Comparison of Reverse Triage with National Early Warning Score, Sequential Organ Failure Assessment and Charlson Comorbidity Index to classify medical inpatients of an Italian II level hospital according to their resource's need.

Resource allocation in our overcrowded hospitals would require classification of inpatients according to the severity of illness, the evolving risk and the clinical complexity. Reverse triage (RT) is a method used in disasters to identify inpatients according to their use of hospital resources. The aim of this observational prospective study is to evaluate the use of RT in medical inpatients of an Italian Hospital and to compare the RT score with National Early Warning Score, Sequential Organ Failure Assessment and Charlson Comorbidity Index. Cluster sampling was performed on high dependency unit (HDU), geriatrics (Ger) and internal medicine (IM) wards. We calculate RT, NEWS, SOFA and CCI from inpatient charts. Length of stay (LOS), transfer to a higher level of care, death and discharge date were collected after 30 days. We obtained demographics, comorbidities, severity and clinical complexity of 260 inpatients. We highlighted differences in NEWS, SOFA and CCI in the three divisions. On the contrary RT score was uniformly high (median 7), with 85% of patients with RT = 8. NEWS, SOFA and CCI were higher in patients with higher RT score. We used the sum of the interventions listed by RT (RT sum) as a proxy of the level of care needed. RT-sum showed moderate correlation with NEWS (r = 0.52 Spearman, p < 0.001). RT-sum was the highest in HDU, related to the evolving severity of HDU patients. Ger patients that showed the highest CCI score (with all patients in the CCI ≥ 3 category) had the second highest RT-sum. RT score showed similar values in the majority of the inpatients regardless of differences in NEWS, SOFA and CCI in different ward subgroups. RT-sum is related both to evolving severity (NEWS) and to clinical complexity (CCI). RT and NEWS could predict inpatient level of care and resource need associated with CCI.

Inpatient disposition in overcrowded hospitals: is it safe and effective to use reverse triage and readmission screening tools for appropriate discharge? An observational prospective study of an Italian II level hospital.

BACKGROUND: Reverse triage (RT) identifies patients eligible for discharge and have been proposed to cope with daily surge. Nevertheless, early discharge could increase the rate of readmission. Our aim is to test the effectiveness and safety of RT alone and with readmission screening tools (Identification Senior At Risk [ISAR], HOSPITAL, and Groeningen Frailty Index [GFI] scores) to predict appropriate discharge. MATERIAL AND METHODS: We prospectively assessed every 4 days (t0 ) inpatients of medical divisions (High Dependency Unit (HDU), Internal Medicine (IM), and Geriatrics (Ger)) of an Italian Hospital. RT score was calculated for each patient and an RT ≤3 identified those eligible for safe discharge. ISAR, HOSPITAL, and GFI were then applied. We assessed reinstituting of interventions and transferring to an increased level of care unit at 4 days as an ethical proxy of consequential medical events following hypothetical discharge. Date of effective discharge, death, and readmission were measured at 4, 7, 15, and 30 days after the first evaluation. RESULTS: Twenty-five (9.6%) out of 260 patients in our sample had an RT ≤3. Twenty-four (96%) of them compared with 205 (87%) of the RT >3 group (P = NS) were discharged. Patients with RT ≤3 were discharged significantly earlier (3.5 vs 8 days after t0 [P = 0.0002]). In the RT ≤3 group, all but one patient were alive and healthy at 7, 15, and 30 days. The HOSPITAL score seemed to have the best concordance with RT (84%), in comparison with the ISAR (52%) and the GFI (48%) scores. RT showed a low sensitivity (22%) and high specificity (95%), which was even higher when using RT associated with readmission screening tools. CONCLUSIONS: Reverse triage proved to be a safe and conservative tool, with high specificity alone and with readmission screening tools. RT correctly identifies patients that will be discharged earlier.

Changes in brain oxysterols at different stages of Alzheimer's disease: Their involvement in neuroinflammation.

Alzheimer's disease (AD) is a gradually debilitating disease that leads to dementia. The molecular mechanisms underlying AD are still not clear, and at present no reliable biomarkers are available for the early diagnosis. In the last several years, together with oxidative stress and neuroinflammation, altered cholesterol metabolism in the brain has become increasingly implicated in AD progression. A significant body of evidence indicates that oxidized cholesterol, in the form of oxysterols, is one of the main triggers of AD. The oxysterols potentially most closely involved in the pathogenesis of AD are 24-hydroxycholesterol and 27-hydroxycholesterol, respectively deriving from cholesterol oxidation by the enzymes CYP46A1 and CYP27A1. However, the possible involvement of oxysterols resulting from cholesterol autooxidation, including 7-ketocholesterol and 7ß-hydroxycholesterol, is now emerging. In a systematic analysis of oxysterols in post-mortem human AD brains, classified by the Braak staging system of neurofibrillary pathology, alongside the two oxysterols of enzymatic origin, a variety of oxysterols deriving from cholesterol autoxidation were identified; these included 7-ketocholesterol, 7α-hydroxycholesterol, 4ß-hydroxycholesterol, 5α,6α-epoxycholesterol, and 5ß,6ß-epoxycholesterol. Their levels were quantified and compared across the disease stages. Some inflammatory mediators, and the proteolytic enzyme matrix metalloprotease-9, were also found to be enhanced in the brains, depending on disease progression. This highlights the pathogenic association between the trends of inflammatory molecules and oxysterol levels during the evolution of AD. Conversely, sirtuin 1, an enzyme that regulates several pathways involved in the anti-inflammatory response, was reduced markedly with the progression of AD, supporting the hypothesis that the loss of sirtuin 1 might play a key role in AD. Taken together, these results strongly support the association between changes in oxysterol levels and AD progression.

Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study.

BACKGROUND: The studio di intervento nel decadimento vascolare lieve (IDEALE study) was an open multicenter Italian study, the aim of which was to assess the effectiveness and safety of oral citicoline in elderly people with mild vascular cognitive impairment. METHODS: The study was performed in 349 patients. The active or citicoline group was composed of 265 patients and included 122 men and 143 women of mean age 79.9 ± 7.8 years selected from six Italian regions. Inclusion criteria were age ≥ 65 years, Mini-Mental State Examination (MMSE) score ≥ 21, subjective memory complaints but no evidence of deficits on MMSE, and evidence of vascular lesions on neuroradiology. Those with probable Alzheimer's disease were excluded. The control group consisted of 84 patients, including 36 men and 48 women of mean age 78.9 ± 7.01 (range 67-90) years. Patients included in the study underwent brain computed tomography or magnetic resonance imaging, and plasma dosage of vitamin B12, folate, and thyroid hormones. Functional dependence was investigated by scores on the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales, mood was assessed by the Geriatric Depression Scale (GDS), and behavioral disorders using the Neuropsychiatric Inventory scale. Comorbidity was assessed using the Cumulative Illness Rating Scale. An assessment was made at baseline (T0), after 3 months (T1), and after 9 months (T2, ie, 6 months after T1). The main outcomes were an improvement in MMSE, ADL, and IADL scores in the study group compared with the control group. Side effects were also investigated. The study group was administered oral citicoline 500 mg twice a day throughout the study. RESULTS: MMSE scores remained unchanged over time (22.4 ± 4 at T0; 22.7 ± 4 at T1; 22.9 ± 4 at T2), whereas a significant difference was found between the study and control groups, both in T1 and in T2. No differences were found in ADL and IADL scores between the two groups. A slight but not statistically significant difference was found in GDS score between the study and control groups (P = 0.06). No adverse events were recorded. CONCLUSION: In this study, citicoline was effective and well tolerated in patients with mild vascular cognitive impairment. Citicoline activates biosynthesis of phospholipids in neuronal membranes, increases brain metabolism as well as norepinephrine and dopamine levels in the central nervous system, and has neuroprotective effects during hypoxia and ischemia. Therefore, citicoline may be recommended for patients with mild vascular cognitive impairment.

Neuroendocrine immunity in patients with Alzheimer's disease: toward translational epigenetics.

The emerging domain of epigenetics in molecular medicine finds application for a variety of patient populations. Here, we present fundamental neuroendocrine immune evidence obtained in patients with senile dementia of the Alzheimer's type (sDAT), and discuss the implications of these data from the viewpoint of translational epigenetics of Alzheimer's disease. We followed 18 subjects with mild sDAT treated with acetylcholinesterase inhibitors, and 10 control subjects matched for age in a repeated measure design every six months for 18 months. We monitored psychosocial profile (Mini-Mental State Examination, Functional Assessment Staging, Independence in Activities of Daily Living, Depression, Profile of Moods States) in parallel to immunophenotypic parameters of T cell subpopulations by flow cytometry. Based on change in the mini-mental state score at entry and at 18 months, patients with sDAT were assigned to a "fast progression" (delta greater than 2 points) or to a "slow progression" group (delta less than or equal to 2 points). The change in circulating activated T cells (CD3+Dr+) with time in patients with sDAT was significantly inversely correlated with the change in time in natural killer (NK) cytotoxic activity to cortisol modulation in these patients, which was greater in patients with fast progression, compared to slow progression sDAT. These data indicate underlying neuroendocrine immune processes during progression of sDAT. Our observations suggest that psychoimmune measures such as those we have monitored in this study provide relevant information about the evolving physiological modulation in patients with sDAT during progression of Alzheimer's disease, and point to new or improved translational epigenetic treatment interventions.

Aluminium blunts the proliferative response and increases apoptosis of cultured human cells: putative relationship to Alzheimer's disease.

Aluminium (Al) has been investigated as a neurotoxic substance. Al ranks among the potential environmental risk factors for Alzheimer's disease (AD). Epidemiological studies tested the relationship between Al in drinking water and AD, showing a significant correlation between elevated levels of monomeric Al in water and AD, although data to date remain inconclusive with respect to total Al. The aim of this study was to test whether or not Al exacerbates cellular toxicity mediated by the amyloid beta (Abeta) peptide. We evaluated the role of Al in modulating programmed cell death (apoptosis) in human cell cultures. We used the osteosarcoma cell line monolayer (SaOs-2) to demonstrate that treatment of SaOs-2 cultures with the Abeta peptide mid-fragment (25 to 35) at nano M, followed by co-incubation with physiological concentrations of aluminium chloride, which release monomeric Al in solution, led to marked expression of caspase 3, but not caspase 9, key markers of the apoptotic process. The same experimental conditions were shown to blunt significantly the proliferative response of normal human peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA) stimulation. Our observations support the hypothesis that Al significantly impairs certain cellular immune responses, and confirm that Al-mediated cell toxicity may play an important role in AD.

Physiologic modulation of natural killer cell activity as an index of Alzheimer's disease progression.

Patients with Alzheimer's disease (AD) are characterized by an altered sensitivity to cortisol-mediated modulation of circulating lymphocytes. Longitudinal studies are needed to address the clinical applicability of these abnormalities as prognostic factors. Therefore, we designed a longitudinal study to address the clinical applicability of physiologic modulation of Natural Killer (NK) cell activity as a prognostic factor in AD. NK activity was assessed as baseline measurement and in response to modulation by cortisol at 10(-6)M. To verify the immunophysiological integrity of the NK cell population, we tested augmentation of NK cytotoxicity by human recombinant interleukin (IL)-2 (100 IU/ml) as control. The response to modulation by cortisol or by IL-2 was significantly greater in patients with AD. Based on change in the Mini-Mental State score at entry and at 18 months, patients with AD could be assigned to a "fast progression" (Delta > 2 points) or to a "slow progression" group (Delta