Intracranial atherosclerotic plaque enhancement and long-term risk of future strokes: A prospective, longitudinal study

Background and Purpose The prognostic significance of postcontrast enhancement of intracranial atheromatous plaque is uncertain. Prospective, long-term follow-up studies in Caucasians, using a multicenter design, are lacking. We aimed to evaluate whether this radiological sign predicts long-term new stroke in symptomatic and asymptomatic intracranial atherosclerotic disease (ICAD) patients. Methods This was a prospective, observational, longitudinal, multicenter study. We included a symptomatic and an asymptomatic cohort of ICAD patients that underwent 3T MRI including high-resolution sequences focused on the atheromatous plaque. We evaluated grade of stenosis, plaque characteristics, and gadolinium enhancement ratio (postcontrast plaque signal/postcontrast corpus callosum signal). The occurrence of new events was evaluated at 3, 6, 9, and 12 months and annually thereafter. The association between plaque characteristics and new stroke was studied using Cox multiple regression survival analysis and Kaplan-Meier curves. Results Forty-eight symptomatic and 13 asymptomatic patients were included. During 56.3 ± 16.9 months, 11 patients (18%) suffered a new event (seven ischemic, two hemorrhagic, and two transient ischemic attacks). A receiver operating characteristic curve identified an enhancement ratio of >1.77 to predict a new event. In a multivariable Cox regression, postcontrast enhancement ratio >1.77 (hazard ratio [HR]= 3.632; 95% confidence interval [CI], 1.082-12.101) and cerebral microbleeds (HR = 5.244; 95% CI, 1.476-18.629) were independent predictors of future strokes. Patients with a plaque enhancement ratio >1.77 had a lower survival free of events (p < .05). Conclusions High intracranial postcontrast enhancement is a long-term predictor of new stroke in ICAD patients. Further studies are needed to elucidate whether postcontrast enhancement reflects inflammatory activity of intracranial atheromatous plaque.This study has been funded by the Spanish Ministry of Science, via FIS project PI13/02544, PI16/01396, and PI19/01398 and through the INVICTUS PLUS research network RD16/0019. Beatriz Gómez-Vicente received a research contract from the Junta de Castilla y León and European Social Fund, Spain. María Hernandez-Perez was funded by The Instituto de Salud Carlos III, Spain (JR17/00006)

Epidemiologic Features and Control Measures during Monkeypox Outbreak, Spain, June 2022

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.S

Brain atrophy and the risk of futile endovascular reperfusion in acute ischemic stroke

[Background and Purpose]: We aimed to evaluate the impact of brain atrophy on long-term clinical outcome in patients with acute ischemic stroke treated with endovascular therapy, and more specifically, to test whether there are interactions between the degree of atrophy and infarct volume, and between atrophy and age, in determining the risk of futile reperfusion.[Methods]: We studied consecutive patients with acute ischemic stroke with proximal anterior circulation intracranial arterial occlusions treated with endovascular therapy achieving successful arterial recanalization. Brain atrophy was evaluated on baseline computed tomography with the global cortical atrophy scale, and Evans index was calculated to assess subcortical atrophy. Infarct volume was assessed on control computed tomography at 24 hours using the formula for irregular volumes (A×B×C/2). Main outcome variable was futile recanalization, defined by functional dependence (modified Rankin Scale score >2) at 3 months. The predefined interactions of atrophy with age and infarct volume were studied in regression models.[Results]: From 361 consecutive patients with anterior circulation acute ischemic stroke treated with endovascular therapy, 295 met all inclusion criteria. Futile reperfusion was observed in 144 out of 295 (48.8%) patients. Cortical atrophy affecting parieto-occipital and temporal regions was associated with futile recanalization. Total global cortical atrophy score and Evans index were independently associated with futile recanalization in an adjusted logistic regression. Multivariable adjusted regression models disclosed significant interactions between global cortical atrophy score and infarct volume (odds ratio, 1.003 [95%CI, 1.002–1.004], P<0.001) and between global cortical atrophy score and age (odds ratio, 1.001 [95% CI, 1.001–1.002], P<0.001) in determining the risk of futile reperfusion.[Conclusions]: A higher degree of cortical and subcortical brain atrophy is associated with futile endovascular reperfusion in anterior circulation acute ischemic stroke. The impact of brain atrophy on insufficient clinical recovery after endovascular reperfusion appears to be independently amplified by age and by infarct volume.This study has been partially funded by the Spanish Ministry of Science, via FIS projects PI13/02544 and PI16/01396, and through the INVICTUS PLUS research network RD16/0019.Peer reviewe

Utilidad pronóstica de las diferentes secuencias de la tomografía computerizada de perfusión en el tratamiento trombolítico del ictus isquémico

La Tomografía Computerizada de Perfusión (PCT) con su mapas de imagen es capaz de definir la penumbra isquémica y el core del infarto. La imagen fuente del PCT (PCT-SI), gracias a su adquisición dinámica de imágenes surge como una técnica prometedora para evaluar la circulación arterial colateral leptomeníngea (CCAL) y predecir el pronóstico de los pacientes con ictus isquémico. Objetivos: 1) Evaluar la frecuencia, seguridad y eficacia de la trombólisis-endovenosa guiada por criterios-PCT en pacientes con ictus isquémico a priori excluibles por criterios tradicionales de SIST-MOST. 2) En pacientes con ictus de >4.5h de evolución seleccionados por PCT, estudiar si la elegibilidad y la respuesta a la trombólisis esndovenosa es comparable entre los pacientes con inicio conocido vs desconocido de los síntomas. 3) Estudiar el impacto pronóstico de la CCAL evaluada por la PCT-SI sobre la respuesta al tPA-intravenoso (iv) en pacientes con ictus isquémico de arteria cerebral media (ACM). 4)Identificar el mejor predictor de la CCAL entre los parámetros cuantitativos de los mapas de PCT y 5) analizar si una respuesta a la recanalización arterial precoz tras el tPA-iv está modulada por dichos parámetros. Métodos: se trata de 4 trabajos longitudinales de cohortes hospitalarias de pacientes con ictus isquémico ingresados en la Unidad de Ictus, tratados con trombólisis-endovenosa y con PCT previo. El primer trabajo, incluyó a los pacientes que cumplían los siguientes supuestos: inicio>4.5h, inicio desconocido ó del despertar, signos precoces de infarto extenso, ictus minor ó severo, inicio con crisis epilépticas. En el segundo trabajo, se incluyeron pacientes con ictus de >4.5h de evolución, dividiendo la muestra en función si el inicio del ictus era conocido ó desconocido. El tercer y cuarto trabajo incluyó pacientes con ictus de ACM y oclusión de la misma detectada con estudio neurosonológico, los pacientes del último trabajo debían presentar un patrón target-mismatch. En el tercer y cuarto trabajo se analizaron las PCT-SI para evaluar el grado de la CCAL. Las variables pronósticas de los trabajos fueron: buen pronóstico 3-mes, mejoría neurológica <24h, recanalización arterial, volumen infarto 24h y transformación hemorrágica sintomática (THS) Resultados: En el primer trabajo, de los 66 pacientes incluidos, 29 (44%) recibieron tPA-iv según criterios-PCT. De ellos 2 (6.9%) presentaron THS y 18 (62.1%) tuvieron buen pornóstico en el día-90. En el segundo trabajo, se incluyeron 147 pacientes, de los cuales 74 tenían inicio conocido vs 73 que desconocian el inicio de la clínica. 37 (50%) del primer grupo y 32 (44%) del segundo fueron tratados con trombólisis-endovenosa según criterios-PCT. No hubo diferencias respectos al buen pronóstico (62.2% vs 56.3%) ni a la THS (3% vs 0%). En el tercer trabajo, presentar buenas CCAL predecia de manera independiente el buen pronóstico al 3-mes (OR 21.02 (95%CI 2.23-197.75, p=0.008). En el cuarto trabajo, el rCBV (volumen sanguíneo cerebral relativo) fue el único predictor independiente de la circulación colateral (OR 12.6 (95% CI 2.9-55.9,p=0.001) Ningun paciente con rCBV<0.93 presentó buen pronóstico al 3-mes en ausencia de recanalización-arterial precoz. Conclusiones: 1) Un 44% de los pacientes con ictus isquémico a priori excluibles según criterios tradicionales, cumplen los criterios de PCT para recibir trombólsis-endovenosa y podrían beneficiarse de él. El tratamiento trombolítico-endovenoso realizado según criterios de PCT parece tan eficaz y seguro como el realizado según criterios SIST-MOST. 2) La eligibilidad y la respuesta al tratamiento trombolítico-endovenoso guiado por criterios de PCT en pacientes con ictus de >4.5h, es comparable entre los pacientes con inicio conocido vs desconocido de la clínica. 3) La CCAL evaluada mediante la PCT-SI predice el pronóstico a largo plazo en los pacientes con ictus isquémico de ACM tratados con tPA-iv. 4) El rCBV es el parámetro de PCT que mejor predice el estado de la circulación colateral. Un valor de rCBV>0.93 se asocia de manera independiente con buenas colaterales. 5)El beneficio de la recanalización-arterial-precoz en pacientes con patrón target-mismatch parece estar modulado por el valor de rCBV previo al tratamiento trombolítico.Departamento de Medicina, Dermatología y Toxicologí

Relative cerebral blood volume is associated with collateral status and infarct growth in stroke patients in SWIFT PRIME

We aimed to evaluate how predefined candidate cerebral perfusion parameters correlate with collateral circulation status and to assess their capacity to predict infarct growth in patients with acute ischemic stroke (AIS) eligible for endovascular therapy. Patients enrolled in the SWIFT PRIME trial with baseline computed tomography perfusion (CTP) scans were included. RAPID software was used to calculate mean relative cerebral blood volume (rCBV) in hypoperfused regions, and hypoperfusion index ratio (HIR). Blind assessments of collaterals were performed using CT angiography in the whole sample and cerebral angiogram in the endovascular group. Reperfusion was assessed on 27-h CTP; infarct volume was assessed on 27-h magnetic resonance imaging/CT scans. Logistic and rank linear regression models were conducted. We included 158 patients. High rCBV ( p = 0.03) and low HIR ( p = 0.03) were associated with good collaterals. A positive association was found between rCBV and better collateral grades on cerebral angiography ( p = 0.01). Baseline and 27-h follow-up CTP were available for 115 patients, of whom 74 (64%) achieved successful reperfusion. Lower rCBV predicted a higher infarct growth in successfully reperfused patients ( p = 0.038) and in the endovascular treatment group ( p = 0.049). Finally, rCBV and HIR may serve as markers of collateral circulation in AIS patients prior to endovascular therapy.Peer reviewe

Quantified ischemic core’s radiological hypodensity and risk of parenchymal hematoma in > 4.5 h-window stroke thrombectomy

We aimed to study the relationship between the ischemic core’s (IC) radiological hypodensity and the risk of parenchymal haematoma after endovascular therapy (EVT) in acute ischemic stroke (AIS) presenting > 4.5 h from onset. We studied AIS patients with a proximal anterior circulation occlusion > 4.5 h from symptoms onset treated with primary EVT. The IC regions of interest (ROI) were manually delineated on pretreatment CT within the affected hemisphere and their specular ROIs on the unaffected side. IC hypodensity ratio was calculated by dividing mean Hounsfield Unit (HU) value from all ROIs in affected/unaffected hemisphere. Primary endpoint: parenchymal hematoma (PH) type hemorrhagic transformation. Secondary: poor long-term clinical outcome. From May 2015 to November 2018, 648 consecutive AIS patients received reperfusion therapies and 107 met all inclusion criteria. PH after EVT was diagnosed in 33 (31%) patients. In bivariate analyses, IC hypodensity ratio (p  4.5 h-window AIS patients treated with primary EVT, although it was not independently associated with a worse clinical outcome.This research has been partially funded by the INVICTUS PLUS Research Network in Cerebrovascular Diseases from the Instituto Carlos III, Ministery of Science, Madrid, Spain (Code RD16/0019) and by the Research Project FIS PI 16/01396 (PI Dr Arenillas), Ministery of Science, Madrid, Spain. Beatriz Gómez-Vicente received a research contract by the Junta de Castilla y León, Spain

Neuronal ischemic tolerance is conditioned by the Tp53 Arg72Pro polymorphism

Trabajo presentado en el 17º Congreso Nacional de la Sociedad Española de Neurociencia, celebrado en Valencia (España), del 27 al 30 de septiembre de 2017Peer reviewe

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017. Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR+/HER2- mBC who had progressed on ≥4 treatments for advanced disease were eligible. A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7-7.0) and the median overall survival was 19.0 months (95% CI 16.4-21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus ≤6 months; HR 1.93, 95% CI 1.37-2.73, p 6 versus ≤6 months; HR 1.93, 95% CI 1.37-2.73, p  Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols