Medicine (RMH) - Research Publications
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ItemProspective analysis of stroke recognition, stroke risk factors, thrombolysis rates and outcomes in Indigenous Australians from a large rural referral hospital(WILEY, 2022-03)BACKGROUND: Cardiovascular disease is the most common cause of death and disability in indigenous communities but limited prospective data exist about stroke. AIMS: To estimate the difference in stroke recognition, risk factors, treatment rates and outcomes between indigenous and non-indigenous peoples admitted to the Wagga Wagga Rural Referral Hospital (WWRRH) over a 5-year period with a suspected acute stroke. METHODS: All suspected strokes presenting to the 33 peripheral hospitals within the Murrumbidgee Local Health District (MLHD) were transferred to the WWRRH and prospectively assessed over a 5-year period from 1 January 2012 to 31 December 2017. Actions at stroke onset, risks factors, stroke type, treatment and outcomes were analysed. RESULTS: A total of 1843 patients were included. Of these, 45 (2.5%) patients were indigenous. Only 26.6% of indigenous and 34% of non-indigenous patients knew of the face, arm, speech, time (FAST) acronym. Indigenous patients were younger (mean age 62.0āyears vs 74.4āyears) and more likely to have diabetes (risk difference (RD) 22.3% (95% CI: 3%, 41.7%)), dyslipidaemia (RD 19.4% (95% CI: 21.%, 36.7%)), and be ever smokers (RD 24.9% (95% CI: 9.5%, 40.3%)). Stroke types were similar except lacunar infarcts were more common (19.2% vs 8.4%). Treatment rates and outcomes were similar between the two groups. CONCLUSIONS: Indigenous Australians with stroke are a decade younger and have a higher prevalence of important, modifiable stroke-risk factors. Delayed presentation to hospital is more common, due in part to stroke symptoms being underrecognised. When admitted to a specialised stroke unit, treatment rates and outcomes are comparable.
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ItemNo Preview AvailableAssociation of Endovascular Thrombectomy With Functional Outcome in Patients With Acute Stroke With a Large Ischemic Core(LIPPINCOTT WILLIAMS & WILKINS, 2022-09-27)BACKGROUND AND OBJECTIVES: Endovascular thrombectomy (EVT) is effective for patients with large vessel occlusion (LVO) stroke with smaller volumes of CT perfusion (CTP)-defined ischemic core. However, the benefit of EVT is unclear in those with a core volume >70 mL. We aimed to compare outcomes of EVT and non-EVT patients with an ischemic core volume ā„70 mL, hypothesizing that there would be a benefit from EVT for fair outcome (3-month modified Rankin scale [mRS] 0-3) after stroke. METHODS: A retrospective analysis of patients enrolled into a multicenter (Australia, China, and Canada) registry (2012-2020) who underwent CTP within 24 hours of stroke onset and had a baseline ischemic core volume ā„70 mL was performed. The primary outcome was the estimation of the association of EVT in patients with core volume ā„70 mL and within 70-100 and ā„100 mL subgroups with fair outcome. RESULTS: Of the 3,283 patients in the registry, 299 had CTP core volume ā„70 mL and 269 complete data (135 had core volume between 70 and 100 mL and 134 had core volume ā„100 mL). EVT was performed in 121 (45%) patients. EVT-treated patients were younger (median 69 vs 75 years; p = 0.011), had lower prestroke mRS, and smaller median core volumes (92 [79-116.5] mL vs 105.5 [85.75-138] mL, p = 0.004). EVT-treated patients had higher odds of achieving fair outcome in adjusted analysis (30% vs 13.9% in the non-EVT group; adjusted odds ratio [aOR] 2.1, 95% CI 1-4.2, p = 0.038). The benefit was seen predominantly in those with 70-100 mL core volume (71/135 [52.6%] EVT-treated), with 54.3% in the EVT-treated vs 21% in the non-EVT group achieving a fair outcome (aOR 2.5, 95% CI 1-6.2, p = 0.005). Of those with a core volume ā„100 mL, 50 of the 134 (37.3%) underwent EVT. Proportions of fair outcome were very low in both groups (8.1% vs 8.7%; p = 0.908). DISCUSSION: We found a positive association of EVT with the 3-month outcome after stroke in patients with a baseline CTP ischemic core volume 70-100 mL but not in those with core volume ā„100 mL. Randomized data to confirm these findings are required. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that EVT is associated with better motor outcomes 3 months after CTP-defined ischemic stroke with a core volume of 70-100 mL.
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ItemNo Preview AvailablePrevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow)(LIPPINCOTT WILLIAMS & WILKINS, 2022-02-22)BACKGROUND AND OBJECTIVES: The relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiologic features of this phenomenon and its associations with outcomes in 3 international randomized controlled thrombectomy trials with prespecified follow-up perfusion imaging. METHODS: In a pooled analysis of the Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA; ClinicalTrials.gov NCT01492725), Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK; NCT02388061), and Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2; NCT03340493) trials, patients undergoing thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c to 3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative cerebral blood volume or flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homolog in the absence of carotid stenosis or reocclusion. RESULTS: Regions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (interquartile range 47.8%-70.7%) of the infarct volume, and involved both subcortical (n = 26 of 33, 78.8%) and cortical (n = 10 of 33, 30.3%) regions. Patients with no-reflow had a median 25.2% (interquartile range 16.4%-32.2%, p < 0.00001) relative cerebral blood volume interside reduction and 19.1% (interquartile range 3.9%-28.3%, p = 0.00011) relative cerebral blood flow reduction but similar mean transit time (median -3.3%, interquartile range -11.9% to 24.4%, p = 0.24) within the infarcted region. Baseline characteristics were similar between patients with and those without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (adjusted odds ratio [aOR] 1.79, 95% confidence interval [CI] 2.32-15.57, p = 0.0002), greater infarct growth (Ī² = 11.00, 95% CI 5.22-16.78, p = 0.00027), reduced NIH Stroke Scale score improvement at 24 hours (Ī² = -4.06, 95% CI 6.78-1.34, p = 0.004) and being dependent or dead at 90 days as assessed by the modified Rankin Scale (aOR 3.72, 95% CI 1.35-10.20, p = 0.011) in multivariable analysis. DISCUSSION: Cerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with posttreatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24 hours is associated with posttreatment complications and poor 3-month functional outcome.
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ItemNo Preview AvailableEndovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies(WILEY, 2022-05)OBJECTIVE: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. RESULTS: We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, pā<ā0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.
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ItemEndovascular Treatment of ICAS Patients: Targeting Reperfusion Rather than Residual Stenosis.(MDPI AG, 2022-07-22)BACKGROUND AND PURPOSE: Previous studies showed that acute reocclusion after endovascular therapy is related to residual stenosis. However, we observed that reperfusion status but not residual stenosis severity is related to acute reocclusion. This study aimed to assess which factor mention above is more likely to be associated with artery reocclusion after endovascular treatment. METHODS: This study included 86 acute ischemic stroke patients who had middle cerebral artery (MCA) atherosclerotic occlusions and received endovascular treatment within 24 h of a stroke. The primary outcomes included intraprocedural reocclusion assessed during endovascular treatment and delayed reocclusion assessed through follow-up angiography. RESULTS: Of the 86 patients, the intraprocedural reocclusion rate was 7.0% (6/86) and the delayed reocclusion rate was 2.3% (2/86). Regarding intraprocedural occlusion, for patients with severe residual stenosis, patients with successful thrombectomy reperfusion showed a significantly lower rate than unsuccessful thrombectomy reperfusion (0/30 vs. 6/31, p = 0.003); on the other hand, for patients with successful thrombectomy reperfusion, patients with severe residual stenosis showed no difference from those with mild to moderate residual stenosis in terms of intraprocedural occlusion (0/30 vs. 0/25, p = 1.00). In addition, after endovascular treatment, all patients achieved successful reperfusion. There was no significant difference in the delayed reocclusion rate between patients with severe residual stenosis and those with mild to moderate residual stenosis (2/25 vs. 0/61, p = 0.085). CONCLUSION: Reperfusion status rather than residual stenosis severity is associated with artery reocclusion after endovascular treatment. Once successful reperfusion was achieved, the reocclusion occurrence was fairly low in MCA atherosclerosis stroke patients, even with severe residual stenosis.
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ItemNet water uptake, a neuroimaging marker of early brain edema, as a predictor of symptomatic intracranial hemorrhage after acute ischemic stroke.(Frontiers Media SA, 2022)OBJECTIVE: We hypothesized that quantitative net water uptake (NWU), a novel neuroimaging marker of early brain edema, can predict symptomatic intracranial hemorrhage (sICH) after acute ischemic stroke (AIS). METHODS: We enrolled patients with AIS who completed admission multimodal computed tomography (CT) within 24 h after stroke onset. NWU within the ischemic core and penumbra was calculated based on admission CT, namely NWU-core and NWU-penumbra. sICH was defined as the presence of ICH in the infarct area within 7 days after stroke onset, accompanied by clinical deterioration. The predictive value of NWU-core and NWU-penumbra on sICH was evaluated by logistic regression analyses and the receiver operating characteristic (ROC) curve. A pure neuroimaging prediction model was built considering imaging markers, which has the potential to be automatically quantified with an artificial algorithm on image workstation. RESULTS: 154 patients were included, of which 93 underwent mechanical thrombectomy (MT). The median time from symptom onset to admission CT was 262 min (interquartile range, 198-368). In patients with MT, NWU-penumbra (OR =1.442; 95% CI = 1.177-1.766; P < 0.001) and NWU-core (OR = 1.155; 95% CI = 1.027-1.299; P = 0.016) were independently associated with sICH with adjustments for age, sex, time from symptom onset to CT, hypertension, lesion volume, and admission National Institutes of Health Stroke Scale (NIHSS) score. ROC curve showed that NWU-penumbra had better predictive performance than NWU-core on sICH [area under the curve (AUC): 0.773 vs. 0.673]. The diagnostic efficiency of the predictive model was improved with the containing of NWU-penumbra (AUC: 0.853 vs. 0.760). A pure imaging model also presented stable predictive power (AUC = 0.812). In patients without MT, however, only admission NIHSS score (OR = 1.440; 95% CI = 1.055-1.965; P = 0.022) showed significance in predicting sICH in multivariate analyses. CONCLUSIONS: NWU-penumbra may have better predictive performance than NWU-core on sICH after MT. A pure imaging model showed potential value to automatically screen patients with sICH risk by image recognition, which may optimize treatment strategy.
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ItemNo Preview AvailableComparison of functional outcomes after endovascular thrombectomy in patients with and without atrial fibrillation(OAE Publishing Inc., 2021-01-01)
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ItemNo Preview AvailableAssociations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis-Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study(LIPPINCOTT WILLIAMS & WILKINS, 2022-03)BACKGROUND AND PURPOSE: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. METHODS: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150-180 mmāHg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130-140 mmāHg) or guideline-recommended (target SBP <180 mmāHg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1-24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. RESULTS: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mmāHg increase: odds ratio, 0.76 [95% CI, 0.71-0.82]; P<0.001 and 0.86 [95% CI, 0.76-0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93-1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06-1.31]; P=0.002 and 1.34 [1.11-1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98-1.14]; P=0.184). CONCLUSIONS: Attaining early and consistent low levels in SBP <140 mmāHg, even as low as 110 to 120 mmāHg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01422616.
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ItemNo Preview AvailableReview of CT perfusion and current applications in posterior circulation stroke(OAE Publishing Inc., 2021-01-01)Acute ischemic stroke is a leading cause of death and disability. Treatment efficacy is highly time-dependent. Approximately 20% of acute ischaemic stroke occurs in the posterior circulation. Clinical presentation of posterior circulation stroke is subtle. Diagnosis is often delayed and frequently missed. CT perfusion has improved diagnostic accuracy and been integral to guiding acute therapy in patients with anterior circulation stroke. There are limited studies assessing the role of CT perfusion in posterior circulation stroke. This review provides a reference for interpretation of CT perfusion and summarises current evidence relating to applications in acute posterior circulation stroke.
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ItemNo Preview AvailableHealthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials(AMER MEDICAL ASSOC, 2021-06)IMPORTANCE: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. OBJECTIVE: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). DATA SOURCES: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. STUDY SELECTION: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. DATA EXTRACTION/SYNTHESIS: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. MAIN OUTCOMES AND MEASURES: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. RESULTS: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ā¤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; Pā<ā.001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. CONCLUSIONS AND RELEVANCE: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.
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