated acute type B aortic dissection requiring urgent aortic repair. Recurrence of symptoms, aortic aneurysmal dilation (>55 mm), or a yearly increase of >4 mm after the acute phase are predictors of adverse outcome and need for delayed aortic repair (“complicated chronic aortic dissections”). The expert panel is aware that this consensus document provides proposal for strategies based on nonrobust evidence for management of type B aortic dissection, and that literature results were largely heterogeneous and should be interpreted cautiously.

Urinary incontinence (UI) is very common in the elderly and has personal and social implications. Many authors have pointed out the necessity to analyze UI in correlation with the overall quality of aging, to better understand this syndrome and define measures for its prevention and treatment. In the present study, we addressed this problem by analyzing the UI correlation with frailty, which has emerged in the last decade as the geriatric syndrome correlated with individual homeostatic capacity and then as the basis of the age-related physical decline. In addition, the monitoring of our sample for a long period allowed us to estimate the prognostic significance of UI by analyzing the correlation between UI and mortality. The analysis was performed in a large sample that included numerous ultra-nonagenarians, a population segment that is still poorly known for UI and other geriatric parameters. We found a strict correlation between UI and frailty, suggesting that UI is correlated to the homeostatic and physiological decline leading to frailty. In addition, we found that UI is an independent mortality risk factor in ultra-nonagenarians, suggesting that the neurological sensitivity needed to be continent is lost very soon when the frailty associated physiological decline begins. On the whole, our study suggests that UI is a marker of frailty and that UI patients should be monitored and, in case, treated in a timely manner to avoid, or to limit, the effects of frailty such as malnutrition, falls, and the consequent accumulation of disabilities.

Sex differences in presentation and outcomes of abdominal aortic aneurysms (AAA) with increased mortality rates in women are suggested. This study aimed to assess mortality risk after repair of ruptured AAA (rAAA) in women in the endovascular abdominal aortic repair (EVAR) era.Patients treated between 2006 and 2015 for rAAA were included in a prospective database. Characteristics at presentation and outcomes were compared between women and men. Multivariable logistic regression and Cox proportional analyses were performed to identify the effect of sex adjusted for other predictors on mortality.One hundred thirteen patients were identified; of these, 17.7% (20/113) of the patients were women. Forty-four procedures (38.9%) were by EVAR, with comparable rates in women (45%) and men (37.6%, P = 0.62). On admission, women and men shared similar comorbidities and presentation (shock 45% vs. 43.0%, P = 0.81; free rupture 65.0% vs. 67.7%, P = 0.80) and comparable mean aneurysm diameter (76.5 vs. 78.8 mm, P = 0.68), but women were older (mean age 86.4 + 5.5 vs. 75.2 ± 10.6 years, P 0.0001) and octogenarian women were twice as likely as men (90% vs. 40%, P 0.0001). Perioperative mortality was comparable between women and men (40.0% vs. 38.7%) either after EVAR (22.2% vs. 40.0% in women and men respectively; odds ratio [OR] 0.45, 95% confidence interval [CI] 0.77-2.37) or after open surgery (54.5% vs. 37.9%; OR 2.0, 95% CI 0.54-7.21), even though there was a trend for lower mortality in women with EVAR. In adjusted analyses, female sex was not associated with perioperative mortality as it was for older age (octogenarians: OR 6.6, 95% CI 2.08-20.82, P = 0.001) and free rupture (OR 4.2, 95% CI 1.29-13.73, P = 0.02). Mean follow-up was 34.32 months. After controlling for age, surgical repair, free rupture, cardiac disease, and shock at presentation, female sex was not a predictor of late mortality.AAA repair is often delayed in women and applied at older age; nevertheless, currently women do not show increased perioperative mortality risks from rAAA treatment after the introduction of EVAR.

Repair of isolated iliac aneurysm with stent-graft implantation and internal iliac coverage may induce significant type II endoleak from patent internal iliac refilling leading to ongoing aneurysm growth. Subsequent treatment of such complication can be challenging especially in case of bilateral iliac involvement. Open repair is technically demanding and often a high risk procedure, while embolization via transfemoral approach is unviable due to the stent-graft coverage precluding direct antegrade access between the common and the internal iliac lumen. Percutaneous retrograde embolization from superior gluteal artery is a feasible technique in case of impossible access through the origin of internal iliac artery.

Objective/Background A consistent number of elderly patients with ruptured abdominal aortic aneurysms (rAAAs) are deemed unfit for repair and excluded from any treatment. The objective of this study was to examine the impact on survival of endovascular repair and open surgery with restricted turndown in acute AAA repair. Methods A prospective database for patients treated for rAAA was established. None of the patients admitted alive with rAAA were denied treatment. Multivariate regression models, the predictive risk assessment Glasgow Aneurysm Score (GAS), and subgroup analyses in older patients were applied to identify indicators of excessive 30 day mortality risk that could affect the decision for turndown. Results From 2006 to 2015, 113 consecutive patients (93 males; mean age 77.2 years) with rAAAs were treated (69 open surgery; 44 EVAR). Overall peri-operative (30 day) mortality was 38.9% (44/113): 40.6% (28/69), and 36.4% (16/44) after open surgery and EVAR, respectively ( p = .70). Multivariate logistic regression identified old age as an indicator of increased peri-operative mortality (odd ratio [OR] 1.2, 95% confidence interval [CI] 1.1–1.3; p = .001), as well as free aneurysm rupture (OR 5.0, 95% CI 1.3–19.9; p = .02). GAS was higher in patients who died (97.75 vs. 86.62), but the score failed to identify increased peri-operative mortality risk in adjusted analyses (OR 1.0; p = .06). Almost two thirds of the patients ( n = 71) were older than 75 at the time of aneurysm rupture (48.6% octogenarians) and EVAR was more commonly applied than open surgery (86.4% vs. 47.8%; p 75 year old patients was 46.5% compared with 26.2% in younger patients ( p = .05), with rates increased after open surgery (54.5% vs. 27.8%, p = .03) but not after EVAR (39.5% vs. 16.7%; p = .39). According to Kaplan–Meier estimates, mean survival was 39.7 ± 4.8 months. Patients older than 75 years of age survived for a mean of 23.0 ± 4.47 months after rupture. Conclusion In this study aggressive treatment with a very restricted or no turndown strategy for any rAAA, also applied to older patients, allowed for an additional mean 40 months of survival after aneurysm rupture. In the contemporary endovascular era the decision to deny repair arbitrarily to older patients with rAAAs must be revisited.

Objective: In the last years, development of materials allowed notably improvements in interventional approach to stroke. Tapered stents were specifically designed for extracranial carotid stenting (CAS) to deal with vessels mismatch decreasing the risk of thrombosis. Nevertheless, as to whether the stent geometry may affect the hemodynamic consequences of CAS remains uncertain. This study aims to investigate the impact of stent configuration on postprocedural sustained hemodynamic depression (HD) requiring action of care after carotid stenting (CAS). Methods: Data on 391 consecutive CAS performed over a 4-year period (2011-2014) were reviewed. Postprocedural sustained HD was defined as any severe hypotension (2 measurements after the end of the procedure and requiring care support or delaying hospital discharge. Stent configuration (tapered or straight) was tested for association with sustained HD using multivariable models adjusted for other confounders (medical therapy, comorbidities, symptoms, stenosis, carotid plaque and demographics).The relation with stroke and death outcomes within 30 days of treatment was also analyzed. Results: Mean age of patients was 70.7y + 7.14 and 66.2% were males. Sustained HD developed after 144 (36.8%) CAS. Tapered stents were applied in 289 (73.9%) CAS, and more frequently in patients with higher degree of stenosis (mean 79% vs 77%, in tapered and straight stents respectively; P=0.007) or asymptomatic (93.8% vs. 85.3% in tapered and straight stents respectively;P=0.012). Diabetes (HR 1.6, 95% CI, 1.01-2.44;P=0.044) and tapered stent configuration (HR, 1.7, 95% CI, 1.05-2.82;P=0.033) were the only factors that showed independent association with sustained HD. At 30-day, 3 strokes and no death occurred. There was no statistically significant association between 30-day outcomes and sustained HD depression or stent configuration. Conclusions: A strong hemodynamic effect, requiring additional actions of care or prolonged hospital stay, is expected after CAS when using tapered stent configuration. These findings alert on the overall benefit and costs of CAS and the requirements for accurate material selection especially in diabetic patients.

Age is a main risk factor for stroke and perioperative risk. This study aims to analyze the effect of age by symptomatic status in young patients receiving carotid revascularization.Consecutive carotid revascularization procedures performed during the period 2001-2009 were reviewed. Patients were analyzed by age using the 70-year threshold as suggested by trials. Primary end point was perioperative stroke or death rate. Secondary end points included survival and late stroke incidence at 6 years.A total of 2,196 procedures (1,080 by carotid artery stenting [CAS] and 1,116 by carotid endarterectomy [CEA]) were analyzed. Symptomatic patients (n = 684) showed higher perioperative stroke or death risks (24 of 684 [3.5%] versus 29 of 1,512 [1.9%], odds ratio [OR] 1.8; 95% confidence interval [CI] 1.07-3.22; P = 0.034) and lower 6-year survival (74% vs. 82%, P0.0001) or freedom from late stroke (93% vs. 97%, P = 0.001) when compared with asymptomatic patients with similar differences detected within CEA or CAS procedure. Overall 949 procedures were in patients with 70 years or less at the time of intervention (500 CEA and 449 CAS); 282 were in patients symptomatic for minor stroke or transient ischemic attack within 6 months before revascularization. For young symptomatic patients, primary end point rates were2.5% after both CEA and CAS procedure. Perioperative stroke or death rates were 2.4% in symptomatic versus 1.5% in asymptomatic (4 of 170 vs. 5 of 330; OR 1.57; 95% CI 0.42-5.91; P = 0.50) within the CEA group and 1.8% in symptomatic versus 1.2% in asymptomatic (2 of 112 vs. 4 of 337; OR 1.51; 95% CI 0.27-8.38; P = 0.64) within the CAS group. At 6 years, symptomatic young patients showed survival (89.5% vs. 89%, P = 0.76) and freedom from late stroke (97% vs. 98%, P = 0.56) rates comparable to those found in asymptomatic patients, with similar incidences after CAS or CEA procedure.Outcomes after carotid revascularization are related to patients' age. At younger ages (70 years), after carotid revascularization, symptomatic patients show low perioperative risks of stroke or death, comparable with those in asymptomatic patients. The same, 2.5% or lower, threshold for perioperative stroke or death risk related to asymptomatic carotid procedures must be applied today to symptomatic patients when younger than age of 70 years.

This review article presents a summary of recent efforts to understand brain temperature and its regulation under different conditions. Brain temperature has a crucial influence on brain processes. Its regulation is the outcome of the balance of core and arterial blood temperatures, cerebral blood flow, brain metabolism, functional conditions, and external temperature. However, the relationship between these factors is not fully understood and several uncertainties remain. There are no satisfactory normative data on temperatures throughout the brain, but new technologies promise to fill this gap. Brain temperature changes with brain functional activation and under pathological conditions in ways that are not understood. A full understanding of brain temperature control is mandatory to optimize attempts at brain cooling during clinical conditions such as stroke and head injury.

Background Iliac branch device (IBD) technique has been introduced as an appealing and effective solution to avoid complications occurring during repair of aorto-iliac aneurysm with extensive iliac involvement. Nevertheless, no large series with long-term follow-up of IBD are available. The aim of this study was to analyse safety and long-term efficacy of IBD in a consecutive series of patients. Methods Between 2006 and 2011, 100 consecutive patients were enrolled in a prospective database on IBD. Indications included unilateral or bilateral common iliac artery aneurysms combined or not with abdominal aneurysms. Patients were routinely followed up with computed tomography. Data were reported according to the Kaplan–Meier method. Results There were 96 males, mean age 74.1 years. Preoperative median common iliac aneurysm diameter was 40 mm (interquartile range (IQR): 35–44 mm). Sixty-seven patients had abdominal aortic aneurysm >35 mm (IQR: 40–57 mm) associated with iliac aneurysm. Eleven patients presented hypogastric aneurysm. Twelve patients underwent isolated iliac repair with IBD and 88 patients received associated endovascular aortic repair. Periprocedural technical success rate was 95%, with no mortality. Two patients experienced external iliac occlusion in the first month. At a median follow-up of 21 months (range 1–60) aneurysm growth >3 mm was detected in four iliac (4%) arteries. Iliac endoleak (one type III and two distal type I) developed in three patients and buttock claudication in four patients. Estimated patency rate of internal iliac branch was 91.4% at 1 and 5 years. Freedom from any reintervention rate was 90% at 1 year and 81.4% at 5 years. No late ruptures occurred. Conclusions Long-term results show that IBD use can ensure persistent iliac aneurysm exclusion at 5 years, with low risk of reintervention. This technique can be considered as a first endovascular option in patients with extensive iliac aneurysm disease and favourable anatomy.

The maintenance of a stable temperature is of the utmost importance for the proper functioning of the brain. Brain temperature is tightly linked to mitochondrial energetics. Although Parkinson's disease is characterized by mitochondrial dysfunction, no data are available on brain temperature. We measured the temperature in the visual cortex and in the centrum semiovale at rest by proton magnetic resonance spectroscopy in patients with Parkinson's disease and in age-matched and sex-matched control participants. We report evidence of increased temperature in the visual cortex and, to a minor extent, in the centrum semiovale of patients with Parkinson's disease. The increase in brain temperature is best explained by an energy loss along the oxidative phosphorylation/respiratory chain.

Introduction: Current stroke guidelines suggest performing carotid endarterectomy (CEA) within 2 weeks after an ischemic stroke or TIA caused by severe carotid stenosis. However, early carotid revascularization in patients in unstable neurological condition after acute stroke (“stroke in evolution”, SIE) is controversial because of the risk of new ischemic stroke, intracerebral hemorrhage (ICH) and death. Published studies have not found a consistent benefit in this cohort. Hypothesis: The aim of this systematic review and meta-analysis was to document outcomes after urgent carotid intervention performed within 2 weeks from SIE. Methods: A systematic review of studies published in the last 8 years (2008-2015) reporting the risk of stroke, death and ICH following carotid intervention performed within 2 weeks from acute stroke in patients with SIE, was undertaken. Pooled proportion of periprocedural stroke, stroke or death and ICH were obtained with proportion meta-analysis and random effects model. Results: Out of 47 published series reporting on 2-week timing of carotid intervention after ischemic neurological event, only 15 separately described periprocedural risks for patients with SIE. In 8 studies patients underwent thrombolysis for acute stroke management of SIE before carotid revascularization. The pooled proportion of periprocedural stroke was 5.0% (95% Confidence Intervals, CI, 3.3 - 7.1), ranging 0 -14.2% among different studies. Figure. The pooled proportion of periprocedural risk for the combined of stroke or death was 4.7% (95% CI 2.9 -7.0) and that of periprocedural ICH, 1.2% (95% CI 0.4-2.4). Conclusions: The current risk of stroke, death and ICH after urgent carotid revascularization performed within 2 weeks for patients with stroke in evolution is lower than that anticipated in previous studies. Nevertheless, due to the heterogeneity in reporting and differential in patient selection, these findings should be interpreted with caution.

Ulcerated diabetic foot is a complex problem. Ischaemia, neuropathy and infection are the three pathological components that lead to diabetic foot complications, and they frequently occur together as an aetiologic triad. Neuropathy and ischaemia are the initiating factors, most often together as neuroischaemia, whereas infection is mostly a consequence. The role of peripheral arterial disease in diabetic foot has long been underestimated as typical ischaemic symptoms are less frequent in diabetics with ischaemia than in non-diabetics. Furthermore, the healing of a neuroischaemic ulcer is hampered by microvascular dysfunction. Therefore, the threshold for revascularising neuroischaemic ulcers should be lower than that for purely ischaemic ulcers. Previous guidelines have largely ignored these specific demands related to ulcerated neuroischaemic diabetic feet. Any diabetic foot ulcer should always be considered to have vascular impairment unless otherwise proven. Early referral, non-invasive vascular testing, imaging and intervention are crucial to improve diabetic foot ulcer healing and to prevent amputation. Timing is essential, as the window of opportunity to heal the ulcer and save the leg is easily missed.This chapter underlines the paucity of data on the best way to diagnose and treat these diabetic patients. Most of the studies dealing with neuroischaemic diabetic feet are not comparable in terms of patient populations, interventions or outcome. Therefore, there is an urgent need for a paradigm shift in diabetic foot care; that is, a new approach and classification of diabetics with vascular impairment in regard to clinical practice and research. A multidisciplinary approach needs to implemented systematically with a vascular surgeon as an integrated member. New strategies must be developed and implemented for diabetic foot patients with vascular impairment, to improve healing, to speed up healing rate and to avoid amputation, irrespective of the intervention technology chosen. Focused studies on the value of predictive tests, new treatment modalities as well as selective and targeted strategies are needed. As specific data on ulcerated neuroischaemic diabetic feet are scarce, recommendations are often of low grade.

Objectives This study sought to evaluate long-term outcomes of carotid stenting (CAS) versus carotid endarterectomy (CEA) based on physician-guided indications. Background The issue regarding long-term outcome of CAS versus CEA in patients with carotid stenosis is clinically relevant but remains unsettled. Methods Consecutive patients (71% men, mean age 71.3 years) treated by CEA (n = 1,118) or CAS (n = 1,084) after a training phase were reviewed. Selection of treatment was based on better-suitability characteristics (morphology and clinical). Data were adjusted with propensity score analysis and stratified by symptoms, age, and sex. Results Thirty-day stroke/death rates were similar: 2.8% in CAS and 2.0% in CEA (p = 0.27). The risk was higher in symptomatic (3.5%) versus asymptomatic (2.0%) patients (p = 0.04) but without significant difference between CAS and CEA groups. Five-year survival rates were 82.0% in CAS and 87.7% in CEA (p = 0.05). Kaplan-Meier estimates of the composite of any periprocedural stroke/death and ipsilateral stroke at 5 years after the procedure were similar in all patients (4.7% vs. 3.7%; p = 0.4) and the subgroups of symptomatic (8.7% vs. 4.9%; p = 0.7) and asymptomatic (2.5% vs. 3.3%; p = 0.2) patients in CEA versus CAS, respectively. Cox analysis, adjusted by propensity score, identified statin treatment (p = 0.016) and symptomatic disease (p = 0.003) associated with the composite end point. There were no sex- or age-related significant outcome differences. Conclusions When physicians use their clinical judgment to select the appropriate technique for carotid revascularization CAS can offer efficacy and durability comparable to CEA with benefits persisting at 5 years.

Background Pre-manufactured branched grafts now allow an endovascular approach to the repair of thoraco-abdominal aortic aneurysm (TAAA) with visceral vessels' involvement. Similar grafts have been employed in open surgery, generally as a second choice for TAAAs, which are not amenable to patch/inclusion technique for visceral vessel attachment. Results with branched grafts have not been reported in series of open TAAA repairs. The purpose of this report is to describe perioperative risks and outcomes in a consecutive series of patients with pre-manufactured side-branched thoracoabdominal aortic grafts (STAGs) for surgical TAAA repair. Methods Between 1996 and 2009, pre-manufactured STAGs were used in 50 patients with TAAA that required reattachment of the visceral and renal arteries. Operative details, perioperative mortality and ischaemic complications were examined. Results Mean age was 53 years; 18 patients were females. The cases included redo ( n = 24), patients affected by genetic disorder (Marfan) ( n = 20) and patients with aortic dissection ( n = 27). The mean clamp time was 84.1 min. Perioperative mortality was 12.0% (6/50). Neurologic deficits occurred in 2% (1/50). Postoperative renal dysfunction was detected in 19 patients (38%). Conclusion The use of a STAG produced acceptable mortality, bowel and neurological ischaemic risks. Improved strategies to prevent renal ischaemia before and during repair of TAAA with visceral involvement are needed.

Objectives Increasing data suggest that statins can significantly decrease cardiovascular and cerebrovascular events due to a plaque stabilization effect. However, the benefit of statins in patients undergoing carotid angioplasty and stenting (CAS) for carotid stenosis is not well defined. The aim of this study was to investigate whether statins use was associated with decreased perioperative and late risks of stroke, mortality, and restenosis in patients undergoing CAS. Methods All patients undergoing CAS for primary carotid stenosis from 2004 to 2009 were reviewed. The independent association of statins and perioperative morbidity was assessed using multivariable analysis. Survival curves and Cox regression models were used to assess late morbidity and restenosis. Propensity score adjustment was employed. Results A total of 1083 consecutive CAS were performed (29% females, mean age 71.5 years; 24.7% symptomatic); 465 (43%) were on statins medication before treatment that was not discontinued at discharge. Statins use was associated with a reduction of perioperative stroke and death (odds ratio [OR] 0.327, 95% confidence interval [CI] 0.13-0.80, P = .016) according to multivariable analysis. Statins effect was more significant in reducing stroke and death in symptomatic patients (OR 0.13; P = .032) and in males (OR 0.27, P = .01). At 5 years, survival (87.2% vs 78.3%; P = .009) and ischemic stroke-free interval (88.9% vs 99.7%; P = .02) rates were higher in the statins group of patients. Adjusting for propensity score and covariates in Cox regression analyses, statins use was independently associated with reduced long-term mortality risk (HR 0.56, 95% CI 0.32-0.97; P = .039) and borderline associated with decreased late ischemic stroke risk (HR 0.14; 95% CI 0.018-1.08, P = .059). There was no effect on restenosis rates. Conclusions These data suggest that statins use is associated with decreased perioperative and late ischemic strokes risk and reduced mortality rates in patients undergoing CAS. Statins therapy should be considered part of the best medical treatment in current CAS practice.

Objective To examine different stages of dendritic cells (DCs) in intrauterine (IUPs) and viable tubal (VTPs) pregnancies to further elucidate mechanisms of fetomaternal tolerance and extravillous trophoblast invasion. Design Experimental study on patient-controlled material. Setting University hospital. Patient(s) Seven women with normal IUPs and ten with VTPs in the first trimester. Intervention(s) Suction curettage in IUP, laparoscopy in VTP. Main Outcome Measure(s) Immunohistochemistry for cytokeratin-7 (trophoblast), CD83 (mature DCs), DEC205 (activated but not fully mature DCs), DC-SIGN (immature macrophage-like DCs), and CD14 (macrophages) alone and in double staining. Result(s) The numbers of CD83 + and DEC205 + cells were similarly low in IUP and VTP (0.83 and 0.44 cells/mm 2 ; 2.28 and 2.96 cells/mm 2 ). The number of DC-SIGN + cells was higher, though without significant differences among the entities examined (57.5 and 47.4 cells/mm 2 ). About two-thirds of DC-SIGN + cells were also CD14 + in IUP and VTP. Conclusion(s) The almost equal distribution of CD83 + , DEC205 + , and DC-SIGN + cells in IUP and VTP suggests analogue control mechanisms in intrauterine and extrauterine DC differentiation and a comparable role of these DCs for the development of fetomaternal tolerance.

BackgroundRandomised trials have failed to demonstrate benefit from early surgical repair of small abdominal aortic aneurysm (AAA) compared with surveillance. This study aimed to compare results after endovascular aortic aneurysm repair (EVAR) or surveillance in AAA 1 cm /year, symptoms) was achieved. The main end point was all-cause mortality. Recruitment is closed; results at a median follow-up of 32.4 months are here reported.ResultsBetween 2004 and 2008, 360 patients (early EVAR = 182; surveillance = 178) were enrolled. One perioperative death after EVAR and two late ruptures (both in the surveillance group) occurred. At 54 months, there was no significant difference in the main end-point rate [hazard ratio (HR) 0.76; 95% confidence interval (CI) 0.30–1.93; p = 0.6] with Kaplan–Meier estimates of all-cause mortality of 14.5% in the EVAR and 10.1% in the surveillance group. Aneurysm-related mortality, aneurysm rupture and major morbidity rates were similar. Kaplan–Meier estimates of aneurysms growth ≥5 mm at 36 months were 8.4% in the EVAR group and 67.5% in the surveillance group (HR 10.49; 95% CI 6.88–15.96; p

Background: several studies suggest that a decreased thyroid activity might be favourable in oldest-old subjects and that subclinical thyroid hyperfunction may be detrimental. Objectives: to verify whether declining levels of circulating thyroid hormones may contribute to longevity. Design: cross-sectional observational study. Setting: all subjects were born in Calabria (southern Italy) and their ancestry in the region was ascertained up to the grandparents. Subjects: six hundred and four home-dwelling subjects (301 females, 303 males), divided into three groups: 278 individuals 60–85 years old; 179 children or nieces/nephews of centenarians who are 60–85 years old; 147 individuals older than 85 years. Methods: thyroid function parameters were measured in the frame of a comprehensive geriatric assessment. Results: FT3 and FT4 levels were negatively associated with age. Lower levels of FT3, FT4 and TSH were found in centenarians’ children and nieces/nephews with respect to age-matched controls. Indeed, being a relative of centenarians qualified as an independent correlate of thyroid parameters. Conclusions: age-related subtle thyroid hypofunction (either due to a familial component or due to a reset of the thyroid function occurring between the sixth and the eighth decade of life) appears to be related to longevity.

SummaryBackgroundIf carotid artery narrowing remains asymptomatic (ie, has caused no recent stroke or other neurological symptoms), successful carotid endarterectomy (CEA) reduces stroke incidence for some years. We assessed the long-term effects of successful CEA.MethodsBetween 1993 and 2003, 3120 asymptomatic patients from 126 centres in 30 countries were allocated equally, by blinded minimised randomisation, to immediate CEA (median delay 1 month, IQR 0·3–2·5) or to indefinite deferral of any carotid procedure, and were followed up until death or for a median among survivors of 9 years (IQR 6–11). The primary outcomes were perioperative mortality and morbidity (death or stroke within 30 days) and non-perioperative stroke. Kaplan-Meier percentages and logrank p values are from intention-to-treat analyses. This study is registered, number ISRCTN26156392.Findings1560 patients were allocated immediate CEA versus 1560 allocated deferral of any carotid procedure. The proportions operated on while still asymptomatic were 89·7% versus 4·8% at 1 year (and 92·1% vs 16·5% at 5 years). Perioperative risk of stroke or death within 30 days was 3·0% (95% CI 2·4–3·9; 26 non-disabling strokes plus 34 disabling or fatal perioperative events in 1979 CEAs). Excluding perioperative events and non-stroke mortality, stroke risks (immediate vs deferred CEA) were 4·1% versus 10·0% at 5 years (gain 5·9%, 95% CI 4·0–7·8) and 10·8% versus 16·9% at 10 years (gain 6·1%, 2·7–9·4); ratio of stroke incidence rates 0·54, 95% CI 0·43–0·68, p

Background: The unprecedented growth of the elderly population is posing important social and medical problems as management of this population is highly demanding in terms of assistance and care. Consequently, many studies are focusing on the elderly subjects in order to better understand their needs by identifying various environmental, social, psychological, and genetic factors determining the quality of ageing. Objectives: Our aim was to carry out a survey of the elderly Calabrian population in order to highlight the social and medical conditions of this continuously growing population group. Methods: We have been monitoring the elderly population of Calabria for more than 10 years. For the present study, we collected data regarding 853 subjects by using two specific questionnaires, one for the subjects older than 90 years (400 subjects) and one for the subjects aged between 65 and 85 years (453 subjects). Results: The survey allowed us to carry out an extensive description of the ageing Calabrian population regarding the sociodemographic characteristics, living conditions, cognitive functioning, level of independence in activities of daily living, former and current diseases and health disorders. We could notice that males were in a better condition than females. In fact, male subjects turned out to have better physical performance and lower comorbidity, although their life expectancy is lower. Ultranonagenarians had a lower incidence of serious diseases (such as diabetes, osteoporosis and gastric ulcer), but a higher incidence of non-fatal chronic, debilitating conditions (cataract and bronchitis among others). Conclusion: The data we collected and analyzed offer a portrait of elderly Calabrian subjects, on who they are, how they feel, which social and psychological resources they have, and what their health status is. Analysis of the data highlighted that they are characterized by a lower physical performance in comparison to other European populations. Finally, the data presented here may also serve as a valuable source of information to characterize the ageing Calabrian population and improve the care of these subjects.

This paper reconsiders the role of mitochondria in aging and in Parkinson's Disease (PD). The most important risk factor for PD is aging. Alterations in mitochondrial activity are typical of aging. Mitochondrial aging is characterized by decreased oxidative phosphorylation, proteasome activity decrease, altered autophagy, and mitochondrial dysfunction. Beyond declined oxidative phosphorylation, mitochondrial dysfunction consists of a decline of beta-oxidation as well as of the Krebs cycle. Not inherited mitochondrial DNA (mtDNA) mutations are acquired over time and parallel the decrease in oxidative phosphorylation. Many of these mitochondrial alterations are also found in the PD brain specifically in the substantia nigra (SN). mtDNA deletions and development of respiratory chain deficiency in SN neurons of aged individuals as well as of individuals with PD converge towards a shared pathway, which leads to neuronal dysfunction and death. Finally, several nuclear genes that are mutated in hereditary PD are usually implicated in mitochondrial functioning to a various extent and their mutation may cause mitochondrial impairment. In conclusion, a tight link exists between mitochondria, aging, and PD.