Association between time to reperfusion and outcome is primarily driven by the time from imaging to reperfusion

Background and Purpose A progressive decline in the odds of favorable outcome as time to reperfusion increases is well known. However, the impact of specific workflow intervals is not clear.; Methods We studied the mechanical thrombectomy group (n=103) of the prospective, randomized REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset) trial. We defined 3 workflow metrics: time from symptom onset to reperfusion (OTR), time from symptom onset to computed tomography, and time from computed tomography (CT) to reperfusion. Clinical characteristics, core laboratory-evaluated Alberta Stroke Program Early CT Scores (ASPECTS) and 90-day outcome data were analyzed. The effect of time on favorable outcome (modified Rankin scale, 0-2) was described via adjusted odds ratios (ORs) for every 30-minute delay.; Results Median admission National Institutes of Health Stroke Scale was 17.0 (14.0-20.0), reperfusion rate was 66%, and rate of favorable outcome was 43.7%. Mean (SD) workflow times were as follows: OTR: 342 (107) minute, onset to CT: 204 (93) minute, and CT to reperfusion: 138 (56) minute. Longer OTR time was associated with a reduced likelihood of good outcome (OR for 30-minute delay, 0.74; 95% confidence interval [CI], 0.59-0.93). The onset to CT time did not show a significant association with clinical outcome (OR, 0.87; 95% CI, 0.67-1.12), whereas the CT to reperfusion interval showed a negative association with favorable outcome (OR, 0.72; 95% CI, 0.54-0.95). A similar subgroup analysis according to admission ASPECTS showed this relationship for OTR time in ASPECTS<8 patients (OR, 0.56; 95% CI, 0.35-0.9) but not in ASPECTS8 (OR, 0.99; 95% CI, 0.68-1.44).; Conclusions Time to reperfusion is negatively associated with favorable outcome, being CT to reperfusion, as opposed to onset to CT, the main determinant of this association. In addition, OTR was strongly associated to outcome in patients with low ASPECTS scores but not in patients with high ASPECTS scores.; Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.Peer ReviewedPostprint (author's final draft

Rendimiento cognitivo y síntomas afectivos en la fase aguda y tres meses después de un ictus isquémico

After an ictus, decline of cognitive function, mood and behaviour have been described. Our aim is to correlate the volume of the lesion (in sequences DRM and FLAIR) with the raw scores of cognitive and affective tests. Patients (N = 24) with vascular subcortical cerebral lesions were studied, and cognitive and affective behaviour tests were administered twice. The results show a negative correlation be-tween the volume of the lesion in the DRM sequence and the verbal phonetic fluency (r = -0,42) and naming scores (r = -0,64). A negative correlation is also observed with the Naming Boston Test (r = -0,50) in the FLAIR sequence. Correlations between the volume of the lesion in the left hemisphere and the Trail Making Test part B and the naming test, were statistically significant. With relationship to the second evaluation carried out after three months, a certain improvement of the raw scores of the tests was observed.Después de un ictus, se ha descrito deterioro de la cognición, del humor y de la conducta. Nuestro objetivo fue correlacionar el volumen de la lesión (en secuencias DRM y FLAIR) con puntuaciones directas en test cognitivos y afectivos. Se estudian 24 pacientes con lesiones vasculares cerebrales subcorticales, aplicando en dos ocasiones pruebas cognitivas y afectivas. Los resultados muestran una correlación negativa entre el volumen de la lesión en la secuencia DRM y las pruebas de fluencia verbal fonética (r = -0,42) y denominación (r = -0,64). También se observa una correlación negativa con la prueba de denominación de Boston (r = -0,50) en la secuencia FLAIR. Según la lateralización de la lesión, resultan significativas las correlaciones entre el volumen de la misma en el hemisferio izquierdo y el TMT-B, y con el test de denominación. Con relación a la segunda evaluación llevada a cabo tres meses después, se observa una cierta mejoría de las puntuaciones directas

Circadian rhythms in the efficacy of intravenous alteplase in patients with acute ischemic stroke and middle cerebral artery occlusion

Peer ReviewedPostprint (author's final draft

Analysis and prediction of COVID-19 for EU-EFTA-UK and other countries

The present report aims to provide a comprehensive picture of the pandemic situation of COVID-19 in the EU countries, and to be able to foresee the situation in the next coming days. We employ an empirical model, verified with the evolution of the number of confirmed cases in previous countries where the epidemic is close to conclude, including all provinces of China. The model does not pretend to interpret the causes of the evolution of the cases but to permit the evaluation of the quality of control measures made in each state and a short-term prediction of trends. Note, however, that the effects of the measures’ control that start on a given day are not observed until approximately 7-10 days later. The model and predictions are based on two parameters that are daily fitted to available data: a: the velocity at which spreading specific rate slows down; the higher the value, the better the control. K: the final number of expected cumulated cases, which cannot be evaluated at the initial stages because growth is still exponential. We show an individual report with 8 graphs and a table with the short-term predictions for different countries and regions. We are adjusting the model to countries and regions with at least 4 days with more than 100 confirmed cases and a current load over 200 cases. The predicted period of a country depends on the number of datapoints over this 100 cases threshold, and is of 5 days for those that have reported more than 100 cumulated cases for 10 consecutive days or more. For short-term predictions, we assign higher weight to last 3 points in the fittings, so that changes are rapidly captured by the model. The whole methodology employed in the inform is explained in the last pages of this document. In addition to the individual reports, the reader will find an initial dashboard with a brief analysis of the situation in EU-EFTA-UK countries, some summary figures and tables as well as long-term predictions for some of them, when possible. These long-term predictions are evaluated without different weights to datapoints. We also discuss a specific issue every day.These reports are funded by the European Commission (DG CONNECT, LC-01485746) PJC and MC received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/GN17/50300003; CP, DL, SA, MC, received funding from Ministerio de Ciencia, Innovación y Universidades and FEDER, with the project PGC2018-095456-B-I00Postprint (published version

Transfer to the Local Stroke Center vs Direct Transfer to Endovascular Center of Acute Stroke Patients with Suspected Large Vessel Occlusion in the Catalan Territory (RACECAT): study protocol of a cluster randomized within a cohort trial

Rationale: Optimal pre-hospital delivery pathways for acute stroke patients suspected to harbor a large vessel occlusion (LVO) have not been assessed in randomized trials. Aim: To establish whether stroke subjects with RACE scale based suspicion of LVO evaluated by Emergency Medical Services in the field, have higher rates of favorable outcome when transferred directly to an Endovascular Center (EVT-SC), as compared to the standard transfer to the closest Local Stroke Center (Local-SC).Design: Multicenter, superiority, cluster randomized within a cohort trial with blinded endpoint assessment. Procedure: Eligible patients must be 18 or older, have acute stroke symptoms and not have an immediate life threatening condition requiring emergent medical intervention. They must be suspected to have intracranial LVO based on a pre-hospital RACE scale of ≥5, be located in geographical areas where the default health authority assigned referral stroke center is a non-thrombectomy capable hospital, and estimated arrival at a thrombectomy capable stroke hospital in less than 7 hours from time last seen well. Cluster randomization is performed according to a pre-established temporal sequence (temporal cluster design) with 3 strata: day/night, distance to the EVT-SC and week/week-end day. Study outcome: The primary endpoint is the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome is mortality at 90 days. Analysis: The primary endpoint based on the modified intention-to-treat population is the distribution of modified Rankin Scale scores (mRS) at 90 days analyzed under a sequential triangular design. The maximum sample size is 1754 patients, with two planned interim analyses when 701 (40%) and 1227 patients have completed follow-up. Hypothesized common odds ratio is 1.35.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The trial is sponsored by the nonprofit foundation Fundació Privada Ictus Malaltia Vascular, beneficiary of an unrestricted grant by Medtronic. Trial sponsor: Fundació Privada Ictus Malaltia Vascular. Elisabeth Ortínez ([email protected]). Study sponsor and funders do not participate in the study design, collection, management, analysis and interpretation of data, writing of the report or the decision to submit results for publication

Aterosclerosis cérvico-cerebral subclínica : evaluación del índice REGICOR, el grosor íntima-media y el índice tobillo-brazo en la detección de sujetos en riesgo en la población

La aterosclerosis cérvico-cerebral es una de las principales causas de ictus isquémico, y por tanto, de morbimortalidad en nuestro medio. La detección de la misma en su fase asintomática mediante instrumentos como la función REGICOR, el grosor íntima-media y el índice tobillo-brazo podría mejorar las estrategias de prevención primaria. Comprobamos que, en nuestra cohorte de 933 sujetos sin antecedentes cardiovasculares, los tres factores (REGICOR≥10, GIM≥0.9, ITB≤ 0.9) se asociaron de forma independiente con la presencia de aterosclerosis cérvico-cerebral y de cualquier localización (extracraneal-intracraneal-combinada). La utilización conjunta de REGICOR e ITB podría facilitar el diagnóstico precoz de la aterosclerosis cérvico-cerebral subclínica.L'aterosclerosi cèrvico-cerebral és una de les principals causes d'ictus isquèmic, i per tant, de morbimortalitat al nostre medi. La detecció de la mateixa en la seva fase assimptomàtica mitjançant instruments com la funció REGICOR, el gruix íntima-mitja i l'índex turmell-braç podria millorar les estratègies de prevenció primària. Vam comprovar que, a la nostra cohort de 933 individus sense antecedents cardiovasculars, el tres factors (REGICOR≥10, GIM≥0.9, ITB≤ 0.9) es van associar de forma independent amb la presència d'aterosclerosi cèrvico-cerebral i de qualsevol localització (extracranial-intracranial-combinada). La utilització conjunta de REGICOR i ITB podria facilitar el diagnòstic precoç de l'aterosclerosi cèrvico-cerebral

Impacto de la implementación de un centro terciario de ictus en la atención médica de pacientes con ictus isquémico agudo por disección de arterias cervicales

Evaluamos el impacto que la implementación del centro terciario de ictus (CTI) en nuestro hospital ha tenido sobre el manejo de los pacientes con ictus isquémico por disección de arterias cervicales (DAC) comparando características diagnósticas, tratamiento y pronóstico en los 9 pacientes atendidos antes de la implementación del CTI frente a los 26 atendidos tras la implementación del CTI. Observamos que la implementación del CTI ha incrementado la frecuencia en el diagnóstico de las DAC, ha facilitado realizar un diagnóstico más precoz y ha permitido aumentar las opciones terapéuticas de los pacientes con un ictus agudo por DAC.Avaluem l'impacte que la implementació del centre terciari d'ictus (CTI) en el nostre hospital ha tingut sobre el maneig dels pacients amb ictus isquèmic per dissecció d'artèries cervicals (DAC) comparant característiques diagnòstiques, tractament i pronòstic en els 9 pacients atesos abans de la implementació del CTI davant dels 26 atesos després de la implementació del CTI. Observem que la implementació del CTI ha incrementat la freqüència en el diagnòstic de les DAC, ha facilitat fer un diagnòstic més precoç i ha permès augmentar les opcions terapèutiques dels pacients amb un ictus agut per DAC

MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence

Large cell carcinoma (LCC) is a rare and aggressive lung cancer subtype with poor prognosis and no targeted therapies. Tumor-associated fibroblasts (TAFs) derived from LCC tumors exhibit premature senescence, and coculture of pulmonary fibroblasts with LCC cell lines selectively induces fibroblast senescence, which in turn drives LCC cell growth and invasion. Here we identify MMP1 as overexpressed specifically in LCC cell lines, and we show that expression of MMP1 by LCC cells is necessary for induction of fibroblast senescence and consequent tumor promotion in both cell culture and mouse models. We also show that MMP1, in combination with TGF-ß1, is sufficient to induce fibroblast senescence and consequent LCC promotion. Furthermore, we implicate PAR-1 and oxidative stress in MMP1/TGF-ß1-induced TAF senescence. Our results establish an entirely new role for MMP1 in cancer, and support a novel therapeutic strategy in LCC based on targeting senescent TAFs.Peer ReviewedPostprint (published version

Association between time to reperfusion and outcome is primarily driven by the time from imaging to reperfusion

Background and Purpose A progressive decline in the odds of favorable outcome as time to reperfusion increases is well known. However, the impact of specific workflow intervals is not clear.; Methods We studied the mechanical thrombectomy group (n=103) of the prospective, randomized REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset) trial. We defined 3 workflow metrics: time from symptom onset to reperfusion (OTR), time from symptom onset to computed tomography, and time from computed tomography (CT) to reperfusion. Clinical characteristics, core laboratory-evaluated Alberta Stroke Program Early CT Scores (ASPECTS) and 90-day outcome data were analyzed. The effect of time on favorable outcome (modified Rankin scale, 0-2) was described via adjusted odds ratios (ORs) for every 30-minute delay.; Results Median admission National Institutes of Health Stroke Scale was 17.0 (14.0-20.0), reperfusion rate was 66%, and rate of favorable outcome was 43.7%. Mean (SD) workflow times were as follows: OTR: 342 (107) minute, onset to CT: 204 (93) minute, and CT to reperfusion: 138 (56) minute. Longer OTR time was associated with a reduced likelihood of good outcome (OR for 30-minute delay, 0.74; 95% confidence interval [CI], 0.59-0.93). The onset to CT time did not show a significant association with clinical outcome (OR, 0.87; 95% CI, 0.67-1.12), whereas the CT to reperfusion interval showed a negative association with favorable outcome (OR, 0.72; 95% CI, 0.54-0.95). A similar subgroup analysis according to admission ASPECTS showed this relationship for OTR time in ASPECTS<8 patients (OR, 0.56; 95% CI, 0.35-0.9) but not in ASPECTS8 (OR, 0.99; 95% CI, 0.68-1.44).; Conclusions Time to reperfusion is negatively associated with favorable outcome, being CT to reperfusion, as opposed to onset to CT, the main determinant of this association. In addition, OTR was strongly associated to outcome in patients with low ASPECTS scores but not in patients with high ASPECTS scores.; Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.Peer Reviewe

Influencia del ingreso en una Unidad de Monitorización vídeo-EEG prolongada en función del tiempo de evolución de epilèpsia

Se desconoce si existe un tiempo de evolución límite a partir del cual ingresar en una UMVEEG* no suponga una mejoría del pronóstico del paciente epiléptico. El estudio analiza el efecto del ingreso en la UMVEEG sobre una serie de variables pronósticas (FC**, NFAE***, CVP****) en función del tiempo de evolución desde el diagnóstico. Analizamos epilépticos diagnosticados con certeza y pacientes con crisis psicógenas. Se estudiaron 135 pacientes(Edad:39+13,5años,Sexo(55,6%mujeres).Se obtuvo una mejoría significativa de FC**(p 0,001)y CVP****(p 0,005)en los grupos estudiados independientemente del tiempo de evolución.El tiempo de evolución determinó una respuesta diferencial sobre la reducción del NFAE***excepto para crisis psicógenas,en que hubo una reducción significativa(p=0,004)independientemente del tiempo de evolución.Actualment es desconeix si existeix un temps límit d'evolució a partir del qual l'ingrés a una UMVEEG*no millori el pronòstic del pacient epilèptic.L'estudi analitza l'efecte ingrés a UMVEEG* sobre una sèrie de variables pronòstic(FC**,NFAE***,QVP****)segons el temps d'evolució des del diagnòstic.Es van analitzar pacients epilèptics confirmats i pacients amb crisis psicògenes. Es van estudiar 135 pacients(Edat:39+13,5anys,Sexe(55,6%dones).Es va obtenir una milloria significativa de FC**(p 0,001)i CVP****(p 0,005)a tots els grups estudiats independentment del temps d'evolució.El temps d'evolució va determinar una resposta diferencial sobre la reducció del NFAE***amb l'excepció de crisis psicògenes,que varen reduir significativament(p=0,004)el NFAE***independentment del temps d'evolució