Early mandated social distancing is a strong predictor of reduction in peak daily new COVID-19 cases.

OBJECTIVES: Mandated social distancing has been applied globally to reduce the spread of coronavirus disease 2019 (COVID-19). However, the beneficial effects of this community-based intervention have not been proven or quantified for the COVID-19 pandemic. STUDY DESIGN: This is a regional population-level observational study. METHODS: Using publicly available data, we examined the effect of timing of mandated social distancing on the rate of COVID-19 cases in 119 geographic regions, derived from 41 states within the United States and 78 other countries. The highest number of new COVID-19 cases per day recorded within a geographic unit was the primary outcome. The total number of COVID-19 cases in regions where case numbers had reached the tail end of the outbreak was an exploratory outcome. RESULTS: We found that the highest number of new COVID-19 cases per day per million persons was significantly associated with the total number of COVID-19 cases per million persons on the day before mandated social distancing (ß = 0.66, P < 0.0001). These findings suggest that if mandated social distancing is not initiated until the number of existing COVID-19 cases has doubled, the eventual peak would result in 58% more COVID-19 cases per day. Subgroup analysis on those regions where the highest number of new COVID-19 cases per day has peaked showed increase in ß values to 0.85 (P < 0.0001). The total number of cases during the outbreak in a region was strongly predicted by the total number of COVID-19 cases on the day before mandated social distancing (ß = 0.97, P < 0.0001). CONCLUSIONS: Initiating mandated social distancing when the numbers of COVID-19 cases are low within a region significantly reduces the number of new daily COVID-19 cases and perhaps also reduces the total number of cases in the region.

Intracranial-derived atherosclerosis assessment: an in vitro comparison between virtual histology by intravascular ultrasonography, 7T MRI, and histopathologic findings.

BACKGROUND AND PURPOSE: Atherosclerotic plaque composition and structure contribute to the risk of plaque rupture and embolization. Virtual histology by intravascular ultrasonography and high-resolution MR imaging are new imaging modalities that have been used to characterize plaque morphology and composition in peripheral arteries. MATERIALS AND METHODS: The objectives of this study were 1) to determine the correlation between virtual histology-intravascular ultrasonography and histopathologic analysis (reference standard) and 2) to explore the comparative results of 7T MR imaging (versus histopathologic analysis), both to be performed in vitro by use of intracranial arterial segments with atherosclerotic plaques. Thirty sets of postmortem samples of intracranial circulation were prepared for the study. These samples included the middle cerebral artery (n = 20), basilar artery (n = 8), and anterior cerebral artery (n = 2). Virtual histology-intravascular ultrasonography and 7T MR imaging were performed in 34 and 10 points of interest, respectively. The formalin-fixed arteries underwent tissue processing and hematoxylin-eosin staining. The plaques were independently categorized according to revised Stary classification after review of plaque morphology and characteristics obtained from 3 modalities. The proportion of fibrous, fibrofatty, attenuated calcium, and necrotic components in the plaques were determined in histology slides and compared with virtual histology-intravascular ultrasonography and MR imaging. RESULTS: Of 34 points of interest in the vessels, 32 had atherosclerotic plaques under direct visualization. Plaques were visualized in gray-scale intravascular ultrasonography as increased wall thickness, outer wall irregularity, and protrusion. The positive predictive value of virtual histology-intravascular ultrasonography for identifying fibroatheroma was 80%. Overall, virtual histology-intravascular ultrasonography accurately diagnosed the type of the plaque in 25 of 34 samples, and κ agreement was 0.58 (moderate agreement). The sensitivity and specificity of virtual histology-intravascular ultrasonography readings for fibroatheroma were 78.9% and 73.3%, respectively. The overall sensitivity and specificity for virtual histology-intravascular ultrasonography were 73.5% and 96.6%, respectively. Plaques were identified in 7T MR imaging as increased wall thickness, luminal stenosis, or outer wall protrusion. The positive predictive value of 7T MR imaging for detecting fibrous and attenuated calcium deposits was 88% and 93%, respectively. CONCLUSIONS: This in vitro study demonstrated that virtual histology-intravascular ultrasonography and high-resolution MR imaging are reliable imaging tools to detect atherosclerotic plaques within the intracranial arterial wall, though both imaging modalities have some limitations in accurate characterization of the plaque components. Further clinical studies are needed to determine the clinical utility of plaque morphology and composition assessment by noninvasive tests.

Microcatheter to recanalization (procedure time) predicts outcomes in endovascular treatment in patients with acute ischemic stroke: when do we stop?

BACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke consists of various mechanical and pharmacologic modalities used for recanalization of arterial occlusions. We performed this study to determine the relationship among procedure time, recanalization, and clinical outcomes in patients with acute ischemic stroke undergoing endovascular treatment. MATERIALS AND METHODS: We analyzed data from consecutive patients with acute ischemic stroke who underwent endovascular treatment during a 6-year period. Demographic characteristics, NIHSS score before and 24 hours after the procedure, and discharge mRS score were ascertained. Procedure time was defined by the time interval between microcatheter placement and recanalization or completion of the procedure. We estimated the procedure time after which favorable clinical outcome was unlikely, even after adjustment for age, time from symptom onset, and admission NIHSS scores. RESULTS: We analyzed 209 patients undergoing endovascular treatment (mean age, 65 ± 16 years; 109 [52%] men; mean admission/preprocedural NIHSS score, 15.3 ± 6.8). Complete or partial recanalization was observed in 176 (84.2%) patients, while unfavorable outcome (mRS 3-6) was observed in 138 (66%) patients at discharge. In univariate analysis, patients with procedure time ≤30 minutes had lower rates of unfavorable outcome at discharge compared with patients with procedure time ≥30 minutes (52.3% versus 72.2%, P = .0049). In our analysis, the rates of favorable outcomes in endovascularly treated patients after 60 minutes were lower than rates observed with placebo treatment in the Prourokinase for Acute Ischemic Stroke Trial. In logistic regression analysis, unfavorable outcome was positively associated with age (P = .0012), admission NIHSS strata (P = .0017), and longer procedure times (P = .0379). CONCLUSIONS: Procedure time in patients with acute ischemic stroke appears to be a critical determinant of outcomes following endovascular treatment. This highlights the need for procedure time guidelines for patients being considered for endovascular treatment in acute ischemic stroke.

Short- and intermediate-term angiographic and clinical outcomes of patients with various grades of coil protrusions following embolization of intracranial aneurysms.

BACKGROUND AND PURPOSE: An infrequent occurrence during endovascular treatment is protusion of detachable coils into the parent lumen with a subsequent thrombosis within in the parent vessel or embolic events. We report the short- and intermediate-term angiographic and clinical outcomes of patients who experience coil or loop protrusions and are managed with medical or additional endovascular treatments. MATERIALS AND METHODS: The coil protrusions were identified by retrospective review of 256 consecutive patients treated at 3 centers with endovascular embolizations for intracranial aneurysms and subsequently categorized as grade I when a single loop or coil protruded into the parent vessel lumen less than half the parent artery diameter; grades II and III were assigned when a single coil or loop protruded more than half the parent artery diameter, respectively. RESULTS: There were 19 patients with grade I (n = 9), grade II (n = 4), or grade III (n = 6) coil protrusions. Patients with active hemodynamic compromise (n = 6) had intracranial stents placed in addition to aspirin (indefinitely) and clopidogrel (range, 1-12 months; mean, 4.5 months) treatment. The remaining patients were placed on aspirin indefinitely. Complete aneurysm obliteration was achieved in all patients except in 3 in whom near-complete obliteration was achieved. Two patients had intraprocedural aneurysm ruptures, both of whom survived hospitalization. There were 4 deaths (4-21 days), all due to major strokes in different vascular distributions related to vasospasm (unrelated to the coil protrusion). CONCLUSIONS: Management of coil protrusions with antiplatelet therapy and placement of stents (in selected patients) appears efficacious in preventing vessel thrombosis.

Intra-arterial recanalization techniques for patients 80 years or older with acute ischemic stroke: pooled analysis from 4 prospective studies.

BACKGROUND AND PURPOSE: Previous studies have demonstrated limited benefit with endovascular procedures such as stent placement in octogenarians. We evaluated the safety and effectiveness of intra-arterial recanalization techniques to treat ischemic stroke in patients 80 years or older presenting within 6 hours of symptom onset. MATERIALS AND METHODS: We pooled the data from 4 prospective studies by evaluating intra-arterial recanalization techniques for treatment of ischemic stroke. Clinical and radiologic evaluations were performed before treatment and at 24 hours, 7 to 10 days, and 1 to 3 months after treatment. We performed multivariate analyses to evaluate the effect of ages 80 years and older on angiographic recanalization, favorable outcome (modified Rankin scale of 0-2), and mortality rate at 1 to 3 months. RESULTS: A total of 101 patients were treated in the 4 protocols. Of these, 24 were 80 years or older. There was no significant difference between the 2 age groups in sex, initial stroke severity, time to treatment, site of vascular occlusion, and rate of symptomatic and asymptomatic intracranial hemorrhage (ICH). In logistic regression analysis, age 80 years or older was associated with a lower likelihood of a favorable outcome (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.13-1.2; P = .11) and recanalization (OR, 0.36; 95% CI, 0.12-1.1; P = .07) and with higher mortality rate (OR, 3.17; 95% CI, 1.05-9.55; P = .04) after adjusting for study protocol. After adjusting for recanalization in addition to study protocol, the older age group still had a lower likelihood of favorable outcomes (OR, 0.34; 95% CI, 0.1-1.1; P = .07) and higher mortality rates (OR, 3.62; 95% CI, 1.15-11.36; P = .027). CONCLUSIONS: Our study demonstrates that patients 80 years and older are at higher risk for poor outcome at 1 to 3 months following intra-arterial recanalization techniques. This relationship is independent of recanalization rate and symptomatic ICH supporting the role of other mechanisms.

Impact of arterial reocclusion and distal fragmentation during thrombolysis among patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Arterial reocclusion and distal embolization are known complications of ischemic stroke intervention, impacting treatment strategies and device design. We sought to determine their rates of occurrence and effects on long-term outcomes during endovascular treatment of patients with acute ischemic stroke. MATERIALS AND METHODS: Retrospective analysis of data from 4 prospective acute stroke protocols was performed. Patients underwent the standard technique for parent vessel angiography followed by pharmacologic thrombolysis and/or sonographic thrombolysis and/or mechanical thrombus disruption. Certain patients also received systemic heparin or abciximab therapy. Demographic, clinical, and angiographic variables were assessed at onset, 24 hours, 1 week, and 1-3 months after the event. "Distal embolization" was defined qualitatively as appearance of an occlusion on a downstream vessel. "Arterial reocclusion" was defined as subsequent reocclusion of the target vessel after initial recanalization had been achieved. RESULTS: Arterial reocclusion occurred in 18% of these patients, whereas distal embolization occurred in 16% of the 91 patients treated in these protocols. Arterial reocclusion, but not distal embolization, was associated with a lower likelihood of favorable outcome at 1-3 months (P = .05; odds ratio, 3.9; 95% confidence interval, 0.01-0.98) after adjusting for age, initial National Institutes of Health Stroke Scale scores, sex, time to treatment, initial angiographic grade, symptomatic intracranial hemorrhage, and final recanalization. CONCLUSIONS: Arterial reocclusion and distal embolization occur in 16%-18% of patients with stroke undergoing endovascular intervention. Only arterial reocclusion is associated with poor long-term outcome. Prospective studies are needed to identify risk factors for their occurrence and possible preventive therapies.

Is IV tissue plasminogen activator beneficial in patients with hyperdense artery sign?

OBJECTIVE: To evaluate the effect of IV recombinant tissue plasminogen activator (rt-PA) in patients with hyperdense artery sign (HAS) on initial CT scan. METHODS: The authors determined the differential effect of IV rt-PA (0.9 mg/kg) in patients with HAS by testing the interaction of rt-PA and HAS in a logistic regression model after adjusting for age, sex, initial NIH Stroke Scale score (NIHSSS), time to randomization, systolic blood pressure, serum glucose, body temperature, and rt-PA in 616 patients treated within 3 hours of symptom onset. Outcomes evaluated included intracranial hemorrhage, modified Rankin scale (mRS) 0-1, Barthel Index (BI) of > or = 95, Glasgow Outcome Scale (GOS) of 0-1, NIHSSS 0-1, and death at 90 days. RESULTS: HAS was detected on the initial CT scan in 91 (15%) of the 616 patients by an independent neuroradiologist. Significantly lower rates of mRS 0-1, BI > or = 95, GOS of 0-1, or NIHSSS 0-1 at 90 days were observed among patients with HAS. IV rt-PA significantly increased the rates of mRS 0-1, BI > or = 95, GOS of 0-1, or NIHSSS 0-1 at 90 days after adjusting for potential confounders without any significant modifying effect (interaction) of HAS. Among the 91 patients with HAS, rt-PA use demonstrated a trend or significance for increased adjusted rates of favorable outcomes by mRS (p = 0.04), BI (p = 0.1), GOS (p = 0.03), and NIHSSS (p = 0.01). CONCLUSION: Although hyperdense artery sign is associated with poor outcome, IV recombinant tissue plasminogen activator may be beneficial in this subgroup of patients with ischemic stroke.

Randomized comparison of intra-arterial and intravenous thrombolysis in a canine model of acute basilar artery thrombosis.

We compared the rates of recanalization cerebral infarct and hemorrhage between intra-arterial (i.a.) reteplase and intravenous (i.v.) alteplase thrombolysis in a canine model of basilar artery thrombosis. Thrombosis was induced by injecting a clot in the basilar artery of 13 anesthetized dogs via superselective catheterization. The animals were randomized in a blinded fashion, 2 h after clot injection and verification of arterial occlusion, to receive i.v. alteplase 0.9 mg/kg over 60 min and i.a. placebo, or i.a. reteplase 0.09 units/kg over 20 min, equivalent to one-half the alteplase dose, and i.v. placebo. Recanalization was studied for 6 h after treatment with serial angiography; the images were later graded in a blinded fashion. Blinded interpretation of postmortem MRI was performed to assess the presence of brain infarcts and/or hemorrhage. At 3 h after initiation of treatment, partial or complete recanalization was observed in one of six dogs in the i.v. alteplase group and in five of seven in the i.a. reteplase group (P = 0.08). At 6 h, no significant difference in partial or complete recanalization was observed between the groups (two of six vs. five of seven; P = 0.20). Postmortem MRI revealed infarcts in four of six animals treated with i.v. alteplase and three of seven treated with i.a. reteplase (P = 0.4). Intracerebral hemorrhage was more common in the i.v. alteplase group (four of six vs. none of seven; P = 0.02). This study thus suggests that i.a. thrombolysis affords a recanalization rate similar to that of i.v. thrombolysis, but with a lower rate of intracerebral hemorrhage.