OBJECTIVES: To identify prognostic factors that are independently predictive of in‐hospital mortality in older patients hospitalized in a medical intensive care unit (MICU). DESIGN: Prospective cohort study. SETTING: A MICU in an Italian university hospital. PARTICIPANTS: Patients aged 65 and older consecutively admitted to the MICU directly from the first‐aid unit. MEASUREMENTS: Upon admission, the following variables were examined: demographics, clinical history (diabetes mellitus, active neoplasm, cognitive impairment, immobilization, pressure ulcers, use of nutritional support, home oxygen therapy), physiopathology (Acute Physiology and Chronic Health Evaluation (APACHE) II), and cognition/function (activity of daily living (ADL), instrumental activity of daily living (IADL), Short Portable Mental Status Questionnaire (SPMSQ)). The vital status of the patient at the end of hospitalization was recorded. RESULTS: Over a period of 10 months, 659 patients were recruited (mean age ± standard deviation = 76.6 ± 7.5; 352 men and 307 women). There were 97 deaths (14.71%). The following factors proved to be significantly associated with in‐hospital mortality: old age, low body mass index (BMI) values, low values of albumin, high scores on APACHE II, functional impairment (ADL, IADL), cognitive impairment (SPMSQ), history of cognitive deterioration, history of confinement to bed, and presence of pressure ulcers. Using multivariate analysis, the following variables were independently predictive of in‐hospital mortality: lack of independence in ADLs (P < .001), moderate‐to‐severe cognitive impairment on SPMSQ (P < .001), score on APACHE II (P = .002), and low BMI values (P = .031). CONCLUSION: The prognosis of older patients hospitalized in medical intensive care units depends not only on the acute physiological impairments, but also on a series of preexisting conditions, such as loss of functional independence, severe and moderate cognitive impairment, and low BMI.

No abstract

Polyunsaturated fatty acids (n-3 PUFAs) are long-chain polyunsaturated fatty acids with 18, 20 or 22 carbon atoms, which have been found able to counteract cardiovascular diseases. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in particular, have been found to produce both vaso- and cardio-protective response via modulation of membrane phospholipids thereby improving cardiac mitochondrial functions and energy production. However, antioxidant properties of n-3 PUFAs, along with their anti-inflammatory effect in both blood vessels and cardiac cells, seem to exert beneficial effects in cardiovascular impairment. In fact, dietary supplementation with n-3 PUFAs has been demonstrated to reduce oxidative stress-related mitochondrial dysfunction and endothelial cell apoptosis, an effect occurring via an increased activity of endogenous antioxidant enzymes. On the other hand, n-3 PUFAs have been shown to counteract the release of pro-inflammatory cytokines in both vascular tissues and in the myocardium, thereby restoring vascular reactivity and myocardial performance. Here we summarize the molecular mechanisms underlying the anti-oxidant and anti-inflammatory effect of n-3 PUFAs in vascular and cardiac tissues and their implication in the prevention and treatment of cardiovascular disease.

No abstract

The Assessment Battery for Communication (ABaCo) was introduced to evaluate pragmatic abilities in patients with cerebral lesions. In the present study we present normative data for individuals aged 15-75 (N = 300). The sample was stratified by age, sex and years of education, according to ISTAT (Italian National Institute of Statistics) indications in order to be representative of the general national population. As performance on the ABaCo decreases with age and lower years of education, the norms were stratified for both age and education.The ABaCo is a valuable tool in clinical practice; the normative data provided here will enable clinicians to determine different kinds and specific levels of communicative impairments more precisely. The assessment of pragmatic abilities emerged as a central issue in the evaluation of patients with communicative impairments and related disorders in the early 1980s (e.g., Prutting, 1982), and the influence of pragmatic variables in treatment plans and goals has been more fully appreciated in the last 30 years. Pragmatic ability refers to a wide range of communicative behaviors concerning the way language is used in context to convey meanings (Adams, 2002;Bates, 1976; Kempson, 1975), and in the population of individuals with cerebral lesions, numerous patients have been found to have difficulties that lie principally with pragmatics. Patients typically show poor turn-taking skills and difficulty with topic maintenance, have problems understanding discourse and non-literal meanings, and may find it difficult to interpret subtle meanings or idiomatic statements and make knowledge-based inferences in social scripts (e.g., Dennis & Barnes, 1990; Friedland & Miller, 1998; McDonald, 1993). Moreover, people with brain injury often demonstrate normal basic linguistic skills, but have difficulty adapting their communication to specific ABACO -NORMATIVE DATA 4 contexts (e.g., different social situations or different communicative partners) and managing complex pragmatic phenomena, such as irony and deceit (Angeleri et al., 2008;Bara, Tirassa, & Zettin, 1997; Cutica, Bucciarelli, & Bara, 2006). The recognition of pragmatic components as a crucial feature in rehabilitation programs thus led to the need to deal with the pervasiveness of these communicative disorders and the consequent social isolation suffered by brain-injured individuals. Importantly, in a two-year follow-up study, Snow, Douglas, and Ponsford (1998) showed that pragmatic disorders do not spontaneously improve over time, providing evidence that communicative difficulties do not resolve as a consequence of recovery over time or speech-language input. These findings suggest that careful efforts should be made to identify and manage pragmatic disorders early on following brain injury. Finally, normative data offer the opportunity to operationalize pragmatic functioning within a normal range, and obtain a precise evaluation of domains of impairment, a crucial step in planning clinical pathways of recovery. ABaCo -As...

The maintenance of physiological levels of nitric oxide (NO) produced by eNOS represents a key element for vascular endothelial homeostasis. On the other hand, NO overproduction, due to the activation of iNOS under different stress conditions, leads to endothelial dysfunction and, in the late stages, to the development of atherosclerosis. Oxidized LDLs (oxLDLs) represent the major candidates to trigger biomolecular processes accompanying endothelial dysfunction and vascular inflammation leading to atherosclerosis, though the pathophysiological mechanism still remains to be elucidated. Here, we summarize recent evidence suggesting that oxLDLs produce significant impairment in the modulation of the eNOS/iNOS machinery, downregulating eNOS via the HMGB1-TLR4-Caveolin-1 pathway. On the other hand, increased oxLDLs lead to sustained activation of the scavenger receptor LOX-1 and, subsequently, to NFkB activation, which, in turn, increases iNOS, leading to EC oxidative stress. Finally, these events are associated with reduced protective autophagic response and accelerated apoptotic EC death, which activates atherosclerotic development. Taken together, this information sheds new light on the pathophysiological mechanisms of oxLDL-related impairment of EC functionality and opens new perspectives in atherothrombosis prevention.

No abstract

Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).