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This randomized clinical trial investigates if the oral selective vasopressin 1a receptor antagonist, balovaptan, improves socialization and communication difficulties in children and adolescents with autism spectrum disorder.
This randomized clinical trial examines the efficacy and safety of treatment with apatinib plus pegylated liposomal doxorubicin in Chinese patients with platinum-resistant recurrent ovarian cancer.
This randomized clinical trial investigates the efficacy of trastuzumab and PD-1 inhibitor with CTLA-4 inhibitor or FOLFOX in first-line treatment of advanced ERBB2-positive esophagogastric adenocarcinoma.
Objectives
Although exercise is considered the preferred approach for tendinopathies, the actual load that acts on the tendon in loading programmes is usually unknown. The objective of this study was to review the techniques that have been applied in vivo to estimate the forces and strain that act on the human tendon in dynamic exercises used during rehabilitation.
Design
Scoping review.
Data sources
Embase, PubMed, Web of Science and Google Scholar were searched from database inception to February 2021.
Eligibility criteria
Cross-sectional studies available in English or Spanish language were included if they focused on evaluating the forces or strain of human tendons in vivo during dynamic exercises. Studies were excluded if they did not evaluate tendon forces or strain; if they evaluated running, walking, jumping, landing or no dynamic exercise at all; and if they were conference proceedings or book chapters.
Data extraction and synthesis
Data extracted included year of publication, study setting, study population characteristics, technique used and exercises evaluated. The studies were grouped by the types of techniques and the tendon location.
Results
Twenty-one studies were included. Fourteen studies used an indirect methodology based on inverse dynamics, nine of them in the Achilles and five in the patellar tendon. Six studies implemented force transducers for measuring tendon forces in open carpal tunnel release surgery patients. One study applied an optic fibre technique to detect forces in the patellar tendon. Four studies measured strain using ultrasound-based techniques.
Conclusions
There is a predominant use of inverse dynamics, but force transducers, optic fibre and estimations from strain data are also used. Although these tools may be used to make general estimates of tendon forces and strains, the invasiveness of some methods and the loss of immediacy of others make it difficult to provide immediate feedback to the individuals.
This comparative effectiveness study compares the cure rates of battery-powered electrocautery and curettage vs electrodesiccation and curettage in treating nonmelanoma skin cancer.
Stroke, Volume 53, Issue Suppl_1, Page A106-A106, February 1, 2022. Introduction:After decades of consistent declines, stroke mortality started to level off beginning in 2013, with increases seen in younger stroke patients.Methods:We performed a post hoc analysis of county-level stroke death rate per 100,000 adults, for ischemic and hemorrhagic stroke, from 1999-2018 using CDC estimates. We stratified by age 35-64 (young) and ≥65 (old), and by county-level geographic factors and unemployment rate.Results:We included data from over 3,000 counties. Figure 1 shows stroke mortality began to increase for younger patients in 2013-14, but continued to decline for older patients. The second row shows that the disparity in stroke death rate for younger rural patients was no longer significant from 2005-13 (overlapping 95% CIs), but from 2014-18, younger rural patients had a significantly higher rate of stroke death compared to urban/suburban patients. Younger patients in counties with more unemployment (vs. less) or in the South (vs. other Census regions) had higher rates of stroke death. Figure 2 shows county-level changes by 5-year periods (e.g. 1999-2003 vs. 2004-08), which highlight the spread over time of increased stroke death rate in all regions of the contiguous United States for younger patients.Conclusions:The trend of consistently decreasing stroke death rate stabilized in 2013, with subsequent increase seen for younger adults aged 35-64, particularly in rural, Southern, and high unemployment counties.
Stroke, Volume 53, Issue Suppl_1, Page ATP224-ATP224, February 1, 2022. Background:Aortic arch atherosclerotic plaques of >4mm thickness, evaluated by a transesophageal echocardiogram (TEE) correlate with embolic ischemic stroke. Computed tomography angiography (CTA) of the neck, routinely done during stroke evaluation, is an alternative for the evaluation of aortic arch plaque. We hypothesized that CTA evaluation of the aortic arch plaque is comparable to TEE.Methods:We prospectively measured thickness, extent through different parts of the aortic arch (ascending, arch, and descending aorta), location of the maximal plaque thickness, calcification, mobility, and presence of thrombus in the aortic arch plaque on CTA neck and TEE exams in non-consecutive stroke patients from the hospital database. All measurements were done independently by 2 radiologists for the CTA of neck and 2 cardiologists for TEE. Paired t-test was used for mean difference and Wilcoxon signed-rank test for median difference between TEE and CTA.Results:Of 63 patients who had both CTA and TEE, 31 (mean age ± SD; 54 ± 14.46 years) were included in this analysis; as in 32 patients, aortic arch was not included on the CTA neck. Although maximal plaque thickness was comparable for both methods (CTA 3.0 ± 1.10 vs TEE 3.18 ± 2.54, p=0.68), CTA more commonly showed the extent of the plaque throughout all areas (ascending, arch, and descending) of the aorta (CTA: 25/31 vs TEE: 15/31, p
Stroke, Volume 53, Issue Suppl_1, Page ATP244-ATP244, February 1, 2022. Background:Stroke is one of the leading causes of death and disability. Some aspects of inflammation are known to be detrimental and arresting these aspects may improve stroke outcomes. Neutrophils are critical neuroinflammatory mediators and among the first immune cells to respond to the onset of stroke. As the stroke evolves, neutrophils may expel their intracellular contents, referred to as Neutrophil Extracellular Traps (NETs), in a process called NETosis. NETs increase microvascular occlusion and lead to further progression of stroke. However, the interaction of NETs with the cerebral microvascular endothelial cells and the effect of this interaction on stroke outcomes is poorly understood. This project aims to investigate this relationship.Methods:Leukocytes and plasma from C57BL/6 wildtype mice were isolated from whole blood. The leukocytes were then plated in 24-well plates and divided into control and Oxygen Glucose Deprivation (OGD) simulating a stroke environment in vitro. Thereafter, leukocytes were subjected to immunofluorescent staining for neutrophils (Ly6G), and the NETosis markers citrullinated histones (CitH3) and dsDNA. Media from both groups was assayed for Neutrophil Elastase, IL-6, TNF-α, and lactate dehydrogenase (LDH). The remaining media was used to treat primary microvascular endothelial cells to assess inflammation and cell death.Results:Ly6G antibody staining verified that most of the leukocytes plated were neutrophils. The CitH3 and dsDNA immunostaining confirmed induction of NETosis in the OGD group. We also found a significant increase in IL-6 and LDH levels suggesting significant inflammation and cell death in OGD treated leukocytes. Exposure of endothelial cells with NETs enriched media obtained from OGD exposed leukocytes resulted in significant decrease in cell count and increase in IL-6 and LDH levels, suggesting that NETs promoted inflammation and death in the endothelial cells. Nuclear staining of the endothelial cells also exhibited significant decrease in cell count in cohorts treated with the OGD exposed leukocyte media.Conclusion:These pilot data suggest that NETosis may contribute to the cytotoxicity of cerebral endothelial cells during stroke and serve as a potential therapeutic target.
Stroke, Volume 53, Issue Suppl_1, Page A131-A131, February 1, 2022. Background:In acute ischemic stroke (AIS), Computed Tomography Perfusion (CT, CTP) is the most widely used technique for determining extent of tissue likely to die even after successful reperfusion. However, CTP results in higher radiation dose to the patient, is affected by motion, and is not widely available. Multiphase CT Angiography (mCTA), by contrast, is a low radiation extension to the ubiquitous CT Angiography workflow. Here, we evaluate StrokeSENS mCTA Perfusion, a software tool that uses mCTA to estimate brain tissue perfusion, and compare it to CTP in its ability to predict final infarction.Methods:551 subjects with baseline mCTA, Non-contrast CT (NCCT), and CTP were included. Of these, 480 were part of the development dataset used to derive the mCTA Perfusion algorithm while the remaining 71 were included in the test dataset. Tmaxand CBF perfusion maps were generated on CTP using GE CTP-4D Perfusion, and on mCTA using StrokeSENS mCTA Perfusion. Final infarction was manually segmented on 24-48h MRI/NCCT by 2 experts using ITK-SNAP. Voxel values from CTP and mCTA were assessed in their ability to predict final infarction at an individual patient level (AUC calculated for each patient, then averaged across patients) and for the combined patient data (voxels pooled across patients, then one AUC calculated), then compared (two-sided difference test p-value, p).Results:At patient level, mCTA Perfusion TmaxAUC was 77.7% (95% c.i.: [74%, 82%]) while CTP TmaxAUC was 74.6% (95% c.i.: [71%, 79%]), p=0.15. mCTA Perfusion CBF AUC was 68.5% (95% c.i.: [65%, 72%]) while CTP CBF AUC was 69.8% (95% c.i.: [67%, 73%]), p=0.43. In combined patient data analysis, mCTA perfusion TmaxAUC was 84.13% while CTP TmaxAUC was 81.36%, p=0. mCTA perfusion CBF AUC was 74.44% while CTP CBF AUC was 72.51%, p=0.Conclusion:StrokeSENS mCTA Perfusion software is similar to traditional CT Perfusion in its ability to predict final infarction in patients with acute ischemic stroke.
Stroke, Volume 53, Issue Suppl_1, Page AWP85-AWP85, February 1, 2022. Introduction:Mission: Lifeline Stroke Nebraska (NE) is a four-year project which aims to improve stroke systems of care within the state through various interventions, including education of healthcare providers. Timely in-hospital treatment of stroke patients is key to reducing death and disability in stroke patients.Methods:An anonymous survey was administered to physicians and advanced practice providers that work in the ED at NE hospitals to assess the comfort/confidence level in administering IV thrombolytics and to learn more about the reasons for giving (and not giving) IV thrombolytics in various scenarios, including when an ischemic stroke is mild (NIHSS
Stroke, Volume 53, Issue Suppl_1, Page A30-A30, February 1, 2022. Introduction:Black individuals are disproportionally affected by stroke, yet little is known about the effect of region of origin and acculturation on stroke mortality. We examined associations between nativity and stroke outcomes among Black individuals in the US.Methods:Using the National Health Interview Service 2000-2014 data and mortality linked files through 2015, we identified participants aged 25-74 years who self-identified as Black (n=64,717). We categorized Black race by birth region, i.e. foreign-born (Caribbean, South and Central American, and African) vs. US-born. Stroke was determined by self-report. Using Cox regression, we examined the association between nativity and all-cause, cardiovascular (CV), and stroke mortality, adjusting for age, sex, education, income, smoking, and body mass index, overall and by time since migration.Results:Overall, 4329 deaths (including 205 stroke and 932 CV deaths) were recorded during the study period. Weighted cumulative incidence of all-cause, CV, and stroke mortality at 10 years follow up were 12.62%, 2.76%, and 0.59% for those born in the US; 6.12%, 1.58%, and 0.45% for those born in the Caribbean, South and Central America; and 3.15%, 0.54%, and 0.08% for those born in Africa. In the model adjusted for demographic factors, compared to US-born Black individuals, rates of all cause and CV mortality were lower among Black individuals born in the Caribbean, South and Central America [all-cause mortality: aHR (95%CI): 0.46 (0.38-0.55); CV mortality [0.60 (0.40-0.89)], but rates of stroke mortality were similar [1.00 (0.55-1.99)]. African-born Black individuals had lower all-cause mortality rates [0.50 (0.32-0.80)] and trended toward having lower CV [0.47 (0.20-1.13)] mortality rates compared to those born in the US. The above findings remained similar after adjusting for smoking and BMI. Time since migration did not significantly affect mortality outcomes among foreign born Blacks.Conclusion:Foreign-born Black individuals generally have lower all cause and CV mortality regardless of time since migration. These findings highlight the need for more granular information regarding region of origin and acculturation to understand and target racial disparities.
Stroke, Volume 53, Issue Suppl_1, Page AWP160-AWP160, February 1, 2022. Modified first pass effect (mFPE) of TICI 2B or greater is an independent predictor of clinical outcome in patients who undergo mechanical thrombectomy (MT). Location of the occlusion in the M1 segment may affect the mFPE and may influence clinical outcomes. A comparison of mFPE between occlusions of the proximal and distal (sparing lenticulostriate branches) M1 segments of the MCA has yet to be performed. We aim to examine the interaction between first pass effect and clinical outcomes in proximal versus distal M1 occlusions. We performed retrospective analysis of patients who underwent MT between 2014 and 2020. Patients were included if they were treated for M1 occlusion within 24 hours from last seen normal, and achieved successful recanalization (TICI2b or greater). Patients were excluded if they were not successfully recanalized, or if they had other intracranial or multifocal occlusions. A total of 264 patients were included in this analysis. Ninety two patients had proximal M1 occlusions and 172 had distal M1 occlusions. Patients with proximal M1 occlusions had higher NIHSS (median 18 vs. 16, p=0.003), lower ASPECTS (mean 8.5 vs 9, p=0.02), and were less likely to be females (44.6% vs. 62.8%, p=0.006). Modified first pass effect was achieved in 45.3% of distal M1 occlusions compared to 31.9% of proximal (p=0.047). Excellent clinical outcome, defined as mRS of 0-1 at 90 days was higher in distal occlusion group (38.8% vs. 24.7%, p=0.03). Additionally, the proximal occlusion group was more likely to experience any grade of hemorrhagic transformation (HT) (37.4 vs. 23.3, p=0.02). Other baseline characteristics and time metrics did not differ between the two groups. In a multivariate analysis of predictors of excellent outcome in the overall cohort, ASPECTS (OR=1.39, p=0.026) and proximal occlusion site (OR=0.485, p=0.037) were the only two independent predictors. Therefore, mFPE was not a predictor of excellent outcome when adjusted for exact location of occlusion.
Stroke, Volume 53, Issue Suppl_1, Page ATMP43-ATMP43, February 1, 2022. Background:Health equity and the reduced socioeconomic gap between communities are the main objectives of healthcare delivery in the US with a shifting focus towards social determinants of health. We aimed to compare stroke hospitalizations and outcomes in young patients with low median household income (LMHI) across two national cohorts a decade apart (2007 vs. 2017).Methods:We used National Inpatient Sample (2007 & 2017) to identify young-onset stroke hospitalizations (18-44 years, YOS) belonging to LMHI (0-25th quartile) using relevant codes. Demographics, comorbidities, adjusted risk of YOS and outcomes were compared between two cohorts.Results:Of 34249 LMHI YOS admissions, 13749 belonged to 2007 and 20500 to 2017 (median age 39 vs 38 years, p
Stroke, Volume 53, Issue Suppl_1, Page ANS2-ANS2, February 1, 2022. Introduction:Post-stroke depression (PSD) is under-recognized and affects the recovery and rehabilitation of stroke patients. PSD affects one-third of stroke survivors, but there is little known when to screen for depressive symptoms. The purpose of this study is to determine the optimal timing of depression screening at 7 days vs. 30-45 days post discharge.Methods:All stroke patients received a phone call from a stroke certified RN (SCRN) to assess depression within 7 days and within 30-45 days post discharge using the Patient Health Questionnaire Screening Tool (PHQ9). Three call attempts were made. Data were analyzed from 2018 to 2020. Based on the PHQ9 scores, patients were referred to different clinical care pathways. Patients who scored 1-9 received lifestyle modification information, 10-19 were referred to depression care management, 20 and above were referred to psychiatry. The number of patients evaluated and the percentage of those who were referred to specific pathways were assessed. Data were analyzed using a t-test.Results:Stroke subtype were as follows: 17% ICH, 80% ischemic, 2% SAH. 1001 patients were called: 564 at 7 days, 437 at 30-45 days. 421 (75%) at 7 days and 277 (63%) at 30-45 days were reached. 11 (3%) at 7 days, 30 (11%) (p=0.045) at 30-45 days scored ≥10 on the PHQ9. Of those who scored ≥10 on PHQ9, 28 (68%) were female and more than half were over the age of 65. 91% of patients had NIHSS ≤5.Conclusion:A higher percentage of patients with PHQ9 ≥10 was detected within 30-45 days post discharge. The 30-45 day time period is more optimal to detect PSD than the 7-day time period post discharge.
Stroke, Volume 53, Issue Suppl_1, Page ATMP74-ATMP74, February 1, 2022. Introduction:Direct oral anticoagulants (DOACs) have emerged as a potential anticoagulant therapy for patients with cerebral venous thrombosis (CVT). We conducted a systematic review and meta-analysis comparing DOACs versus vitamin K antagonists (VKAs) for treatment of CVT.Methods:We registered the review in PROSPERO (registration number CRD42021228800). We searched Medline, Embase, CINAHL, and the Web of Science Core Collection from January 1, 2007, to May 26, 2021. We included randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) evaluating key outcomes for efficacy (recurrent venous thromboembolism [VTE] and complete recanalization) and safety (major hemorrhage). We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0 (for RCTs) and the ROBINS-I tool (for NRCSs). Where studies were sufficiently similar, we performed meta-analyses using random-effects models. This review was funded by Brown Neurology.Results:Of 8213 identified records,10 studies (1 RCT and 9 NRCSs) with a total of 662 patients (33% DOAC and 67% VKAs) met the inclusion criteria. We will present our risk of bias assessment at the conference. DOACs and VKAs had comparable efficacy: recurrent VTE (risk ratio [RR] 1.00, 95% confidence interval [CI] 0.44-2.23; I2=0%; 10 studies) and complete recanalization (RR 1.00, 95% CI 0.77-1.28; I2=0%; 6 studies). DOAC and VKA also had comparable safety: major hemorrhage (RR 0.89, 95% CI 0.37-2.14; I2=0%; 9 studies).Conclusions:Studies comparing DOACs with VKAs in patients with CVT consist mostly of small, non-randomized, poorly controlled studies. While the two treatments appear comparable for major efficacy and safety outcomes, large, rigorously conducted studies, preferably randomized, are needed to overcome these limitations and permit development of clinical practice guidelines for the use of DOACs in patients with CVT.
Stroke, Volume 53, Issue 2, Page 404-415, February 1, 2022. Sporadic cerebral small vessel disease (SVD) is a major contributor to vascular cognitive impairment and dementia in the aging human brain. On neuropathology, sporadic SVD is characterized by abnormalities to the small vessels of the brain predominantly in the form of cerebral amyloid angiopathy and arteriolosclerosis. These pathologies frequently coexist with Alzheimer disease changes, such as plaques and tangles, in a single brain. Conversely, during life, magnetic resonance imaging (MRI) only captures the larger manifestations of SVD in the form of parenchymal brain abnormalities. There appears to be a major knowledge gap regarding the underlying neuropathology of individual MRI-detectable SVD abnormalities. Ex vivo MRI in postmortem human brain tissue is a powerful tool to bridge this gap. This review summarizes current insights into the histopathologic correlations of MRI manifestations of SVD, their underlying cause, presumed pathophysiology, and associated secondary tissue injury. Moreover, we discuss the advantages and limitations of ex vivo MRI-guided histopathologic investigations and make recommendations for future studies.
