The balance between the risk of early stroke recurrence and hemorrhagic transformation represents the cornerstone of practical management of non-valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS). Patients who receive antithrombotic therapy as secondary prevention in the early phase of NVAF-related AIS have a better prognosis compared with patients who do not receive antithrombotic treatment. Recently, the RAF study showed that the best efficacy/safety profile was associated with anticoagulation started between 4 and 14 days from stroke onset. Based on the RAF study, the 2018 American Heart Association/American Stroke Association (AHA/ASA) guidelines suggest starting anticoagulants between 4 and 14 days from stroke onset with a class of recommendation IIa. Strong evidence for the use of direct oral anticoagulants (DOACs) in the early phase of NVAF-related AIS is lacking, because this kind of patients were excluded from phase III randomized clinical trials (RCT) and ad hoc RCTs are ongoing. However, the real life evidence suggests that early starting time of DOACs in patients with NVAF-related AIS is safe and associated with low recurrence risk and all-cause mortality. In the present review the Authors provide an update on anticoagulation in the early phase of NVAF-related AIS with focus on DOACs.

Introduction The optimal timing for starting anticoagulation in the early phase of nonvalvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) remains a challenge, especially in patients undergoing urgent reperfusion by systemic thrombolysis or mechanical thrombectomy. The aim of our study was to review the literature evidence reporting on safety of direct oral anticoagulants (DOACs) starting in the early phase of NVAF-related AIS undergoing systemic thrombolysis and/or mechanical thrombectomy. Materials and Methods We reviewed the PubMed databases searching articles reporting on efficacy and safety of DOACs starting time within two weeks from AIS onset in patients undergoing systemic thrombolysis and/or mechanical thrombectomy. Results Three studies were selected, overall including one hundred and six patients (62 females, 58.4%). Median National Institute of Health Stroke Scale (NIHSS) score at hospital admission ranged from 9 to 13 points. Median DOACs starting time ranged from 2 to 6 days. Median CHA2DS2-VASC score ranged from 4 to 6 points. Follow-up was limited to 14 days in one study, 30 days in another, and 90 days in a third one. Overall, stroke recurrence and/or intracranial bleeding occurred in two patients (1.9%) and no patient died at follow-up. Conclusion Small sample size real life studies seem to demonstrate that the introduction of DOACs in the early phase of NVAF-related AIS undergoing urgent reperfusion is efficacious and safe. Prospective RCTs are necessary to confirm these findings.

•The optimal starting time of anticoagulation in the early phase of NVAF-related AIS is unclear•Balancing the risk of early stroke recurrence and hemorrhagic transformation is the key-point of NVAF-related AIS management•Patients with acute stroke were excluded from randomized clinical trials of DOACs on stroke prevention in atrial fibrillation•Real life studies showed an optimal efficacy/safety profile of DOACs in the early phase of NVAF-related AIS•Results of randomized clinical trials on DOACs aimed to confirm the real life evidence in this clinical setting are awaited

Strong evidence for the use of direct oral anticoagulants (DOACs) in the early phase of non valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) is lacking, because this kind of patients were excluded from phase III randomized clinical trials (RCT) and ad hoc RCTs are ongoing. In the latest years a lot of real life studies on this topic have been published. The aim of our review was to focus on these. We reviewed the PubMed databases searching articles reporting on DOACs starting time within 2 weeks from AIS onset. We selected fifteen studies, eight with retrospective, six with prospective observational and one with a prospective, open-label, single arm design. Overall, 2920 patients (47.8% females) were included. In twelve studies median or mean age of patients was over 75 years. Mean or median NIHSS ad hospital admission was ≤ 12 in all studies. About one-third of patients (32.4%) received urgent reperfusion by systemic thrombolysis or mechanical thrombectomy. About one-fifth of patients (22.8%) had large infarct size. Median starting time of DOACs was reported in thirteen studies and it ranged from 2 to 8 days. About one-half of patients (45.9%) received a low dose of DOACs. In studies reporting on median or mean CHA 2 DS 2 -VASC score, it was ≥ 3 in all. In studies reporting on median or mean HAS-BLED score, it was ≥ 2 in all. Ninety-day follow-up was available for nine studies, overall including about 2200 patients. Incidence of 90-day TIA/stroke recurrence, symptomatic haemorrhagic transformation or intracranial bleeding and all cause mortality was 2.25%, 0.90% and 1.5%, respectively. The real life evidence suggests that early starting of DOACs in patients with NVAF-related AIS is safe and associated with low recurrence risk and all-cause mortality.

RATIONALE Complexity is increasingly recognized as a critical variable in health care. However, there is still lack of practical tools to assess it and tackle the challenges that stem from it, particularly within hospitals. AIMS AND OBJECTIVE To validate a simple novel screening method based on both objective and subjective criteria to identify patients with clinically complex hospitalization events. To evaluate the prevalence of patients with complex events, identify their features, and compare them with those of the other patients and to those of patients with multimorbidities. METHOD We monitored the level of complexity of the hospitalization events of 240 patients admitted to an internal medicine ward in Tuscany over the course of 56 days. We compared the demographic features, the length of stay, and the prognosis of patients with and without complex events. RESULTS Sixty-nine patients (28.8% of the sample) had a complex episode during their stay, and 115 (47.9%) had phases of low complexity. Patients with complex episodes were younger and more comorbid than patients without. They stayed longer in-hospital (+4.5 days; 95% CI: 2.5-6.5) and had higher mortality (OR: 24.93; 95% CI: 6.97-171.63) and a lower probability of home discharge (OR: 0.25; 95% CI: 0.13-0.48). CONCLUSIONS The results show that using a simple screening method is possible to identify complex patients within IM wards and that every day, about one-third of the patients are complex. The results are discussed in implications for the dynamic management of patients with complex and simple phases during hospitalization.

BACKGROUND:Guidelines recommend triple therapy (TT) with ACE inhibitors or ARBs, beta-blockers and mineralcorticoid receptor antagonists in symptomatic heart failure patients with ejection fraction <35 % (HFrEF). Nevertheless, many patients remain untreated. This study was aimed to evaluate the use of TT in HFrEF patients discharged from internal medicine wards of Tuscany, Italy.METHODS AND RESULTS:We analyzed the database of a multicenter observational study which included 770 patients consecutively hospitalized for HF in 32out of 36 Internal Medicine Units of Tuscany, Italy. The value of ejection fraction was available in 490 of the 725 patients discharged alive. Of the 117 patients with HFrEF, only 46 (39.3%) were on TT at discharge while 71 (60.7%) were not. In the latter group we observed a significantly greater percentage of patients with cognitive deficit (25.3% vs 10.8%, p=0.05). In the same group there was a slightly greater percentage of patients with hypertension (61.9% vs 58.6%), diabetes (43.6% vs 36.9%), GFR<60 ml/min (74.6% vs 67.3%), anemia (52.1% vs 45.6%) and atrial fibrillation (40.8% vs 34.7%), but the differences were not statistically significant.CONSLUSIONS:These results indicate that TT is underutilized in internal medicine wards of Tuscany. Untreated patients had a greater rate of cognitive deficit and were probably sicker, more complex and fragile.

Spontaneous intracerebral hemorrhage (ICH) represents the most feared stroke subtype. Real world epidemiological data about trends in incident cases and in-hospital mortality lack. Therefore we performed this study aimed to answer this concern. International Classification of Diseases, 9th revision, Clinical Modification (ICD-9 th CM) database referred to patients discharged from six Hospitals of Florence district, Tuscany, Italy in a period fifteen years long (2001-2015)was analyzed. We searched for code 431 as primary or secondary diagnosis at hospital discharge. Overall, 7452 patients were discharged with ICH as primary or secondary diagnosis. Of them, 3695 (49.5%) were females and 4363 (59.1%) were 75-years old and over. Cases of ICH increased from 461 in 2001 to 568 in 2015. The greatest increase was observed in patients 75 years old and over (216 cases in 2001, 339 cases in 2015). Overall, 2273 patients died during hospital stay, in-hospital mortality being 30.5%. In-hospital mortality increased according to age, being 18% in under 65 years and 35.9% in 75-years old and over. In-hospital mortality decreased from 30.8% in 2001 to 25.1% in 2015. The decrease in in-hospital mortality was observed irrespective of age. In Florence district, cases of ICH increased over the years, especially in very old people, whereas in-hospital mortality decreased irrespective of age.

BACKGROUD AND AIM:The use of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) is controversial. The aims of our study were to analyze physicians' confidence in prescribing DOACs in NVAF-related AIS, the characteristics of patients receiving DOACs, and their 90-day prognosis. MATERIAL AND METHODS:Clinical records of consecutive patients admitted to our wards for NVAF-related AIS over the years 2014-2016 were reviewed. RESULTS:One hundred forty-seven patients, 72.7% females, mean age ± standard deviation 83.4 ± 8.8 years, were admitted to our ward for atrial fibrillation (AF)-related AIS (38 in 2014, 47 in 2015, 62 in 2016). Of these patients, 141 had NVAF-related AIS. Median length of hospital stay was 8 days (interquartile range [IQR], 6-11). In-hospital mortality was 10.8%. Ninety-eight patients (69.5%) received DOACs for secondary prevention, with increasing percentages from 2014 (62.5%) to 2016 (88%). In 88% of them, DOACs were started during hospital stay, whereas in 12% DOACs were started during ambulatory follow-up. The median time for starting DOACs was 5 days (IQR, 3-8). In patients receiving DOACs, the median National Institutes of Health Stroke Scale score was 6 (IQR, 3-12), and large ischemic lesions were present in 48%; the median modified Rankin Scale score at hospital discharge was 3 (IQR, 1-4), whereas the score at 90 days was 2 (IQR, 1-3). At the 90-day follow-up, in patients receiving DOACs, overall mortality was 3.0%, stroke recurrence was 1%, and no patients had major intracranial or extracranial bleedings. CONCLUSION:Our study suggests that physicians are becoming increasingly confident in the use of DOACs in NVAF-related AIS. The use of DOACs seems effective and safe even when started in the acute phase of stroke.

Background: Prognostic stratification is of utmost importance for management of acute Pulmonary Embolism (PE) in clinical practice. Many prognostic models have been proposed, but which is the best prognosticator in real life remains unclear. The aim of our study was to compare and combine the predictive values of the hemodynamics/biomarkers based prognostic model proposed by European Society of Cardiology (ESC) in 2008 and simplified PESI score (sPESI). Methods: Data records of 452 patients discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. The ESC model and sPESI were retrospectively calculated and compared by using Areas under Receiver Operating Characteristics (ROC) Curves (AUCs) and finally the combination of the two models was tested in hemodinamically stable patients. All cause and PE-related in-hospital mortality and fatal or major bleedings were the analyzed endpoints Results: All cause in-hospital mortality was 25% (16.6% PE related) in high risk, 8.7% (4.7%) in intermediate risk and 3.8% (1.2%) in low risk patients according to ESC model. All cause in-hospital mortality was 10.95% (5.75% PE related) in patients with sPESI score ≥1 and 0% (0%) in sPESI score 0. Predictive performance of sPESI was not significantly different compared with 2008 ESC model both for all cause (AUC sPESI 0.711, 95% CI: 0.661-0.758 versus ESC 0.619, 95% CI: 0.567-0.670, difference between AUCs 0.0916, p=0.084) and for PE-related mortality (AUC sPESI 0.764, 95% CI: 0.717-0.808 versus ESC 0.650, 95% CI: 0.598-0.700, difference between AUCs 0.114, p=0.11). Fatal or major bleedings occurred in 4.30% of high risk, 1.60% of intermediate risk and 2.50% of low risk patients according to 2008 ESC model, whereas these occurred in 1.80% of high risk and 1.45% of low risk patients according to sPESI, respectively. Predictive performance for fatal or major bleeding between two models was not significantly different (AUC sPESI 0.658, 95% CI: 0.606-0.707 versus ESC 0.512, 95% CI: 0.459-0.565, difference between AUCs 0.145, p=0.34). In hemodynamically stable patients, the combined endpoint in-hospital PE-related mortality and/or fatal or major bleeding (adverse events) occurred in 0% of patients with low risk ESC model and sPESI score 0, whilst it occurred in 5.5% of patients with low-risk ESC model but sPESI ≥1. In intermediate risk patients according to ESC model, adverse events occurred in 3.6% of patients with sPESI score 0 and 6.65% of patients with sPESI score ≥1. Conclusions: In real world, predictive performance of sPESI and the hemodynamic/biomarkers-based ESC model as prognosticator of in-hospital mortality and bleedings is similar. Combination of sPESI 0 with low risk ESC model may identify patients with very low risk of adverse events and candidate for early hospital discharge or home treatment.

Despite vitamin K antagonists (VKAs) are considered the first choice treatment for stroke prevention in atrial fibrillation (AF), literature shows their underuse in this context. Since data about VKAs use prior and after acute stroke lack, the aim of this study was to focus on management of anticoagulation with VKAs in this context. Data were retrieved from Tuscan FADOI Stroke Registry, an online data bank aimed to report on characteristics of stroke patients consecutively admitted in Internal Medicine wards in 2010 and 2011. In this period 819 patients with mean age 76.5±12.3 years were enrolled. Data on etiology were available for 715 of them (88.1%), 87% being ischemic and 13% hemorrhagic strokes. AF was present in 238 patients (33%), 165 (69.3%) having a known AF before hospitalization, whereas 73 patients (31.7%) received a new diagnosis of AF. A percentage of 89% of strokes in patients with known AF were ischemic and 11% hemorrhagic. A percentage of 86.7% of patients with known AF had a CHADS 2 ≥2, but only 28.3% were on VKAs before hospitalization. A percentage of 78.8% of patients treated with VKAs before stroke had an international normalized ratio (INR) ≤2.0; 68.7% of patients with VKAs-related hemorrhagic strokes had INR ≤3.0. Combined endpoint mortality or severe disability in patients with ischemic stroke associated with AF was present in 47%, while it was present in 19.30% and 19.20% of atherothrombotic and lacunar strokes, respectively. At hospital discharge, VKAs were prescribed in 25.9% of AF related ischemic stroke patients. AF related strokes are burdened by severe outcome but VKAs are dramatically underused in patients with AF, even in higher risk patients. Efforts to improve anticoagulation in this stroke subtype are warranted.

Spontaneous non traumatic intracerebral haemorrhage (ICH) is usually caused by many different interacting factors, such as the use of alcohol or fibrinolitic drugs, congenital aneurysm, brain tumors, and blood dyscrasia. Age and hypertension-related small vessel diseases, and cerebral amyloid angiopathy are the most common forms of vascular damage which can lead to ICH. Furthermore, a group of inherited cerebral small vessel diseases linked to ICH have been reported recently and the number of these forms is increasing. The presence of leukoaraiosis, lacunar infarcts and microbleeds has been suggested to indicate a higher risk for cerebral hemorrhage. In recent years, MRI and neuroimaging techniques contributed to the understanding and the diagnosis of this disease.