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N-acetyl glucosamine (NAG) is a natural amino sugar found in various human tissues with previously described anti-inflammatory effects. Various chemical modifications of NAG have been made to promote its biomedical applications. In this study, we synthesized two bi-deoxygenated NAG, BNAG1 and BNAG2 and investigated their anti-inflammatory properties, using an in vivo and in vitro inflammation mouse model induced by lipopolysaccharide (LPS). Among the parent molecule NAG, BNAG1 and BNAG2, BNAG1 showed the highest inhibition against serum levels of IL-6 and TNF α and the leukocyte migration to lungs and peritoneal cavity in LPS challenged mice, as well as IL-6 and TNF α production in LPS-stimulated primary peritoneal macrophages. BNAG2 displayed an anti-inflammatory effect which was comparable to NAG. These findings implied potential application of these novel NAG derivatives, especially BNAG1, in treatment of certain inflammation-related diseases.

BackgroundPrior studies evaluating the Wingspan stent for treatment of symptomatic intracranial atherosclerotic disease have included patients with a spectrum of both on-label and off-label indications for the stent. The WEAVE trial assessed 152 patients stented with the Wingspan stent strictly by its current on-label indication and found a 2.6% periprocedural stroke and death rate.ObjectiveThis WOVEN study assesses the 1-year follow-up from this cohort.MethodsTwelve of the original 24 sites enrolling patients in the WEAVE trial performed follow-up chart review and imaging analysis up to 1 year after stenting. Assessment of delayed stroke and death was made in 129 patients, as well as vascular imaging follow-up to assess for in-stent re-stenosis.ResultsIn the 1-year follow-up period, seven patients had a stroke (six minor, one major). Subsequent to the periprocedural period, no deaths were recorded in the cohort. Including the four patients who had periprocedural events in the WEAVE study, there were 11 strokes or deaths of the 129 patients (8.5%) at the 1-year follow-up.ConclusionsThe WOVEN study provides the 1-year follow-up on a cohort of 129 patients who were stented according to the current on-label use. It provides a more homogeneous patient group for analysis than prior studies, and demonstrates a relatively low 8.5% 1-year stroke and death rate in stented patients.

Background and purposeReversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches associated with segmental vasoconstriction of cerebral arteries, which may result in intracranial hemorrhage (ICH). There is a lack of contemporary data available regarding the ICH burden in RCVS cohort. Our aim of the study is to assess the ICH burden, associated risk factors, and discharge outcome of ICH in patients with RCVS.MethodsAll patients diagnosed with RCVS in the 2016 Nationwide Readmission Database were identified using ICD-10 code after excluding patients with the concurrent diagnosis of primary angiitis. ICH was defined as both intraparenchymal (IPH), subarachnoid hemorrhage (SAH), and subdural hematoma (SDH). Categorical and continuous variables were assessed by the Rao-Scott Chi-square test and the Wilcoxon signed-rank sum test respectively. We used a multivariable survey-weighted logistic model to determine the association between ICH and RCVS patient-level characteristics.FindingsA total of 799 patients were identified with RCVS. Total hospitalization of ICH was 43.4% [(95% CI 36.4–50.4%); (n = 346)] including SAH 35.9% [(95% CI 29.7–42.1%); (n = 287)], IPH 13.1% [(95% CI 9.5–16.7%); (n = 105)] and SDH 3.6% [(95% CI 1.5–5.6%); (n = 28)]. Patients with hemorrhagic RCVS (H-RCVS) had a mean age (years ± SE) of 47.4 ± 1.1 vs. 45.5 ± 1.2 years in R-RCVS (p = 0.247); and were predominantly female (84.0% vs. 68.8%; p = 0.001); with longer inpatient stays (10.9 vs. 6.8 days; p = 0.016); and a higher inpatient cost ($44,300 vs. $21,350; p < 0.001). On multivariable analyses, higher odds of ICH were female sex 2.57 (95% CI 1.45–4.55; p = 0.001), middle age-group (45–64 years) 1.87 (CI: 1.11–3.15; p = 0.018) and older age group (> 64 years) 3.72 (CI: 1.15–12.03; p = 0.029). About 67.0% of all H-RCVS patients were discharged home, with no observed inpatient mortality.InterpretationIntracerebral hemorrhage is the most common vascular complication in hospitalized RCVS patients, resulting in longer hospitalizations with more invasive procedures and higher healthcare expenditure. However, overall outcomes are excellent regardless of types of ICH, with no inpatient mortality observed in patients with hemorrhagic RCVS. Female sex and middle to older age-group are associated with higher odds of ICH.

Thrombectomy has been proven to be a highly effective treatment for acute ischemic stroke, and we know that patients do significantly better the sooner they are treated.6 It has been estimated that in each minute of an ongoing stroke, 1.9 million neurons, 14 billion synapses, and 12 km (7.5 miles) of myelinated fibers are destroyed and that the ischemic brain loses neurons at an hourly rate equivalent to 3.6 years of normal aging.7 8 Data from the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaborative suggests that every minute delay results in a loss of 4 days of disability-free life.9 Clearly, delays in stroke care result in significant negative outcomes both for patients and for the financial well-being of the healthcare system. Cost-benefit analysis of thrombectomy yields similarly striking results: achieving expanded treatment in cerebral ischemia 3 (eTICI 3) over eTICI 2b reperfusion resulted on average in 1.31 incremental quality-adjusted life-years (QALYs) as well as healthcare and societal cost savings of $10 327 and $20 224 per patient, respectively. An estimated $21 million and $36.8 million for the US healthcare system and society, respectively, could be saved by a 10% increase in the eTICI 2/3 reperfusion rate of all endovascular thrombectomy-treated patients with stroke.10 The median loss in net monetary benefit of thrombectomy per minute was calculated to be $1059, and saving 10 min on average across the USA would save $249 million annually.9 Implementation of Viz LVO has been demonstrated to save 66 min on average,11 suggesting a significant return on investment for CMS. Why this is a big deal for health care CMS has previously proposed reimbursement for use of AI-enabled technology—specifically automated retinal imaging—in its 2021 Medicare physician fee schedule proposed rule.13 This reimbursement model addresses diagnostic applications that perform functions analogous to those otherwise performed by physicians, but it is insufficient for novel uses, such as parallel processing and triage.

Background Stroke has been linked to a lack of physical activity; however, the extent of the association between inactive lifestyles and stroke risk has yet to be characterized across large populations. Purpose This study aimed to explore the association between activity‐related behaviors and stroke incidence. Methods Data from 1999 to 2018 waves of the concurrent cross‐sectional National Health and Nutrition Examination Survey (NHANES) were extracted. We analyzed participants characteristics and outcomes for all participants with data on whether they had a stroke or not and assessed how different forms of physical activity affect the incidence of disease. Results Of the 102,578 individuals included, 3851 had a history of stroke. A range of activity‐related behaviors was protective against stroke, including engaging in moderate‐intensity work over the last 30 days (OR = 0.8, 95% CI = 0.7–0.9; P = 0.001) and vigorous‐intensity work activities over the last 30 days (OR = 0.6, 95% CI = 0.5–0.8; P < 0.001), and muscle‐strengthening exercises (OR = 0.6, 95% CI = 0.5–0.8; P < 0.001). Conversely, more than 4 h of daily TV, video, or computer use was positively associated with the likelihood of stroke (OR = 11.7, 95% CI = 2.1–219.2; P = 0.022). Conclusion Different types, frequencies, and intensities of physical activity were associated with reduced stroke incidence, implying that there is an option for everyone. Daily or every other day activities are more critical in reducing stroke than reducing sedentary behavior duration.

Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group. Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).

To assess the impact of COVID-19 on neurovascular research and deal with the challenges imposed by the pandemic.MethodsA survey-based study focused on randomized controlled trials (RCTs) and single-arm studies for acute ischemic stroke and cerebral aneurysms was developed by a group of senior neurointerventionalists and sent to sites identified through the clinical trials website (https://clinicaltrials.gov/), study sponsors, and physician investigators.ResultsThe survey was sent to 101 institutions, with 65 responding (64%). Stroke RCTs were being conducted at 40 (62%) sites, aneurysm RCTs at 22 (34%) sites, stroke single-arm studies at 37 (57%) sites, and aneurysm single-arm studies at 43 (66%) sites. Following COVID-19, enrollment was suspended at 51 (78%) sites—completely at 21 (32%) and partially at 30 (46%) sites. Missed trial-related clinics and imaging follow-ups and protocol deviations were reported by 27 (42%), 24 (37%), and 27 (42%) sites, respectively. Negative reimbursements were reported at 17 (26%) sites. The majority of sites, 49 (75%), had put new trials on hold. Of the coordinators, 41 (63%) worked from home and 20 (31%) reported a personal financial impact. Remote consent was possible for some studies at 34 (52%) sites and for all studies at 5 (8%) sites. At sites with suspended trials (n=51), endovascular treatment without enrollment occurred at 31 (61%) sites for stroke and 23 (45%) sites for aneurysms. A total of 277 patients with acute ischemic stroke and 184 with cerebral aneurysms were treated without consideration for trial enrollment.ConclusionWidespread disruption of neuroendovascular trials occurred because of COVID-19. As sites resume clinical research, steps to mitigate similar challenges in the future should be considered.

In patients with subdural hematoma and an indication for surgical evacuation, middle meningeal artery embolization plus surgery led to a lower risk of reoperation for recurrence or progression within 90 days than surgery alone.

•Multicenter study evaluating the impact of COVID-19 pandemic on ischemic stroke volumes, subtypes, and clinical presentation in US.•Significant decline was observed in the mean weekly volumes of newly diagnosed ischemic strokes, LVOs, and IV-tPA administration.•Patients admitted to the hospital had severe disease (NIHSS>14) and were more likely to discharge home. To evaluate overall ischemic stroke volumes and rates, specific subtypes, and clinical presentation during the COVID-19 pandemic in a multicenter observational study from eight states across US. We compared all ischemic strokes admitted between January 2019 and May 2020, grouped as; March-May 2020 (COVID-19 period) and March-May 2019 (seasonal pre-COVID-19 period). Primary outcome was stroke severity at admission measured by NIHSS stratified as mild (0−7), moderate [8–14], and severe (>14). Secondary outcomes were volume of large vessel occlusions (LVOs), stroke etiology, IV-tPA rates, and discharge disposition. Of the 7969 patients diagnosed with acute ischemic stroke during the study period, 933 (12 %) presented in the COVID-19 period while 1319 (17 %) presented in the seasonal pre-COVID-19 period. Significant decline was observed in the mean weekly volumes of newly diagnosed ischemic strokes (98 ± 3 vs 50 ± 20,p = 0.003), LVOs (16.5 ± 3.8 vs 8.3 ± 5.9,p = 0.008), and IV-tPA (10.9 ± 3.4 vs 5.3 ± 2.9,p = 0.0047), whereas the mean weekly proportion of LVOs (18 % ±5 vs 16 % ±7,p = 0.24) and IV-tPA (10.4 % ±4.5 vs. 9.9 % ±2.4,p = 0.66) remained the same, when compared to the seasonal pre-COVID-19 period. Additionally, an increased proportion of patients presented with a severe disease (NIHSS > 14) during the COVID-19 period (29.7 % vs 24.5 %,p < 0.025). The odds of being discharged to home were 26 % greater in the COVID-19 period when compared to seasonal pre-COVID-19 period (OR:1.26, 95 % CI:1.07–1.49,p = 0.016). During COVID-19 period there was a decrease in volume of newly diagnosed ischemic stroke cases and IV-tPA administration. Patients admitted to the hospital had severe neurological clinical presentation and were more likely to discharge home.

Background The natural history and epidemiological aspects of traumatic vertebral artery dissection (VAD) are not fully understood. We determined the prevalence of VAD and impact on outcome of patients with head and neck trauma. Methods All the patients who were admitted with traumatic brain injury or head and neck trauma were identified by ICD-9-CM codes from the National Trauma Data Bank (NTDB), using data files from 2009 to 2010. NTDB represents one of the largest trauma databases and contains data from over 900 trauma centers across the United States. Presence of VAD was identified in these patients by using ICD-9-CM codes. Admission Glasgow Coma Scale (GCS) score, injury severity score (ISS), in-hospital complications, and treatment outcome were compared between patients with and without VAD. Results A total of 84 VAD patients were identified which comprised 0.01 % of all patients admitted with head and neck trauma. The mean age (in years) for patients with VAD was significantly higher than patients without dissection [46 (95 % CI 41–50) vs. 41.3 (95 % CI 41.2–41.4); p  = 0.003]. The proportion of patients presenting with GCS score <9 was significantly higher in patients with VAD (31 vs. 12 %, p  < 0.0001). The rate of cervical vertebral fracture was significantly higher in patients with VAD (71 vs. 11 %, p  < 0.0001). Patients with VAD had higher rates of in-hospital stroke than patients without dissection (5 vs. 0.2 %, p  < 0.0001). Numbers of ICU days, ventilator days, and hospital length of stays were all significantly higher in patients with VAD. These differences remained significant after adjusting for the demographics, admission GCS score, and ISS ( p  < 0.0001). A total of 7 % ( N  = 6) of the patients with VAD received endovascular treatment and there was no in-hospital stroke in these patients. Patients with VAD had a higher chance of discharge to nursing facilities in comparison to head trauma patients without VAD (OR: 2.1; 95 % CI 1.4–3.5; p  < 0.0001). Conclusion Although infrequent, VAD in head and neck trauma is associated with higher rates of in-hospital stroke and longer length of ICU stay and total hospital stay. Early diagnosis and endovascular treatment may be an alternative option to reduce the rate of in-hospital stroke in these patients.