Influence of vascular imaging acquisition at local stroke centers on workflows in the drip-n-ship model: a RACECAT post hoc analysis.

BACKGROUND: The influence of vascular imaging acquisition on workflows at local stroke centers (LSCs) not capable of performing thrombectomy in patients with a suspected large vessel occlusion (LVO) stroke remains uncertain. We analyzed the impact of performing vascular imaging (VI+) or not (VI- at LSC arrival on variables related to workflows using data from the RACECAT Trial. OBJECTIVE: To compare workflows at the LSC among patients enrolled in the RACECAT Trial with or without VI acquisition. METHODS: We included patients with a diagnosis of ischemic stroke who were enrolled in the RACECAT Trial, a cluster-randomized trial that compared drip-n-ship versus mothership triage paradigms in patients with suspected acute LVO stroke allocated at the LSC. Outcome measures included time metrics related to workflows and the rate of interhospital transfers and thrombectomy among transferred patients. RESULTS: Among 467 patients allocated to a LSC, vascular imaging was acquired in 277 patients (59%), of whom 198 (71%) had a LVO. As compared with patients without vascular imaging, patients in the VI+ group were transferred less frequently as thrombectomy candidates to a thrombectomy-capable center (58% vs 74%, P=0.004), without significant differences in door-indoor-out time at the LSC (median minutes, VI+ 78 (IQR 69-96) vs VI- 76 (IQR 59-98), P=0.6). Among transferred patients, the VI+ group had higher rate of thrombectomy (69% vs 55%, P=0.016) and shorter door to puncture time (median minutes, VI+ 41 (IQR 26-53) vs VI- 54 (IQR 40-70), P<0.001). CONCLUSION: Among patients with a suspected LVO stroke initially evaluated at a LSC, vascular imaging acquisition might improve workflow times at thrombectomy-capable centers and reduce the rate of futile interhospital transfers. These results deserve further evaluation and should be replicated in other settings and geographies.

Prehospital care process and hospital outcomes in stroke-code cases: comparison of basic and advance life support ambulance attendance. / Proceso de atención prehospitalaria y resultados hospitalarios del código ictus: estudio comparativo entre unidades de soporte vital básico y avanzado.

OBJECTIVES: To study prehospital care process in relation to hospital outcomes in stroke-code cases first attended by 2 different levels of ambulance. To analyze factors associated with a satisfactory functional outcome at 3 months. MATERIAL AND METHODS: Prospective multicenter observational cohort study. All stroke-code cases attended by prehospital emergency services from January 2016 to April 2022 were included. Prehospital and hospital variables were collected. The classificatory variable was type of ambulance attending (basic vs advanced life support). The main outcome variables were mortality and functional status after ischemic strokes in patients who underwent reperfusion treatment 90 days after the ischemic episode. RESULTS: Out of 22 968 stroke-code activations, ischemic stroke was diagnosed in 12 467 patients (54.3%) whose functional status was good before the episode. Basic ambulances attended 93.1%; an advanced ambulance was ordered in 1.6% of the patients. Even though there were differences in patient and clinical characteristics recorded during the prehospital process, type of ambulance was not independently associated with mortality (adjusted odds ratio [aOR], 1.1; 95% CI, 0.77-1.59) or functional status at 3 months (aOR, 1.05; 95% CI, 0,72-1,47). CONCLUSION: The percentage of patient complications in stroke-code cases attended by basic ambulance teams is low. Type of ambulance responding was not associated with either mortality or functional outcome at 3 months in this study.

OBJETIVO: Comparar el proceso asistencial prehospitalario y los resultados hospitalarios de los pacientes categorizados como Código Ictus (CI) en función del tipo de ambulancia que realiza la primera valoración, y analizar los factores asociados con un buen resultado funcional y la mortalidad a los 3 meses. METODO: Estudio observacional de cohortes prospectivo multicéntrico. Incluyó todos los CI atendidos por un sistema de emergencias prehospitalario desde enero del 2016 a abril del 2022. Se recogieron variables prehospitalarias y hospitalarias. La variable de clasificación fue el tipo de ambulancia que asiste el CI: unidad de soporte vital básico (USVB) o avanzado (USVA). Las variables de resultado principal fueron la mortalidad y el estado funcional de los ictus isquémicos sometidos a tratamiento de reperfusión a los 90 días del episodio. RESULTADOS: Se incluyeron 22.968 pacientes, de los cuales 12.467 (54,3%) presentaron un ictus isquémico con un buen estado funcional previo. El 93,1% fueron asistidos por USVB y se solicitó una USVA en el 1,6% de los casos. A pesar de presentar diferencias en el perfil clínico del paciente atendido y en los tiempos del proceso CI prehospitalario, el tipo de unidad no mostró una asociación independiente con la mortalidad (OR ajustada 1,1; IC 95%: 0,77- 1,59) ni con el estado funcional a los 3 meses (OR ajustada 1,05; IC 95%: 0,72-1,47). CONCLUSIONES: El porcentaje de complicaciones de los pacientes con CI atendidos por USVB es bajo. El tipo de unidad que asistió al paciente inicialmente no se asoció ni con el resultado funcional ni con la mortalidad a los 3 meses.

Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment: A Phase 1/2 Randomized Clinical Trial.

Importance: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers. Objective: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. Design, Setting, and Participants: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT. Interventions: In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated. Main Outcomes and Measures: The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score). Results: In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:√2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 patients (36%) receiving ApTOLL, 0.05 mg/kg (11 deaths [26.2%], 3 sICH [7.2%], 2 malignant strokes [4.8%], and 2 recurrent strokes [4.8%]); and in 6 of 42 patients (14%) receiving ApTOLL, 0.2 mg/kg (2 deaths [4.8%], 2 sICH [4.8%], and 3 recurrent strokes [7.1%]). ApTOLL, 0.2 mg/kg, was associated with lower NIHSS score at 72 hours (mean difference log-transformed vs placebo, -45%; 95% CI, -67% to -10%), smaller final infarct volume (mean difference log-transformed vs placebo, -42%; 95% CI, -66% to 1%), and lower degrees of disability at 90 days (common odds ratio for a better outcome vs placebo, 2.44; 95% CI, 1.76 to 5.00). Conclusions and Relevance: In acute ischemic stroke, 0.2 mg/kg of ApTOLL administered within 6 hours of onset in combination with EVT was safe and associated with a potential meaningful clinical effect, reducing mortality and disability at 90 days compared with placebo. These preliminary findings await confirmation from larger pivotal trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04734548.

APRIL: A double-blind, placebo-controlled, randomized, Phase Ib/IIa clinical study of ApTOLL for the treatment of acute ischemic stroke.

In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect in preclinical models of stroke and a very good pharmacokinetic and safety profile in healthy volunteers, is a promising first-in-class aptamer with the potential to address this huge unmet need. This protocol establishes the clinical trial procedures to conduct a Phase Ib/IIa clinical study (APRIL) to assess ApTOLL tolerability, safety, pharmacokinetics, and biological effect in patients with AIS who are eligible for EVT. This will be a multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to evaluate the administration of ApTOLL together with EVT in patients with AIS. The study population will be composed of men and non-pregnant women with confirmed AIS with a <6h window from symptoms onset to ApTOLL/placebo administration. The trial is currently being conducted and is divided into two parts: Phase Ib and Phase IIa. In Phase Ib, 32 patients will be allocated to four dose ascending levels to select, based on safety criteria, the best two doses to be administered in the following Phase IIa in which 119 patients will be randomized to three arms of treatment (dose A, dose B, and placebo). Identification of the trial: EudraCT: 2020-002059-38 and ClinicalTrials.gov Identifier: NCT04734548 https://clinicaltrials.gov/ct2/show/NCT04734548?term=ApTOLL&cond=Stroke&draw=2&rank=1.

Association of Time of Day With Outcomes Among Patients Triaged for a Suspected Severe Stroke in Nonurban Catalonia.

BACKGROUND: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. METHODS: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am-8:59 pm) and nighttime (9:00 pm-7:59 am). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. RESULTS: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR], 1.620 [95% CI, 1.020-2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680-1.163]; P interaction=0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548-1.072]; nighttime, acOR, 1.785 [95% CI, 1.024-3.112] ; P interaction<0.01); no heterogeneity was observed for other stroke subtypes (P interaction>0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. CONCLUSIONS: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795962.

Evolution of quality indicators in acute stroke during the RACECAT Trial: Impact in the general population.

BACKGROUND: Acute ischemic stroke patients not referred directly to a comprehensive stroke center (CSC) have reduced access to endovascular treatment (EVT). The RACECAT trial is a population-based cluster-randomized trial, designed to compare mothership and drip-and-ship strategies in acute ischemic stroke patients outside the catchment area of a CSC. AIMS: To analyze the evolution of performance indicators in the regions that participated in RACECAT. METHODS: This retrospective longitudinal observational study included all stroke alerts evaluated by emergency medical services in Catalonia between February 2016 and February 2020. Cases were classified geographically according to the nearest SC: local SC (Local-SC) and CSC catchment areas. We analyzed the evolution of EVT rates and relevant workflow times in Local-SC versus CSC catchment areas over three study periods: P1 (February 2016 to April 2017: before RACECAT initiation), P2 (May 2017 to September 2018), and P3 (October 2018 to February 2020). RESULTS: We included 20603 stroke alerts, 10,694 (51.9%) of which were activated within Local-SC catchment areas. The proportion of patients receiving EVT within Local-SC catchment areas increased (P1 vs. P3: 7.5% (95% confidence interval (CI), 6.4-8.7) to 22.5% (95% CI, 20.8-24.4) p < 0.001). Inequalities in the odds of receiving EVT were reduced for patients from CSC versus Local-SC catchment areas (P1: odds ratio (OR) 3.9 (95% CI, 3.2-5) vs. P3: OR 1.5 (95% CI, 1.3-1.7) In Local-SC, door-to-image (P1: 24 (interquartile range (IQR) 15-36), P2: 24 (15-35), P3: 21 (13-32) min, p < 0.001) and door-to-needle times (P1: 42 (31-60), P2: 41 (29-58), P3: 35 (25-50) p < 0.001) reduced. Time from Local-SC arrival to groin puncture also decreased over time (P1: 188 [151-229], P2: 190 (157-233), P3: 168 (127-215) min, p < 0.001). CONCLUSION: An increase in EVT rates in Local-SC regions with a significant decrease in workflow times occurred during the period of the RACECAT trial.

Unique Challenges to Diagnosing Human Herpesvirus-6 (HHV-6) Encephalitis Following Post-Hematopoietic Stem Cell Transplant: A Case and Brief Review.

A patient with an ultimate diagnosis of human herpesvirus-6 (HHV-6) encephalitis developed central nervous system (CNS) symptoms 13 days after undergoing myeloablative haploidentical allogeneic hematopoietic stem cell transplant (HSCT). Due to the patient's body habitus, magnetic resonance (MR) imaging was not obtained until the onset of retrograde amnesia on day +24. MR imaging and other clinical findings eliminated all skepticism of HHV-6 encephalitis and HHV-6 antivirals were initiated on day +28, leading to gradual recovery. This case demonstrates some of the factors that may complicate the diagnosis of post-alloHSCT HHV-6 encephalitis. Because HHV-6 encephalitis and viremia can occur without warning, a single negative study should not exclude future development, especially if CNS symptoms are present. Acute graft-versus-host disease and cord blood transplantation are both significant risk factors for HHV-6 encephalitis. Human leukocyte antigen (HLA) mismatch, engraftment complications, or certain HLA alleles have also been associated with HHV-6 encephalitis. Chromosomally integrated HHV-6 must also be ruled out to prevent inappropriate and potentially harmful administration of antivirals. Due to the severe short- and long-term sequelae of HHV-6 encephalitis, appropriate treatment should be administered as soon as possible.

Transcranial Doppler findings in reversible cerebral vasoconstriction syndrome.

BACKGROUND AND PURPOSE: Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome characterized by reversible segmental vasoconstriction of cerebral arteries. Digital subtraction and noninvasive angiograms are typically used to detect vasospasm; however, due to the dynamic nature of RCVS these tests are often negative initially and may need to be repeated multiple times. Transcranial Doppler (TCD) offers many advantages as it is a noninvasive and nonradiating modality. Studies investigating its diagnostic utility for capturing vasospasm and studying temporal evolution of RCVS are limited. METHODS: We conducted a retrospective analysis on all patients admitted with suspected RCVS from 2009 to 2014 to a single center at Jackson Memorial Hospital. RESULTS: We identified 9 patients (88.9% women, age 46.6 ± 13.5 years) who met diagnostic criteria for RCVS. All patients presented with headache, 5 developed nonaneurysmal subarachnoid hemorrhage, 5 developed ischemic stroke, and 1 developed posterior reversible encephalopathy syndrome. At initial TCD, 8 patients had increased flow velocities in at least one large intracranial artery and ultimately all patients had abnormal middle cerebral artery flow velocity over the course of RCVS. We found that the number of vessels with abnormal velocities increases gradually and peaks between 13 and 14 days after first symptom onset. Finally, mean flow velocity of affected vessels also increases around the same time frame and normalizes at 60 days. CONCLUSIONS: In this case series, we found TCD to be useful in detecting vasospasm and monitoring the temporal evolution of RCVS. TCD could be a helpful clinical tool to diagnose and monitor RCVS.

The Role of Vascular Imaging atReferral Centers in the Drip and Ship Paradigm.

BACKGROUND: In drip-and-ship protocols, non-invasive vascular imaging (NIVI) at Referral Centers (RC), although recommended, is not consistently performed and its value is uncertain. We evaluated the role of NIVI at RC, comparing patients with (VI+) and without (VI-) vascular imaging in several outcomes. METHODS: Observational, multicenter study from a prospective government-mandated population-based registry of code stroke patients. We selected acute ischemic stroke patients, initially assessed at RC from January-2016 to June-2020. We compared and analyzed the rates of patients transferred to a Comprehensive Stroke Center (CSC) for Endovascular Treatment (EVT), rates of EVT and workflow times between VI+ and VI- patients. RESULTS: From 5128 ischemic code stroke patients admitted at RC; 3067 (59.8%) were VI+, 1822 (35.5%) were secondarily transferred to a CSC and 600 (11.7%) received EVT. Among all patients with severe stroke (NIHSS ≥16) at RC, a multivariate analysis showed that lower age, thrombolytic treatment, and VI+ (OR:1.479, CI95%: 1.117-1.960, p=0.006) were independent factors associated to EVT. The rate of secondary transfer to a CSC was lower in VI+ group (24.6% vs. 51.6%, p<0.001). Among transferred patients, EVT was more frequent in VI+ than VI- (48.6% vs. 21.7%, p<0.001). Interval times as door-in door-out (median-minutes 83.5 vs. 82, p= 0.13) and RC-Door to puncture (median-minutes 189 vs. 178, p= 0.47) did not show differences between both groups. CONCLUSION: In the present study, NIVI at RC improves selection for EVT, and is associated with receiving EVT in severe stroke patients. Time-metrics related to drip-and-ship model were not affected by NIVI.

Tratamiento del embarazo ectópico no complicado con inyección local de metotrexato / Management of uncomplicated ectopic pregnancy with local injection of methotrexate

Resumen OBJETIVO: Describir la experiencia en la atención de pacientes con embarazo ectópico no complicado con una inyección local de metotrexato guiada por ecografía. MATERIALES Y MÉTODOS: Estudio retrospectivo, descriptivo y de serie de casos llevado a cabo del 1 de enero del 2021 al 28 de febrero del 2022 en el Instituto Nacional Materno Perinatal, Lima, Perú. Las participantes tuvieron embarazo ectópico no complicado, tratado con inyección local de metotrexato guiada por ecografía. Los datos se obtuvieron de los registros en las historias clínicas. El análisis estadístico se procesó en el programa SPSS 19. RESULTADOS: Se registraron 222 casos de embarazo ectópico y se aplicaron 11 inyecciones locales con metotrexato guiadas por ecografía. De acuerdo con su localización 4 embarazos fueron tubáricos, 1 cervical y 6 en cicatriz de cesárea. La edad promedio de las embarazadas fue de 34.5 años. El promedio de semanas de embarazo fue de 7. La concentración inicial de b-hCG fue de 42812.55 mU/mL. El tamaño promedio del saco gestacional fue de 22.8 mm. El tamaño medio de los embriones fue de 7.81 mm. Se detectó actividad cardiaca embrionaria en 10 casos que recibieron una inyección intratorácica de cloruro de potasio hasta que no se evidenció el latido cardiaco. Un solo caso recibió una dosis sistémica adicional de metotrexato. Otro caso resultó con hemoperitoneo, por rotura de embarazo ectópico luego de la inyección local. CONCLUSIONES: La inyección local de metotrexato, guiada por ecografía, es una alternativa a otras técnicas quirúrgicas aplicadas para tratar pacientes con embarazo ectópico no complicado, con indicación quirúrgica.

Abstract OBJECTIVE: To describe the experience in the care of patients with uncomplicated ectopic pregnancy with ultrasound-guided local injection of methotrexate. MATERIALS AND METHODS: Retrospective, descriptive, case series study conducted from January 1, 2021 to February 28, 2022 at the Instituto Nacional Materno Perinatal, Lima, Peru. Participants had uncomplicated ectopic pregnancy treated with ultrasound-guided local injection of methotrexate. Data were obtained from medical records. Statistical analysis was processed in SPSS 19. RESULTS: 11 ultrasound-guided local methotrexate injections were performed. According to their location 4 pregnancies were tubal, 1 cervical and 6 in cesarean scar. The average age of the pregnant women was 34.5 years. The average number of weeks of pregnancy was 7. The initial b-hCG concentration was 42812.55 mU/mL. The mean gestational sac size was 22.8 mm. The mean embryo size was 7.81 mm. Embryonic cardiac activity was detected in 10 cases that received an intrathoracic injection of potassium chloride until no heartbeat was evident. A single case received an additional systemic dose of methotrexate. Another case resulted in hemoperitoneum, due to rupture of ectopic pregnancy after local injection. CONCLUSIONS: Ultrasound-guided local injection of methotrexate is an alternative to other surgical techniques applied to treat patients with uncomplicated ectopic pregnancy with surgical indication.

Fighting Against Stroke in Latin America: A Joint Effort of Medical Professional Societies and Governments.

Introduction: Stroke is one of the leading causes of death in Latin America, a region with countless gaps to be addressed to decrease its burden. In 2018, at the first Latin American Stroke Ministerial Meeting, stroke physician and healthcare manager representatives from 13 countries signed the Declaration of Gramado with the priorities to improve the region, with the commitment to implement all evidence-based strategies for stroke care. The second meeting in March 2020 reviewed the achievements in 2 years and discussed new objectives. This paper will review the 2-year advances and future plans of the Latin American alliance for stroke. Method: In March 2020, a survey based on the Declaration of Gramado items was sent to the neurologists participants of the Stroke Ministerial Meetings. The results were confirmed with representatives of the Ministries of Health and leaders from the countries at the second Latin American Stroke Ministerial Meeting. Results: In 2 years, public stroke awareness initiatives increased from 25 to 75% of countries. All countries have started programs to encourage physical activity, and there has been an increase in the number of countries that implement, at least partially, strategies to identify and treat hypertension, diabetes, and lifestyle risk factors. Programs to identify and treat dyslipidemia and atrial fibrillation still remained poor. The number of stroke centers increased from 322 to 448, all of them providing intravenous thrombolysis, with an increase in countries with stroke units. All countries have mechanical thrombectomy, but mostly restricted to a few private hospitals. Pre-hospital organization remains limited. The utilization of telemedicine has increased but is restricted to a few hospitals and is not widely available throughout the country. Patients have late, if any, access to rehabilitation after hospital discharge. Conclusion: The initiative to collaborate, exchange experiences, and unite societies and governments to improve stroke care in Latin America has yielded good results. Important advances have been made in the region in terms of increasing the number of acute stroke care services, implementing reperfusion treatments and creating programs for the detection and treatment of risk factors. We hope that this approach can reduce inequalities in stroke care in Latin America and serves as a model for other under-resourced environments.

COVID-19 Lockdown Effects on Acute Stroke Care in Latin America.

OBJECTIVES: COVID-19 pandemic has forced important changes in health care worldwide. Stroke care networks have been affected, especially during peak periods. We assessed the impact of the pandemic and lockdowns in stroke admissions and care in Latin America. MATERIALS AND METHODS: A multinational study (7 countries, 18 centers) of patients admitted during the pandemic outbreak (March-June 2020). Comparisons were made with the same period in 2019. Numbers of cases, stroke etiology and severity, acute care and hospitalization outcomes were assessed. RESULTS: Most countries reported mild decreases in stroke admissions compared to the same period of 2019 (1187 vs. 1166, p = 0.03). Among stroke subtypes, there was a reduction in ischemic strokes (IS) admissions (78.3% vs. 73.9%, p = 0.01) compared with 2019, especially in IS with NIHSS 0-5 (50.1% vs. 44.9%, p = 0.03). A substantial increase in the proportion of stroke admissions beyond 48 h from symptoms onset was observed (13.8% vs. 20.5%, p < 0.001). Nevertheless, no differences in total reperfusion treatment rates were observed, with similar door-to-needle, door-to-CT, and door-to-groin times in both periods. Other stroke outcomes, as all-type mortality during hospitalization (4.9% vs. 9.7%, p < 0.001), length of stay (IQR 1-5 days vs. 0-9 days, p < 0.001), and likelihood to be discharged home (91.6% vs. 83.0%, p < 0.001), were compromised during COVID-19 lockdown period. CONCLUSIONS: In this Latin America survey, there was a mild decrease in admissions of IS during the COVID-19 lockdown period, with a significant delay in time to consultations and worse hospitalization outcomes.

Vascular Occlusion Evolution in Endovascular Reperfusion Candidates Transferred from Primary to Comprehensive Stroke Centers.

BACKGROUND: The evolution of the symptomatic intracranial occlusion during transfers from primary stroke centers (PSCs) to comprehensive stroke centers (CSCs) for endovascular treatment (EVT) is not widely known. Our aim was to identify factors related to partial or complete recanalization (REC) at CSC arrival in patients with a documented large vessel occlusion (LVO) in PSC transferred for EVT evaluation to better define the workflow at CSC of this group of patients. METHODS: We conducted an observational, multicenter study from a prospective, government-mandated, population-based registry of stroke patients with documented LVO at PSC transferred to CSC for EVT from January 2017 to June 2019. The primary end point was defined as partial or complete REC that precluded EVT at CSC arrival (REC). We evaluated the association between baseline, treatment variables and time intervals with the presence of REC. RESULTS: From 589 patients, the rate of REC at CSC was 10.5% in all LVO patients transferred from PSC to CSC for EVT evaluation. On univariate analysis, lower PSC-NIHSS (median 12vs.16, p = 0.001), tPA treatment at PSC (13.7 vs. 5.0%; p = 0.001), presence of M2 occlusion on PSC (16.8 vs. 9%; p = 0.023), and clinical improvement at CSC arrival (21.7 vs. 9.6% p = 0.001) were associated with REC at CSC. On multivariate analysis, clinical improvement at CSC arrival (p < 0.001, OR: 5.96 95% CI: 2.5-13.9) and PSC tPA treatment predicted REC (p = 0.003, OR: 4.65, 95% CI: 1.73-12.4). CONCLUSION: REC at CSC arrival occurs exceptionally in patients with a documented LVO on PSC. Repeating a second vascular study before EVT would not be necessary in most patients. Despite its modest effect, tPA treatment at PSC was an independent predictor of REC.

Factores de riesgo cardiovascular en pacientes con accidente cerebrovascular

RESUMEN Introducción: la enfermedad cerebro vascular es causa de discapacidad y de muerte en las personas. Se presenta cada vez más en la población de adultos jóvenes. Objetivo: determinar los factores de riesgo cardiovascular en pacientes con accidente cerebro vascular ingresados en el Hospital de Clínicas (San Lorenzo, Paraguay). Material y método: diseño observacional, descriptivo, retrospectivo de corte transversal, que incluyó a pacientes adultos con diagnóstico de accidente cerebro vascular en la Unidad de ictus del Servicio de Urgencias del Hospital de Clínicas desde enero 2015 a marzo 2018. Se determinaron las variables demográficas, diagnóstico de accidente cerebro vascular, antecedentes de ictus previo, presencia de factores de riesgo cardiovascular (hipertensión arterial, diabetes mellitus, consumo de tabaco y fibrilación auricular). Resultados: se incluyeron 618 pacientes con diagnóstico de accidente cerebro vascular, de los cuales 119 pacientes (19,3%) fueron menores de 50 años, de los cuales 75 (63%) fueron de tipo isquémico. Los factores de riesgo cardiovascular más frecuentes fueron la hipertensión arterial (47,9%) y la diabetes mellitus (9,2%). Conclusión: el tipo más frecuente de accidente cerebro vascular fue el isquémico. Los factores de riesgo cardiovascular más frecuentes en los adultos jóvenes con accidente cerebro vascular fueron la hipertensión arterial y la diabetes mellitus.

ABSTRACT Introduction: Cerebrovascular disease is the cause of disability and death in people. It occurs more and more in the population of young adults. Objective: To determine the cardiovascular risk factors in patients with cerebrovascular accident admitted to the Hospital de Clínicas (San Lorenzo, Paraguay). Material and method: Observational, descriptive, retrospective cross-sectional design, which included adult patients with a diagnosis of stroke in the Ictus Unit of the Emergency Department of the Hospital de Clínicas from January 2015 to March 2018. Demographic variables, diagnosis of stroke, history of previous stroke, presence of cardiovascular risk factors (arterial hypertension, diabetes mellitus, smoking and atrial fibrillation) were determined. Results: Six hundred eighteen patients with a diagnosis of stroke were included, 119 patients (19.3%) of them were younger than 50 years, and 75 (63%) were ischemic. The most frequent cardiovascular risk factors were high blood pressure (47.9%) and diabetes mellitus (9.2%). Conclusion: The most frequent type of stroke was ischemic. The most frequent cardiovascular risk factors in young adults with stroke were arterial hypertension and diabetes mellitus.

Sex Differences Among Participants in the Latin American Stroke Registry.

Background Reports on sex differences in stroke outcome and risk factors are scarce in Latin America. Our objective was to analyze clinical and prognostic differences according to sex among participants in the LASE (Latin American Stroke Registry). Methods and Results Nineteen centers across Central and South America compiled data on demographics, vascular risk factors, clinical stroke description, ancillary tests, and functional outcomes at short-term follow-up of patients included from January 2012 to January 2017. For the present study, all these variables were analyzed according to sex at hospital discharge. We included 4788 patients with a median in-hospital stay of 8 days (interquartile range, 5-8); 2677 were male (median age, 66 years) and 2111 female (median age, 60 years). Ischemic stroke occurred in 4293: 3686 as cerebral infarction (77%) and 607 as transient ischemic attack cases (12.7%); 495 patients (10.3%) corresponded to intracerebral hemorrhage. Poor functional outcome (modified Rankin scale, 3-6) was present in 1662 (34.7%) patients and 38.2% of women (P<0.001). Mortality was present in 6.8% of the registry, with 7.8% in women compared with 6.0% in men (P=0.01). Death and poor functional outcome for all-type stroke showed a higher risk in female patients (hazard ratio, 1.3, P=0.03; and hazard ratio, 1.1, P=0.001, respectively). Conclusions A worse functional outcome and higher mortality rates occurred in women compared with men in the LASE, confirming sex differences issues at short-term follow-up.

Priorities to reduce the burden of stroke in Latin American countries.

The large and increasing burden of stroke in Latin American countries, and the need to meet the UN and WHO requirements for reducing the burden from non-communicable disorders (including stroke), brought together stroke experts and representatives of the Ministries of Health of 13 Latin American countries for the 1st Latin American Stroke Ministerial meeting in Gramado, Brazil, to discuss the problem and identify ways of cooperating to reduce the burden of stroke in the region. Discussions were focused on the regional and country-specific activities associated with stroke prevention and treatment, including public stroke awareness, prevention strategies, delivery and organisation of care, clinical practice gaps, and unmet needs. The meeting culminated with the adoption of the special Gramado Declaration, signed by all Ministerial officials who attended the meeting. With agreed priorities for stroke prevention, treatment, and research, an opportunity now exists to translate this Declaration into an action plan to reduce the burden of stroke.

Impact of prehospital stroke code in a public center in Paraguay: A pilot study.

Prehospital stroke code activation results in reduced pre- and in-hospital delays and triage and transport of stroke patients to the right centers. In Paraguay, data about acute reper fusion treatment are not available. Recently, a pilot prehospital stroke code program was implemented in the country in November 2016. In an observational, single-center cohort study with a before-after design, from April 2015 to July 2018, we found that 193/832 (23.1%) of stroke patients were stroke code activated, and from these, 54 (6.5%) were brought to hospital under the prehospital stroke code protocol. Fifty-eight patients (58 alteplase and 2 additional endovascular treatment) received reperfusion therapy. Prehospital stroke code patients had a lower mean door-to-CT time (24 vs. 33 min, p = 0.021) and lower mean door-to-needle time (35.3 vs.76.3 min, p < 0.001) compared to in-hospital stroke code patients. Prehospital stroke code is feasible in Paraguay and has a positive impact on in-hospital acute stroke management, reducing delays and increasing the rates of reperfusion treatments.

Admission CT perfusion may overestimate initial infarct core: the ghost infarct core concept.

BACKGROUND: Identifying infarct core on admission is essential to establish the amount of salvageable tissue and indicate reperfusion therapies. Infarct core is established on CT perfusion (CTP) as the severely hypoperfused area, however the correlation between hypoperfusion and infarct core may be time-dependent as it is not a direct indicator of tissue damage. This study aims to characterize those cases in which the admission core lesion on CTP does not reflect an infarct on follow-up imaging. METHODS: We studied patients with cerebral large vessel occlusion who underwent CTP on admission but received endovascular thrombectomy based on a non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS) >6. Admission infarct core was measured on initial cerebral blood volume (CBV) CTP and final infarct on follow-up CT. We defined ghost infarct core (GIC) as initial core minus final infarct >10 mL. RESULTS: 79 patients were studied. Median National Institutes of Health Stroke Scale (NIHSS) score was 17 (11-20), median time from symptoms to CTP was 215 (87-327) min, and recanalization rate (TICI 2b-3) was 77%. Thirty patients (38%) presented with a GIC >10 mL. GIC >10 mL was associated with recanalization (TICI 2b-3: 90% vs 68%; p=0.026), admission glycemia (<185 mg/dL: 42% vs 0%; p=0.028), and time to CTP (<185 min: 51% vs >185 min: 26%; p=0.033). An adjusted logistic regression model identified time from symptom to CTP imaging <185 min as the only predictor of GIC >10 mL (OR 2.89, 95% CI 1.04 to 8.09). At 24 hours, clinical improvement was more frequent in patients with GIC >10 mL (66.6% vs 39%; p=0.017). CONCLUSIONS: CT perfusion may overestimate final infarct core, especially in the early time window. Selecting patients for reperfusion therapies based on the CTP mismatch concept may deny treatment to patients who might still benefit from reperfusion.

Improving the Evaluation of Collateral Circulation by Multiphase Computed Tomography Angiography in Acute Stroke Patients Treated with Endovascular Reperfusion Therapies.

Good collateral circulation (CC) is associated with favorable outcomes in acute stroke, but the best technique to evaluate collaterals is controversial. Single-phase computed tomography angiography (sCTA) is widely used but lacks temporal resolution. We aim to compare CC evaluation by sCTA and multiphase CTA (mCTA) as predictors of outcome in endovascular treated patients. METHODS: Consecutive endovascular treated patients with M1 middle cerebral artery (MCA) or terminal intracranial carotid artery (TICA) occlusion confirmed by sCTA were included. Two more CTA acquisitions with 8- and 16-second delays were performed for mCTA. Endovascular thrombectomy was performed independently of the CC status according to a local protocol [Alberta Stroke Program Early CT score (ASPECTS) >6, modified Rankin scale (mRS) score <3]. CC on sCTA and mCTA were compared. RESULTS: 108 patients were included. Their mean age was 69.6 ± 13 years and their median National Institutes of Health Stroke Scale (NIHSS) score was 17 (interquartile range 8). 79 (73.1%) had M1 MCA and 29 (26.9%) TICA occlusions. The mean time from symptom onset to CTA was 146.8 ± 96.5 min. On sCTA, 50.9% patients presented good CC vs. 57.5% on mCTA. Good CC status in both sCTA and mCTA had a lower 24-hour infarct volume (27.4 vs. 74.8 cm3 on sCTA, p = 0.04; 17.2 vs. 97.8 cm3 on mCTA, p < 0.01). However, only good CC on mCTA was associated with lower 24-hour (5 vs. 8.5, p = 0.04) and median discharge NIHSS (2 vs. 4.5, p = 0.04) scores and functional independency (mRS score <3) at 3 months (76.9 vs. 23.1%, p < 0.01). In a logistic regression model including age, NIHSS, ASPECTS and recanalization, only age (OR 0.96, 95% CI 0.93-0.99, p = 0.02) and good CC on mCTA (OR 5, 95% CI 1.99-12.6, p < 0.01) were independent predictors of functional outcome at 3 months. CONCLUSION: CC evaluation by mCTA is a better prognostic marker than CC evaluation by sCTA for clinical and functional endpoints in acute stroke patients treated with endovascular thrombectomy.

Nivel de proteína C-reactiva en comparación con el recuento leucocitario materno en la predicción de corioamnionitis histológica en gestantes con rotura prematura de membranas pretérmino / Levels of C-reacti ve protein compared with mat ernal leukocyte count in predicting histological chorioa mnionitis in pregnant women with preterm prematur e rupture of membranes

Objetivo: Demostrar la utilidad del nivel de proteína C- reactiva en comparación con el recuento leucocitario materno en la predicción de corioamnionitis histológica en gestantes con rotura prematura de membranas pretérmino. Diseño: Estudio no experimental, tipo validación de prueba diagnóstica. Institución: Instituto Nacional Materno Perinatal, Lima, Perú. Participantes: Gestantes con rotura prematura de membranas pretérmino, entre enero y junio del 2013. Intervenciones: Se incluyó gestantes pretérmino con edad gestacional ≥22 semanas y < 37 semanas, con rotura prematura de membranas, fetos únicos e historia clínica disponible con información requerida completa. Para el análisis estadístico se usó el programa SPSS 19. Principales medidas de resultados: Índices diagnósticos del nivel de proteína C-reactiva y recuento leucocitario. Resultados: La incidencia de corioamnionitis histológica fue 76,3% (71/93). La edad promedio de las gestantes fue 29,0 +- 6,6 años. La rotura ocurrió con más frecuencia con edad materna de 25 a 30 años (31,2%) y en nulíparas; la edad gestacional promedio fue 29,2 + 3,4 semanas, más frecuente entre las 27 y 31 semanas (51,6%) y en nulíparas de riesgo social mediano. El periodo de latencia promedio fue 12,6 + 10,9 días y el parto ocurrió dentro de los 15 días de la rotura (74%). El nivel de PCR promedio fue 29,6 + 26,9 mg/L, con diferencia altamente significativa (p=0,00) para la corioamnionitis histológica. Su sensibilidad fue 98,6%, especificidad 45,5%, valor predictivo positivo 85,4% y valor predictivo negativo 90,9%. La curva ROC predijo corioamnionitis histológica con un área bajo la curva de 0,861 (IC95%: 0,77 a 0,95) (p = 0,000); estableciendo en 12,45 mg/L el punto de corte por encima del cual se puede predecir el riesgo de corioamnionitis histológica. El recuento leucocitario fue 15 519,5 + 4 410,5 cel/mL, sin diferencia significativa (p=0,790). Su sensibilidad fue 52,1%, especificidad 63,6%, valor predictivo positivo 82,2% y valor predictivo negativo 29,2%.El área bajo la curva ROC 0,714 (IC 95% 0,587 a 0,84) demostró significancia estadística (p= 0,002), teniendo como punto de corte 13 490 cel/mL. Conclusiones: El nivel de proteína C-reactiva fue más confiable que el recuento leucocitario materno en la predicción de corioamnionitis histológica en gestantes con rotura prematura de membranas pretérmino.

Objectives: To determine the usefulness of C-reactive protein level compared with maternal leukocyte count in the prediction of histological chorioamnionitis in pregnant women with preterm premature rupture of membranes. Design: Non-experimental, validation of diagnostic test study. Setting: Instituto Nacional Materno Perinatal, Lima, Peru. Participants: Pregnant women with preterm premature rupture of membranes (PTPROM), between January and June, 2013. Interventions: Pregnant women with gestational age ≥ 22 weeks and <37 weeks, with premature rupture of membranes, single fetus, medical history available and complete required information were included. The SPSS 19 program was used for statistical analysis. Main outcome measures: C-reactive protein level and leukocyte count diagnostic indices. Results: The incidence of histological chorioamnionitis was 76.3% (71/93). The mean age of pregnant women was 29.0+ -6.6 years. The rupture occurred more frequently in women 25-30 years (31.2%) at mean gestational age 29.3+ -3.4 weeks; it was more prevalent at 27-31 weeks of gestation (51.6%), in middle social risk nulliparae. The average latency period was 12.6+-10.9 days and birth occurred within 15 days of PTPROM (74%). The average CRP level was 29.6+-26.9 mg/L for histological chorioamnionitis with significant difference (p =0.00). Its sensitivity was 98.6%, specificity 45.5%, positive predictive value 85.4% and negative predictive value 90.9%. The ROC curve predicted histological chorioamnionitis with an area under the curve of 0.861 (95% CI: 0.77 to 0.95) (p=0.000); the cutoff point above which the risk of histological chorioamnionitis could be predicted was 12.45 mg/L. The white blood cell count was 15 519.5+-4 410.5 cells/mL, with no significant difference (p = 0.790). Its sensitivity was 52.1%, specificity 63.6%, positive predictive value 82.2% and negative predictive value 29.2%. The area under the ROC curve 0.714. (95% CI 0.587 to 0.84) showed statistical significance (p = 0.002), with the cutoff 13 490 cells/mL. Conclusions: The level of C-reactive protein was more reliable than the maternal leukocyte count in predicting histological chorioamnionitis in pregnant women with premature rupture of fetal membranes.