Post-stroke dysphagia: Clinical characteristics and evolution in a single-primary stroke center.

BACKGROUND: Dysphagia is a common manifestation after stroke and seems to play a major role in clinical and functional outcomes. OBJECTIVES: To identify clinical predictors of higher degrees of dysphagia, as well as assess its burden in our hospital, in order to understand how to improve the approach to this symptom. METHODS: We included 311 patients admitted in an acute stroke unit in a year-long period. The relationship of dysphagia with different outcomes, both in acute phase and within the first year after stroke, were investigated. RESULTS: Using the Pearson Correlation Coefficient, NIHSS score at admission was positively correlated with the degree of dysphagia (r = 0,783; p < 0,001) and total anterior circulation infarcts and age (> 70 years) were also associated with higher risk of dysphagia (p < 0.001). During hospitalization both respiratory infections and mortality occurred at significantly higher rates for dysphagic patients (p < 0.001) and we observed an increasing trend towards a higher mortality rate, the higher the degree of dysphagia. These patients stayed longer in the stroke unit, with less chance to be discharged home and more frequently transferred to inpatient rehabilitation care. One year after admission, dysphagic patients were more frequently readmitted due to pneumonia and we observed a higher mortality rate compared to patients without dysphagia (p < 0.001). CONCLUSION: The presence of the above-mentioned dysphagia predictive factors should alert us to the need for an early approach, starting in the stroke unit, but also after discharge, taking into account its impact on clinical outcomes, mortality and healthcare costs.

Meniscus Sign in Patients with Anterior Circulation Large Vessel Occlusion Stroke does not Predict Outcome.

PURPOSE: The angiographic appearance of the occlusion site was suggested to influence outcomes of stroke patients with large vessel occlusion (LVO) who undergo endovascular treatment (EVT). We aimed to study the impact of the meniscus sign (MS) on outcomes of stroke patients with anterior circulation LVO. METHODS: Based on two prospective registries of acute ischemic stroke, we selected patients with carotid­T, M1 or M2 occlusion who underwent EVT. Clinical characteristics and outcomes were collected from the registries or from individual records. Two independent observers blinded to outcomes assessed the presence of MS in digital subtraction angiography before thrombectomy. Angiographic and clinical outcomes of patients with and without MS were compared. RESULTS: We included 903 patients, with median age of 78 years, 59.8% were male, median baseline NIHSS was 14 and 39.5% received intravenous thrombolysis. Patients with MS (n = 170, 18.8%) were more frequently female, presented with higher NIHSS scores and more frequently underwent intravenous thrombolysis. Presence of MS was significantly associated with cardioembolic etiology. Successful reperfusion, number of passes, first pass effect, procedural time, symptomatic intracerebral hemorrhage, in-hospital mortality and favorable 3­month functional outcome were similar in the groups of patients with and without MS. In the multivariable analyses, MS was not associated with successful reperfusion (odds ratio, OR = 1.08, 95% confidence interval, CI = 0.76-1.55), first pass effect (OR = 0.96, 95%CI = 0.48-1.92) or favorable 3­month outcome (OR = 1.40, 95%CI = 0.88-2.24). CONCLUSION: The presence of MS in acute ischemic stroke patients with anterior circulation large vessel occlusion who undergo EVT does not appear to influence angiographic or clinical outcomes.

Acute Ischemic Stroke in Pregnancy.

Stroke is an uncommon but serious potential complication of pregnancy. The management of acute ischemic stroke in pregnant women remains a complex challenge that extends beyond the limits of clinical trial evidence. Patient 1 was a 29-year-old woman 27 weeks into her first pregnancy, without remarkable past medical history or vascular risk factors. She was admitted 1 h after sudden onset of a left total anterior circulation syndrome (National Institute of Health Stroke Scale [NIHSS] score of 23). CT and angio-CT scans were normal. Thrombolysis was performed, with mild clinical improvement. Brain MRI showed multi-territorial embolic events. Extended blood panel, cervical-transcranial ultrasound, 48-h ECG monitoring, and transthoracic echocardiogram were unremarkable. She was started on aspirin and low-molecular-weight heparin (LMWH), giving birth to a healthy child 10 weeks later. Patient 2 was a 45-year-old woman 34 weeks into her pregnancy, without remarkable past medical history or vascular risk factors. She was admitted 30 min after sudden onset of a left partial anterior circulation syndrome, already partially recovered (NIHSS score of 4). The CT scan showed only a subacute right incidental middle cerebral artery infarct, while the angio-CT confirmed a left M3 branch occlusion. Thrombolysis and thrombectomy were contraindicated by the recent contralateral infarct, mild deficits, and distal occlusion site. Brain MRI also suggested an embolic etiology and LMWH was started. Extended blood panel, 48-h ECG monitoring, and transthoracic echocardiogram were normal. She gave birth to a healthy baby 4 weeks later. These cases emphasize the growing real-world evidence of the emergent use of CT, IV contrast, and recombinant tissue plasminogen activator in pregnant women with acute stroke, while also illustrating the importance of an individualized management, accounting for the safety of both mother and child.

Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis: A Randomized Clinical Trial.

Importance: Patients with cerebral venous thrombosis (CVT) are at risk of recurrent venous thrombotic events (VTEs). Non-vitamin K oral anticoagulants have not been evaluated in randomized controlled trials in CVT. Objective: To compare the efficacy and safety of dabigatran etexilate with those of dose-adjusted warfarin in preventing recurrent VTEs in patients who have experienced a CVT. Design, Setting, and Participants: RE-SPECT CVT is an exploratory, prospective, randomized (1:1), parallel-group, open-label, multicenter clinical trial with blinded end-point adjudication (PROBE design). It was performed from December 21, 2016, to June 22, 2018, with a follow-up of 25 weeks, at 51 tertiary sites in 9 countries (France, Germany, India, Italy, the Netherlands, Poland, Portugal, Russia, and Spain). Adult consecutive patients with acute CVT, who were stable after 5 to 15 days of treatment with parenteral heparin, were screened for eligibility. Patients with CVT associated with central nervous system infection or major trauma were excluded, but those with intracranial hemorrhage from index CVT were allowed to participate. After exclusions, 120 patients were randomized. Data were analyzed following the intention-to-treat approach. Interventions: Dabigatran, 150 mg twice daily, or dose-adjusted warfarin for a treatment period of 24 weeks. Main Outcomes and Measures: Primary outcome was a composite of patients with a new VTE (recurrent CVT, deep vein thrombosis of any limb, pulmonary embolism, and splanchnic vein thrombosis) or major bleeding during the study period. Secondary outcomes were cerebral venous recanalization and clinically relevant non-major bleeding events. Results: In total, 120 patients with CVT were randomized to the 2 treatment groups (60 to dabigatran and 60 to dose-adjusted warfarin). Of the randomized patients, the mean (SD) age was 45.2 (13.8) years, and 66 (55.0%) were women. The mean (SD) duration of exposure was 22.3 (6.16) weeks for the dabigatran group and 23.0 (5.20) weeks for the warfarin group. No recurrent VTEs were observed. One (1.7%; 95% CI, 0.0-8.9) major bleeding event (intestinal) was recorded in the dabigatran group, and 2 (3.3%; 95% CI, 0.4-11.5) (intracranial) in the warfarin group. One additional patient (1.7; 95% CI, 0.0-8.9) in the warfarin group experienced a clinically relevant non-major bleeding event. Recanalization occurred in 33 patients in the dabigatran group (60.0%; 95% CI, 45.9-73.0) and in 35 patients in the warfarin group (67.3%; 95% CI, 52.9-79.7). Conclusions and Relevance: This trial found that patients who had CVT anticoagulated with either dabigatran or warfarin had low risk of recurrent VTEs, and the risk of bleeding was similar with both medications, suggesting that both dabigatran and warfarin may be safe and effective for preventing recurrent VTEs in patients with CVT. Trial Registration: ClinicalTrials.gov identifier: NCT02913326.

NCCT and CTA-based imaging protocol for endovascular treatment selection in late presenting or wake-up strokes.

INTRODUCTION: Recently, the benefit of selecting patients for endovascular treatment (EVT) beyond the 6-hour time window using a tissue-based approach was demonstrated in two randomized trials. The optimal imaging protocol for selecting patients is under debate, and it is still unknown if a simpler and faster protocol may adequately select patients with wake-up stroke (WUS) and late-presenting stroke (LPS) for EVT. OBJECTIVE: To compare outcomes of patients submitted to EVT presenting within 6 hours of symptom onset or 6-24 hours after last seen well, selected using non-contrast computed tomography (NCCT) and CT angiography (CTA). METHODS: An observational study was performed, which included consecutive patients with anterior circulation ischemic stroke with large vessel occlusion treated with EVT. Patients presenting within 6 hours were treated if their NIH Stroke Scale (NIHSS) score was ≥6 and Alberta Stroke Program Early CT score (ASPECTS) was ≥6, while patients presenting with WUS or 6-24 hours after last seen well (WUS/LPS) were treated if their NIHSSscore was ≥12 and ASPECTS was ≥7. RESULTS: 249 patients were included, 63 of whom were in the WUS/LPS group. Baseline characteristics were similar between groups, except for longer symptom-recanalization time, lower admission NIHSS (16 vs 17, P=0.038), more frequent tandem occlusions (25.4% vs 11.8%, P=0.010), and large artery atherosclerosis etiology (22.2% vs 11.8%, P=0.043) in the WUS/LPS group. No differences in symptomatic intracranial hemorrhage, peri-procedural complications or mortality were found between groups. Three-month functional independence was similar in both groups (65.1% in WUS/LPS vs 57.0% in ≤6 hours, P=0.259) and no differences were found after adjustment for confounders. CONCLUSIONS: This real-world observational study suggests that EVT may be safe and effective in patients with WUS and LPS selected using clinical-core mismatch (high NIHSS/high ASPECTS in NCCT).

Mechanical Thrombectomy in Acute Ischemic Stroke: Initial Single-Center Experience and Comparison with Randomized Controlled Trials.

BACKGROUND: Until recently, intravenous thrombolysis was the only reperfusion therapy with proven efficacy in patients with acute ischemic stroke. However, this treatment option has low recanalization rates in large-vessel occlusions. The search for additional treatments continued until 5 randomized trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, and REVASCAT) revealed the superiority of mechanical thrombectomy for anterior circulation large-vessel occlusion. After 1 year of performing thrombectomy with stent retrievers in our tertiary hospital, we intended to answer the question: is it possible to achieve similar results in a "real-world" setting? METHODS: We analyzed data from our prospective observational registry, compared it with the trials aforementioned, and concluded that the answer is affirmative. RESULTS: Our study population of 77 patients, with a mean age of 68,2 years and 48,1% men, is comparable with these trials in much of selection criteria, baseline characteristics, and rate of previous intravenous thrombolysis (72,7%). Recovery of functional independence at 90 days was achieved in almost two thirds of patients, similarly to the referred trials. We devoted special emphasis on fast recanalization, keeping a simple image selection protocol (based on non-enhanced and computed tomography angiography) and not waiting for clinical response to thrombolysis in patients eligible for mechanical thrombectomy. We emphasize a successful recanalization rate of 87% and only 2,6% symptomatic intracranial hemorrhage. CONCLUSION: In summary, mechanical thrombectomy seems to be a safe and effective treatment option in a "real-world" scenario, with results similar to those of the recent randomized controlled trials.

Myocardium expression of connexin 43, SERCA2a, and myosin heavy chain isoforms are preserved in nitrofen-induced congenital diaphragmatic hernia rat model.

BACKGROUND: Previous morphological studies had produced controversial results with regard to heart development in congenital diaphragmatic hernia (CDH), whereas a few publications investigated cardiac function and myocardial maturation. Myocardium maturation is associated with age-dependent increasing of gene expression of gap junction protein connexin 43 (Cx43), adenosine triphosphatase of the sarcoplasmic reticulum (SERCA2a), as well as switching of myosin heavy chains (MHCs) from beta to alpha isoforms. Our aim was to evaluate myocardium maturity in nitrofen-induced CDH rat model. METHODS: Fetuses from dated pregnant Sprague-Dawley rats were assigned to 3 experimental groups: control, nitrofen (exposed to nitrofen, without CDH), and CDH (exposed to nitrofen, with CDH). Myocardial samples collected from left ventricle free wall were processed to (i) quantification of messenger RNA (mRNA) of Cx43, SERCA2a, alpha and beta MHC isoforms, as well as beta-actin (housekeeping gene); and (ii) separation of MHC isoforms (alpha and beta isoforms) by sodium dodecyl sulfate polyacrylamide gel electrophoresis silver stained. RESULTS: We demonstrated that there is no difference in myocardial gene expression of Cx43 (control, 1.0 +/- 0.1; nitrofen, 1.1 +/- 0.2; CDH, 1.3 +/- 0.2) and SERCA2a (control, 1.0 +/- 0.1; nitrofen, 0.9 +/- 0.1; CDH, 1.0 +/- 0.2). Myocardial gene expressions of alpha and beta mRNA of MHC isoforms were slightly decreased both in nitrofen and CDH fetuses when compared with control fetuses, but evaluation of the alpha-to-beta ratios of MHC isoforms at protein level revealed no significant differences between CDH and control (control, 16.9 +/- 2.5; CDH, 17.0 +/- 2.0). CONCLUSIONS: Myocardial quantification of Cx43 and SERCA2a mRNA, as well as the expression pattern of MHC isoforms at protein levels, was similar in all studied groups. We predict, therefore, that acute heart failure commonly observed in CDH infants might be attributed predominantly to cardiac overload secondary to severe pulmonary hypertension rather than to myocardial immaturity.

Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen-induced congenital diaphragmatic hernia.

Ghrelin is a strong physiologic growth hormone secretagogue that exhibits endocrine and non-endocrine actions. In this study, ghrelin expression in humans and rats was evaluated throughout development of normal and hypoplastic lungs associated with congenital diaphragmatic hernia (CDH). Additionally, the effect of antenatal treatment with ghrelin in the nitrofen-induced CDH rat model was tested. In normal lungs, ghrelin was expressed in the primitive epithelium at early stages of development and decreased in levels of expression with gestational age. In hypoplastic lungs ghrelin was overexpressed in both human and rat CDH fetuses when compared with controls. Exogenous administration of ghrelin to nitrofen-treated dams led to an attenuation of pulmonary hypoplasia of CDH pups. Furthermore, the growth hormone, secretagogue receptor (GHSR1a), could not be amplified from human or rat fetal lungs by RT-PCR. In conclusion, of all the lungs studied so far, the fetal lung is one of the first to express ghrelin during development and might be considered a new source of circulating fetal ghrelin. Overexpression of ghrelin in hypoplastic lungs and the effect of exogenous administration of ghrelin to nitrofen-treated dams strongly suggest a role for ghrelin in mechanisms involved in attenuation of fetal lung hypoplasia, most likely through a GHSR1a-independent pathway.