Variability in Alzheimer's disease mortality from European vital statistics, 2012-2020.

OBJECTIVE: Data regarding the trends in Alzheimer's disease (AD) mortality in the modern European Union (EU-27) member states are lacking. We assess the sex- and age-specific trends in AD mortality in the EU-27 member states between years 2012 and 2020. METHODS: Data on cause-specific deaths and population numbers by sex for each country of the EU-27 were retrieved through publicly available European Statistical Office (EUROSTAT) dataset from 2012 to 2020. AD-related deaths were ascertained when the ICD-10 code G30 was listed as the primary cause of death in the medical death certificate. To calculate annual trends, we assessed the average annual percent change (AAPC) with relative 95% confidence intervals (CIs) using Joinpoint regression. RESULTS: During the study period, 751,493 deaths (1.7%, 233,271 males and 518,222 females) occurred in the EU-27 because of AD. Trends in the proportion of AD-related deaths per 1000 total deaths slightly increased from 16.8% to 17.5% (p for trend <0.001). The age-adjusted mortality rate was higher in women over the entire study period. Joinpoint regression analysis revealed a stagnation in age-adjusted AD-related mortality from 2012 to 2020 among EU-27 Member States (AAMR: -0.1% [95% CI: -1.8-1.79], p = 0.94). Stratification by Country showed relevant regional disparities, especially in the Northern and Eastern EU-27 member states. CONCLUSIONS: Over the last decade, the age-adjusted AD-related mortality rate has plateaued in EU-27. Important disparities still exist between Western and Eastern European countries.

Neutrophil-Lymphocytes Ratio as Potential Early Marker for Alzheimer's Disease.

Background: Neutrophil-lymphocyte ratio (NLR) is a noninvasive, inexpensive, and easily applicable marker of inflammation. Since immune dysregulation leading to inflammation is regarded as a hallmark of dementia, in particular Alzheimer's disease (AD), we decided to investigate the potentials of NLR as a diagnostic and predictive biomarker in this clinical setting. Materials and Methods: NLR was measured in the blood of patients with AD (n = 103), amnestic type mild cognitive impairment (aMCI, n = 212), vascular dementia (VAD, n = 34), and cognitively healthy Controls (n = 61). One hundred twelve MCI patients underwent a regular clinical follow-up. Over a 36-months median follow-up, 80 remained stable, while 32 progressed to overt dementia. Results: NLR was higher in patients with aMCI or dementia compared to Controls; however, the difference was statistically significant only for aMCI (+13%, p=0.04) and AD (+20%, p=0.03). These results were confirmed by multivariate logistic analysis, which showed that high NLR was associated with an increase in the likelihood of receiving a diagnosis of aMCI (odd ratio (OR): 2.58, 95% confidence interval (CI): 1.36-4.89) or AD (OR: 3.13, 95%CI: 1.47-6.70), but not of VAD. NLR did not differ when comparing stable vs. progressing aMCI. Conclusions: This is the first report showing that NLR is significantly increased in MCI and AD but not in VAD. We also found that NLR was unable to predict the conversion from aMCI to AD. Further research on larger cohorts is warranted to definitely ascertain the application of NLR as a possible marker for aMCI and AD.

Acetyl-cholinesterase-inhibitors reconsidered. A narrative review of post-marketing studies on Alzheimer's disease.

The real efficacy of Acetyl-cholinesterase-inhibitors (AChEI) has been questioned. In this narrative review we evaluated their effect on cognitive decline, measured by Mini Mental State Examination (MMSE), and on total mortality rates in patients with Alzheimer's disease (AD) recruited into post-marketing open/non-randomized/retrospective studies. In AD patients treated with AChEI, the mean MMSE loss ranged from 0.2 to 1.37 points/years, compared with 1.07-3.4 points/years in non-treated patients. Six studies also reported data about survival; a reduction in total mortality relative risk between 27% and 42% was observed, over a period of 2-8 years. The type of studies and the use of MMSE to assess cognitive decline, may have introduced several biases. However, the clinical effects of AChEI seem to be of the same order of magnitude as the drugs currently used in most common chronic disorders, as regards progression of the disease and total mortality. In the absence of long-term randomized trials on "standard" unselected AD outpatients, open/retrospective studies and health databases represent the best available evidence on the possible effect of AChEI in the real-word setting. Our data support the clinical benefit of AChEI in older patients affected by AD.

Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer's Disease and Frontotemporal Dementia: A Pilot Study.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two major neurodegenerative diseases causing dementia. Due to similar clinical phenotypes, differential diagnosis is challenging without specific biomarkers. Beta-site Amyloid Precursor Protein cleaving enzyme 1 (BACE1) is a ß-secretase pivotal in AD pathogenesis. In AD and mild cognitive impairment subjects, BACE1 activity is increased in brain/cerebrospinal fluid, and plasma levels appear to reflect those in the brain. In this study, we aim to evaluate serum BACE1 activity in FTD, since, to date, there is no evidence about its role. The serum of 30 FTD patients and 30 controls was analyzed to evaluate (i) BACE1 activity, using a fluorescent assay, and (ii) Glial Fibrillary Acid Protein (GFAP) and Neurofilament Light chain (NfL) levels, using a Simoa kit. As expected, a significant increase in GFAP and NfL levels was observed in FTD patients compared to controls. Serum BACE1 activity was not altered in FTD patients. A significant increase in serum BACE1 activity was shown in AD vs. FTD and controls. Our results support the hypothesis that serum BACE1 activity is a potential biomarker for the differential diagnosis between AD and FTD.

Serum zonulin levels are increased in Alzheimer's disease but not in vascular dementia.

BACKGROUND: Zonulin is involved in the integrity and functioning of both intestinal-epithelial barrier and blood-brain barrier (BBB) by regulating tight junction molecular assembly. AIM: Since changes in microbiota and BBB may play a role in neurodegenerative disorders, we aimed to determine whether serum zonulin levels change in older patients affected by different types of dementia or mild cognitive impairment (MCI). METHODS: We evaluated serum zonulin levels in patients with late-onset AD (LOAD), vascular dementia (VAD), MIXED (AD + VAD) dementia, amnestic MCI, and in healthy controls. RESULTS: Compared with controls, serum zonulin increased in LOAD, MIXED dementia, and aMCI but not in VAD, independent of potential confounders (ANCOVA p = 0.01; LOAD vs controls, p = 0.01; MIXED vs. controls, p = 0.003; aMCI vs. controls, p = 0.04). Notably, aMCI converting to dementia showed significantly higher levels of zonulin compared with stable aMCI (p = 0.04). Serum zonulin inversely correlated with the standardized Mini-Mental State Examination (MMSE) score (p < 0.05), regardless of potential confounders. DISCUSSION: We found increased serum zonulin levels in patients with aMCI, LOAD and MIXED dementia, but not in VAD; moreover, zonulin levels were higher in aMCI converting to AD compared with stable ones. CONCLUSIONS: Our findings suggest that a dysregulation of intestinal-epithelial barrier and/or BBB may be an early specific event in AD-related neurodegeneration.

Frontier on Alzheimer's Disease.

Although substantial progress has been made in the last two decades, there are still important unfilled gaps in the understanding of the pathomechanism of Alzheimer's disease (AD) [...].

Dementia and Related Comorbidity: Analysis of 2 Years of Admissions to Italian Hospitals.

BACKGROUND: The aim of the present study was to examine the prevalence of dementia, related comorbidities, and mortality rates in hospitalized elderly patients in Italy. METHODS: Data were obtained from the Italian Ministry of Health and included all discharge records from Italian hospitals concerning subjects aged 65 years or above admitted to acute Internal Medicine during 2 years (n=3,695,278 admissions). Discharge diagnoses were re-classified into 24 clusters, each including homogeneous diseases by the ICD-9-CM code classification. Dementia was identified by the presence of ICD-9-CM codes 290, 294, or 331 series. RESULTS: Patients with dementia represented 7.5% of the sample; compared with those without dementia, they were older and more often female, had a greater length of hospital stay and higher mortality rate. Besides delirium [odds ratio (OR): 54.20], enthesopaties (OR: 2.19), diseases of fluids and electrolytes (OR:1.96), diseases of arteries (OR: 1.69), skin diseases (OR: 1.64), and pneumonia and pleurisy (OR: 1.53) were the diseases more strongly associated with the diagnosis of dementia, independent of other clusters, age, sex, and length of stay. CONCLUSIONS: Some comorbidities are specifically associated with the diagnosis of dementia among hospitalized elderly patients. Overall, these comorbidities describe the typical clinical profile of the patient with advanced dementia and could be treated in the context of the primary care, since they do not require specific skills belonging to hospital settings.

Orthostatic hypotension and vitamin D deficiency in older adults: systematic review and meta-analysis.

BACKGROUND: Over the latest years different studies have investigated the possible relationship between D deficiency and occurrence of orthostatic hypotension (OH), often reaching controversial results. We perform an update meta-analysis providing an update overview on the association between hypovitaminosis D and orthostatic hypotension (OH) in older adults. METHODS: Data extraction was independently performed by two authors and based upon predefined criteria. The meta-analysis was performed using a random-effects model. Statistical heterogeneity between groups was measured using the Higgins I2 statistic. RESULTS: Eight investigations enrolling 16.326 patients (mean age 75.5 years) met the inclusion criteria and were considered for the analysis. Patients with vitamin D deficiency were more likely to have OH compared to those without (OR: 1.36, 95% CI 1.14-1.63, p = 0.0001, I2 = 43.6%). A further sub-analysis, based on three studies, estimating the risk of OH in patients with hypovitaminosis D receiving antihypertensive treatment, did not reach the statistical significance (OR: 1.40, 95% CI 0.61-3.18, p = 0.418, I2 = 53.3%). Meta-regression performed using age (p = 0.12), BMI (p = 0.73) and gender (p = 0.62) as moderators did not reveal any statistical significance in influencing OH. Conversely, physical activity, Vitamin D supplementation and use of radioimmunoassay for the measurement of vitamin D serum levels showed a significant inverse relationship towards the risk of OH (Coeff.-0.09, p = 0.002, Coeff. - 0.12, p < 0.001 and Coeff. - 0.08, p = 0.03, respectively) among patients with hypovitaminosis D. A direct correlation between the administration of antihypertensive treatment and the risk of OH in older patients with low vitamin D level was observed (Coeff. 0.05, p < 0.001). CONCLUSIONS: Hypovitaminosis D is significantly associated with OH in older adults and directly influence by the administration of antihypertensive drugs. Conversely, physical activity, vitamin D supplementation and use of radioimmunoassay as analytic method inversely correlated with the risk of OH in older patients.

Inflammatory bowel disease as a new risk factor for dementia.

The prognostic impact of inflammatory bowel disease (IBD), chronic inflammatory conditions consisting of ulcerative colitis (UC), and Crohn's disease (CD) on the risk of dementia has been poorly investigated. We evaluated the risk of dementia in IBD patients by a systematic review and meta-analysis of the available data. Three studies, enrolling 121.827 patients [14.839 IBD (12.1%) and 106.961 (87.7%) controls, respectively] were included in the analysis. Of these, 57.7% (n = 8.571) had UC, while 42.2% (n = 6268) had CD. The mean follow-up period was 21.3 years. A random effect model revealed an aHR of 1.52 (95% CI 1.04-2.020, p = 0.01; I2 = 91.1%) for dementia in IBD patients. Sensitivity analysis confirmed yielded results. Subjects having a CD showed an aHR for dementia of 1.48 (95% CI 1.07-2.03, p = 0.001, I2 = 68.9%), while the risk among those with a history of UC did not reach the statistical significance (aHR: 1.47, 95% CI 0.95-2.82, p = 0.81, I2 = 89.9%). IBD males had an increased risk of dementia compared to women. IBD patients and in particular those with CD have an increased risk of dementia in the long-term period.

Dementia and in-hospital mortality: retrospective analysis of a nationwide administrative database of elderly subjects in Italy.

AIMS:  To evaluate the relationship between comorbidity and in-hospital mortality in elderly patients affected by dementia. METHODS: Data were obtained from the Italian Ministry of Health and included all discharge records from Italian hospitals concerning subjects aged ≥ 65 years admitted to acute Internal Medicine or Geriatrics wards between January 2015 and December 2016 (3.695.278 admissions). The variables analyzed included age, sex, and in-hospital death. Twenty-five homogeneous clusters of diseases were identified in discharge codes according to the ICD-9-CM classification. RESULTS: Patients with dementia represented 7.5% of the sample (n. 278.149); they were older, more often males (51.9%), and had a higher in-hospital mortality (24.3%) compared to patients without dementia (9.7%). Dementia per se doubled the odds of death (OR 1.98; 95% CI 1.95-2.00), independent of age, sex, and comorbidities. Seven clusters of disease (pneumonia, heart failure, kidneys disease, cancer, infectious diseases, diseases of fluids/electrolytes and general symptoms) were associated with increased in-hospital mortality, independent of the presence/absence of dementia. Among patients with dementia, heart failure, pneumonia and kidney disease on their own substantially doubled/tripled mortality risk. The risk increased from 10.1% (none of selected conditions), up to 28.9% when only one of selected comorbidities was present, rising to 52.3% (OR: 9.34; p < 0.001) when two or more comorbidities were simultaneously diagnosed, besides general symptoms. CONCLUSIONS: Our study confirmed an important increase of in-hospital mortality in older subjects with dementia. Despite a different comorbidity, the conditions associated with in-hospital mortality were substantially the same in patients with or without dementia. Heart failure, pneumonia, and kidney disease identified a high risk of in-hospital mortality among subjects with dementia.

Serum beta-secretase 1 (BACE1) activity increases in patients with mild cognitive impairment.

Beta-secretase 1 (BACE1) is considered as the key enzyme in amyloid-ß formation. Previous works suggest that high BACE1 activity may be present in brain, cerebrospinal fluid and serum of patients with late-onset Alzheimer's disease (LOAD) as well as mild cognitive impairment (MCI). Therefore, we evaluated whether serum BACE1 activity increases in MCI patients and is associated with the progression from MCI to dementia. BACE1 activity was measured in the serum of 259 MCI patients (162 amnestic-aMCI, 97 non-amnestic-naMCI) and 204 healthy Controls. After a median follow-up of 32 months (range: 10-153), 116 MCI progressed to dementia (87 aMCI and 29 naMCI). Serum BACE1 activity was higher in MCI compared with Controls (p < 0.001), and in aMCI with brain atrophy compared with naMCI without brain atrophy (p = 0.04). No difference in BACE1 activity emerged between converter and non-converter MCI, and this was true for both aMCI and naMCI. However, among aMCI with better cognitive performance (n. 163, MMSE score ≥24/30) those converting to dementia had higher BACE1 activity compared to stable ones (p = 0.05). This was not associated with an increased risk to develop dementia (hazard ratio: 1.65; 95% confidence interval: 0.67-4.01). In conclusion, serum BACE1 activity significantly increased in MCI patients (both amnestic and non-amnestic) compared with Controls. Moreover, higher serum BACE1 activity was observed only among aMCI with a better cognitive performance who progressed to dementia, suggesting that a dysregulation of this enzyme might be an early event primarily associated with neurodegeneration.

Risk of dementia in patients with atrial fibrillation: Short versus long follow-up. A systematic review and meta-analysis.

BACKGROUND: No previous meta-analyses have compared the risk of dementia, due to an underlying atrial fibrillation (AF), in the short-term versus the long-term period. AIM: To perform an update meta-analysis of studies examining the association between AF and dementia and the relative impact of follow-up period. METHODS: Data were obtained searching MEDLINE and Scopus for all investigations published between 1 January 2000 and March 1, 2021 reporting the risk of dementia in AF patients. The following MeSH terms were used for the search: "Atrial Fibrillation" AND "Dementia" OR "Alzheimer's disease". From each study, the adjusted hazard ratio (aHR) with the related 95% confidence interval (CI) was pooled using a random effect model. RESULTS: The analysis was carried out on 18 studies involving 3.559.349 subjects, of which 902.741 (25.3%) developed dementia during follow-up. A random effect model revealed an aHR of 1.40 (95% CI: 1.27-1.54, p < 0.0001; I2  = 93.5%) for dementia in subjects with AF. Stratifying the studies according to follow-up duration, those having a follow-up ≥10 years showed an aHR for dementia of 1.37 (95% CI: 1.21-1.55, p < 0.0001, I2  = 96.6%), while those with a follow-up duration <10 years has a slightly higher aHR for dementia (HR: 1.59, 95%CI: 1.51-1.67, p < 0.0001, I2  = 49%). Nine studies showed that the aHR for Alzheimer's disease (AD) in AF patients was 1.30 (95%CI: 1.12-1.51, p < 0.0001, I2  = 87.6%). CONCLUSIONS: Evidence suggests that patients with AF have an increased risk of developing dementia and AD. The risk of dementia was slightly higher when the follow-up was shorter than 10 years.

Metabolic syndrome and the risk of late onset Alzheimer's disease: An updated review and meta-analysis.

AIMS: This study aims to provide an updated systematic review and meta-analysis on the risk of Alzheimer's disease (AD) in patients with metabolic syndrome (MetS) and to analyze the contribution of each MetS component on AD onset. DATA SYNTHESIS: The study was performed according to the PRISMA guideline. Data were obtained searching MEDLINE, Scopus, Web of Science, and EMBASE for studies published between January 1, 2010 and July 30, 2020, evaluating the association between MetS and AD risk. A total of 255 articles were retrieved and 6 investigations (4 prospective and 2 retrospective) met the inclusion criteria. Overall, 9.788.021 patients with a mean follow-up of 4.5 years were analyzed. The pooled analysis revealed a slight increased risk of AD in MetS (hazard ratio, HR: 1.10, 95% and confidence interval, CI: 1.05-1.15). Egger's test indicated the absence of publication bias (t = 2.095 and p = 0.104). However, while analysis based on prospective studies failed to show a significant association between MetS and AD (HR: 0.80 and 95% CI: 0.61-1.05), analysis based on retrospective studies demonstrated a significant, slight increased risk (HR:1.11 and 95% CI: 1.08-1.66). With regard to MetS components, the risk was: arterial hypertension, HR: 1.05 (95% CI: 1.04-10.6); hyperglycemia/diabetes, HR: 1.19 (95% CI: 1.18-1.99); low high-density lipoprotein cholesterol (HDL-C), HR: 1.07 (95% CI: 1.06-1.07); hypertriglyceridemia, HR: 1.06 (95% CI: 1.05-1.06); and abdominal obesity, HR: 0.84 (95% CI: 0.74-0.95). CONCLUSIONS: We found a significant association between MetS and AD, mainly driven by large retrospective studies. Our data also support the association of single MetS components with AD incidence, while increased waist circumference seems to have a "protective role" probably due to reverse causality.

Relationship between echocardiographic tricuspid annular plane systolic excursion and mortality in COVID-19 patients: A Meta-analysis.

BACKGROUND: The evaluation of the tricuspid annular plane systolic excursion (TAPSE) is recommended to assess the right ventricular (RV) systolic function. We performed an updated meta-analysis of the association between TAPSE and short-term mortality in COVID-19 patients. METHODS: MEDLINE and Scopus databases were searched to locate all the articles published up to May 1, 2021, reporting data on TAPSE among COVID-19 survivors and non-survivors. The difference of TAPSE between the two groups was expressed as mean difference (MD) with the corresponding 95% confidence interval (CI) using the Mantel-Haenszel random effects model. Both Q value and I2 statistics were used to assess heterogeneity across studies. Sensitivity analysis, meta-regression, and evaluation of bias were performed. RESULTS: Twelve studies, enrolling 1272 COVID-19 patients (778 males, mean age 69.3 years), met the inclusion criteria and were included in the final analysis. Non-survivors had a lower TAPSE compared to survivors (MD =  -3.089 mm, 95% CI =  -4.087 to -2.091, p < 0.0001, I2  = 79.0%). Both the visual inspection of the funnel plot and the Egger's tests (t = 1.195, p = 0.259) revealed no evidence of publication bias. Sensitivity analysis confirmed yielded results. Meta-regression analysis evidenced that the difference in TAPSE between the two groups was only influenced by pre-existing chronic obstructive pulmonary disease (COPD, p = 0.02). CONCLUSION: COVID-19 non-survivors have a lower TAPSE when compared to survivors, especially in COPD subjects. Current data suggest that the TAPSE assessment may provide useful information regarding the short-term prognosis of COVID-19 patients during the infection.

Clinical and demographic parameters predict the progression from mild cognitive impairment to dementia in elderly patients.

OBJECTIVES: To evaluate the possibility of predicting the risk of progression from mild cognitive impairment (MCI) to dementia using a combination of clinical/demographic parameters. METHODS: A total of 462 MCI elderly patients (follow-up: 33 months). Variable measured included cognitive functions, age, gender, MCI type, education, comorbidities, clinical chemistry, and functional status. RESULTS: Amnestic type (aMCI) represented 63% of the sample, non-amnestic (naMCI) 37%; 190 subjects progressed to dementia, 49% among aMCI, and 28% among naMCI. At Cox multivariate regression analysis, only MMSE (one point increase HR 0.84; 95% CI 0.79-0.90), aMCI (HR 2.35; 95% CI 1.39-3.98), and age (1 year increase HR 1.05; 95% CI 1.01-1.10) were independently associated with progression to dementia. A score was created based on these dichotomized variables (score 0-3): age (≥ or < 78 years), MMSE score (≥ or < 25/30) and aMCI type. The conversion rate progressed from 6% in subjects with score 0 (negative predictive value: 0.94), to 31% in individuals with score 1, to 53% in subjects with score 2, to 72% in individuals with score 3 (positive predictive value: 0.72). ROC curve analysis showed an area under the curve of 0.72 (95% CI 0.66-0.75, p 0.0001). CONCLUSIONS: We have described a simple score, based on previously recognized predictors such as age, MMSE, and MCI type, which may be useful for an initial stratification of the risk of progression to dementia in patients affected by MCI. The score might help the clinicians to evaluate the need for more expansive/invasive examinations and for a closer follow-up in MCI patients.

Development, optimization and validation of an absolute specific assay for active myeloperoxidase (MPO) and its application in a clinical context: role of MPO specific activity in coronary artery disease.

Background Myeloperoxidase (MPO) is an enzyme with a recognized prognostic role in coronary artery disease (CAD), which is also emerging as a promising biomarker for cardiac risk stratification. However, the lack of a consensus method for its quantification has hindered its implementation in clinical practice. The aim of our work was to optimize an absolute sensitive assay for active MPO without external standards, to validate the method in the clinical context of CAD patients, and to estimate the enzyme specific activity. Methods In order to determine the MPO concentration using fluorescence readings, this ELISA assay exploits the activity of the enzyme recognized by specific antibodies. The assay was validated in a small cohort of patients that included: healthy subjects (n=60); patients with acute myocardial infarction (AMI, n=25); patients with stable CAD (SCAD, n=25) and a concomitant chronic obstructive pulmonary disease (COPD). Then, total MPO concentration and specific activity (activity/total MPO) were determined. Results The assay showed an intra- and inter-assay coefficient of variation of 5.8% and 10.4%, respectively, with a limit of detection (LoD) of 0.074 µU. Both AMI and SCAD patients had higher active and total MPO than controls (p<0.0001 and p<0.01, respectively). The specific activity of MPO was higher in SCAD patients compared to both controls and AMI (p<0.0001). Conclusions The study presents a robust and sensitive method for assaying MPO activity in biological fluids with low variability. Moreover, the determination of the specific activity could provide novel insight into the role of MPO in cardiovascular diseases (CVDs).

Left atrial size measured on CT pulmonary angiography: another parameter of pulmonary embolism severity? A systematic review.

We systematically review the potential role of left atrial (LA) size, evaluated at computed tomography angiography (CTA) in patients with acute pulmonary embolism (PE), as a new parameter of PE severity. A literature search based on PubMed (MEDLINE), Scopus, Cochrane library and Google Scholar databases was performed to locate previous published investigations reporting data on the severity of acute PE based on the evaluation of LA size (either volume, diameter or area). Six studies, corresponding to a total of 990 patients, published between 2012 and 2019 were included into the analysis. The severity of acute PE, in terms of hemodynamic impairment, increases with the reduction of the LA volume and a significant negative correlation was observed between the pulmonary artery obstruction index (PAOI) and the LA area. Similarly, the longest left-to-right as well as the anteroposterior diameters of the LA had a significant positive correlation with the PAOI index for both the measurement. The LA volume significantly decreased with the increasing of the PAOI index. Moreover, a lower LA volume was observed in those subjects with a saddle PE appearing as the best single parameter able to discriminate between patients having or not a saddle acute PE. Intriguingly, PE patients died within 30 days from the acute event had a significant small LA volume compared to survivors. Data obtained from the current medical literature seem to suggest that the evaluation of LA size evaluation could be a new parameter of PE severity. Further and larger prospective studies are needed to confirm preliminary findings.

Seizures as the first clinical manifestation of acute pulmonary embolism: an underestimate issue in neurocritical care.

BACKGROUND: The aim of the present review is to analyze the clinical characteristics of patients with acute pulmonary embolism (PE) which seizures were the first clinical manifestation of the disease. METHODS: After screening 258 articles in PubMed, Scopus, Cochrane Library, and Google Scholar databases, we identified 16 case reports meeting the inclusion criteria. RESULTS: The mean age of the population was 48.4 ± 19.8 years (9 males and 7 females). About three of four patients (68.7%) were hemodynamically stable at admission, having a systolic blood pressure > 90 mmHg. Intriguingly, the doubt of acute PE was based on clinical suspicion or on instrumental findings in 62.5% and 18.7% of patients, respectively. In 3 subjects (18.7%), the acute cardiovascular disease was not suspected. Half of patients had an unremarkable previous medical history while neurological comorbidities were present in 4 patients (25.0%). During seizures, a transient loss of consciousness (TLOC) was reported in 6 cases. Seizures were retrospectively classified according to the 2017 ILAE classification, whenever possible. A focal and generalized onset was reported in 37.5% and 50% of cases, respectively, in 12.5% of patient's data that were insufficient to classify the events. The mean number of seizure episodes in the population enrolled was 2.0 ± 1.1. Mortality rate was 54.5% but one investigation did not report the patient's outcome. CONCLUSIONS: The relationship between seizures and acute PE is probably underrecognized. Identifying patients that have a high probability of acute PE is fundamental to avoid any treatment delay and ameliorate their outcomes.

Herpes zoster infection and statins: which implications in clinical practice?

Herpes zoster (HZ), which is caused by reactivation of latent varicella zoster virus (VZV), constitutes a major public health concern in both short- and long-term periods. Over the last years, several epidemiological studies have demonstrated that statin use is associated with increased risk of HZ at cerebral level. Because statins are among the most popular and best-selling drugs in western countries, this potential negative pleiotropic effect could have important implications in the daily clinical practice. In the present manuscript, we reviewed the available data on the statin use and the relative risk of HZ infection.

Uric acid within the "normal" range predict 9-year cardiovascular mortality in older individuals. The InCHIANTI study.

BACKGROUND AND AIMS: Increased uric acid levels correlate with cardiovascular disease and cardiovascular/overall mortality. To identify a uric acid threshold above which cardiovascular mortality rises, we studied the relationship between uric acid concentration and overall/cardiovascular mortality. METHODS AND RESULTS: We analyzed data from the InCHIANTI study, a cohort study of Italian community-dwelling people with 9 years of follow-up. We selected a sample of 947 individuals over 64 years of age, free from cardio-cerebrovascular disease and with available uric acid measurement at baseline. The sample was divided according to plasma uric acid tertiles. The Hazard ratio (HR) for mortality was calculated by multivariate Cox proportional hazard model. Mean age of participants was 75.3 ± 7.3 years; the mean value of uric acid was 5.1 ± 1.4 mg/dl. Over 9-years of follow-up, 342 (36.1%) participants died, 143 deaths (15.1%) were due to cardiovascular disease. Subjects with higher uric acid concentrations presented a higher cardiovascular mortality [II (4.6-5.5 mg/dl) vs I (1.8-4.5 mg/dl) tertile HR: 1.98, 95%C.I. 1.22-3.23; III (≥5.6 mg/dl) vs I tertile HR: 1.87, 95%C.I. 1.13-3.09]. We found a non-linear association between uric acid concentrations and cardiovascular mortality with the lowest mortality for values of about 4.1 mg/dl and a significant risk increment for values above 4.3 mg/dl. CONCLUSION: In community-dwelling older individuals free from cardio-cerebrovascular events, the lowest 9-year cardiovascular mortality was observed for uric acid values far below current target values. If confirmed, these data might represent the background for investigating the efficacy of uric acid levels reduction in similar populations.