The Usefulness of Biological and Neuroimaging Markers for the Diagnosis of Early-Onset Alzheimer's Disease

The recent proposed criteria for Alzheimer's Disease (AD) have strongly claimed the usefulness of biological and neuroimaging markers for early identification AD. Cerebrospinal fluid (CSF) Tau/Abeta ratio, hippocampal atrophy, posterior cingulate, and neocortical associative area hypometabolism, or amyloid burden evaluated by PiB compound, held the premises to increase diagnostic accuracy in the preclinical disease stages. Despite many efforts to identify subjects at risk of developing AD, less attention has been paid to presenile AD diagnosis. A few data are already available in early onset AD, mainly obtained in cases of monogenic disorder. In this paper, we discuss the current literature on the role of biological and neuroimaging markers in presenile AD

The use of competition and creativity as key driver to promote scientific culture among students

The use of didactic games in order to promote scientific culture leads to innovative methodologies and technologies that can be very effective for the learning process of students or simply to make them more curious about critical disciplines

Primjena programa ubrzanog oporavka nakon barijatrijske kirurgije: analiza kliničkih ishoda i isplativosti

Enhanced recovery after surgery (ERAS) programs are perioperative evidencebased interventions that have the purpose of making the perioperative pathway more efficient in safeguarding patient safety and quality of care. Recently, several ERAS components have been introduced in the setting of bariatric surgery (Enhanced Recovery After Bariatric Surgery, ERABS). The aim of the present study was to evaluate clinical efficiency and cost-effectiveness of the implementation of an ERABS program. It was a retrospective case-control study comparing a group of adult obese (body mass index >40) patients treated according to the ERABS protocol (2014-2015) with a historical control group that received standard care (2013-2014) in the General and Emergency Surgery Department, Arcispedale S. Maria Nuova Hospital, Reggio Emilia, Italy. Data on the occurrence of complications, mortality, re-admissions and re-operations were extracted retrospectively from medical case notes and emergency patient admission lists. Length of hospital stay was significantly different between the two cohort patients. In the control group, the mean length of stay was 12.6±10.9 days, whereas in the ERABS cohort it was 7.1±2.9 days (p=0.02). During hospital stay, seven patients in the control group developed surgical complications, including one patient with major complications, whereas in the ERABS group three patients developed minor complications. Economic analysis revealed a different cost distribution between the two groups. On the whole, there were significant savings for almost all the variables taken into consideration, mainly driven by exclusion of using intensive are unit, which is by far more expensive than the average cost of post-anesthesia care unit. Our study confirmed the implementation of an ERABS protocol to have shortened hospital stay and was cost-saving while safeguarding patient safety.Programi ubrzanog oporavka nakon operacije (Enhanced Recovery After Surgery, ERAS) su perioperacijske intervencije zasnovane na dokazima kojima je svrha učiniti perioperacijski tijek učinkovitijim osiguravajući bolesnikovu sigurnost i kvalitetu skrbi. Odnedavno je nekoliko sastavnica programa ERAS uvedeno u okruženje barijatrijske kirurgije (Enhanced Recovery After Bariatric Surgery, ERABS). Cilj ovoga istraživanja bio je procijeniti kliničku učinkovitost i isplativost provođenja programa ERABS. U ovoj retrospektivnoj studiji slučaja i kontrola uspoređena je skupina odraslih pretilih bolesnika (indeks tjelesne mase >40) liječenih prema protokolu ERABS (2014.-2015.) s povijesnom kontrolnom skupinom koja je primala standardnu skrb (2013.-2014.) u Klinici za opću i hitnu kirurgiju, Bolnica Arcispedale S. Maria Nuova, Reggio Emilia, Italija. Podaci o pojavnosti komplikacija, smrtnosti, ponovnom prijmu i ponovljenim operacijama retrospektivno su izvedeni iz bolesničkih kartona i prijamnih lista. Duljina boravka u bolnici značajno se razlikovala među dvjema skupinama bolesnika. U kontrolnoj skupini srednja duljina boravka u bolnici bila je 12,6±10,9 dana, dok je skupini ERABS iznosila 7,1±2,9 dana (p=0,02). Kod prijma se kirurška komplikacija razvila u 7 osoba iz kontrolne skupine; od toga je jedan bolesnik imao teže komplikacije, dok su u skupini ERABS manje komplikacije zabilježene kod 3 bolesnika. Ekonomska analiza pokazala je drukčiju raspoređenost troškova u dvjema skupinama. Sve u svemu, značajne uštede u gotovo svim ispitivanim varijablama uglavnom su nastale zbog isključenja uporabe jedinice intenzivnog liječenja, što je daleko skuplje od prosječnih troškova u jedinici skrbi poslije anestezije. Naše je istraživanje potvrdilo da primjena protokola ERABS skraćuje boravak u bolnici i snižava troškove pritom osiguravajući sigurnost bolesnika

Effects of dopaminergic treatment on inhibitory control differ across Hoehn and Yahr stages of Parkinson's disease

: Motor inhibitory control, a core component of cognitive control, is impaired in Parkinson's disease, dramatically impacting patients' abilities to implement goal-oriented adaptive strategies. A progressive loss of the midbrain's dopamine neurons characterizes Parkinson's disease and causes motor features responsive to dopaminergic treatments. Although such treatments restore motor symptoms, their impact on response inhibition is controversial. Most studies failed to show any effect of dopaminergic medicaments, although three studies found that these drugs selectively improved inhibitory control in early-stage patients. Importantly, all previous studies assessed only one domain of motor inhibition, i.e. reactive inhibition (the ability to react to a stop signal). The other domain, i.e. proactive inhibition (the ability to modulate reactive inhibition pre-emptively according to the current context), was utterly neglected. To re-examine this issue, we recruited cognitively unimpaired Parkinson's patients under dopaminergic treatment in the early (Hoehn and Yahr, 1-1.5, n = 20), intermediate (Hoehn and Yahr 2, n = 20), and moderate/advanced (Hoehn and Yahr, 2.5-3, n = 20) stages of the disease. Using a cross-sectional study design, we compared their performance on a simple reaction-time task and a stop-signal task randomly performed twice on dopaminergic medication (ON) and after medication withdrawal (OFF). Normative data were collected on 30 healthy controls. Results suggest that medication effects are stage-dependent. In Hoehn and Yahr 1-1.5 patients, drugs selectively impair reactive inhibition, leaving proactive inhibition unaffected. In the ON state, Hoehn and Yahr two patients experienced impaired proactive inhibition, whereas reactive inhibition is no longer affected, as it deteriorates even during the OFF state. By contrast, Hoehn and Yahr 2.5-3 patients exhibited less efficient reactive and proactive inhibition in the OFF state, and medication slightly improved proactive inhibition. This evidence aligns with the dopamine overdose hypothesis, indicating that drug administration may overdose intact dopamine circuitry in the earliest stages, impairing associated cognitive functions. In later stages, the progressive degeneration of dopaminergic neurons prevents the overdose and can exert some beneficial effects. Thus, our findings suggest that inhibitory control assessment might help tailor pharmacological therapy across the disease stage to enhance Parkinson's disease patients' quality of life by minimizing the hampering of inhibitory control and maximizing the reduction of motor symptoms

Cortical Inhibitory Imbalance in functional paralysis

Background: Functional neurological disorders are characterized by neurological symptoms that have no identifiable pathology and little is known about their underlying pathophysiology. Objectives: To analyze motor cortex excitability and intracortical inhibitory and excitatory circuits' imbalance in patients with flaccid functional weakness. Methods: Twenty-one consecutive patients with acute onset of flaccid functional weakness were recruited. Single and paired-pulse transcranial magnetic stimulation (TMS) protocols were used to analyze resting motor thresholds (RMT) and intracortical inhibitory (short interval intracortical inhibition - SICI) and excitatory (intracortical facilitation - ICF) circuits' imbalance between the affected and non-affected motor cortices. Results: We observed a significant increase in RMT and SICI in the affected motor cortex (p < 0.001), but not for ICF, compared to the contralateral unaffected side. Conclusion: This study extends current knowledge of functional weakness, arguing for a specific central nervous system abnormality which may be involved in the symptoms' pathophysiology

Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

Background and Purposes—This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods—The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P=0.10) for major bleedings. Results—The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P=0.009) for ischemic outcome events and 0.407 (0.275–0.540; P=0.14) for hemorrhagic outcome events. Conclusions—In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p < 0.001) and younger (p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p < 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes