27 research outputs found
Transcranial direct current stimulation of the mouse prefrontal cortex modulates serotonergic neural activity of the dorsal raphe nucleus
No full text[no abstract available
Allosteric sodium binding cavity in GPR3: a novel player in modulation of Aβ production
No full textThe orphan G-protein coupled receptor 3 (GPR3) belongs to class A G-protein coupled receptors (GPCRs) and is highly expressed in central nervous system neurons. Among other functions, it is likely associated with neuron differentiation and maturation. Recently, GPR3 has also been linked to the production of Aβ peptides in neurons. Unfortunately, the lack of experimental structural information for this receptor hampers a deep characterization of its function. Here, using an in-silico and in-vitro combined approach, we describe, for the first time, structural characteristics of GPR3 receptor underlying its function: the agonist binding site and the allosteric sodium binding cavity. We identified and validated by alanine-scanning mutagenesis the role of three functionally relevant residues: Cys2676.55, Phe1203.36 and Asp2.50. The latter, when mutated into alanine, completely abolished the constitutive and agonist-stimulated adenylate cyclase activity of GPR3 receptor by disrupting its sodium binding cavity. Interestingly, this is correlated with a decrease in Aβ production in a model cell line. Taken together, these results suggest an important role of the allosteric sodium binding site for GPR3 activity and open a possible avenue for the modulation of Aβ production in the Alzheimer's Disease
When is myocarditis indeed the cause of death?
No full textAttribution of death to myocarditis continues to be a controversial issue in forensic pathology, despite the existence of established histopathological criteria as well as complementary investigations. The aim of the study was two-fold: (a) to retrospectively analyse the data obtained from a series of clinical and forensic autopsies in order to assess the number of cases with death attributed to myocarditis, and (b) to reevaluate these cases in order to assess how properly the histopathological diagnosis of myocarditis conformed to established criteria and therefore how accurately these were used on the basis of all postmortem investigation findings to conclude the cause of death. 2474 clinical and forensic autopsies were taken into consideration. Myocarditis was recorded as the official, underlying cause of death in 48 cases. Of those, 8 cases were considered to accurately conform to the histopathological Dallas criteria for the presence of myocarditis and could therefore be classified as cases of fatal myocarditis. In 19 out of 48 cases, description of focal myocarditis was considered to accurately fulfill the histopathological Dallas criteria for the presence of myocarditis. However, data provided by histological analysis and virology testing result reevaluation allowed alternative causes of death to be speculated. In another 21 out of 48 cases, description of focal myocardial inflammation was considered to inaccurately meet the histopathological Dallas criteria for the presence of myocarditis. The findings of our own study appear to be in agreement with previous observations in similar study groups and highlight that since myocarditis may occur in association with many diseases, a great deal of evidence is required before settling on categorical conclusions
Intensivists Performed Percutaneous Bicaval Double-Lumen Echo-Guided Extracorporeal Membrane Oxygenation Cannulation at Bedside in Newborns and Children: A Retrospective Analysis
No full textLetter to the editor regarding A. Bonsignore, C. Palmiere, F. Buffelli, E. Maselli, A. Marzullo, G. Fraternali Orcioni, F. Ventura, F. de Stefano, A. Dell’Erba. When is myocarditis indeed the cause of death? Forensic Sci. Int. 285 (2018) 72–76
No full textRelation between drug therapy-based comorbidity indices, Charlson's comorbidity index, polypharmacy and mortality in three samples of older adults
No full textBackground: Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available.
Aims: This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy.
Methods: Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE).
Results: Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings.
Conclusion: On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality
Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both
No full textBackground and objective
Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF.
Methods
We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death.
Results
We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009).
Conclusion
In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population
The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes
No full text(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes
Prescription appropriateness of anticoagulant drugs for prophylaxis of venous thromboembolism in hospitalized multimorbid older patients
No full textThe aims were to assess: the prescription prevalence of anticoagulant drugs for thromboprophylaxis (TP) in hospitalized older patients; the appropriateness of their prescription or non-prescription; the in-hospital mortality in appropriately versus non-appropriately prescribed or not prescribed patients. 4836 patients aged 65 or older, admitted to the Italian internal medicine and geriatric wards participating to the REPOSI register from 2012 to 2019 were assessed for prescription of anticoagulant drugs for TP at admission and/or during hospital stay. The Padua Prediction Score (PPS) and the IMPROVE score were used to assess the thrombotic and bleeding risk. Patients were considered to be appropriately prescribed when had PPS ≥ 4 and IMPROVE < 7, and appropriately not prescribed when PPS < 4. Logistic regression model was used to assess whether appropriateness was associated with in-hospital mortality. Among 4836 patients included, anticoagulants were prescribed for TP in 1233 (25.5%). In all, 4461 patients were assessable for appropriateness: 3136 (70.3%) were appropriately prescribed or non-prescribed according to their thrombotic and bleeding risk. Among 1138 patients receiving prophylaxis, only 360 (31.7%) were appropriately prescribed, while among 3323 non-prescribed patients, 2776 (83.5%) were appropriately non-prescribed. The in-hospital mortality rate was lower in patients appropriately prescribed or non-prescribed than in those inappropriately prescribed or non-prescribed (OR: 0.63; 95% CI: 0.46-0.83). In conclusion, a high prevalence of multimorbid hospitalized patients were appropriately prescribed or non-prescribed for TP with anticoagulants, appropriate non-prescription being mainly driven by a high bleeding risk. The appropriateness of prescription or non-prescription was associated with lower in-hospital mortality
Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes
No full textObjective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription
