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The large, randomized, double-blind, placebo-controlled trial VITAL (Vitamin D and omega 3 trial) recently confirmed that vitamin D and omega-3 polyunsaturated fatty acid (PUFA) co-supplementation (VIDOM) can reduce the incidence of autoimmune diseases. Based on these relevant results, this commentary summarizes the molecular mechanisms behind the anti-inflammatory and immunomodulatory properties of vitamin D and omega-3 PUFAs. We also describe the potential bidirectional interplay between vitamin D metabolism and omega-3 PUFA metabolism that underlies the rationale for VIDOM co-supplementation and that may contribute to enhance the anti-inflammatory and immunomodulatory actions of vitamin D and omega-3 PUFAs when these compounds are administered in combination.

The aim of this study was to assess the impact of glucose control, diabetes-related complications and cardiometabolic risk factors on the risk of diabetic foot ulcers (DFUs) and DFU complications in Albanian adult inpatients with T2D.We conducted a retrospective case-control study on 482 Albanian adult inpatients with T2D. DFU was defined as a full-thickness skin lesion requiring ≥14 days for healing and was classified at the time of hospital admission. Demographic and biochemical parameters of the study participants, the presence of comorbidities and diabetes-related complications at the time of hospital admission were evaluated through a retrospective chart review.Mean age of study participants was 54.8±10.7 years. Participants (284 males and 198 females) were divided into two groups: DFU (cases; n=104) and non-DFU (controls; n=378). Multivariate analysis (performed by a logistic regression model) revealed that the most relevant independent variables associated with DFU were BMI [OR=0.62; p=0.007], HDL-cholesterol [OR=0.00; p0.0001], triglycerides [OR=7.48; p=0.0004], cigarette smoking [OR=26.46; p=0.005], duration of diabetes [OR=1.53; p0.0001], fasting plasma glucose (FPG) [OR=1.06; p0.0001], systolic blood pressure (SBP) [OR=1.13; p=0.0004] and insulin therapy alone [OR=0.11; p=0.02]. ROC curve analysis showed that FPG (AUC=0.83), glycated hemoglobin (HbA1c) (AUC=0.75), triglycerides (AUC=0.78) and HDL-cholesterol (AUC=0.82) were the most reliable biomarkers able to detect DFU. In the DFU group, the most relevant independent variables associated with previous minor lower-extremity amputations (LEAs) were represented by HbA1c [OR=1.47; p=0.03], age55 years [OR=0.12; p=0.05] and female sex [OR=4.18; p=0.03]; whereas the most relevant independent variables associated with diabetic peripheral neuropathy (DPN) were HbA1c [OR=1.70; p=0.006], SBP [OR=1.08; p=0.05], BMI [OR=1.20; p=0.03] and lack of cigarette smoking [OR=0.07; p=0.01]. Correlation analysis (performed through the nonparametric Spearman's rank correlation test or through the parametric Pearson test, as appropriate) revealed a significant positive relationship between HbA1c and FPG (r=0.58; p0.0001), ulcer surface area (r=0.50; p0.0001), ulcer grade (r=0.23; p=0.02), minor LEAs (r=0.20; p=0.04), DPN (r=0.41; p0.0001), and metformin therapy alone (r=0.72; p0.0001). There was a significant inverse correlation between HbA1c and insulin therapy alone (r=-0.31; p=0.01) and combined metformin and insulin therapy (r=-0.60; p0.0001). Both DFU and non-DFU groups exhibited suboptimal mean LDL-cholesterol levels (100 mg/dl) and mean HbA1c values7.5%. Moreover, in DFU group HbA1c values were markedly elevated (≥10%) particularly in patients with a grade 3 ulcer and an ulcer surface area ≥4 cm2, as well as in patients with history of minor LEAs and in patients affected by DPN.The present study suggested that longer duration of diabetes, cigarette smoking, lower HDL-cholesterol levels, poor glucose control, and elevated triglyceride and SBP values may all represent major risk factors for the development of DFU in Albanian patients with T2D. Thus, community interventions and health policies aimed to improve the management of diabetes and related cardiometabolic risk factors should be urgently implemented in Albania, in order to prevent DFUs and other diabetes complications in patients with T2D.

The role of atenolol, a non-vasodilating beta-blocker drug, on long-term mortality in hypertensive older adults is still unclear. The aim of the present study was to evaluate long-term mortality in community-dwelling hypertensive older adults taking atenolol.Long-term mortality after 12-year follow up in isolated hypertensive older adults (n = 972) was analyzed. The patients were stratified in the presence and absence of atenolol use. Systolic, diastolic and pulse arterial pressure were measured.Older adults taking atenolol showed a greater mortality and higher pulse arterial pressure values than those not taking atenolol (73.9% vs 55.0%; P = 0.047 and 74.7 ± 14.1 vs 63.0 ± 14.2 mmHg, P 0.001, respectively). Cox regression analysis showed that atenolol use (hazard risk 1.91; 95% confidence interval 1.04-4.31; P = 0.04) and pulse arterial pressure (hazard risk 1.02; 95% confidence interval 1.01-1.03; P = 0.032) were predictive of long-term mortality.Atenolol use was related to increased mortality in community-dwelling hypertensive Older adults. This increase in mortality risk seems to be related to an increase of pulse arterial pressure.

The growing demand of personalized medicine marked the transition from an empirical medicine to a molecular one, aimed at predicting safer and more effective medical treatment for every patient, while minimizing adverse effects. This passage has emphasized the importance of biomarker discovery studies, and has led sample availability to assume a crucial role in biomedical research. Accordingly, a great interest in Biological Bank science has grown concomitantly. In biobanks, biological material and its accompanying data are collected, handled and stored in accordance with standard operating procedures (SOPs) and existing legislation. Sample quality is ensured by adherence to SOPs and sample whole life-cycle can be recorded by innovative tracking systems employing information technology (IT) tools for monitoring storage conditions and characterization of vast amount of data. All the above will ensure proper sample exchangeability among research facilities and will represent the starting point of all future personalized medicine-based clinical trials.

Despite recent advances in pharmacological treatment, chronic heart failure (CHF) is highly prevalent in older adults, with an incidence greater than 20% in individuals aged 80 and older.1 CHF is frequently unstable, and several precipitating factors may lead to decompensation, 2 but data on possible differences in such triggers between younger and older adults with CHF are sparse. Thus, the aim of this study was to prospectively determine whether precipitants of decompensated CHF are different in younger and older adults.

Treatment of chronic heart failure (CHF) is strongly focused on evidence-based medicine. However, large trials are often far away from the "real world" of geriatric patients and their messages are poorly transferable to the clinical management of CHF elderly patients. Precipitating factors and especially non-cardiac comorbility may decompensate CHF in the elderly. More importantly, drugs of first choice, such as Angiotensin Converting Enzyme inhibitors and β-blockers, are still underused and effective drugs on diastolic dysfunction are not available. Poor adherence to therapy, especially due to cognitive disorders and depression, worsens the management. Electrical therapy is indicated, but attention to the older age groups with reduced life expectancy has to be paid. Physical exercise, stem cells, gene therapy and new devices are encouraging, but definitive results are not available yet. Palliative care plays a key role in the end-stage of the disease. Follow-up of CHF elderly patient is very important but tele-medicine is the future. Finally, self-care management, caregiver training and multidimensional team represent the critical point of the treatment of CHF elderly patients.

Background Chronic heart failure (CHF) is characterized by a high mortality in the elderly. Moreover, depression status is also related to poor prognosis in advancing age. Thus, we sought to determine whether depressive status predicts long-term mortality in subject with or without CHF. Methods and results Long-term mortality after 12-year follow-up in 125 elderly subjects with CHF and 1143 elderly subjects without CHF was studied. Depression was evaluated using the Geriatric Depression Scale (GDS), and all subjects were stratified in tertiles according to GDS score (0–10, 11–20 and 21–30). With increasing GDS score, long-term mortality at the end of follow-up increased from 43Æ4% to 72Æ0% in subjects without (P < 0Æ001) and from 52Æ6% to 83Æ9% in subjects with (P < 0Æ007) CHF. In multivariate analysis, GDS appeared to be predictive of long-term mortality in the absence (Hazard ratio = 1Æ01; confidence interval 95% 1Æ00–1Æ05; P = 0Æ04) and, even more, in the presence of CHF (Hazard ratio = 1Æ08; confidence interval 95% 1Æ01–1Æ15; P < 0Æ01). Conclusions Depression symptoms predict long-term mortality in elderly subjects without and, even more, with CHF. Thus, depression can be considered a strong predictor of death in CHF elderly subjects.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the digestive tract characterized, in the majority of cases, by activating mutations in the KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) genes. Mutations affecting these tyrosine kinase receptors are also responsible for the mechanisms of primary and secondary drug resistance during the treatment with tyrosine kinase inhibitors. We performed mutational analysis to evaluate the pharmacotherapy susceptibility of GISTs, adopting a comprehensive procedural approach, in order to optimize the identification of mutations that may result in cellular resistance to conventional therapy.DNA from paraffin-embedded tumor sections from 40 GISTs were analyzed using microdissection, direct sequencing analysis and allelic separation by cloning.KIT mutations were found in 55.0% of the tumor samples. PDGFRA mutations were present in 5.0% of cases. Allelic cloning assay allowed for better definition of the extent of the mutations and clarification of the exact nucleotidic position of complex mutations.Our experience suggests that sequential microdissection, direct sequencing and allelic separation by PCR cloning of large variants may improve the approach to mutational analysis and interpretation of sequence data of KIT and PDGFRA in patients with GIST.

International audience; Cell-based therapies for global cerebral ischemia represent promising approaches for neuronal damage prevention and tissue repair promotion. We examined the potential of marrow-isolated adult multilineage-inducible (MIAMI) cells, a homogeneous subpopulation of immature human mesenchymal stromal cell, injected into the hippocampus to prevent neuronal damage induced by global ischemia using rat organotypic hippocampal slices exposed to oxygen-glucose deprivation and rats subjected to asphyxial cardiac arrest. We next examined the value of combining fibronectin-coated biomimetic microcarriers (FN-BMMs) with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) pre-treated MIAMI compared to EGF/bFGF pre-treated MIAMI cells alone, for their in vitro and in vivo neuroprotective capacity. Naive and EGF/bFGF pre-treated MIAMI cells significantly protected the Cornu Ammonis layer 1 (CA1) against ischemic death in hippocampal slices and increased CA1 survival in rats. MIAMI cells therapeutic value was significantly increased when delivering the cells complexed with FN-BMMs, probably by increasing stem cell survival and paracrine secretion of pro-survival and/or anti-inflammatory molecules as concluded from survival, differentiation and gene expression analysis. Four days after oxygen and glucose deprivation and asphyxial cardiac arrest, few transplanted cells administered alone survived in the brain whereas stem cell survival improved when injected complexed with FN-BMMs. Interestingly, a large fraction of the transplanted cells administered alone or in complexes expressed betaIII-tubulin suggesting that partial neuronal transdifferentiation may be a contributing factor to the neuroprotective mechanism of MIAMI cells.