Publications by authors named "Rishi Gupta"

358 Publications

Efficacy of Autologous Conditioned Serum (ACS), Platelet-Rich Plasma (PRP), Hyaluronic Acid (HA) and Steroid for Early Osteoarthritis Knee: A Comparative Analysis.

Indian J Orthop 2021 May 8;55(Suppl 1):217-227. Epub 2020 Oct 8.

Department of Orthopaedics, Dr. BSA Medical College and Hospital, Rohini Sector 6, Delhi, 110009 India.

Background: Intra-articular injection therapy constituting corticosteroids, viscosupplements and blood-derived products are considered to have a key role in non-operative management of osteoarthritis knee. While corticosteroids and viscosupplements have proven short-term efficacy in early osteoarthritis; orthobiologics are gaining increased attention in osteoarthritis management. The aim of present study was thus to compare two commonly used biologics (platelet-rich plasma/PRP and autologous conditioned serum/ACS) to each other and to established therapies.

Methods: After required institutional clearances, all patients presenting with early primary osteoarthritis knee who had failed initial conservative management and received only unilateral knee injection were included. Patients in the PRP group were compared to the other groups (comprising the HA/hyaluronic acid group, steroid group, and a matched cohort who had been administered ACS for the same indication earlier). Clinical outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire and Visual Analogue scale (VAS) pre-injection and at 6 months.

Results: ACS and PRP did not have any significant difference in terms of either WOMAC score ( = 0.154) or VAS score at 6 months ( = 0.850). The scores for both these orthobiologics were better than the control groups (HA group and Steroid group). Between the two control groups, HA group had better VAS scores as compared to the Steroid group ( = 0.008).

Conclusion: The clinical outcomes following intra-articular injection of ACS and PRP are better than controls (HA and steroid), but a difference between the two orthobiologics could not be demonstrated.

Level Of Evidence: 3b.
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http://dx.doi.org/10.1007/s43465-020-00274-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149550PMC
May 2021

Correction: Bueckert et al. Infectivity of SARS-CoV-2 and Other Coronaviruses on Dry Surfaces: Potential for Indirect Transmission. 2020, , 5211.

Materials (Basel) 2021 May 25;14(11). Epub 2021 May 25.

Department of Biology, University of Victoria, 3800 Finnerty Road, Victoria, BC V8P 5C2, Canada.

The authors wish to make the following corrections to this paper [1]:Throughout the paper's text and in the table, "HCoV-299E" is referred to a few times [...].
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http://dx.doi.org/10.3390/ma14112816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197464PMC
May 2021

Early Experience with Comaneci, a Newly FDA-Approved Controllable Assist Device for Wide-Necked Intracranial Aneurysm Coiling.

Cerebrovasc Dis 2021 May 10:1-8. Epub 2021 May 10.

Department of Neurosurgery, NYU Langone Health, New York, New York, USA.

Background: Comaneci (Rapid Medical) is a compliant, adjustable mesh that provides temporary scaffolding during coiling of wide-necked intracranial aneurysms (WNAs) that preserves antegrade flow. We report our early multi-institutional experience with the Comaneci device in the USA.

Method: We reviewed all patients with WNAs that were treated using the Comaneci device for coil remodeling of ruptured and unruptured aneurysms at 4 institutions between July 2019 and May 2020. Clinical characteristics, angiographic variables, and endovascular results were assessed.

Results: A total of 26 patients were included (18 women). The mean age was 62.7 years (range 44-81). Fifteen patients presented with ruptured aneurysms and 11 with unruptured aneurysms. The mean aneurysm neck width was 3.91 mm (range 1.9-6.5) with a mean dome-to-neck ratio of 1.57 (range 0.59-3.39). The mean maximum width was 5.80 mm (range 3.0-9.9) and the mean maximum height was 5.61 mm (range 2.0-11.8). Successful aneurysm occlusion was achieved in 25 of 26 patients. Complete occlusion was achieved in 16 patients, near-complete occlusion was observed in 9 patients, and 1 patient demonstrated residual filling. The mean time of device exposure was 24 min (range 8-76). No vasospasm was observed at the device location. Clot formation on the device was noted in 2 separate cases, but there were no clinical sequelae. There was 1 intraprocedural complication in a case that involved the simultaneous use of 2 Comaneci devices.

Conclusions: Our initial experience shows that the Comaneci device is a promising and reliable tool that can safely support coil remodeling of WNAs.
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http://dx.doi.org/10.1159/000514371DOI Listing
May 2021

Bayesian Regularized Artificial Neural Network Model to Predict Strength Characteristics of Fly-Ash and Bottom-Ash Based Geopolymer Concrete.

Materials (Basel) 2021 Apr 1;14(7). Epub 2021 Apr 1.

Department of Architectural Engineering, Hanyang University, Seoul 04763, Korea.

Geopolymer concrete (GPC) offers a potential solution for sustainable construction by utilizing waste materials. However, the production and testing procedures for GPC are quite cumbersome and expensive, which can slow down the development of mix design and the implementation of GPC. The basic characteristics of GPC depend on numerous factors such as type of precursor material, type of alkali activators and their concentration, and liquid to solid (precursor material) ratio. To optimize time and cost, Artificial Neural Network (ANN) can be a lucrative technique for exploring and predicting GPC characteristics. In this study, the compressive strength of fly-ash based GPC with bottom ash as a replacement of fine aggregates, as well as fly ash, is predicted using a machine learning-based ANN model. The data inputs are taken from the literature as well as in-house lab scale testing of GPC. The specifications of GPC specimens act as input features of the ANN model to predict compressive strength as the output, while minimizing error. Fourteen ANN models are designed which differ in backpropagation training algorithm, number of hidden layers, and neurons in each layer. The performance analysis and comparison of these models in terms of mean squared error (MSE) and coefficient of correlation (R) resulted in a Bayesian regularized ANN (BRANN) model for effective prediction of compressive strength of fly-ash and bottom-ash based geopolymer concrete.
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http://dx.doi.org/10.3390/ma14071729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036869PMC
April 2021

Clinical and Neuroimaging Outcomes of Direct Thrombectomy vs Bridging Therapy in Large Vessel Occlusion: Analysis of the SELECT Cohort Study.

Neurology 2021 Jun 19;96(23):e2839-e2853. Epub 2021 Apr 19.

From the Departments of Neurology (A.S., J.G., D.P., H.K., A.D.B.), Neurosurgery (S.B., A.D., M.D.), Radiology (C.S.), and Clinical and Translational Science (C.C.), University of Texas at Houston; Department of Neurology (G.W.A., M.L.), Stanford University, CA; Department of Neurology (A.E.H., W.G.T.), University of Texas Rio Grande Valley, Harlingen; Department of Neurology (M.A.), Kansas University Medical Center, Kansas City; Department of Neurology (W.H., R.B., N.V.), OhioHealth-Riverside Methodist Hospital, Columbus; Cone Health (A.A.), Greensboro, NC; Department of Neurology (B.A.), St. Vincent Mercy Health Medical Center, Toledo, OH; Department of Neurology (O.M.), New York University Langone Health, New York; Department of Neurology (R.G.), WellStar Health System, Atlanta, GA; Department of Neurology (S.M.-S.), Touro Infirmary and New Orleans East Hospital, LA; Department of Neurology (S.S.), Institute for Stroke and Cerebrovascular Diseases-UTHealth, Houston; University of Tennessee Health Science Center (G.T.), Memphis; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, Greece.

Objective: To evaluate the comparative safety and efficacy of direct endovascular thrombectomy (dEVT) compared to bridging therapy (BT; IV tissue plasminogen activator + EVT) and to assess whether BT potential benefit relates to stroke severity, size, and initial presentation to EVT vs non-EVT center.

Methods: In a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke [SELECT]), patients with anterior circulation large vessel occlusion (LVO) presenting to EVT-capable centers within 4.5 hours from last known well were stratified into BT vs dEVT. The primary outcome was 90-day functional independence (modified Rankin Scale [mRS] score 0-2). Secondary outcomes included a shift across 90-day mRS grades, mortality, and symptomatic intracranial hemorrhage. We also performed subgroup analyses according to initial presentation to EVT-capable center (direct vs transfer), stroke severity, and baseline infarct core volume.

Results: We identified 226 LVOs (54% men, mean age 65.6 ± 14.6 years, median NIH Stroke Scale [NIHSS] score 17, 28% received dEVT). Median time from arrival to groin puncture did not differ in patients with BT when presenting directly (dEVT 1.43 [interquartile range (IQR) 1.13-1.90] hours vs BT 1.58 [IQR 1.27-2.02] hours, = 0.40) or transferred to EVT-capable centers (dEVT 1.17 [IQR 0.90-1.48] hours vs BT 1.27 [IQR 0.97-1.87] hours, = 0.24). BT was associated with higher odds of 90-day functional independence (57% vs 44%, adjusted odds ratio [aOR] 2.02, 95% confidence interval [CI] 1.01-4.03, = 0.046) and functional improvement (adjusted common OR 2.06, 95% CI 1.18-3.60, = 0.011) and lower likelihood of 90-day mortality (11% vs 23%, aOR 0.20, 95% CI 0.07-0.58, = 0.003). No differences in any other outcomes were detected. In subgroup analyses, patients with BT with baseline NIHSS scores <15 had higher functional independence likelihood compared to those with dEVT (aOR 4.87, 95% CI 1.56-15.18, = 0.006); this association was not evident for patients with NIHSS scores ≥15 (aOR 1.05, 95% CI 0.40-2.74, = 0.92). Similarly, functional outcomes improvements with BT were detected in patients with core volume strata (ischemic core <50 cm: aOR 2.10, 95% CI 1.02-4.33, = 0.044 vs ischemic core ≥50 cm: aOR 0.41, 95% CI 0.01-16.02, = 0.64) and transfer status (transferred: aOR 2.21, 95% CI 0.93-9.65, = 0.29 vs direct to EVT center: aOR 1.84, 95% CI 0.80-4.23, = 0.15).

Conclusions: BT appears to be associated with better clinical outcomes, especially with milder NIHSS scores, smaller presentation core volumes, and those who were "dripped and shipped." We did not observe any potential benefit of BT in patients with more severe strokes.

Trial Registration Information: ClinicalTrials.gov Identifier: NCT02446587.

Classification Of Evidence: This study provides Class III evidence that for patients with ischemic stroke from anterior circulation LVO within 4.5 hours from last known well, BT compared to dEVT leads to better 90-day functional outcomes.
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http://dx.doi.org/10.1212/WNL.0000000000012063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205460PMC
June 2021

Neuroform Atlas Stent for Treatment of Middle Cerebral Artery Aneurysms: 1-Year Outcomes From Neuroform Atlas Stent Pivotal Trial.

Neurosurgery 2021 Jun;89(1):102-108

Neuroscience Department, Bon Secours Mercy Health St. Vincent Medical Center, Toledo, Ohio, USA.

Background: Heterogeneous effect of endovascular aneurysm therapy has been observed across different anatomic locations. There is a paucity of data for stent-assisted coiling of middle cerebral artery (MCA) aneurysms.

Objective: To present the results of the MCA aneurysm group from the Neuroform Atlas (Stryker Neurovascular) investigational device exemption (IDE) trial.

Methods: The Atlas IDE trial is a prospective, multicenter, single-arm, open-label study of wide-neck aneurysms (neck ≥ 4 mm or dome-to-neck ratio < 2) in the anterior circulation treated with the Neuroform Atlas Stent and approved coils. Follow-up was obtained immediately postprocedure and 2, 6, and 12 mo postoperatively. We herein describe safety and efficacy outcomes, and functional independence of the subjects with aneurysms from all segments of MCA.

Results: A total of 35 patients were included (27 MCA bifurcation, 5 M1, 3 M2). The mean aneurysm size was 6.0 ± 1.8 mm, and the mean neck was 4.4 ± 1.2 mm. Technical procedural success was achieved in all patients. A total of 26 patients had follow-up digital subtraction angiography available at 12 mo, with 80.8% (21/26) having complete aneurysm occlusion. Twelve-month safety data were collected for 91.4% (32/35), 8.5% (3/35) had primary safety endpoint, all 3 major ischemic strokes. Mortality occurred in 2 patients beyond 30 d unrelated to procedure (1 gallbladder cancer and 1 fentanyl intoxication). At 1 yr, modified Rankin Score was 0 to 2 in 84.4% (27/32), 3 in 9.4%, and 3 patients were missing. Approximately 5.7% (2/35) of patients were retreated at 12 mo.

Conclusion: Stent-assisted coiling with the Neuroform Atlas Stent is a viable alternative to clipping for selected MCA aneurysms. Complete aneurysm occlusion rates have improved compared to historical data. Proper case selection can lead to acceptable endovascular results.
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http://dx.doi.org/10.1093/neuros/nyab090DOI Listing
June 2021

Performance of Repaired Concrete under Cyclic Flexural Loading.

Materials (Basel) 2021 Mar 11;14(6). Epub 2021 Mar 11.

Department of Civil Engineering, University of Victoria, 3800 Finnerty Road, Victoria, BC V8W 2Y2, Canada.

There is limited research reported on the effect of cyclic loading on cement-based repair materials as conducting such tests is time consuming. To overcome this issue, this study utilized a novel loading regime consisting of cycle groups with increasing stress amplitude to accelerate the test process. The Palmgren-Minder rule was used to estimate the fatigue life of repaired specimens. Specimens repaired with Mix M (cementitious repair mortar), which was estimated to have the highest 2-million-cycle fatigue endurance limit (77.4%), showed the longest fatigue life (95,991 cycles) during the cyclic loading test, the highest slant, and splitting bond strength among all repair mixes. The estimated two-million cycle fatigue endurance limit of Mix S (70.8%) was very similar to that was reported in literature (71%) using the traditional loading method. This study confirms the usefulness of Palmgren-Minder rule on estimating the fatigue life of repaired specimens. Additionally, the use of the novel loading regime showed the benefit of shortening the test process while producing results similar to those from using traditional loading methods. To improve the prediction accuracy, future research is required to modify the failure criteria to accommodate specimens that may not fail even when the average flexural strength is met.
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http://dx.doi.org/10.3390/ma14061363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999455PMC
March 2021

Unilateral benign yellow dot maculopathy.

Am J Ophthalmol Case Rep 2021 Jun 11;22:101068. Epub 2021 Mar 11.

Department of Ophthalmology and Visual Sciences, Dalhousie University, 1276 South Park Street, Room 2035D, 2 West Victoria Building, Halifax, Nova Scotia, B3H 2Y9, Canada.

Purpose: To describe a unique case of unilateral benign yellow dot maculopathy.

Observations: A 25-year-man was evaluated after incidental finding of yellow dots in the right macula. The findings of examination and multimodal imaging were in keeping with a diagnosis of benign yellow dot maculopathy.

Conclusions And Importance: Benign yellow dot maculopathy is a recently described entity with either a sporadic or dominant inheritance pattern. This is the first known report of the characteristic findings of this phenotype presenting unilaterally.
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http://dx.doi.org/10.1016/j.ajoc.2021.101068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995479PMC
June 2021

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic.

Stroke Vasc Neurol 2021 Mar 26. Epub 2021 Mar 26.

Department of Radiology, Beaumont Hospital, Dublin, Ireland.

Background: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.

Methods: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation.

Findings: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile.

Interpretation: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
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http://dx.doi.org/10.1136/svn-2020-000695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006491PMC
March 2021

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Neurology 2021 06 25;96(23):e2824-e2838. Epub 2021 Mar 25.

Department of Neurology (R.G.N., M.H.M., M.Frankel, D.C.H.), Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine, Atlanta; Department of Radiology (M.M.Q., M.A., T.N.N., A.K.) and Radiation Oncology (M.M.Q.), Boston Medical Center, Boston University School of Medicine, Massachusetts; Department of Neurology (S.O.M.), Federal University of Rio Grande do Sul, Porto Alegre; Hospital de Clínicas de Porto Alegre (S.O.M.), Brazil; Department of Stroke Neurology (H. Yamagami), National Hospital Organization, Osaka National Hospital, Japan; Department of Neurology (Z.Q.), Xinqiao Hospital of the Army Medical University, Chongqing, China; Department of Neurology (O.Y.M.), Stroke and Neurointervention Division, Alexandria University Hospital, Alexandria University, Egypt; Boston University School of Medicine (A.S.), Massachusetts; 2nd Department of Neurology (A.C.), Institute of Psychiatry and Neurology, Warsaw, Poland; Department of Neurology (G.T., L.P.), National & Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece; Faculdade de Medicina (D.A.d.S.), Universidade de Lisboa, Lisbon, Portugal; Department of Neurology (J.D., R.L.), Leuven University Hospital, Belgium; International Clinical Research Center and Department of Neurology (R.M.), St. Anne´s University Hospital in Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Neurology (P.V.), Groeninge Hospital, Kortrijk; Department of Neurology (P.V.), University Hospitals Antwerp; Department of Translational Neuroscience (P.V.), University of Antwerp, Belgium; Department of Neurology (J.E.S., T.G.J.), Cooper Neurological Institute, Cooper University Hospital, Camden, New Jersey; Department of Neurology and Neurosurgery (J. Kõrv), University of Tartu, Estonia; Department of Neurology (J.B., R.V.,S.R.), Loyola University Chicago Stritch School of Medicine, Illinois; Department of Neurosurgery (C.W.L.), Kaiser Permanente Fontana Medical Center; Department of Neurology (N.S.S.), Kaiser Permanente Los Angeles Medical Center; Department of Neurology (A.M.Z., S.A.S.), UT Health McGovern Medical School, Houston, Texas; Department of Neurology (A.L.Z.), Medical University of South Carolina, Charleston; Department of Internal Medicine (G.N.), School of Health Sciences, University of Thessaly, Larissa, Greece; Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, Pennsylvania; Department of Neurology (A.L.), Ohio Health Riverside Methodist Hospital Columbus; Department of Medicine and Neurology (A.R.), University of Otago and Wellington Hospital, New Zealand; Department of Neurology (E.A.M.), Vanderbilt University Medical Center, Nashville, Tennessee; Department of Neurology (A.W.A., D. Alsbrook), University of Tennessee Health Center, Memphis; Department of Neurology (D.Y.H.), University of North Carolina at Chapel Hill; Departments of Neurology (S.Y.) and Radiology (E.R.), New York University Grossman School of Medicine; Douala Gynaeco-Obstetric and Pediatric Hospital (E.G.B.L.), University of Douala, Faculty of Medicine and Pharmaceutical Science, Cameroon; Ain Shams University Specialized Hospital (H.M.A., H.M.S., A.E., T.R.); Cairo University Affiliated MOH Network (F.H.); Department of Neurology (TM.), Nasser Institute for Research and Treatment, Cairo; Mansoura University Affiliated Private Hospitals Network (W.M.), Egypt; Kwame Nkrumah University of Science and Technology (F.S.S.), Kumasi, Ghana; Stroke Unit (T.O.A., K.W.), University of Ilorin Teaching Hospital; Neurology Unit (B.A.), Department of Medicine, Lagos State University Teaching Hospital; Department of Medicine (E.O.N.), Federal Medical Centre Owerri, Imo State, Nigeria; Neurology Unit (T.A.S.), Department of Medicine, Federal Medical Centre, Owo, Ondo State, Nigeria; University College Hospital (J.Y.), Ibadan, Nigeria; The National Ribat University Affiliated Hospitals (H.H.M.), Khartoum, Sudan; Neurology Section (P.B.A.), Department of Internal Medicine, Aga-Khan University, Medical College East Africa, Dar es Salaam, Tanzania; Tunis El Manar University (A.D.R.), Military Hospital of Tunis; Department of Neurology (S.B.S.), Mongi Ben Hmida National Institute of Neurology, Faculty of Medicine of Tunis, University Tunis El Manar, Tunisia; Department of Physiology (L.G.), Parirenyatwa Hospital, and Departments of Physiology and Medicine (G.W.N.), University of Zimbabwe, Harare; Department of Cerebrovascular/Endovascular Neurosurgery Division (D.S.), Erebouni Medical Center, Yerevan, Armenia; Department of Neurology (A.R.), Sir Salimulah College, Dhaka, Bangladesh; Department of Neurology (Z.A.), Taihe Hospital of Shiyan City, Hubei; Department of Neurology (F.B.), Nanyang Central Hospital, Henan; Department of Neurology (Z.D.), Wuhan No. 1 Hospital, Hubei, China; Department of Neurology (Y. Hao.), Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Department of Neurology (W.H.), Traditional Chinese Medicine Hospital of Maoming, Guangdong; Department of Neurology (G.Li.), Affiliated Hospital of Qingdao University, Shandong; Department of Neurology (W.L), The First Affiliated Hospital of Hainan Medical College; Department of Neurology (G.Liu.), Wuhan Central Hospital, Hubei; Department of Neurology (J.L.), Mianyang 404th Hospital, Sichuan; Department of Neurology (X.S.), Yijishan Hospital of Wannan Medical College, Anhui; Department of Neurology and Neuroscience (Y.S.), Shenyang Brain Institute, Shenyang First People's Hospital, Shenyang Medical College Affiliated Brain Hospital; Department of Neurology (L.T.), Affiliated Yantai Yuhuangding Hospital of Qingdao University, Shandong; Department of Neurology (H.W.), Xiangyang Central Hospital, Hubei; Department of Neurology (B.W., Y.Yan), West China Hospital, Sichuan University, Chengdu; Department of Neurology (Z.Y.), Affiliated Hospital of Southwest Medical University, Sichuan; Department of Neurology (H.Z.), Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine; Department of Neurology (J.Z.), The First Affiliated Hospital of Shandong First Medical University; Department of Neurology (W.Z.), First Affiliated Hospital of Fujian Medical University, China; Acute Stroke Unit (T.W.L.), The Prince of Wales Hospital, Kwok Tak Seng Centre for Stroke Research and Intervention, The Chinese University of Hong Kong; Interventional Neurology (C.C.), MAX Superspecialty Hospital, Saket, New Delhi; NH Institute of Neurosciences (V.H.), NH Mazumdar Shaw Medical Center, Bangalore; Department of Neurology (B.M.), Apollo Speciality Hospitals Nellore; Department of Neurology (J.D.P.), Christian Medical College, Ludhiana, Punjab; Sree Chitra Tirunal Institute for Medical Sciences and Technology (P.N.S.), Kerala, India; Stroke Unit (F.S.U.), Pelni Hospital, Jakarta, Indonesia; Neurosciences Research Center (M. Farhoudi, E.S.H.), Tabriz University of Medical Sciences, Tabriz, Iran; Beer Sheva Hospital (A.H.); Department of Interventional Neuroradiology, Rambam Healthcare Campus, Haifa, Israel (A.R., R.S.H.); Departments of Neurology (N.O.) and Neurosurgery (N.S.), Kobe City Medical Center General Hospital, Kobe; Department of Stroke and Neurovascular Surgery (D.W.), IMS Tokyo-Katsushika General Hospital; Yokohama Brain and Spine Center (R.Y.); Iwate Prefectural Central (R.D.); Department of Neurology and Stroke Treatment (N.T.), Japanese Red Cross Kyoto Daiichi Hospital; Department of Neurology (T.Y.), Kyoto Second Red Cross Hospital; Department of Neurology (T.T.), Japanese Red Cross Kumamoto Hospital; Department of Stroke Neurology (Y. Yazawa), Kohnan Hospital, Sendai; Department of Cerebrovascular Medicine (T.U.), Saga-Ken Medical Centre; Department of Neurology (T.D.), Saitama Medical Center, Kawagoe; Department of Neurology (H.S.), Nara City Hospital; Department of Neurology (Y.S.), Toyonaka Municipal Hospital, Osaka; Department of Neurology (F. Miyashita), Kagoshima City Hospital; Department of Neurology (H.F.), Japanese Red Cross Matsue Hospital, Shimane; Department of Neurology (K.M.), Shiroyama Hospital, Osaka; Department of Cerebrovascular Medicine (J.E.S.), Niigata City General Hospital; Department of Neurology (Y.S.), Sugimura Hospital, Kumamoto; Stroke Medicine (Y. Yagita), Kawasaki Medical School, Okayama; Department of Neurology (Y.T.), Osaka Red Cross Hospital; Department of Stroke Prevention and Treatment (Y.M.), Department of Neurosurgery, University of Tsukuba, Ibaraki; Department of Neurology (S.Y.), Stroke Center and Neuroendovascular Therapy, Saiseikai Central Hospital, Tokyo; Department of Neurology (R.K.), Kin-ikyo Chuo Hospital, Hokkaido; Department of Cerebrovascular Medicine (T.K.), NTT Medical Center Tokyo; Department of Neurology and Neuroendovascular Treatment (H. Yamazaki), Yokohama Shintoshi Neurosurgical Hospital; Department of Neurology (M.S.), Osaka General Medical Center; Department of Neurology (K.T.), Osaka University Hospital; Department of Advanced Brain Research (N.Y.), Tokushima University Hospital Tokushima; Department of Neurology (K.S.), Saiseikai Fukuoka General Hospital, Fukuoka; Department of Neurology (T.Y.), Tane General Hospital, Osaka; Division of Stroke (H.H.), Department of Internal Medicine, Osaka Rosai Hospital; Department of Comprehensive Stroke (I.N.), Fujita Health University School of Medicine, Toyoake, Japan; Department of Neurology (A.K.), Asfendiyarov Kazakh National Medical University; Republican Center for eHealth (K.F.), Ministry of Health of the Republic of Kazakhstan; Department of Medicine (S.K.), Al-Farabi Kazakh National University; Kazakh-Russian Medical University (M.Z.), Kazakhstan; Department of Neurology (J.-H.B.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (Y. Hwang), Kyungpook National University Hospital, School of Medicine, Kyungpook National University; Ajou University Hospital (J.S.L.); Department of Neurology (S.B.L.), Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Department of Neurology (J.M.), National Medical Center, Seoul; Department of Neurology (H.P., S.I.S.), Keimyung University School of Medicine, Dongsan Medical Center, Daegu; Department of Neurology (J.H.S.), Busan Paik Hospital, School of Medicine, Inje University, Busan; Department of Neurology (K.-D.S.), National Health Insurance Service Ilsan Hospital, Goyang; Asan Medical Center (C.J.Y.), Seoul, South Korea; Department of Neurology (R.A.), LAU Medical Center-Rizk Hospital, Beirut, Lebanon; Department of Medicine (W.A.W.Z., N.W.Y.), Pusat Perubatan Universiti Kebangsaan Malaysia, Kuala Lumpur; Sultanah Nur Zahirah (Z.A.A., K.A.I.), Kuala Terengganu; University Putra Malaysia (H.b.B.); Sarawak General Hospital, Kuching (L.W.C.); Hospital Sultan Abdul Halim (A.B.I.), Sungai Petani Kedah; Hospital Seberang Jaya (I.L.), Pulau Pinang; Thomson Hospital Kota Damansara (W.Y.T.), Malaysia; "Nicolae Testemitanu" State University of Medicine and Pharmacy (S.G., P.L.), and Department of Neurology, Emergency Medicine Institute, Chisinau, Republic of Moldova; Department of Stroke Unit (A.M.A.H.), Royal Hospital Muscat, Oman; Neuroscience Institute (Y.Z.I., N.A.), Hamad Medical Corporation, Doha, Qatar; St. Luke's Medical Center-Institute of Neurosciences (M.C.P.-F., C.O.C.), Quezon City, Philippines; Endovascular Neurosurgery (D.K.), Saint-Petersburg Dzhanelidze Research Institute of Emergency Medicine, St. Petersburg, Russia; Department of Neurology (A.A.), Stroke Unit, King Saud University, College of Medicine, Riyadh; Department of Neurosurgery (H.A.-J.), Interventional Radiology, and Critical Care Medicine, King Fahad Hospital of the University, Imam Abdulrahman bin Faisal University, Saudi Arabia; Singapore National Neuroscience Institute (C.H.T.); Changi General Hospital (M.J.M.), Singapore; Neuroscience Center, Raffles Hospital (N.V.), Singapore; Department of Neurology (C.-H.C., S.-C.T.), National Taiwan University Hospital; Department of Radiology (A.C.), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Dicle University Medical School and Hospital (E.A.), Diyarbakir; Stroke and Neurointervention Unit (O.A., A.O.O.), Eskisehir Osmangazi University; Gaziantep University Faculty of Medicine (S.G.), Turkey; Department of Neurology (S.I.H., S.J.), Neurological Institute at Cleveland Clinic Abu Dhabi, United Arab Emirates; Stroke Center (H.L.V., A.D.C.), Hue Central Hospital, Hue, Vietnam; Stroke Department (H.H.N., T.N.P.), Da Nang Hospital, Da Nang City; 115 People's Hospital (T.H.N., T.Q.N.), Ho Chi Minh City, Vietnam; Department of Neurology (T.G., C.E.), Medical University of Graz; Department of Neurology (M. K.-O.), Research Institute of Neurointervention, University Hospital Salzburg/Paracelsus Medical University, Austria; Department of Neurology (F.B., A.D.), Centre Hospitalier Universitaire de Charleroi, Belgium; Department of Neurology (S.D.B., G.V.), Sint Jan Hospital, Bruges; Department of Neurology (S.D.R.), Brussels University Hospital (UZ Brussel); Department of Neurology (N.L.), ULB Erasme Hospitals Brussels; Department of Neurology (M.P.R.), Europe Hospitals Brussels; Department of Neurology (L.Y.), Antwerp University Hospital, Belgium; Neurology Clinic (F.A., T.S.), St. Anna University Hospital, Sofia, Bulgaria; Department of Neurology (M.R.B.), Sestre Milosrdnice University Hospital, Zagreb; Department of Neurology (H.B.), Sveti Duh University Hospital, Zagreb; Department of Neurology (I.C.), General Hospital Virovitica; Department of Neurology (Z.H.), General Hospital Zabok; Department of Radiology (F. Pfeifer), University Hospital Centre Zagreb, Croatia; Regional Hospital Karlovy Vary (I.K.); Masaryk Hospital Usti nad Labem (D.C.); Military University Hospital Praha (M. Sramek); Oblastní Nemocnice Náchod (M. Skoda); Regional Hospital Pribram (H.H.); Municipal Hospital Ostrava (L.K.); Hospital Mlada Boleslav (M. Koutny); Hospital Vitkovice (D.V.); Hospital Jihlava (O.S.); General University Hospital Praha (J.F.); Hospital Litomysl (K.H.); Hospital České Budejovice (M.N.); Hospital Pisek (R.R.); Hospital Uherske Hradiste (P.P.); Hospital Prostejov (G.K.); Regional Hospital Chomutov (J.N.); Hospital Teplice (M.V.); Mining Hospital Karvina (H.B.); Thomayer Hospital Praha (D.H.); Hospital Blansko (D.T.); University Hospital Brno (R.J.); Regional Hospital Liberec (L.J.); Hospital Ceska Lipa (J.N.); Hospital Sokolov (A.N.); Regional Hospital Kolin (Z.T.); Hospital Trutnov (P. Fibrich); Hospital Trinec (H.S.); Department of Neurology (O.V.), University Hospital Ostrava, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Bispebjerg Hospital (H.K.C.), University of Copenhagen; Stroke Center (H.K.I., T.C.T.), Rigshospitalet, University of Copenhagen; Aarhus University Hospital (C.Z.S.), Aarhus; Neurovascular Center, Zealand University Hospital, University of Copenhagen (T.W.), Roskilde, Denmark; Department of Neurology and Neurosurgery (R.V.), University of Tartu, Estonia; Neurology Clinic (K.G.-P.), West Tallinn Central Hospital; Center of Neurology (T.T.), East Tallinn Central Hospital, School of Natural Sciences and Health, Tallinn University; Internal Medicine Clinic (K.A.), Pärnu Hospital, Estonia; Université Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition (C.C., F.C.); Centre Hospitalier d'Arcachon (M.D.), Gujan-Mestras; Centre Hospitalier d'Agen (J.-M.F.); Neurologie Vasculaire (L.M.) and Neuroradiologie (O.E.), Hospices Civils de Lyon, Hôpital Pierre Wertheimer, Bron; Centre Hospitalier et Universitaire de Bordeaux (E.L., F.R.); Centre Hospitalier de Mont de Marsan (B.O.); Neurologie (R.P.), Fondation Ophtalmologique Adolphe de Rothschild; Versailles Saint-Quentin-en-Yvelines University (F. Pico); Neuroradiologie Interventionelle (M.P.), Fondation Ophtalmologique Adolphe de Rothschild; Neuroradiologie Interventionelle (R.P.), Hôpitaux Universitaires de Strasbourg, France; K. Eristavi National Center of Experimental and Clinical Surgery (T.G.), Tbilisi; Department of Neurosurgery (M. Khinikadze), New Vision University Hospital, Tbilisi; Vivamedi Medical Center (M. Khinikadze), Tbilisi; Pineo Medical Ecosystem (N.L.), Tbilisi; Ivane Javakhishvili Tbilisi State University (A.T.), Tbilisi, Georgia; Department of Neurology (S.N., P.A.R.), University Hospital Heidelberg; Department of Neurology (M. Rosenkranz), Albertinen Krankenhaus, Hamburg; Department of Neurology (H.S.), Elbe Klinken Stade, University Medical Center Göttingen; Department of Neurology (T.S.), University Hospital Carl Gustav Carus, Dresden; Kristina Szabo (K.S.), Department of Neurology, Medical Faculty Mannheim, University Heidelberg, Mannheim; Klinik und Poliklinik für Neurologie (G.T.), Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany; Department of Internal Medicine (D.S.), School of Health Sciences, University of Thessaly, Larissa; Second Department of Neurology (O.K.), Stroke Unit, Metropolitan Hospital, Piraeus, Greece; University of Szeged (P.K.), Szeged; University of Pecs (L.S., G.T.), Hungary; Stroke Center (A.A.), IRCCS Istituto di Ricovero e Cura a Carattere Scientifico, Negrar, Verona; Department of Neurology (F.B.), Ospedale San Paolo, Savona,; Institute of Neurology (P.C., G.F.), Fondazione Policlinico Universitario Agostino Gemelli, Rome; Interventional Neurovascular Unit (L.R.), Careggi University Hospital, Florence; Stroke Unit (D.S.), Azienda Socio Sanitaria Territoriale (ASST) di Lecco, Italy; Maastricht University Medical Center; Department of Neurology (M.U.), Radiology, University Medical Center Groningen; Department of Neurology (I.v.d.W.), Haaglanden Medical Center, the Hague, the Netherlands; Department of Neurology (E.S.K.), Akershus University Hospital, Lørenskog, General Practice, HELSAM, University of Oslo, Norway; Neurological Ward with Stroke Unit (W.B.), Specialist Hospital in Konskie, Gimnazjalna, Poland and Collegium Medicum, Jan Kochanowski University, Kielce, Poland; Neurological Ward with Stroke Unit (M.F.), District Hospital in Skarzysko-Kamienna; Department of Neurology (E.H.L.), Szpitala im T. Marciniaka in Wroclaw; 2nd Department of Neurology (M. Karlinski), Institute of Psychiatry and Neurology, Warsaw; Department of Neurology and Cerebrovascular Disorders (R.K., P.K.), Poznan University of Medical Sciences; 107th Military Hospital with Polyclinic (M.R.), Walcz; Department of Neurology (R.K.), St. Queen Jadwiga, Clinical Regional Hospital No. 2, Rzeszow; Department of Neurology (P.L.), Medical University of Lublin; 1st Department of Neurology (H.S.-J.), Institute of Psychiatry and Neurology, Warsaw; Department of Neurology and Stroke Unit (P.S.), Holy Spirit Specialist Hospital in Sandomierz, Collegium Medicum Jan Kochanowski University in Kielce; Copernicus PL (W.F.), Neurology and Stroke Department, Hospital M. Kopernik, Gdansk; Stroke Unit (M.W.), Neurological Department, Stanislaw Staszic University of Applied Sciences, Pila, Poland; Hospital São José (Patricia Ferreira), Centro Hospitalar Universitário de Lisboa Central, Lisbon; Stroke Unit (Paulo Ferreira, V.T.C.), Hospital Pedro Hispano, Matosinhos; Stroke Unit, Internal Medicine Department (L.F.), Neuroradiology Department, Centro Hospitalar Universitário de São João, Porto; Department of Neurology (J.P.M.), Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal; Department of Neurosciences (T.P.e.M.), Hospital de Santa Maria-CHLN, North Lisbon University Hospital; Hospital São José (A.P.N.), Centro Hospitalar Universitário de Lisboa Central, Lisbon; Department of Neurology (M. Rodrigues), Hospital Garcia de Orta, Portugal; Department of Neurology (C.F.-P.), Transilvania University, Brasov, Romania; Department of Neurology (G.K., M. Mako), Faculty Hospital Trnava, Slovakia; Department of Neurology and Stroke Center (M.A.d.L., E.D.T.), Hospital Universitario La Paz, Madrid; Department of Neurology (J.F.A.), Hospital Clínico Universitario, Universidad de Valladolid; Department of Neurology (O.A.-M.), Complejo Hospitalario Universitario de Albacete; Department of Neurology (A.C.C.), Unidad de Ictus, Hospital Universitario Ramon y Cajal, Madrid; Department of Neurology (S.P.-S), Hospital Universitario Virgen Macarena & Neurovascular Research Laboratory (J.M.), Instituto de Biomedicina de Sevilla-IbiS; Rio Hortega University Hospital (M.A.T.A.), University of Valladolid; Cerebrovascular Diseases (A.R.V.), Hospital Clinic of Barcelona, Spain; Department of Neurology (M. Mazya), Karolinska University Hospital and Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Interventional Neuroradiology (G.B.), University Hospitals of Geneva; Department of Interventional and Diagnostic Neuroradiology (A.B., M.-N.P.), Radiology and Nuclear Medicine, University Hospital Basel; Department of Neurology (U.F.), University of Bern; Department of Neuroradiology (J.G.), University of Bern; Department of Neuroscience (P.L.M., D.S.), Lausanne University Hospital, Switzerland; Department of Stroke Medicine (S.B., J. Kwan), Imperial College Healthcare NHS Trust, Charing Cross Hospital, London; Department of Neurology (K.K.), Queen's Medical Centre, Nottingham University Hospitals NHS Trust, United Kingdom; Department of Neurology (A.B., A. Shuaib), University of Alberta, Edmonton; Department of Neurology (L.C., A. Shoamanesh), McMaster University, Hamilton; Department of Clinical Neurosciences and Hotchkiss Brain Institute (A.M.D., M.D.H.), University of Calgary; Department of Neurology (T.F., S.Y.), University of British Columbia, Vancouver; Mackenzie Health (J.H., C.A.S.) Richmond Hill, Ontario; Department of Neurology (H.K.), Sunnybrook Health Sciences Centre, University of Toronto; Department of Neurology (A. Mackey), Hopital Enfant Jesus, Centre Hospitalier de l'Universite Laval, Quebec City; Department of Neurology (A.P.), University of Toronto; Medicine (G.S.), St. Michael's Hospital, University of Toronto, Canada; Department of Neurosciences (M.A.B.), Hospital Dr. Rafael A. Calderon Guardia, CCSS. San Jose, Costa Rica; Neurovascular Service (J.D.B.), Hospital General San Juan de Dios, Guatemala City; Department of Neurología (L.I.P.R.), Hospital General de Enfermedades, Instituto Guatemalteco de Seguridad Social, Guatemala City, Guatemala; Department of Neurology (F.G.-R.), University Hospital Jose Eleuterio Gonzalez, Universidad Autonoma de Nuevo Leon, Mexico; Pacífica Salud-Hospital Punta Pacífica (N.N.-E., A.B., R.K.), Panama; Department of Neurology, Radiology (M.A.), University of Kansas Medical Center; Department of Neurointerventional Neurosurgery (D. Altschul), The Valley Baptist Hospital, Ridgewood, New Jersey; Palmetto General Hospital (A.J.A.-O.), Tenet, Florida; Neurology (I.B., P.K.), University Hospital Newark, New Jersey Medical School, Rutgers, Newark, New Jersey; Community Healthcare System (A.B.), Munster, Indiana; Department of Neurology (N.B., C.B.N.), California Pacific Medical Center, San Francisco; Department of Neurology (C.B.), Mount Sinai South Nassau, New York; University of Toledo (A.C.), Ohio; Department of Neurology (S.C.), University of Maryland School of Medicine, Baltimore, Maryland; Neuroscience (S.A.C.), Inova Fairfax Hospital, Virginia; Department of Neurology (H.C.), Abington Jefferson Hospital, Pennsylvania; Department of Neurology (J.H.C.), Mount Sinai South Nassau, New York; Baptist Health Medical Center (S.D.), Little Rock, Arkansas; Department of Neurology (K.D.), HCA Houston Healthcare Clearlake, Texas; Department of Neurology (T.G.D., R.S.), Erlanger, Tennessee; Wilmington North Carolina (V.T.D.); Department of Vascular and Neurointerventional Services (R.E.), St. Louis University, Missouri; Department of Neurology (M.E.), Massachusetts General Hospital, Boston; Department of Neurology, Neurosurgery, and Radiology (M.F., S.O.-G., N.R.), University of Iowa Hospitals and Clinics, Iowa City; Department of Radiology (D.F.), Swedish Medical Center, Englewood, Colorado; Department of Radiology (D.G.), Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland; Adventist Health Glendale Comprehensive Stroke Center (M.G.), Los Angeles, California; Wellstar Neuroscience Institute (R.G.), Marietta, Georgia; Department of Neurology (A.E.H.), University of Texas Rio Grande Valley-Valley Baptist Medical Center, Texas; Department of Neurology (J.H., B.V.), Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts; Department of Neurology (A.M.K.), Wayne State, Detroit, Michigan; HSHS St. John's Hospital (N.N.K.), Southern Illinois University School of Medicine, Springfield; Virginia Hospital Center (B.S.K.), Arlington; Department of Neurology, University of Michigan, Ann Arbor; Weill-Cornell Medical College (D.O.K.), New York-Presbyterian Queens; Department of Neurology (V.H.L.), Ohio State University, Columbus; Department of Neurology (L.Y.L.), Tufts Medical Center, Boston, Massachusetts; Vascular and Neurointerventional Services (G.L.), St. Louis University, Missouri; Miami Cardiac & Vascular Institute (I.L., A.K.S.), Florida; Department of Neurology (H.L.L.), Oregon Health & Science University, Portland; Department of Emergency Medicine (L.M., M.S.), Steward Holy Family Hospital, Methuen, MA; Vidant Medical Center (S.M.), Greenville, North Carolina; Department of Neurology (A.M.M., D.R.Y.) and Neurosurgery (D.R.Y.), University of Miami Miller School of Medicine, Florida; Department of Neurology (H.M.), SUNY Upstate New York, Syracuse; Memorial Neuroscience Institute (B.P.M.), Pembroke Pines, Florida; Neurosciences (J.M., J.P.T.), Spectrum Health, Michigan State University College of Medicine, Grand Rapids, Michigan; Sutter Health (M.M.), Sacramento, California; Department of Neurology (J.G.M.), Maine Medical Center, Portland; Department of Neurology (S.S.M.), Bayhealth, Dover, Delaware; Department of Neurology and Pediatrics (F.N.), Emory University, Atlanta, Georgia; Department of Neurology (K.N.), University of Arkansas for Medical Sciences, Little Rock; Department of Radiology and Neurology (R.N.-W.), UT Southwestern Medical Center, Dallas, Texas; Ascension St. John Medical Center (R.H.R.), Tulsa, Oklahoma; Riverside Regional Medical Center (P.R.), Newport, Virginia; Department of Neurology (J.R.R., T.N.N.), Boston University School of Medicine, MA; Department of Neurology (A.R.), Hospital of the University of Pennsylvania, Philadelphia; Department of Neurology (M.S.), University of Washington School Medicine, Seattle; Department of Neurology (B.S.), University of Massachusetts Medical Center, Worcester; Department of Neurology (A.S.), CHI-Immanuel Neurological Institute, Creighton University, Omaha, Nebraska; Holy Cross Hospital (S.L.S.), Fort Lauderdale, Florida; Department of Neurology (V.S.), Interventional Neuroradiology, University of California in Los Angeles; Banner Desert Medical Center (M.T.), Mesa, Arizona; Hospital de Agudos Dr. Ignacio Privano (O.B., A.L.), Argentina; Institute for Neurological Research, FLENI (V.A.P.L.), Buenos Aires, Argentina; Hospital das Clinicas/São Paulo University (M.S.A., A.C.); Sumare State Hospital (F.B.C., L.V.), São Paulo; Hospital Vera Cruz (L.D.D.S.), Deus Campinas; Irmanandade Santa Casa de Porto Alegre (L.V.G.); Stroke Unit (F.O.L., F. Mont'alverne), Hospital Geral de Fortaleza; Stroke Unit (A.L.L., P.S.C.M.), Hospital Sao Jose, Joinville, Santa Catarina; Stroke Unit (R.T.M.), Neurology, Nossa Senhora da Conceição Hospital, Porto Alegre; Department of Neurology (D.L.M.C.), Hospital Moinhos de Vento, Porto Alegre; Department of Neurology (L.C.R.), Hospital de Base do Distrito Federal; Hospital Ana (V.F.C.), Hospital Juliane, Federal University of Parana, Curitiba, Brazil; Vascular Neurology Unit (P.M.L., V.V.O.), Neurology Service, Department of Neurology and Psychiatry, Clínica Alemana, Universidad del Desarrollo, Santiago; Hospital Padre Hurtado (V.N., J.M.A.T.) Santiago, Chile; Fundación Valle del Lili (P.F.R.A.), Cali; Stroke Center (H.B.), Fundación Santa Fe de Bogotá; Department of Neurology (A.B.C.-Q.), Hospital Departamental Universitario del Quindio San Juan de Dios, Armenia; Clinica Universitaria Colombia (C.E.R.O.), Bogotá; University Hospital of San Vicente Foundation (D.K.M.B.), Medellin; Barranquilla, Colombia (O.L.); Hospital Infantil Universitario de San Jose (M.R.P.), Bogota; Stroke Unit (L.F.D.-E.), Hospital de Clínicas, Facultad de Ciencias Médicas, Universidad Nacional de Asunción; Neurology Service (D.E.D.M.F., A.C.V.), Hospital Central del Instituto de Prevision Social, Paraguay; Internal Medicine Service (A.J.Z.Z.), Hospital Central de Policia "Rigoberto Caballero", Paraguay; National Institute of Neurological Sciences of Lima Peru (D.M.B.I.); Hospital Edgardo Rebagliati Martins Lima-Peru (L.R.K.); Department of Neurology (B.C.), Royal Melbourne Hospital; Department of Neurology (G.J.H.), Sir Charles Gairdner Hospital and Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth; University of Melbourne (C.H., R.S.), Ballarat Health Service, Australia University of Melbourne; Department of Neurology (T.K.), Royal Adelaide Hospital; Department of Neurosurgery (A. Ma), Royal North Shore Hospital, Sydney; Department of Neurology (R.T.M.), Mater Hospital, Brisbane; Department of Neurology (R.S.), Austin Health, Victoria; Florey Institute of Neuroscience and Mental Health (R.S.), Parkville, Melbourne, Australia; Greymouth Base Hospital (D.S.), New Zealand; Department of Neurology (T.Y.-H.W.), Christchurch Hospital, New Zealand; Department of Neurology (D.L.), University of California in Los Angeles; and Department of Neurology (O.O.Z.), Mercy Health Neurosciences, Toledo, Ohio.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
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http://dx.doi.org/10.1212/WNL.0000000000011885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205458PMC
June 2021

Influence of time to endovascular stroke treatment on outcomes in the early versus extended window paradigms.

Int J Stroke 2021 Apr 7:17474930211006304. Epub 2021 Apr 7.

Department of Neurosciences, Drexel Neurosciences Institute, Philadelphia, PA, USA.

Background: The effect of time from stroke onset to thrombectomy in the extended time window remains poorly characterized.

Aim: We aimed to analyze the relationship between time to treatment and clinical outcomes in the early versus extended time windows.

Methods: Proximal anterior circulation occlusion patients from a multicentric prospective registry were categorized into early (≤6 h) or extended (>6-24 h) treatment window. Patients with baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 10 and intracranial internal carotid artery or middle cerebral artery-M1-segment occlusion and pre-morbid modified Rankin scale (mRS) 0-1 ("DAWN-like" cohort) served as the population for the primary analysis. The relationship between time to treatment and 90-day mRS, analyzed in ordinal (mRS shift) and dichotomized (good outcome, mRS 0-2) fashion, was compared within and across the extended and early windows.

Results: A total of 1603 out of 2008 patients qualified. Despite longer time to treatment (9[7-13.9] vs. 3.4[2.5-4.3] h,  < 0.001), extended-window patients ( = 257) had similar rates of symptomatic intracranial hemorrhage (sICH; 0.8% vs. 1.7%,  = 0.293) and 90-day-mortality (10.5% vs. 9.6%,  = 0.714) with only slightly lower rates of 90-day good outcomes (50.4% vs. 57.6%,  = 0.047) versus early-window patients ( = 709). Time to treatment was associated with 90-day disability in both ordinal (adjusted odd ratio (aOR), ≥ 1-point mRS shift: 0.75; 95%CI [0.66-0.86],  < 0.001) and dichotomized (aOR, mRS 0-2: 0.73; 95%CI [0.62-0.86],  < 0.001) analyses in the early- but not in the extended-window (aOR, mRS shift: 0.96; 95%CI [0.90-1.02],  = 0.15; aOR, mRS0-2: 0.97; 95%CI [0.90-1.04],  = 0.41). Early-window patients had significantly lower 90-day functional disability (aOR, mRS shift: 1.533; 95%CI [1.138-2.065],  = 0.005) and a trend towards higher rates of good outcomes (aOR, mRS 0-2: 1.391; 95%CI [0.972-1.990],  = 0.071).

Conclusions: The impact of time to thrombectomy on outcomes appears to be time dependent with a steep influence in the early followed by a less significant plateau in the extended window. However, every effort should be made to shorten treatment times regardless of ischemia duration.
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April 2021

Comparison of midterm results of Platelet Rich Plasma (PRP) versus Steroid for plantar fasciitis: A randomized control trial of 118 patients.

J Clin Orthop Trauma 2021 Feb 6;13:9-14. Epub 2020 Sep 6.

Department of Orthopaedics, Dr BSA Medical College and Hospital, Delhi, India.

Background: Plantar fasciitis, which is a common cause of heel pain, often results in significant morbidity. In cases who are not responsive to initial conservative treatment, invasive procedures, often in the form of local infiltration of steroid are required. These procedures are associated with significant complications. Local Platelet Rich Plasma (PRP) infiltration is an emerging addition to these treatments. However, whether it is more effective in reducing pain and improving function than other treatments (such as steroid injections or whole blood) remains controversial.

Methods: Skeletally mature patients with plantar fasciitis who had failed conservative therapy were randomized using envelope method into 2 groups: PRP and Steroid group. The participants were assessed for pain using Visual Analog Scale on the day of presentation, and then after therapy at 2 weeks, 4 weeks, 3 months, and 6 months. They were additionally assessed on final follow-up using AOFAS hind-foot Score.

Results: 118 patients were randomized into 2 groups: 58 patients to the PRP group and 60 to the Steroid group. PRP was associated with greater improvement in VAS score and resulted in superior AOFAS score at 6 months as compared to steroid injection. The authors did not find any local or systemic complications in any of the groups. The result and difference were more pronounced as the time from injection increased and maximal benefit was observed at 6 months follow-up. None of the patients needed a repeat injection at 6 months.

Conclusion: Our study expands on the previous studies to provide a better evidence for superiority of PRP over local injection of steroid in plantar fasciitis, and the authors conclude that PRP provides better pain relief and function as compared to steroid injection.

Level Of Evidence: Level 1 Prospective Randomized Control Trial (RCT).
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http://dx.doi.org/10.1016/j.jcot.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920137PMC
February 2021

Clinical effectiveness of endovascular stroke treatment in the early and extended time windows.

Int J Stroke 2021 Apr 20:17474930211005740. Epub 2021 Apr 20.

Department of Neurosciences, Drexel Neurosciences Institute, Philadelphia, PA, USA.

Background: The clinical efficacy of mechanical thrombectomy has been unequivocally demonstrated in multiple randomized clinical trials. However, these studies were performed in carefully selected centers and utilized strict inclusion criteria.

Aim: We aimed to assess the clinical effectiveness of mechanical thrombectomy in a prospective registry.

Methods: A total of 2008 patients from 76 sites across 12 countries were enrolled in a prospective open-label mechanical thrombectomy registry. Patients were categorized into the corresponding cohorts of the SWIFT-Prime, DAWN, and DEFUSE 3 trials according to the basic demographic and clinical criteria without considering specific parenchymal imaging findings. Baseline and outcome variables were compared across the corresponding groups.

Results: As compared to the treated patients in the actual trials, registry-derived patients tended to be younger and had lower baseline ASPECTS. In addition, time to treatment was earlier and the use of intravenous tissue plasminogen activator (IV-tPA) and general anesthesia were higher in DAWN- and DEFUSE-3 registry derived patients versus their corresponding trials. Reperfusion rates were higher in the registry patients. The rates of 90-day good outcome (mRS0-2) in registry-derived patients were comparable to those of the patients treated in the corresponding randomized clinical trials (SWIFT-Prime, 64.5% vs. 60.2%; DAWN, 50.4% vs. 48.6%; Beyond-DAWN: 52.4% vs. 48.6%; DEFUSE 3, 52% vs. 44.6%, respectively; all  > 0.05). Registry-derived patients had significant less disability than the corresponding randomized clinical trial controls (ordinal modified Rankin Scale (mRS) shift odds ratio (OR),  < 0.05 for all).

Conclusion: Our study provides favorable generalizability data for the safety and efficacy of thrombectomy in the "real-world" setting and supports that patients may be safely treated outside the constraints of randomized clinical trials.
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http://dx.doi.org/10.1177/17474930211005740DOI Listing
April 2021

Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS‑CoV-2 infection.

EBioMedicine 2021 Mar 2;65:103259. Epub 2021 Mar 2.

Institute of Cardiovascular Sciences, University College London, London, UK; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.

Background: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity.

Methods: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n =12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to pseudovirus neutralizing antibody measurements.

Findings: A total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r = 0.57, p<0.0001) but only anti-S1 measurements correlated with near-contemporary pseudovirus neutralising antibody titres (measured at 16-18 weeks, r = 0.57, p<0.0001). By 21 weeks' follow-up, 31/143 (21.7%) anti-S1 and 6/150 (4.0%) anti-NP measurements reverted to negative. Mathematical modelling revealed faster clearance of anti-S1 compared to anti-NP (median half-life of 2.5 weeks versus 4.0 weeks), earlier transition to lower levels of antibody production (median of 8 versus 13 weeks), and greater reductions in relative antibody production rate after the transition (median of 35% versus 50%).

Interpretation: Mild SARS-CoV-2 infection is associated with heterogeneous serological responses in Euroimmun anti-S1 and Roche anti-NP assays. Anti-S1 responses showed faster rates of clearance, more rapid transition from high to low level production rate and greater reduction in production rate after this transition. In mild infection, anti-S1 serology alone may underestimate incident infections. The mechanisms that underpin faster clearance and lower rates of sustained anti-S1 production may impact on the longevity of humoral immunity.

Funding: Charitable donations via Barts Charity, Wellcome Trust, NIHR.
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http://dx.doi.org/10.1016/j.ebiom.2021.103259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920816PMC
March 2021

Epidemiological Surveillance of the Impact of the COVID-19 Pandemic on Stroke Care Using Artificial Intelligence.

Stroke 2021 05 4;52(5):1682-1690. Epub 2021 Mar 4.

Department of Neurosurgery, Mount Sinai Health System, New York (C.P.K., J.M.).

Background And Purpose: The degree to which the coronavirus disease 2019 (COVID-19) pandemic has affected systems of care, in particular, those for time-sensitive conditions such as stroke, remains poorly quantified. We sought to evaluate the impact of COVID-19 in the overall screening for acute stroke utilizing a commercial clinical artificial intelligence platform.

Methods: Data were derived from the Viz Platform, an artificial intelligence application designed to optimize the workflow of patients with acute stroke. Neuroimaging data on suspected patients with stroke across 97 hospitals in 20 US states were collected in real time and retrospectively analyzed with the number of patients undergoing imaging screening serving as a surrogate for the amount of stroke care. The main outcome measures were the number of computed tomography (CT) angiography, CT perfusion, large vessel occlusions (defined according to the automated software detection), and severe strokes on CT perfusion (defined as those with hypoperfusion volumes >70 mL) normalized as number of patients per day per hospital. Data from the prepandemic (November 4, 2019 to February 29, 2020) and pandemic (March 1 to May 10, 2020) periods were compared at national and state levels. Correlations were made between the inter-period changes in imaging screening, stroke hospitalizations, and thrombectomy procedures using state-specific sampling.

Results: A total of 23 223 patients were included. The incidence of large vessel occlusion on CT angiography and severe strokes on CT perfusion were 11.2% (n=2602) and 14.7% (n=1229/8328), respectively. There were significant declines in the overall number of CT angiographies (-22.8%; 1.39-1.07 patients/day per hospital, <0.001) and CT perfusion (-26.1%; 0.50-0.37 patients/day per hospital, <0.001) as well as in the incidence of large vessel occlusion (-17.1%; 0.15-0.13 patients/day per hospital, <0.001) and severe strokes on CT perfusion (-16.7%; 0.12-0.10 patients/day per hospital, <0.005). The sampled cohort showed similar declines in the rates of large vessel occlusions versus thrombectomy (18.8% versus 19.5%, =0.9) and comprehensive stroke center hospitalizations (18.8% versus 11.0%, =0.4).

Conclusions: A significant decline in stroke imaging screening has occurred during the COVID-19 pandemic. This analysis underscores the broader application of artificial intelligence neuroimaging platforms for the real-time monitoring of stroke systems of care.
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http://dx.doi.org/10.1161/STROKEAHA.120.031960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078127PMC
May 2021

Temperature Management in Neurological and Neurosurgical Intensive Care Unit.

Ther Hypothermia Temp Manag 2021 03 16;11(1):7-9. Epub 2021 Feb 16.

Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

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http://dx.doi.org/10.1089/ther.2021.29080.pjlDOI Listing
March 2021

First pass effect in patients with large vessel occlusion strokes undergoing neurothrombectomy: insights from the Trevo Retriever Registry.

J Neurointerv Surg 2021 Jul 21;13(7):619-622. Epub 2021 Jan 21.

Department of Neuroscience, Drexel University, Philadelphia, Pennsylvania, USA.

Background: First pass effect (FPE), defined as near-total/total reperfusion of the territory (modified Thrombolysis in Cerebral Infarction (mTICI) 2c/3) of the occluded artery after a single thrombectomy attempt (single pass), has been associated with superior safety and efficacy outcomes than in patients not experiencing FPE.

Objective: To characterize the clinical features, incidence, and predictors of FPE in the anterior and posterior circulation among patients enrolled in the Trevo Registry.

Methods: Data were analyzed from the Trevo Retriever Registry. Univariate and multivariable analyses were used to assess the relationship of patient (demographics, clinical, occlusion location, collateral grade, Alberta Stroke Program Early CT Score (ASPECTS)) and device/technique characteristics with FPE (mTICI 2c/3 after single pass).

Results: FPE was achieved in 27.8% (378/1358) of patients undergoing anterior large vessel occlusion (LVO) thrombectomy. Multivariable regression analysis identified American Society of Interventional and Therapeutic Neuroradiology (ASITN) levels 2-4, higher ASPECTS, and presence of atrial fibrillation as independent predictors of FPE in anterior LVO thrombectomy. Rates of modified Rankin Scale (mRS) score 0-2 at 90 days were higher (63.9% vs 53.5%, p<0.0006), and 90-day mortality (11.4% vs 12.8%, p=0.49) was comparable in the FPE group and non-FPE group. Rate of FPE was 23.8% (19/80) among basilar artery occlusion strokes, and outcomes were similar between FPE and non-FPE groups (mRS score 0-2, 47.4% vs 52.5%, p=0.70; mortality 26.3% vs 18.0%, p=0.43). Notably, there were no difference in outcomes in FPE versus non-FPE mTICI 2c/3 patients.

Conclusion: Twenty-eight percent of patients undergoing anterior LVO thrombectomy and 24% of patients undergoing basilar artery occlusion thrombectomy experience FPE. Independent predictors of FPE in anterior circulation LVO thrombectomy include higher ASITN levels, higher ASPECTS, and the presence of atrial fibrillation.
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http://dx.doi.org/10.1136/neurintsurg-2020-016952DOI Listing
July 2021

Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study.

BMC Med 2021 01 21;19(1):23. Epub 2021 Jan 21.

Department of Acute Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification.

Methods: Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models.

Results: A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites.

Conclusions: NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.
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http://dx.doi.org/10.1186/s12916-020-01893-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817348PMC
January 2021

Global impact of COVID-19 on stroke care.

Int J Stroke 2021 Mar 29:1747493021991652. Epub 2021 Mar 29.

Neurology, Grady Memorial Hospital, Emory University, Atlanta, Georgia, USA.

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide.

Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior).

Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers.

Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions.

Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.
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http://dx.doi.org/10.1177/1747493021991652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010375PMC
March 2021

Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study.

Lancet Respir Med 2021 04 11;9(4):349-359. Epub 2021 Jan 11.

School of Informatics, University of Edinburgh, Edinburgh, UK.

Background: Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions.

Methods: We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London).

Findings: 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal-external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [-0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model.

Interpretation: The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19.

Funding: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London.
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http://dx.doi.org/10.1016/S2213-2600(20)30559-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832571PMC
April 2021

Stroke Imaging Selection Modality and Endovascular Therapy Outcomes in the Early and Extended Time Windows.

Stroke 2021 Jan 12;52(2):491-497. Epub 2021 Jan 12.

Department of Neurosciences, Drexel Neurosciences Institute, Philadelphia, PA (E.V.).

Background And Purpose: Advanced imaging has been increasingly used for patient selection in endovascular stroke therapy. The impact of imaging selection modality on endovascular stroke therapy clinical outcomes in extended time window remains to be defined. We aimed to study this relationship and compare it to that noted in early-treated patients.

Methods: Patients from a prospective multicentric registry (n=2008) with occlusions involving the intracranial internal carotid or the M1- or M2-segments of the middle cerebral arteries, premorbid modified Rankin Scale score 0 to 2 and time to treatment 0 to 24 hours were categorized according to treatment times within the early (0-6 hour) or extended (6-24 hour) window as well as imaging modality with noncontrast computed tomography (NCCT)±CT angiography (CTA) or NCCT±CTA and CT perfusion (CTP). The association between imaging modality and 90-day modified Rankin Scale, analyzed in ordinal (modified Rankin Scale shift) and dichotomized (functional independence, modified Rankin Scale score 0-2) manner, was evaluated and compared within and across the extended and early windows.

Results: In the early window, 332 patients were selected with NCCT±CTA alone while 373 also underwent CTP. After adjusting for identifiable confounders, there were no significant differences in terms of 90-day functional disability (ordinal shift: adjusted odd ratio [aOR], 0.936 [95% CI, 0.709-1.238], =0.644) or independence (aOR, 1.178 [95% CI, 0.833-1.666], =0.355) across the CTP and NCCT±CTA groups. In the extended window, 67 patients were selected with NCCT±CTA alone while 180 also underwent CTP. No significant differences in 90-day functional disability (aOR, 0.983 [95% CI, 0.81-1.662], =0.949) or independence (aOR, 0.640 [95% CI, 0.318-1.289], =0.212) were seen across the CTP and NCCT±CTA groups. There was no interaction between the treatment time window (0-6 versus 6-24 hours) and CT selection modality (CTP versus NCCT±CTA) in terms of functional disability at 90 days (=0.45).

Conclusions: CTP acquisition was not associated with better outcomes in patients treated in the early or extended time windows. While confirmatory data is needed, our data suggests that extended window endovascular stroke therapy may remain beneficial even in the absence of advanced imaging.
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http://dx.doi.org/10.1161/STROKEAHA.120.031685DOI Listing
January 2021

The Impact of Bariatric Surgery on Diabetic Retinopathy: A Systematic Review and Meta-Analysis.

Am J Ophthalmol 2021 May 9;225:117-127. Epub 2021 Jan 9.

Division of General Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada. Electronic address:

Objective: While bariatric surgery induces remission of type 2 diabetes mellitus and reduces other microvascular complications, its impact on diabetic retinopathy (DR) is unclear. Some trials suggest early worsening of DR postsurgery because of rapid improvements in hyperglycemia. This meta-analysis sought to estimate the impact of bariatric surgery on DR for obese patients compared with medical treatment.

Design: Systematic review and meta-analysis.

Methods: The Medline, Embase, and PubMed Central databases were searched to March 2020. Primary studies comparing DR in patients undergoing bariatric surgery with those undergoing medical management were included. Results were meta-analyzed using a random-effects model. Primary outcomes included prevalence of all DR and sight-threatening DR after surgery. Secondary outcomes included worsening of DR within and beyond 12 months.

Results: Overall, 14 studies comprised of 110,300 surgical patients and 252,289 control subjects were included. Surgical patients had a statistically significantly lower postoperative prevalence of all DR (relative risk [RR] 0.17 [95% confidence interval {CI} 0.13-0.22]) and sight-threatening DR (RR 0.47 [95% CI 0.27-0.82]). Early worsening of DR and progression to sight-threatening DR had occurred more often in those with more severe DR initially. However, beyond 12 months, bariatric surgery resulted in significantly fewer patients with worsened DR (RR 0.29 [95% CI 0.16-0.54]). The overall risk of bias was low; estimates of relative effects had low to moderate certainty of evidence.

Conclusion: While bariatric surgery was associated with fewer cases of all and sight-threatening DR, early worsening was more severe in patients with existing sight-threatening DR. These findings argue for frequent monitoring during the first postoperative year.
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http://dx.doi.org/10.1016/j.ajo.2020.12.033DOI Listing
May 2021

Endovascular therapy in the distal neurovascular territory: results of a large prospective registry.

J Neurointerv Surg 2020 Dec 15. Epub 2020 Dec 15.

Department of Neurosciences, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.

Background: There is a paucity of data regarding mechanical thrombectomy (MT) in distal arterial occlusions (DAO). We aim to evaluate the safety and efficacy of MT in patients with DAO and compare their outcomes with proximal arterial occlusion (PAO) strokes.

Methods: The Trevo Registry was a prospective open-label MT registry including 2008 patients from 76 sites across 12 countries. Patients were categorized into: PAO: intracranial ICA, and MCA-M1; and DAO: MCA-M2, MCA-M3, ACA, and PCA. Baseline and outcome variables were compared across the PAO vs DAO patients with pre-morbid mRS 0-2.

Results: Among 407 DAOs including 350 (86.0%) M2, 25 (6.1%) M3, 10 (2.5%) ACA, and 22 (5.4%) PCA occlusions, there were 376 DAO with pre-morbid mRS 0-2 which were compared with 1268 PAO patients. The median baseline NIHSS score was lower in DAO (13 [8-18] vs 16 [12-20], P<0.001). There were no differences in terms of age, sex, IV-tPA use, co-morbidities, or time to treatment across DAO vs PAO. The rates of post-procedure reperfusion, symptomatic intracranial hemorrhage (sICH), and 90-mortality were comparable between both groups. DAO showed significantly higher rates of 90-day mRS 0-2 (68.3% vs 56.5%, P<0.001). After adjustment for potential confounders, the level of arterial occlusion was not associated with the chances of excellent outcome (DAO for 90-day mRS 0-1: OR; 1.18, 95% CI [0.90 to 1.54], P=0.225), successful reperfusion or SICH. However, DAO patients were more likely to be functionally independent (mRS 0-2: OR; 1.45, 95% CI [1,09 to 1.92], P=0.01) or dead (OR; 1.54, 95% CI [1.06 to 2.27], P=0.02) at 90 days.

Conclusion: Endovascular therapy in DAO appears to result in a comparable safety and technical success profile as in PAO. The potential benefits of DAO thrombectomy should be investigated in future randomized trials.
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http://dx.doi.org/10.1136/neurintsurg-2020-016851DOI Listing
December 2020

The relationship between social risk factors and latent tuberculosis infection among individuals residing in England: a cross-sectional study.

BMJ Glob Health 2020 12;5(12)

Institute for Global Health, University College London, London, UK.

Objective: To investigate the relationship between social risk factors and latent tuberculosis infection (LTBI) among individuals who are eligible for LTBI screening in the United Kingdom (UK).

Methods: This cross-sectional study used data collected in the UK Prognostic Evaluation of Diagnostic Interferon-Gamma Release Assays (IGRAs) Consortium Study which enrolled 9176 recent tuberculosis (TB) contacts and migrants at National Health Service (NHS) facilities and community settings in the UK. The study outcome was LTBI (positive IGRA test (QuantiFERON-TB Gold In-Tube or T-SPOT.TB)). The main exposures were history of smoking, history of substance misuse, homelessness, prison stay and socioeconomic deprivation.

Results: 4914 (56.2%) individuals resided in the most deprived areas and 2536 (27.6%) had LTBI. In the multivariable analysis (adjusting for age, gender, place of birth, ethnicity, HIV status, BCG vaccination and recent TB contact) living in the least deprived areas compared with living in the most deprived areas was associated with reduced odds of LTBI (odds ratio (OR)=0.68, 95% CI: 0.51 to 0.90) while ever been homeless (OR=1.50, 95% CI: 1.02 to 2.21) was associated with increased odds of LTBI. Smoking, homelessness and substance misuse were not associated with LTBI.

Conclusion: Social deprivation could be an important risk factor for LTBI, highlighting the social inequality in the burden of TB infection in the UK. Migrants and TB contacts who were socially deprived or homeless were at a significantly higher risk for LTBI, thus tailored intense public health interventions to these groups may help to reduce the risk of future TB disease.

Trial Registration Number: ClinicalTrials.gov Registry (NCT01162265).
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http://dx.doi.org/10.1136/bmjgh-2020-003550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722758PMC
December 2020

Early Infarct Growth Rate Correlation With Endovascular Thrombectomy Clinical Outcomes: Analysis From the SELECT Study.

Stroke 2021 01 7;52(1):57-69. Epub 2020 Dec 7.

Department of Neurology, Stanford University (M.L., G.W.A.).

Background And Purpose: Time elapsed from last-known well (LKW) and baseline imaging results are influential on endovascular thrombectomy (EVT) outcomes.

Methods: In a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (SELECT [Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke], the early infarct growth rate (EIGR) was defined as ischemic core volume on perfusion imaging (relative cerebral blood flow<30%) divided by the time from LKW to imaging. The optimal EIGR cutoff was identified by maximizing the sum of the sensitivity and specificity to correlate best with favorable outcome and to improve its the predictability. Patients were stratified into slow progressors if EIGR2. The primary outcome was 90-day functional independence (modified Rankin Scale score =0-2).

Results: Of 445 consented, 361 (285 EVT, 76 medical management only) patients met the study inclusion criteria. The optimal EIGR was <10 mL/h; 200 EVT patients were slow and 85 fast progressors. Fast progressors had a higher median National Institutes of Health Stroke Scale (19 versus 15, <0.001), shorter time from LKW to groin puncture (180 versus 266 minutes, <0.001). Slow progressors had better collaterals on computed tomography perfusion: hypoperfusion intensity ratio (adjusted odds ratio [aOR]: 5.11 [2.43-10.76], <0.001) and computed tomography angiography: collaterals-score (aOR: 4.43 [1.83-10.73], =0.001). EIGR independently correlated with functional independence after EVT, adjusting for age, National Institutes of Health Stroke Scale, time LKW to groin puncture, reperfusion (modified Thrombolysis in Cerebral Infarction score of ≥2b), IV-tPA (intravenous tissue-type plasminogen activator), and transfer status (aOR: 0.78 [0.65-0.94], =0.01). Slow progressors had higher functional independence rates (121 [61%] versus 30 [35%], <0.001) and had 3.5 times the likelihood of achieving modified Rankin Scale score =0-2 with EVT (aOR=2.94 [95% CI, 1.53-5.61], =0.001) as compared to fast progressors, who had substantially worse clinical outcomes both in early and late time window. The odds of good outcome decreased by 14% for each 5 mL/h increase in EIGR (aOR, 0.87 [0.80-0.94], <0.001) and declined more rapidly in fast progressors.

Conclusions: The EIGR strongly correlates with both collateral status and clinical outcomes after EVT. Fast progressors demonstrated worse outcomes when receiving EVT beyond 6 hours of stroke onset as compared to those who received EVT within 6 hours. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02446587.
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http://dx.doi.org/10.1161/STROKEAHA.120.030912DOI Listing
January 2021

Electroporation technique for joint pain - Pilot feasibility study on TMD patients.

Clin Exp Dent Res 2020 12 14;6(6):642-649. Epub 2020 Oct 14.

San Francisco Veterans Affairs Health Care System, Department of Oral & Maxillofacial Surgery, University of California, San Francisco, San Francisco, California, USA.

Objective(s): It is well appreciated that traditional analgesic delivery routes used to treat pain associated with temporomandibular disorder (TMD) often have harmful unintended side effects as a consequence of systemic distribution. Further, localized delivery of analgesic medication via intra-articular injections involves a different set of issues limiting their clinical viability. As an option, transdermal analgesic delivery provides for prolonged pain relief and flexibility in dose administration, while limiting systemic exposure and minimizing adverse events. Incorporation of a novel electroporation technique may further increase transdermal drug penetration into synovial tissue/fluid and enhance pain reduction. The present feasibility study compares the effectiveness of an electroporation-enhanced transdermal application of diclofenac sodium to a conventional intra-articular injection of triamcinolone acetonide suspension (corticosteroids) to treat patients with TMD associated pain.

Methods: Pre- and post-treatment maximal incisal mouth opening (MIO), pain visual analog scale (VAS) and surface electromyography (EMG) of 22 patients treated with electroporation-enhanced diclofenac and 37 patients treated with corticosteroids injections were collected and analyzed.

Results: In general, patients treated with electroporation exhibited better results in terms of pain improvement (corrected p-value = .01) compared to the standard treatment, but both methods were similarly effective for improvement of MIO (corrected p-value = .71) and improvement of all EMG indices (corrected p-values ≥ .05).

Conclusion: The enhancing effect of electroporation in transdermal delivery of diclofenac sodium was demonstrated by decreased pain, increase MIO and EMG improvement to normal values. Its analgesic and inflammatory results are comparable with standard treatment offered by corticosteroids.
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http://dx.doi.org/10.1002/cre2.327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745067PMC
December 2020