Emostasi nei pazienti diabetici e uremici: Impatto del trapianto di rene e pancreas

Background and aims. To evaluate the effects of kidney or kidney-pancreas transplantation on platelet and haemostatic abnormalities in uremic type 1 diabetic patients, we conducted a cross-sectional study involving 12 type 1 diabetic patients (T1DM), 30 uremic type 1 diabetic patients (U-T1DM), 27 uremic type 1 diabetic kidney-pancreas transplanted patients (KP), 12 uremic type 1 diabetic kidney-alone transplanted patients (KD), 13 healthy controls (C). Method and result. We evaluated platelet and function, including intracellular calcium level, and clotting system. Resting calcium level were significantly higher in U-T1DM and KD group than KP/C groups (U-T1DM = 137.6 \ub1 11.2, KD = 133.3 \ub1 16.6, T1DM = 60.9 \ub1 7.7, KP = 97.2 \ub1 9.2, C = 72.0 \ub1 11.0 nM, p < 0.01). CD41 expression was significantly reduced in platelet from U-T1DM group compared to the other groups (U-T1DM = 53.2 \ub1 7.7%, KP = 75.7 \ub1 6.2%, KD = 80.4 \ub1 4.3%, C = 81.6 \ub1 2.2%, T1DM = 82.6 \ub1 3.4%, p < 0.05). Diabetic patients showed higher levels of thrombin platelet expression than non diabetic patients. Levels of hypercoagulability markers in the KP group, and to a lesser extent KD group but not the U-T1DM group, were similar to those of the C group. A reduction in the natural anticoagulants was evident in U-T1DM group, while near-normal values were observed in KP and KD groups. Conclusions. Haemostatic abnormalities were not observed in KP patients, but were present in KD patients and in U-T1DM patients. This could contribute to the lower cardiovascular mortality observed in KP patient compared to KD and U-T1DM patients

TIM4 regulates the anti-islet Th2 alloimmune response

The role of the novel costimulatory molecule TIM4 in anti-islet response is unknown. We explored TIM4 expression and targeting in Th1 (BALB/c islets into C57BL/6 mice) and Th2 (BALB/c islets into Tbet-/- C57BL/6 mice) models of anti-islet alloimmune response and in a model of anti-islet autoimmune response (diabetes onset in NOD mice). The targeting of TIM4, using the monoclonal antibody RMT4-53, promotes islet graft survival in a Th1 model, with 30% of the graft surviving in the long term; islet graft protection appears to be mediated by a Th1 to Th2 skewing of the immune response. Differently, in the Th2 model, TIM4 targeting precipitates graft rejection by further enhancing the Th2 response. The effect of anti-TIM4 treatment in preventing autoimmune diabetes was marginal with only minor Th1 to Th2 skewing. B-Cell depletion abolished the effect of TIM4 targeting. TIM4 is expressed on human B-cells and is upregulated in diabetic and islettransplanted patients. Our data suggest a model in which TIM4 targeting promotes Th2 response over Th1 via B-cells. The targeting of TIM4 could become a component of an immunoregulatory protocol in clinical islet transplantation, aiming at redirecting the immune system toward a Th2 response

A Classification of Hyper-heuristics Approaches

Abstract The current state of the art in hyper-heuristic research comprises a set of approaches that share the common goal of automating the design and adaptation of heuristic methods to solve hard computational search problems. The main goal is to produce more generally applicable search methodologies. In this chapter we present and overview of previous categorisations of hyper-heuristics and provide a unified classification and definition which captures the work that is being undertaken in this field. We distinguish between two main hyper-heuristic categories: heuristic selection and heuristic generation. Some representative examples of each category are discussed in detail. Our goal is to both clarify the main features of existing techniques and to suggest new directions for hyper-heuristic research.

Physical activity and amyotrophic lateral sclerosis : a European population-based case-control study

Objective To assess whether physical activity is a risk factor for amyotrophic lateral sclerosis (ALS). Methods From February 2008 to April 2012, 652 patients with ALS from European population-based registries (France, Ireland, Italy, United Kingdom, Serbia) and 1,166 population controls (matched for age, sex, and residency) were assessed. Upon direct interview, data were collected on occupation and history of sport and leisure activities, physical activity, and accidental injuries. Physical exercise was defined as having spent time doing activities that caused an individual to breath hard at least once per month and was coded as none, job-related, and/or sport-related. Sport-related and work-related physical exercise were quantified using metabolic equivalents (METs). Risks were calculated using conditional logistic regression models (adjusting for age, country, trauma, and job-related physical activity) and expressed as odds ratios (ORs) and adjusted ORs (Adj ORs) with 95% confidence intervals (CIs). Results Overall physical activity was associated with reduced odds of having ALS (Adj OR = 0.65, 95% CI = 0.48-0.89) as were work-related physical activity (Adj OR = 0.56, 95% CI = 0.36-0.87) and organized sports (Adj OR = 0.49, 95% CI = 0.32-0.75). An inverse correlation was observed between ALS, the duration of physical activity (p = 0.0041), and the cumulative MET scores, which became significant for the highest exposure (Adj OR = 0.34, 95% CI = 0.21-0.54). An inverse correlation between ALS and sport was found in women but not in men, and in subjects with repeated traumatic events. Interpretation Physical activity is not a risk factor for ALS and may eventually be protective against the disease

Performance of PSI, CURB-65, and SCAP scores in predicting the outcome of patients with community-acquired and healthcare-associated pneumonia

The objective was to compare three score systems, pneumonia severity index (PSI), the Confusion-Urea-Respiratory Rate-Blood pressure-65 (CURB-65), and severe community-acquired pneumonia (SCAP), for prediction of the outcomes in a cohort of patients with community-acquired (CAP) and healthcare-associated pneumonia (HCAP). Large multi-center, prospective, observational study was conducted in 55 hospitals. HCAP patients were included in the high classes of CURB-65, PSI and SCAP scores have a mortality rate higher than that of CAP patients. HCAP patients included in the low class of the three severity rules have a significantly higher incidence of adverse events, including development of septic shock, transfer into an ICU, and death (p < 0.01). At multivariate Cox regression analysis, inclusion in the severe classes of PSI, CURB-65, or SCAP scores and receipt of an empirical therapy not adherent to international guidelines prove to be risk factors independently associated with poor outcome. PSI, CURB-65, and SCAP score have a good performance in patients with CAP but are less useful in patients with HCAP, especially in patients classified in the low-risk classes

Gout, allopurinol intake and clinical outcomes in the hospitalized multimorbid elderly.

Increased serum uric acid has been considered a cardiovascular risk factor but no study has assessed its relation with hospital mortality or length of stay. On the basis of data obtained from a prospective registry, the prevalence of gout/hyperuricemia and its association with these and other clinical parameters was evaluated in an Italian cohort of elderly patients acutely admitted to internal medicine or geriatric wards