Exploring sex differences for acute ischemic stroke clinical, imaging and thrombus characteristics in the INTERRSeCT study

Stroke; Menopause; ThrombusIctus; Menopausia; TromboIctus; Menopausa; TrombeWomen, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of estrogen. Using the INTERRseCT cohort, a multicentre international observational cohort studying recanalization in acute ischemic stroke, we explored the effects of sex, and modifying effects of age, on neuroradiological predictors of recanalization including robustness of leptomeningeal collaterals, thrombus burden and thrombus permeability. Ordinal regression analyses were used to examine the relationship between sex and each of the neuroradiological markers. Further, we explored both multiplicative and additive interactions between age and sex. All patients (n = 575) from INTERRseCT were included. Mean age was 70.2 years (SD: 13.1) and 48.5% were women. In the unadjusted model, female sex was associated with better collaterals (OR 1.37, 95% CIs: 1.01-1.85), however this relationship was not significant after adjusting for age and relevant comorbidities. There were no significant interactions between age and sex. In a large prospective international cohort, we found no association between sex and radiological predictors of recanalization including leptomeningeal collaterals, thrombus permeability and thrombus burden.This prospective cohort study was funded by an operating grant from the Canadian Institutes of Health Research

Stroke-associated pneumonia according to mCDC criteria: impact on prognosis and antibiotic therapy

Antibiotics; Infections; Stroke-associated pneumoniaAntibióticos; Infecciones; Neumonía asociada a ictusAntibiòtics; Infeccions; Pneumònia associada a ictusObjective: The modified Centers for Disease Control and Prevention (mCDC) criteria have been proposed for diagnosing and managing stroke-associated pneumonia (SAP). The objective was to investigate the impact of SAP on stroke outcome depending on whether or not it conforms to mCDC criteria. Our secondary objective was to identify the responsible factors for antibiotic initiation in stroke patients. Methods: We conducted a prospective, multicenter, observational study of ischemic stroke patients with moderate to severe stroke (NIHSS≥4) admitted within 24 h. For 7 days, mCDC criteria were assessed daily, and infections and antibiotics were recorded. Pneumonias were divided into those fulfilling mCDC criteria (mCDC-SAP) or not (other pneumonias, OPn). The effect of each type of pneumonia on 3-month outcome was evaluated in separated logistic regression models. Factors associated with antibiotic initiation were explored using a random forest analysis. Results: Of the 342 patients studied, infections were diagnosed in 72 (21.6%), including 39 (11.7%) cases of pneumonia. Of them, 25 (7.5%) fulfilled mCDC criteria. Antibiotics were used in 92% of mCDC-SAP and 64.3% of OPn. In logistic regression analysis, mCDC-SAP, but not OPn, was an independent predictor of poor outcome [OR, 4.939 (1.022–23.868)]. The random forest analysis revealed that fever had the highest importance for antibiotic initiation. Interpretation: The mCDC criteria might be useful for detecting clinically relevant SAP, which is associated with poor outcomes. Isolated signs of infection were more important for antibiotic initiation than compliance with pre-defined criteria. Therefore, adherence to mCDC criteria might result in antibiotic saving without compromising clinical outcome.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Study supported by Fundació La Marató de TV3 (201706-30-31), Instituto de Salud Carlos III (PI17/02130 and PI21/00949), co-financed by the Fondo Europeo de Desarrollo Regional. Some centres take part in Spanish Stroke Research Network RICORS-ICTUS (RD21/0006/0024, RD21/0006/0007 and RD21/0006/0015)

Combined technique as first approach in mechanical thrombectomy: Efficacy and safety of REACT catheter combined with stent retriever

Acute stroke; Endovascular treatment; Mechanical thrombectomyAccidente cerebrovascular agudo; Tratamiento endovascular; Trombectomía mecánicaAccident cerebrovascular agut; Tractament endovascular; Trombectomia mecànicaIntroduction Mechanical thrombectomy (MT) with combined treatment including both a stent retriever and distal aspiration catheter may improve recanalization rates in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Here, we evaluated the effectiveness and safety of the REACT aspiration catheter used with a stent retriever. Methods This prospective study included consecutive adult patients who underwent MT with a combined technique using REACT 68 and/or 71 between June 2020 and July 2021. The primary endpoints were final and first pass mTICI 2b-3 and mTICI 2c-3 recanalization. Analysis was performed after first pass and after each attempt. Secondary safety outcomes included procedural complications, symptomatic intracranial hemorrhage (sICH) at 24 h, in-hospital mortality, and 90-day functional independence (modified Rankin Scale [mRS] 0–2). Results A total of 102 patients were included (median age 78; IQR: 73–87; 50.0% female). At baseline, median NIHSS score was 19 (IQR: 11–21), and ASPECTS was 9 (IQR: 8–10). Final mTICI 2b-3 recanalization was achieved in 91 (89.2%) patients and mTICI 2c-3 was achieved in 66 (64.7%). At first pass, mTICI 2b-3 was achieved in 55 (53.9%) patients, and mTICI 2c-3 in 37 (36.3%). The rate of procedural complications was 3.9% (4/102), sICH was 6.8% (7/102), in-hospital mortality was 12.7% (13/102), and 90-day functional independence was 35.6% (36/102). Conclusion A combined MT technique using a stent retriever and REACT catheter resulted in a high rate of successful recanalization and first pass recanalization in a sample of consecutive patients with AIS due to LVO in clinical use

Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes

Acute stroke; Flow cytometry; Mechanical thrombectomyIctus agut; Citometria de flux; Trombectomia mecànicaIctus agudo; Citometría de flujo; Trombectomía mecánicaWe aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01–1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson’s r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9–42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment.Open Access Funding provided by Universitat Autonoma de Barcelona. This work was supported by “Project 355/C/2017, Fundació La Marató de TV3 in Strokes and Traumatic Spinal Cord and Brain Injury, 2017 Call of Projects.

Blood Biomarker Panels for the Early Prediction of Stroke‐Associated Complications

Background Acute decompensated heart failure (ADHF) and respiratory tract infections (RTIs) are potentially life-threatening complications in patients experiencing stroke during hospitalization. We aimed to test whether blood biomarker panels might predict these complications early after admission. Methods and Results Nine hundred thirty-eight patients experiencing ischemic stroke were prospectively recruited in the Stroke-Chip study. Post-stroke complications during hospitalization were retrospectively evaluated. Blood samples were drawn within 6 hours after stroke onset, and 14 biomarkers were analyzed by immunoassays. Biomarker values were normalized using log-transformation and Z score. PanelomiX algorithm was used to select panels with the best accuracy for predicting ADHF and RTI. Logistic regression models were constructed with the clinical variables and the biomarker panels. The additional predictive value of the panels compared with the clinical model alone was evaluated by receiver operating characteristic curves. An internal validation through a 10-fold cross-validation with 3 repeats was performed. ADHF and RTI occurred in 19 (2%) and 86 (9.1%) cases, respectively. Three-biomarker panels were developed as predictors: vascular adhesion protein-1 >5.67, NT-proBNP (N-terminal pro-B-type natriuretic peptide) >4.98 and d-dimer >5.38 (sensitivity, 89.5%; specificity, 71.7%) for ADHF; and interleukin-6 >3.97, von Willebrand factor >3.67, and d-dimer >4.58 (sensitivity, 82.6%; specificity, 59.8%) for RTI. Both panels independently predicted stroke complications (panel for ADHF: odds ratio [OR] [95% CI], 10.1 [3-52.2]; panel for RTI: OR, 3.73 [1.95-7.14]) after adjustment by clinical confounders. The addition of the panel to clinical predictors significantly improved areas under the curve of the receiver operating characteristic curves in both cases. Conclusions Blood biomarkers could be useful for the early prediction of ADHF and RTI. Future studies should assess the usefulness of these panels in front of patients experiencing stroke with respiratory symptoms such as dyspnea

Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes

Altres ajuts: acords transformatius de la UABWe aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01-1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson's r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9-42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13311-023-01385-1

Predictores de reoclusión precoz y resistencia a la recanalización en el tratamiento trombolítico endovenoso del ictus isquémico

El ictus isquémico es uno de los problemas más acuciantes de la sociedad actual. Él único tratamiento aprobado en la actualidad para el ictus agudo en el tratamiento trombolítico endovenoso, que sólo consigue una buena respuesta funcional en el 50% de los casos. Dos de las limitaciones fundamentales del tratamiento trombolítico son la reoclusión arterial y la falta de recanalización. La ultrasonografía carotídea y transcraneal es una técnica no invasiva, realizada a la cabecera del enfermo, que nos permite el diagnóstico etiológico precoz y la evaluación del estado vascular en tiempo real. En los trabajos que conforman esta Tesis Doctoral intentamos averiguar los predictores de reoclusión precoz y de ausencia de recanalización, y su impacto en el tratamiento fibrinolítico.La reoclusión arterial ocurre en un 17% de los pacientes tratados con rt-PA endovenoso, y conlleva una mala evolución clínica precoz y un pobre pronóstico funcional. La gravedad inicial del ictus (NIHSS>16 puntos) y la presencia de una oclusión en tandem carótida/media predicen de forma independiente la aparición de reoclusión.Por otra parte, la oclusión en tandem carótida/media (oTCM: estenosis grave u oclusión de la arteria carótida interna extracraneal y oclusión aguda de la arteria cerebral media ipsilateral) se identifica en aproximadamente un 20% de los pacientes tratados con rtPA e.v. Conlleva un menor porcentaje de recanalización arterial y una peor evolución clínica a corto y largo plazo que la de los pacientes con oclusión aislada de la arteria cerebral media. Sin embargo, la localización de la oclusión intracraneal influye en el impacto de la oclusión en tandem: en oclusiones proximales, la presencia de oTCM predice de forma independiente la falta de recanalización arterial, mientras que en oclusiones distales el único predictor de falta de recanalización arterial la hiperglucemia al ingreso (Glc>140 mg/dl).Así pues, la realización de un estudio ultrasonográfico completo carotídeo y transcraneal en la fase aguda del ictus permite detectar de forma precoz los pacientes con mayor probabilidad de falta de recanalización y/o reoclusión, que se podrían beneficiar de terapias de reperfusión más agresivas.Ischemic stroke is one of the most devastating illnesses in our society. Intravenous thrombolysis is the only approved treatment for acute ischemic stroke, but it only confers a good functional outcome in 50% of cases. Two of the main limitations of systemic thrombolysis are the arterial reocclusion and the lack of recanalization. Carotid and transcranial ultrasound is a non-invasive, bed-side technique which allows us an early etiological diagnose and the vascular monitoring in real-time. The objectives of both studies in this Doctoral Thesis are to detect predictors of early reocclusion and lack of recanalization, and to determine its impact on fibrinolytic treatment. Arterial reocclusion appears in 17% of tPA-treated patients, leading to a worse clinical evolution and a poorer long-term outcome. Stroke severity at onset (NIHSS >16 points) and the presence of a tandem internal carotid artery-middle cerebral artery occlusion predict independently reocclusion.Changing subject, tandem internal carotid artery-middle cerebral artery occlusion (Tandem ICA/MCAo: severe stenosis or occlusion in the extracranial internal carotid artery and acute middle cerebral artery occlusion) can be identified in 20% of acute stroke patients treated with iv tPA. Patients with a tandem ICA/MCA occlusion had lower recanalization rate and a worse early and long-term outcome than patients with an isolated MCA occlusion. However, the impact of the tandem ICA/MCAo varied depending on the location of the intracranial occlusion. Tandem ICA/MCAo predicted independently lack of recanalization in patients with proximal MCA occlusion. In contrast, in patients with a distal MCA occlusion, basal hyperglycemia (Glc >140 mg/dl) was the only predictor of lack of recanalization.Therefore, urgent carotid and transcranial Doppler examination on acute stroke allows the detection of patients with lowest probablily of recanalization or prone to reocclusion, whom could benefice of more aggressive reperfusion strategies

Predictores de reoclusión precoz y resistencia a la recanalización en el tratamiento trombolítico endovenoso del ictus isquémico

Títol obtingut de la portada digitalitzadaConsultable des del TDXEl ictus isquémico es uno de los problemas más acuciantes de la sociedad actual. Él único tratamiento aprobado en la actualidad para el ictus agudo en el tratamiento trombolítico endovenoso, que sólo consigue una buena respuesta funcional en el 50% de los casos. Dos de las limitaciones fundamentales del tratamiento trombolítico son la reoclusión arterial y la falta de recanalización. La ultrasonografía carotídea y transcraneal es una técnica no invasiva, realizada a la cabecera del enfermo, que nos permite el diagnóstico etiológico precoz y la evaluación del estado vascular en tiempo real. En los trabajos que conforman esta Tesis Doctoral intentamos averiguar los predictores de reoclusión precoz y de ausencia de recanalización, y su impacto en el tratamiento fibrinolítico. La reoclusión arterial ocurre en un 17% de los pacientes tratados con rt-PA endovenoso, y conlleva una mala evolución clínica precoz y un pobre pronóstico funcional. La gravedad inicial del ictus (NIHSS>16 puntos) y la presencia de una oclusión en tandem carótida/media predicen de forma independiente la aparición de reoclusión. Por otra parte, la oclusión en tandem carótida/media (oTCM: estenosis grave u oclusión de la arteria carótida interna extracraneal y oclusión aguda de la arteria cerebral media ipsilateral) se identifica en aproximadamente un 20% de los pacientes tratados con rtPA e.v. Conlleva un menor porcentaje de recanalización arterial y una peor evolución clínica a corto y largo plazo que la de los pacientes con oclusión aislada de la arteria cerebral media. Sin embargo, la localización de la oclusión intracraneal influye en el impacto de la oclusión en tandem: en oclusiones proximales, la presencia de oTCM predice de forma independiente la falta de recanalización arterial, mientras que en oclusiones distales el único predictor de falta de recanalización arterial la hiperglucemia al ingreso (Glc>140 mg/dl). Así pues, la realización de un estudio ultrasonográfico completo carotídeo y transcraneal en la fase aguda del ictus permite detectar de forma precoz los pacientes con mayor probabilidad de falta de recanalización y/o reoclusión, que se podrían beneficiar de terapias de reperfusión más agresivas.Ischemic stroke is one of the most devastating illnesses in our society. Intravenous thrombolysis is the only approved treatment for acute ischemic stroke, but it only confers a good functional outcome in 50% of cases. Two of the main limitations of systemic thrombolysis are the arterial reocclusion and the lack of recanalization. Carotid and transcranial ultrasound is a non-invasive, bed-side technique which allows us an early etiological diagnose and the vascular monitoring in real-time. The objectives of both studies in this Doctoral Thesis are to detect predictors of early reocclusion and lack of recanalization, and to determine its impact on fibrinolytic treatment. Arterial reocclusion appears in 17% of tPA-treated patients, leading to a worse clinical evolution and a poorer long-term outcome. Stroke severity at onset (NIHSS >16 points) and the presence of a tandem internal carotid artery-middle cerebral artery occlusion predict independently reocclusion. Changing subject, tandem internal carotid artery-middle cerebral artery occlusion (Tandem ICA/MCAo: severe stenosis or occlusion in the extracranial internal carotid artery and acute middle cerebral artery occlusion) can be identified in 20% of acute stroke patients treated with iv tPA. Patients with a tandem ICA/MCA occlusion had lower recanalization rate and a worse early and long-term outcome than patients with an isolated MCA occlusion. However, the impact of the tandem ICA/MCAo varied depending on the location of the intracranial occlusion. Tandem ICA/MCAo predicted independently lack of recanalization in patients with proximal MCA occlusion. In contrast, in patients with a distal MCA occlusion, basal hyperglycemia (Glc >140 mg/dl) was the only predictor of lack of recanalization. Therefore, urgent carotid and transcranial Doppler examination on acute stroke allows the detection of patients with lowest probablily of recanalization or prone to reocclusion, whom could benefice of more aggressive reperfusion strategies

Validation of the transcranial Doppler rescue criteria for mechanical thrombectomy

Reperfusion; Stroke; ThrombectomyReperfusión; Ictus; TrombectomíaReperfusió; Ictus; TrombectomiaBackground and Purpose Transcranial Doppler (TCD) identifies acute stroke patients with arterial occlusion where treatment may not effectively open the blocked vessel. This study aimed to examine the clinical utility and prognostic value of TCD flow findings in patients enrolled in a multicenter prospective study (CLOTBUST-PRO). Methods Patients enrolled with intracranial occlusion on computed tomography angiography (CTA) who underwent urgent TCD evaluation before intravenous thrombolysis was included in this analysis. TCD findings were assessed using the mean flow velocity (MFV) ratio, comparing the reciprocal ratios of the middle cerebral artery (MCA) depths bilaterally (affected MCA-to-contralateral MCA MFV [aMCA/cMCA MFV ratio]). Results A total of 222 patients with intracranial occlusion on CTA were included in the study (mean age: 64 ± 14 years, 62% men). Eighty-eight patients had M1 MCA occlusions; baseline mean National Institutes of Health Stroke Scale (NIHSS) score was 16, and a 24-hour mean NIHSS score was 10 points. An aMCA/cMCA MFV ratio of <.6 had a sensitivity of 99%, specificity of 16%, positive predictive value (PV) of 60%, and negative PV of 94% for identifying large vessel occlusion (LVO) including M1 MCA, terminal internal carotid artery, or tandem ICA/MCA. Thrombolysis in Brain Ischemia scale, with (grade ≥1) compared to without flow (grade 0), showed a sensitivity of 17.1%, specificity of 86.9%, positive PV of 62%, and negative PV of 46% for identifying LVO. Conclusions TCD is a valuable modality for evaluating arterial circulation in acute ischemic stroke patients, demonstrating significant potential as a screening tool for intravenous/intra-arterial lysis protocols