Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively ( P =0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

function is considered to be precisely measurable only by invasive hemodynamics. We aimed to correlate strain values measured by speckle-tracking echocardiography (STE) with sensitive contractility parameters of pressure-volume (P-V) analysis in a rat model of exercise-induced left ventricular (LV) hypertrophy. LV hypertrophy was induced in rats by swim training and was compared with untrained controls. Echocardiography was performed using a 13-MHz linear transducer to obtain LV long-and short-axis recordings for STE analysis (GE EchoPAC). Global longitudinal (GLS) and circumferential strain (GCS) and longitudinal (LSr) and circumferential systolic strain rate (CSr) were measured. LV P-V analysis was performed using a pressure-conductance microcatheter, and load-independent contractility indices [slope of the end-systolic P-V relationship (ESPVR), preload recruitable stroke work (PRSW), and maximal dP/dt-enddiastolic volume relationship (dP/dtmax-EDV)] were calculated. Trained rats had increased LV mass index (trained vs. control; 2.76 Ϯ 0.07 vs. 2.14 Ϯ 0.05 g/kg, P Ͻ 0.001). P-V loop-derived contractility parameters were significantly improved in the trained group (ESPVR: 3.58 Ϯ 0.22 vs. 2.51 Ϯ 0.11 mmHg/ l; PRSW: 131 Ϯ 4 vs. 104 Ϯ 2 mmHg, P Ͻ 0.01). Strain and strain rate parameters were also supernormal in trained rats (GLS: Ϫ18.8 Ϯ 0.3 vs. Ϫ15.8 Ϯ 0.4%; LSr: Ϫ5.0 Ϯ 0.2 vs. Ϫ4.1 Ϯ 0.1 Hz; GCS: Ϫ18.9 Ϯ 0.8 vs. Ϫ14.9 Ϯ 0.6%; CSr: Ϫ4.9 Ϯ 0.2 vs. Ϫ3.8 Ϯ 0.2 Hz, P Ͻ 0.01). ESPVR correlated with GLS (r ϭ Ϫ0.71) and LSr (r ϭ Ϫ0.53) and robustly with GCS (r ϭ Ϫ0.83) and CSr (r ϭ Ϫ0.75, all P Ͻ 0.05). PRSW was strongly related to GLS (r ϭ Ϫ0.64) and LSr (r ϭ Ϫ0.71, both P Ͻ 0.01). STE can be a feasible and useful method for animal experiments. In our rat model, strain and strain rate parameters closely reflected the improvement in intrinsic contractile function induced by exercise training. speckle-tracking echocardiography; pressure-volume analysis; athlete's heart; contractility; strain LONG-TERM EXERCISE TRAINING induces physiological left ventricular (LV) hypertrophy, a molecular and cellular growth process of the heart in response to altered loading conditions (6). In contrast to pathological hypertrophy, this adaptation leads to maintained or even enhanced cardiac function (2, 14). Hemodynamic changes of exercise-induced hypertrophy were characterized by our research group in a rat model, focusing also on the improved LV inotropic state (23). Contractility is the intrinsic ability of the myocardium to generate force and to shorten independently of changes in preload or afterload with fixed heart rates. In the past few decades, efforts have been made to transfer the physiological concept of contractility to the intact beating heart (4).Pressure-volume (P-V) analysis recently became the gold standard to investigate in vivo hemodynamics in animal models. During preload reduction maneuvers such as gradual occlusion of vena cava inferior, load-independent indices of myocardial contractility could be obtained (20). Th...

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT ; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

Left ventricular (LV) hypertrophy is a physiological or pathological response of LV myocardium to increased cardiac load. We aimed at investigating and comparing hemodynamic alterations in well-established rat models of physiological hypertrophy (PhyH) and pathological hypertrophy (PaH) by using LV pressure-volume (P-V) analysis. PhyH and PaH were induced in rats by swim training and by abdominal aortic banding, respectively. Morphology of the heart was investigated by echocardiography. Characterization of cardiac function was completed by LV P-V analysis. In addition, histological and molecular biological measurements were performed. Echocardiography revealed myocardial hypertrophy of similar degree in both models, which was confirmed by post-mortem heart weight data. In aortic-banded rats we detected subendocardial fibrosis. Reactivation of fetal gene program could be observed only in the PaH model. PhyH was associated with increased stroke volume, whereas unaltered stroke volume was detected in PaH along with markedly elevated end-systolic pressure values. Sensitive indexes of LV contractility were increased in both models, in parallel with the degree of hypertrophy. Active relaxation was ameliorated in athlete's heart, whereas it showed marked impairment in PaH. Mechanical efficiency and ventriculo-arterial coupling were improved in PhyH, whereas they remained unchanged in PaH. Myocardial gene expression of mitochondrial regulators showed marked differences between PaH and PhyH. We provided the first comparative hemodynamic characterization of PhyH and PaH in relevant rodent models. Increased LV contractility could be observed in both types of LV hypertrophy; characteristic distinction was detected in diastolic function (active relaxation) and mechanoenergetics (mechanical efficiency), which might be explained by mitochondrial differences.

Background Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the apocrine gland-rich (AGR) skin region. The initial steps of disease development are not fully understood, despite intense investigations into immune alterations in lesional HS skin.Objectives We aimed to systematically investigate the inflammatory molecules involved in three stages of HS pathogenesis, including healthy AGR, non-lesional HS and lesional HS skin, with the parallel application of multiple mRNA and protein-based methods.

Paciaroni, M. et al. (2016) Prognostic value of trans-thoracic echocardiography in patients with acute stroke and atrial fibrillation: findings from the RAF study. Journal of Neurology, 263(2), pp. 231-237. (doi:10.1007/s00415-015-7957-3) There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/117439/ UO Gravi Cerebrolesioni, San Giovanni Battista Hospital, Foligno. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 23 Stroke Unit, Department of Neurology, Sant'Andrea Hospital, La Spezia, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 24 Department of Internal Medicine, Insubria University, Varese, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 25 Stroke Unit, Neurology, Insubria University, Varese, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 26 Stroke Unit, Ospedale di Portogruaro, Portogruaro (Venice), Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 27 Department of Neurology, University of L'Aquila, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 28 Department of Internal Medicine, Ospedale Civile di Piacenza, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 29 Municipal Budgetary Healthcare Institution of Novosibirsk. City Clinical Hospital #1. Novosibirsk (Russia) 30 Stroke Unit, Jazzolino Hospital, Vibo Valentia, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 31 Department of Neurology and Psychiatry, Sapienza University of Rome, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 32 Stroke Unit, Ospedale Civico, Palermo. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. The Authors report that no funding has been received for this study. 4Abstract Background and purposes: Anticoagulant therapy is recommended for the secondary

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.

Background and Purpose-Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods-We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results-Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions-Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.