Early and Delayed Infarct Growth in Patients Undergoing Mechanical Thrombectomy: A Prospective, Serial MRI Study.

BACKGROUND: We studied the evolution over time of diffusion weighted imaging (DWI) lesion volume and the factors involved on early and late infarct growth (EIG and LIG) in stroke patients undergoing endovascular treatment (EVT) according to the final revascularization grade. METHODS: This is a prospective cohort of patients with anterior large artery occlusion undergoing EVT arriving at 1 comprehensive stroke center. Magnetic resonance imaging was performed on arrival (pre-EVT), <2 hours after EVT (post-EVT), and on day 5. DWI lesions and perfusion maps were evaluated. Arterial revascularization was assessed according to the modified Thrombolysis in Cerebral Infarction (mTICI) grades. We recorded National Institutes of Health Stroke Scale at arrival and at day 7. EIG was defined as (DWI volume post-EVT-DWI volume pre-EVT), and LIG was defined as (DWI volume at 5d-DWI volume post-EVT). Factors involved in EIG and LIG were tested via multivariable lineal models. RESULTS: We included 98 patients (mean age 70, median National Institutes of Health Stroke Scale score 17, final mTICI≥2b 86%). Median EIG and LIG were 48 and 63.3 mL in patients with final mTICI<2b, and 3.6 and 3.9 cc in patients with final mTICI≥2b. Both EIG and LIG were associated with higher National Institutes of Health Stroke Scale at day 7 (ρ=0.667; P<0.01 and ρ=0.614; P<0.01, respectively). In patients with final mTICI≥2b, each 10% increase in the volume of DWI pre-EVT and each extra pass leaded to growths of 9% (95% CI, 7%-10%) and 14% (95% CI, 2%-28%) in the DWI volume post-EVT, respectively. Furthermore, each 10% increase in the volume of DWI post-EVT, each extra pass, and each 10 mL increase in TMax6s post-EVT were associated with growths of 8% (95% CI, 6%-9%), 9% (95% CI, 0%-19%), and 12% (95% CI, 5%-20%) in the volume of DWI post-EVT, respectively. CONCLUSIONS: Infarct grows during and after EVT, especially in nonrecanalizers but also to a lesser extent in recanalizers. In recanalizers, number of passes and DWI volume influence EIG, while number of passes, DWI, and hypoperfused volume after the procedure determine LIG.

ZDHHC9 X-linked intellectual disability: Clinical and molecular characterization.

The ZDHHC9 gene encodes the Zinc Finger DHHC-Type Containing 9 protein that functions as a palmitoyltransferase. Variants in this gene have been reported as the cause of Raymond-type X-linked intellectual disability with only 16 families described in the literature. This study reviews molecular and clinical data from previously reported patients and reports the case of a 13-year-old patient with a splicing variant in ZDHHC9 presenting intellectual disability, developmental delay, facial dysmorphisms, and skeletal defects. Although intellectual disability and developmental delay with severe speech delay have been reported in all cases with available clinical data, the remaining clinical signs differ significantly between patients. Missense, nonsense, frameshift, and splicing variants, in addition to large exonic deletions, have been described suggesting a loss of function mechanism. Though variants are distributed in almost all exons, most missense and nonsense variants affect arginine residues located in the cytoplasmic domains of this transmembrane protein, suggesting possible mutational hotspots.

Aortic valve Replacement compared to Transcatheter Implant and its relationship with COgnitive Impairment (ARTICO) evaluated with neuropsychological and advanced neuroimaging: a longitudinal cohort study.

BACKGROUND: Aortic stenosis is the most common valvulopathy in Western countries. The treatment of choice had been surgery aortic valve replacement (SAVR), but the improvement in endovascular approaches as transcatheter aortic valve implantation (TAVI), initially reserved for patients with very high surgical risk, has been extended to high and intermediate, and recently also to low-risk patients. Stroke and vascular cognitive impairment are the most important complications. It is not entirely clear which technique is best to avoid these complications as well as their impact. Our goal is to evaluate changes in cognitive performance in the early (1-month) and late (1-year) postoperative period in patients undergoing SAVR or TAVI, by extensive neuropsychological study (NRP) and advanced Magnetic Resonance Imaging (MRI). Specifically, to compare early and late cognitive changes after the intervention between both groups, the occurrence of stroke during follow-up and to compare the appearance of silent vascular lesions and changes in brain activity and functional connectivity with functional MRI during follow-up between both groups. METHODS/DESIGN: Prospective longitudinal cohort study. A non-selected representative sample of 80 subjects, 40 SAVR and 40 TAVI to obtain a final sample of 36 eligible subjects in each group, ranging from 70 to 85 years old, with indication for aortic replacement and intermediate or high surgical risk will be studied. At baseline, within one month before the treatment, all individuals will undergo an extensive NRP and advanced MRI study. These studies will also be performed 1-month and 1-year after treatment, to assess the appearance of new vascular lesions, as well as changes in cognitive performance with respect to baseline. DISCUSSION: This study aims to evaluate changes in cognitive performance as well as both clinical and silent vascular events occurring in the early (1-month) and late (1-year) periods after SAVR and TAVI. We will also analyze the correlation between neuropsychological and neuroimaging approaches in order to evaluate cognition. Therefore, it may provide high-quality data of cognitive changes and vascular events for both techniques, and be useful to tailor interventions to individual characteristics and ultimately aiding in decision-making. TRIAL REGISTRATION: This study is register in Clinicaltrials.gov (NCT05235529) on 11th February 2022.

Non-Functional Carotid Body Tumors in Patients Without Somatic Mutations May Be Considered for Non-Operative Management.

BACKGROUND: Carotid Body Tumors (CBT) are rare neuroendocrine paragangliomas which are typically asymptomatic and benign, with a low rate of biochemical functionality. Historically, early surgical excision was recommended to prevent development of CBT-related complications. Yet, CBT resection can result in significant cranial nerve and vascular injuries. Recent work has shown successful primary observation without resection of non-carotid body, cranial paragangliomas with slow growth and low rate of neuropathies. We hypothesize that primary observation of CBT is safe and may be considered for majority of CBT. METHODS: Retrospective cohort study of patients at a multi-hospital healthcare system with radiologic identification and/or diagnostic or procedural billing codes for CBT (2000-2019). Tumor size (greatest diameter), associated symptoms, and interventions were recorded at the initial evaluation and throughout follow-up. Multivariable logistic regression investigated the risk of initial surgical resection. RESULTS: A total of 108 patients (mean age, 59 ± 19 years; 67% female), with 123 CBT (mean diameter 23 ± 12 mm; 52% right) were initially evaluated by otolaryngologists (51%), vascular surgeons (25%), neurosurgeons (8%), or other (16%) medical providers. Fity-five CBT were initially resected, 63 observed, and 5 irradiated. Initial resection was associated with younger age (adjusted odd ratios aOR, 0.95 [95% confidence intervals CI, 0.92-0.97]), male sex (aOR, 4.82 [95% CI, 1.47-15.75]), and evaluation by a vascular surgeon (aOR, 6.17 [95% CI, 2.04-18.63]). Overall median follow-up was 4.7 (IQR, 2.6-9.1) years. Initially observed CBT were on an average stable in size (mean 1 ± 5 mm/year), none became biochemically active, and 2 patients became symptomatic. At the final follow-up, 63 (51%) underwent surgical resection, 54 (44%) observation, and 6 (5%) radiation therapy. Of the 63 surgically resected CBT, 5 (8%) patients had malignant CBT of which 3 (60%) had known somatic mutations (polymerase epsilon [n = 1], succinate dehydrogenase-D gene [n = 2]). Thirty percent of CBT resections had in-hospital postoperative complications, notably including 1 stroke which occurred in an initially observed patient and 16 cranial nerve complications which all occurred in immediately resected patients. Three resected CBT locally recurred, only 1 of which had malignant pathology. CONCLUSIONS: Patients with newly diagnosed CBT require biochemical functionality and somatic mutation testing. In the absence of these findings, initial observation of CBTs with annual imaging and symptom monitoring may be considered an alternative to immediate resection which demonstrates a high risk of clinically meaningful postoperative complications.

Effect of irrigation protocol during post space preparation on the dentin adhesive interface: An in vitro study.

STATEMENT OF PROBLEM: The post space must be prepared with techniques that do not interfere with the bond strength. These techniques are related to the availability of opened dentinal tubules and incidence of residue among the dentin, the adhesive, and the cement. Nevertheless, the effect of different irrigants during endodontic instrumentation is unclear. PURPOSE: The purpose of this in vitro study was to assess the incidence of residue, the number of opened dentinal tubules, and the bond strength of the cementation system to root dentin of post space after 3 different irrigation protocols. MATERIAL AND METHODS: The roots of bovine incisors were obturated, prepared to receive a fiber post, and divided into 3 groups as per the irrigation protocol: without irrigation, with alternating irrigation, and with continuous irrigation. Thirty roots (n=10) were evaluated by using scanning electron microscopy to assess the incidence of residue (×100 magnification) and the number of opened dentinal tubules (×2000 magnification). The fiber posts were cemented, and the remaining specimens (n=10) were subjected to pushout testing and failure mode evaluation. RESULTS: All protocols presented a similar incidence of residue, regardless of the post space third (P>.05). The irrigation protocol without irrigation had the lowest number of opened dentinal tubules in the cervical and middle thirds (P<.05). The number of opened dentinal tubules was similar in all protocols in the apical third of the post space (P>.05). The irrigation protocol without irrigation had the lowest bond strength values in the cervical and middle thirds (P<.05). The irrigation protocol with continuous irrigation had the highest bond strength values in the apical third (P<.05). CONCLUSIONS: Post space preparation without irrigation negatively affected the bond strength of the resin cementation system to root dentin.

Specific circulating microRNAs display dose-dependent responses to variable intensity and duration of endurance exercise.

Circulating microRNAs (c-miRNAs), plasma-based noncoding RNAs that control posttranscriptional gene expression, mediate processes that underlie phenotypical plasticity to exercise. The relationship and biological relevance between c-miRNA expression and variable dose exercise exposure remains uncertain. We hypothesized that certain c-miRNAs respond to changes in exercise intensity and/or duration in a dose-dependent fashion. Muscle release of such c-miRNAs may then deplete intracellular stores, thus facilitating gene reprogramming and exercise adaptation. To address these hypotheses, healthy men participated in variable intensity ( n = 12, 30 × 1 min at 6, 7, and 8 miles/h, order randomized) and variable duration ( n = 14, 7 × 1 mile/h for 30, 60, and 90 min, order randomized) treadmill-running protocols. Muscle-enriched c-miRNAs (i.e., miRNA-1 and miRNA-133a) and others with known relevance to exercise were measured before and after exercise. c-miRNA responses followed three profiles: 1) nonresponsive (miRNA-21 and miRNA-210), 2) responsive to exercise at some threshold but without dose dependence (miRNA-24 and miRNA-146a), and 3) responsive to exercise with dose dependence to increasing intensity (miRNA-1) or duration (miRNA-133a and miRNA-222). We also studied aerobic exercise-trained mice, comparing control, low-intensity (0.5 km/h), or high-intensity (1 km/h) treadmill-running protocols over 4 wk. In high- but not low-intensity-trained mice, we found increased plasma c-miR-133a along with decreased intracellular miRNA-133a and increased serum response factor, a known miR-133a target gene, in muscle. Characterization of c-miRNAs that are dose responsive to exercise in humans and mice supports the notion that they directly mediate physiological adaptation to exercise, potentially through depletion of intracellular stores of muscle-specific miRNAs. NEW & NOTEWORTHY In this study of humans and mice, we define circulating microRNAs in plasma that are dose responsive to exercise. Our data support the notion that these microRNAs mediate physiological adaptation to exercise potentially through depletion of intracellular stores of muscle-specific microRNAs and releasing their inhibitory effects on target gene expression.

Evidence for GABA-A receptor dysregulation in gambling disorder: correlation with impulsivity.

As a behavioural addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours, and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. This study therefore investigated GABAA receptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [11 C]Ro15-4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity. We found significantly higher [11 C]Ro15-4513 total distribution volume (VT ) in the right hippocampus in the GD group compared with HV. We found higher levels of the 'Negative Urgency' construct of impulsivity in GD, and these were positively associated with higher [11 C]Ro15-4513 VT in the amygdala in the GD group; no such significant correlations were evident in the HV group. These results contrast with reduced binding of GABAergic PET ligands described previously in alcohol and opiate addiction and add to growing evidence for distinctions in the neuropharmacology between substance and behavioural addictions. These results provide the first characterization of GABAA receptors in GD with [11 C]Ro15-4513 PET and show greater α5 receptor availability and positive correlations with trait impulsivity. This GABAergic dysregulation is potential target for treatment.

Influence of microelement concentration on the intensity of alcohol withdrawal syndrome.

AIMS: To establish a nutritional and constitutional profile concerning the micronutrient plasma concentration of patients who suffer from AWS. METHOD: Observational case control study to determine whether patients who exhibited symptoms of AWS (N = 60) had micronutrient plasmatic concentration deficiencies when compared with healthy controls (N = 34). RESULTS: There were statistically significant differences between the concentrations of nutrients that are correlated with glutamate hyperactivity (zinc, magnesium and folate/vitamin B12/homocysteine). CONCLUSION: Evidence from literature and our experiment suggests that brain activity, especially the glutamatergic system, might be directly involved in micronutrient concentrations. Therefore, their supplementation to the AWS patient might improve symptom evolution.

Ouch, my pouch! a clinician's guide to pouchitis.

Pouchitis is defined as inflammation of the ileal pouch created during a restorative proctocolectomy with ileal pouch-anal anastomosis. Although the incidence of this inflammatory condition is high, the exact etiology often remains unclear and the management challenging. In this review, we summarize the clinical presentation, pathogenesis, diagnosis, and management of this common complication.

The role of cGAS in epithelial dysregulation in inflammatory bowel disease and gastrointestinal malignancies.

The gastrointestinal tract is lined by an epithelial monolayer responsible for selective permeability and absorption, as well as protection against harmful luminal contents. Recognition of foreign or aberrant DNA within these epithelial cells is, in part, regulated by pattern recognition receptors such as cyclic GMP-AMP synthase (cGAS). cGAS binds double-stranded DNA from exogenous and endogenous sources, resulting in the activation of stimulator of interferon genes (STING) and a type 1 interferon response. cGAS is also implicated in non-canonical pathways involving the suppression of DNA repair and the upregulation of autophagy via interactions with PARP1 and Beclin-1, respectively. The importance of cGAS activation in the development and progression of inflammatory bowel disease and gastrointestinal cancers has been and continues to be explored. This review delves into the intricacies of the complex role of cGAS in intestinal epithelial inflammation and gastrointestinal malignancies, as well as recent therapeutic advances targeting cGAS pathways.

The effectiveness of treatments for cocaine dependence in schizophrenic patients: a systematic review.

OBJECTIVES: To evaluate and compare the effectiveness of available treatments for cocaine dependence in schizophrenic patients. METHOD: We searched articles published between May 2002 and June 2012 in the following databases: Scopus, Pubmed and Web of Knowledge. The key words utilised were "schizophrenia", "dementia praecox", "schizophrenic disorder", "cocaine related disorder", "cocaine abuse", "cocaine addiction", "cocaine dependence", "treatment", "therapeutic", and "drug therapy". SELECTION OF STUDIES AND DATA EXTRACTION: Original articles in English, Portuguese and Spanish were selected. Controlled, double-blind and open-label studies involving only human subjects were included in this review. DATA SYNTHESIS: We found studies on typical and atypical antipsychotics and one monoamine transporter antagonist. There were few indications of the effectiveness of atypical antipsychotic medications for the treatment of cocaine dependence in patients with schizophrenia. CONCLUSIONS: We suggest that further studies be conducted with atypical antipsychotic medicationsand greater methodological strictness, including using a placebo group in the studies, so that health professionals can determine the real effectiveness of this class of medication for the treatment of cocaine dependence in schizophrenic patients.

Adult Negative Spectator Behavior at Youth Sporting Events.

Due to its competitive nature, youth sports may provide an environment that invites the display of negative parenting behavior and exposes children to adults outside of their own household. This study aimed to quantify the frequency of negative parent and spectator behavior at youth sporting events and compare incidences across different sports and age ranges. Investigators attended baseball, basketball, soccer, and football events in Central O'ahu, Hawai'i for children ages 6 to 10 years. Recorded spectator behaviors included alcohol use, smoking, swearing, and negative language (such as threats and violent language). Negative behaviors were reported at a majority (68%) of events. The 95% confidence intervals of the means (95% CIM) for all negative behaviors observed were overlapping, and we were not able to demonstrate statistically significant differences between the 4 sports. The lack of significance between sports may be due to the younger-player-age group, small sample size, and time of events.

Effect of aging and cementation systems on the bond strength to root dentin after fiber post cementation.

This study evaluated the effect of aging and cementation of fiber posts using glass ionomer and resin cements on push-out bond strength, failure mode, and resin tag formation. One hundred and twenty bovine incisors were used. After post-space preparation, the specimens were randomly allocated into 12 groups (n = 10) according to the cementation system used: GC - GC Gold Label Luting & Lining); RL - RelyX Luting 2; MC - MaxCem Elite; RU - RelyX U200 and the aging periods (24 hours, 6 months, and 12 months). Slices from the cervical, middle, and apical thirds were obtained and analyzed by push-out bond strength test and confocal laser scanning microscopy. One-way ANOVA and Tukey's post-hoc test was used at a significance level of 5%. For the push-out bond strength test, no differences among GC, RU, and MC in the cervical and middle thirds were observed, regardless of the period of storage (P > 0.05). In the apical third, GC and RU showed similar bond strength but higher than other groups (P > 0.05). After 12 months, GC showed the highest bond strength (P < 0.05). Bond strength to post-space dentin decreased over time, regardless of the cementation system used. Cohesive failure was the most frequent, regardless of the period of storage, cementation system, and post-space third. Tag formation was similar among all groups. After 12 months, GC showed the highest bond strength values.

Effect of irrigation protocols on chemical smear layer formation over the post-space dentin.

This study evaluated the effect of irrigation protocols using 95% ethanol (ET) or 1% peracetic acid (PA) prior the use of 2% chlorhexidine (CHX) compared to distilled water (DW) on the chemical smear layer (CSL) formation and incidence of open dentin tubules at the apical, medium, and cervical third of the post-space dentin. Scanning electron microscopy (SEM) and electron dispersive spectroscopy (EDS) images were used. Forty bovine roots were endodontically treated. After, post-space preparation was performed and the roots were randomized in four groups (n = 10) according to the irrigation protocol: DW, CHX, CHX-ET and CHX-PA. The chemical composition of CSL and the incidence of open dentin tubules at the post-space thirds were evaluated by EDS (500× magnification) and SEM (2000× magnification) images, respectively. Data from chemical composition of CSL were descriptively analyzed, while the incidence of open dentin tubules was evaluated by scores and submitted to Kruskal-Wallis and Dunn test (p = .05). Cl, Bi, and Si were the chemical elements most found over the dentin after the irrigation with CHX and CHX-ET. Moreover, CHX and CHX-ET showed the highest incidence of CSL (p < .05), but without difference between them (p > .05), regardless of the post-space third. DW and CHX-PA showed similar incidence of CSL (p > .05). No difference on the incidence of open dentin tubules was found for any irrigation protocol and post-space third (p > .05). The use of 1% PA prior the post-space irrigation with CHX decrease the incidence of CSL. RESEARCH HIGHLIGHTS: The post-space irrigation with chlorhexidine results in the formation of chemical smear layer. Ethanol is not capable to remove the chemical smear layer. Peracetic acid is more effective to remove the chemical smear layer.

FUNCTIONAL EVALUATION OF THE RESULTS OF REPAIR OF PARTIAL AND COMPLETE ROTATOR CUFF TEARS.

Objective: To perform a comparative analysis of the results of arthroscopic surgical treatment of partial and complete rotator cuff (RC) injuries. Methods: Eighty-four shoulders with partial or complete RC tear that underwent arthroscopic repair were retrospectively evaluated using UCLA and Constant scores, assessment of strength, and range of motion. Fifty-seven shoulders with complete injuries and 27 with partial injuries were identified. Results: Age (p = 0.007) was higher in those with complete lesions (mean 61.4 ± 7.9 years), compared to those with partial lesions (mean 56.5 ± 7.1 years). The complete injuries group showed a higher elevation difference in relation to the contralateral shoulder compared to the partial injuries group (partial injuries: -1.1% vs complete injuries: -16.5%), statistically significant difference (p = 0.0004). In addition, complete lesions presented 96.5% of excellent and good results and a median of 35 in the UCLA score and partial lesions presented 84.6% of good/ excellent results and a median of 34. The Constant score showed 91.2% of satisfactory results in complete lesions and 77% in partial ones. Conclusion: Arthroscopic repair shows satisfactory functional results for both partial and complete rotator cuff injuries, with similar outcomes between groups. Level of Evidence III, Retrospective Comparative Study.

Objetivo: Realizar análise comparativa dos resultados do tratamento cirúrgico artroscópico das lesões parciais e completas do manguito rotador (MR). Métodos: Foram avaliados retrospectivamente 84 ombros com ruptura parcial ou completa do MR submetidos ao reparo artroscópico, por meio dos escores UCLA e Constant, avaliação de força e amplitude de movimento. Foram identificados 57 ombros com lesão completa e 27 com lesão parcial. Resultados: A idade (p = 0,007) foi maior naqueles com lesões completas (média 61,4 ± 7,9 anos), em relação às lesões parciais (média 56,5 ± 7,1 anos). O grupo lesões completas demonstrou diferença de elevação em relação ao ombro contralateral maior comparado ao grupo de lesões parciais (lesões parciais: −1,1% vs lesões completas: −16,5%), diferença estatisticamente significativa (p = 0,0004). Além disso, foi demonstrado 96,5% de resultados excelentes e bons e mediana de 35 no escore UCLA em lesões completas e 84,6% de resultados bons/ excelentes e mediana de 34 nas lesões parciais. O escore Constant mostrou 91,2% de resultados satisfatórios nas lesões completas e 77% nas parciais. Conclusão: O reparo artroscópico mostra resultados funcionais satisfatórios tanto nas lesões parciais quanto nas completas do manguito rotador, com desfechos semelhantes entre os grupos. Nível de Evidência III, Estudo Retrospectivo Comparativo.

Comparison of First-Pass Effect in Aspiration vs. Stent-Retriever for Acute Intracranial ICA Occlusion.

The purpose of this study is to evaluate the best endovascular approach (aspiration or stent-retriever) and the impact of stent retriever size and length on clinical and angiographic outcomes in patients with acute intracranial ICA occlusion. We conducted a retrospective analysis of a prospective database of consecutive patients with acute intracranial ICA occlusion undergoing endovascular treatment in four Comprehensive Stroke Center between June-2019 and December-2020. We include 121 patients; Stent-retriever (SR) was used as first technical approach in 107 patients (88.4%) and aspiration was used in 14 patients (11.6%). SR group had higher rate of FPE compared to aspiration group (29 vs. 0%, p = 0.02). In SR subgroup, treatment highlighted higher FPE in the 6 × 50 SR (37.7%), than in the rest of the SR which are 21.2% (4-5 mm size and 20-50 mm length SR) and 19% (6 mm size and 25-40 mm length SR), but it was not found to be statistically significant. There were no other significant differences across the groups regarding primary angiographic or clinical outcomes. In our intracranial ICA occlusion series, stent retrievers were superior to direct aspiration in obtaining FPEs and mFPEs, and longer devices achieved better results with no statistically significant difference. Further studies evaluating the effects of different ICA clot removal approaches are warranted to confirm these results.

Prehospital Stroke Triage.

PURPOSE OF THE REVIEW: This article reviews prehospital organization in the treatment of acute stroke. Rapid access to an endovascular therapy (EVT) capable center and prehospital assessment of large vessel occlusion (LVO) are 2 important challenges in acute stroke therapy. This article emphasizes the use of transfer protocols to assure the prompt access of patients with an LVO to a comprehensive stroke center where EVT can be offered. Available prehospital clinical tools and novel technologies to identify LVO are also discussed. Moreover, different routing paradigms like first attention at a local stroke center ("drip and ship"), direct transfer of the patient to an endovascular center ("mothership"), transfer of the neurointerventional team to a local primary center ("drip and drive"), mobile stroke units, and prehospital management communication tools all aimed to improve connection and coordination between care levels are reviewed. RECENT FINDINGS: Local observational data and mathematical models suggest that implementing triage tools and bypass protocols may be an efficient solution. Ongoing randomized clinical trials comparing drip and ship vs mothership will elucidate which is the more effective routing protocol. SUMMARY: Prehospital organization is critical in realizing maximum benefit from available therapies in acute stroke. The optimal transfer protocols directed to accelerate EVT are under study, and more accurate prehospital triage tools are needed. To improve care in the prehospital setting, efficient tools based on patient factors, local geography, and hospital capability are needed. These tools would optimally lead to individualized real-time decision-making.

Contribution of ultrasonography to the prediction of the induction-delivery interval: The ECOLDIA prospective multicenter cohort study.

INTRODUCTION: To evaluate the ability of preinduction ultrasonographic cervical length to predict the interval between induction and delivery in women at term with a Bishop score of 4 to 6 at induction. STUDY DESIGN: This multicenter prospective observational cohort recruited 334 women from April 2010 to March 2014. Inclusion criteria were women with singleton pregnancies at a gestational age ≥37 weeks, with no previous caesarean, a medical indication for induction of labor, and a Bishop score of 4, 5, or 6. All women underwent cervical assessment by both transvaginal ultrasound and digital examination (Bishop score). The induction protocol was standardized. The primary outcome measure was the induction-delivery interval. Hazard ratios (HR) and their 95% confidence intervals (95% CI) were used to assess potential predictors. RESULTS: Mean gestational age at induction was 40.1 weeks, 60.8% of the women were nulliparous, and the cesarean rate was 13.4%. The mean induction-delivery interval was 20.8 h (± 10.6). Delivery occurred within 24 h for 56.9% (n=190) of the women. An ultrasonographic cervical length measurement less than 25 mm (HR=1.50, 95% CI 1.18-1.91, P<0.01) and parity (HR=1.41, 95% CI 1.21-1.65, P<0.01) appeared to predict induction-delivery interval. The cervical length cutoff to reduce the induction-delivery interval was 25 mm. CONCLUSION: A cervical length cutoff of 25 mm was associated with shorter induction-delivery interval in women at term with a Bishop score of 4 to 6.

Clinical improvement within 24 hours from mechanical thrombectomy as a predictor of long-term functional outcome in a multicenter population-based cohort of patients with ischemic stroke.

BACKGROUND: Single-center studies have suggested that the early clinical course after mechanical thrombectomy (MT) in patients with ischemic stroke is a clinical predictor of long-term outcome. OBJECTIVE: To analyze the prognostic value of clinical improvement within 24 hours in a population-based multicenter cohort. METHODS: From a total of 3792 patients with acute ischemic stroke in Catalonia (CICAT registry), 1951 patients were treated with MT. The National Institutes of Health Stroke Scale (NIHSS) score within 24 hours, and follow-up was available in 1666 patients. Percentage variation in the NIHSS score was calculated in relation to a baseline assessment. Good outcome was defined as a modified Rankin Scale score ≤2 at 90 days. Predictive values of clinical improvement and adjusted OR to predict good outcomes were assessed in the whole cohort and the subgroup of patients with posterior circulation stroke (n=166). RESULTS: Good outcome was achieved in 656/1666 patients (39%) overall. Percentage improvements both at the end of MT and at 24 hours predicted good outcome, with higher predictive capacity at 24 hours (C-statistic, 0.85 vs 0.73, p<0.001). Positive and negative predictive values were 70% and 74% for the >30% cut-off point at the end of MT, and 69% and 84% for the >50% cut-off point at 24 hours, respectively. The adjusted OR for good outcome was 5.8 (95% CI 4.2 to 8.1) and 12.9 (95% CI 9.7 to 17.1), respectively. In patients with posterior circulation stroke, the predictive value of the improvement at 24 hours was similar (C-statistic 0.90). CONCLUSION: Clinical improvement of patients within 24 hours of MT is a reliable and robust predictor of long-term prognosis, including patients with posterior circulation occlusions.

The Chemical Optimization of Cerebral Embolectomy trial: Study protocol.

RATIONALE: The potential value of rescue intraarterial thrombolysis in patients with large vessel occlusion stroke treated with mechanical thrombectomy has not been assessed in randomized trials. AIM: The CHemical OptImization of Cerebral Embolectomy trial aims to establish whether rescue intraarterial thrombolysis is more effective than placebo in improving suboptimal reperfusion scores in patients with large vessel occlusion stroke treated with mechanical thrombectomy. SAMPLE SIZE ESTIMATES: A sample size of 200 patients allocated 1:1 to intraarterial thrombolysis or intraarterial placebo will have >95% statistical power for achieving the primary outcome (5% in the control versus 60% in the treatment group) for a two-sided (5% alpha, and 5% lost to follow-up). METHODS AND DESIGN: We conducted a multicenter, randomized, placebo-controlled, double blind, phase 2b trial. Eligible patients are 18 or older with symptomatic large vessel occlusion treated with mechanical thrombectomy resulting in a modified treatment in cerebral ischemia score 2b at end of the procedure. Patients will receive 20-30 min intraarterial infusion of recombinant tissue plasminogen activator or placebo (0.5 mg/ml, maximum dose limit 22.5 mg). STUDY OUTCOME(S): The primary outcome is the proportion of patients with an improved modified treatment in cerebral ischemia score 10 min after the end of the study treatment. Secondary outcomes include the shift analysis of the modified Rankin Scale, the infarct expansion ratio, the proportion of excellent outcome (modified Rankin Scale 0-1), the proportion of infarct expansion, and the infarction volume. Mortality and symptomatic intracerebral bleeding will be assessed. DISCUSSION: The study will provide evidence whether rescue intraarterial thrombolysis improves brain reperfusion in patients with large vessel occlusion stroke and incomplete reperfusion (modified treatment in cerebral ischemia 2b) at the end of mechanical thrombectomy.