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Background: The availability of mechanical thrombectomy (MT) for acute ischemic stroke is limited, and vast disparities exist between countries. We aim to create a MT access score to measure the drivers of access to help quantify and accelerate treatment worldwide., Methods: We used a systematic review complemented by a modified Delphi method. In the first of 3 rounds, 4 independent investigators performed a systematic literature review using key search terms that drive MT access, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In the second round, a panel of 6 anonymous international experts selected key attributes needed for scoring. In the final round, a total of 12 attributes were selected on consensus, each given a score on a 0 to 3 scale. An ultimate MT access score (range, 0-36) was proposed as a new tool to use in identifying barriers to MT access and assist in providing an initial framework for public health interventions., Results: Of 2864 abstracts screened, 121 studies were included in the final systematic review. A total of 34 attributes that potentially drive MT access were initially identified. In the final round, 12 attributes were selected by the expert panel: public awareness, emergency medical services transportation, prehospital large vessel occlusion screening, interhospital transfer policy, emergency department protocols, stroke imaging protocols, emergency department stroke expertise or telestroke availability, interventionalists, MT-capable centers, device availability, and insurance coverage. These attributes were weighted as part of the final score of 0 to 36., Conclusions: The MT access score represents the first tool to quantify barriers to global MT access. Its implementation stands not just as an academic achievement but as a beacon of hope for improving stroke care and outcomes worldwide, bringing us a step closer to bridging the gap in stroke treatment disparities.

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution. We identify cell-specific targets and previously unrecognized roles for microglial and ependymal subtypes. Ependymal-4 was a hub of neuroinflammatory signaling. A distinct microglial lineage shared features with disease-associated microglia at 24 h, with persistent gene-expression changes in microglia-4 even 6 months after contusional TBI, contrasting all other cell types that mostly returned to naive levels. Regional and sexual dimorphism were noted. CEREBRI, our searchable atlas (https://shiny.crc.pitt.edu/cerebri/), identifies previously unrecognized cell subtypes/molecular targets and is a leverageable platform for future efforts in TBI and other diseases with overlapping pathophysiology., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The optimal anesthetic strategy for endovascular therapy (EVT) in acute ischemic stroke is still under debate. The aim of this study was to compare the clinical outcomes of patients with isolated posterior cerebral artery (PCA) occlusion stroke undergoing EVT by anesthesia modality with conscious sedation (non-GA) versus general anesthesia (GA)., Methods: Patients from the Posterior CerebraL Artery Occlusion (PLATO) study were analyzed with regard to anesthetic strategy. GA was compared with non-GA using multivariable logistic regression and inverse probability of weighting treatment (IPTW) methods. The primary endpoint was the 90-day distribution of the modified Rankin Scale (mRS) score. Secondary outcomes included functional independence or return to Rankin at day 90, and successful reperfusion, defined as expanded Thrombolysis in Cerebral Infarction (eTICI) 2b to 3. Safety endpoints were symptomatic intracranial hemorrhage and mortality., Results: Among 376 patients with isolated PCA occlusion stroke treated with EVT, 183 (49%) had GA. The treatment groups were comparable, although the GA group contained more patients with severe stroke and lower posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS). On IPTW analysis, there was no difference between groups with regard to ordinal mRS shift analysis (common OR 0.89, 95% CI 0.53 to 1.51, P=0.67) or functional independence (OR 0.84, 95% CI 0.50 to 1.39, P=0.49). There were greater odds for successful reperfusion with GA (OR 1.70, 95% CI 1.17 to 2.47, P=0.01). Safety outcomes were comparable between groups., Conclusion: In patients with isolated PCA occlusion undergoing EVT, patients treated with GA had higher reperfusion rates compared with non-GA. Both GA and non-GA strategies were safe and functional outcomes were similar., Competing Interests: Competing interests: NA reported employment by the American Heart Association. GD reported consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker and stock holdings in RIST and InNeuroCo. JTF reported consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; and stock holdings in Imperative Care and Sim&Cure. UF reported research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; and is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. UF reports patent US11166738B2. DCH reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB from Jacobs Institute; and stock options in Viz AI. CH reported consultancy for Brainomix and Speaker with Stryker. APJ reports consulting with Basking Biosciences; stock options in Gravity Medical Technology; and a patent for a novel stent retriever device licensed to Basking Biosciences. JK reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. DPOK reported grants from the Joachim Herz Foundation. JBK reports grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. JPM reported consulting from Amicus Therapeutics and Boehringer Ingelheim and Speaker with Boehringer Ingelheim. PM reported grants from the University of Lausanne and Swiss National Science Foundation (SNF). MAM reported grants from Medtronic, Stryker, and MicroVention. MaM reported stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology and consulting from MicroVention, Medtronic, and Johnson & Johnson. SN reported consultancy for Brainomix and is a speaker with Boehringer Ingelheim and Pfizer. TNN reported research support from the Society of Vascular and Interventional Neurology (SVIN) and Medtronic and is on the advisory board with Idorsia. RGN reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; and grants from Cerenovus and Stryker. CHN reported compensation (other services) from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen and consultancy for Daiichi Sankyo, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. MP reported grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; and consultancy for Siemens Healthineers. VP reported being a lecturer for Daiichi Sankyo. MR reported consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips and stock holdings in Methinks, Nora, and Anaconda Biomed. PAR reported travel support from Bayer and Bristol Myers Squibb and consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. SAS reported consultancy for Imperative Care, Viz AI, and Penumbra; compensation from Motif Neurosciences (other services); and grants from the National Institutes of Health. AHS reported an ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and Viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in Viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAID, Cerevatech Medical, InspireMD, and PerFlow Medical; and security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. The other authors report no conflicts., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site., Methods: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality., Results: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution ( P interaction =0.312) but did with functional independence ( P interaction =0.010), with a similar trend on excellent outcome ( P interaction =0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score ( P interaction =0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 ( P interaction =0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM., Conclusions: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage., Competing Interests: Disclosures Dr Dabus: consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker; stock holdings in RIST and InNeuroCo. Dr Fifi: consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; stock holdings in Imperative Care and Sim&Cure. Dr Fischer: research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. Dr Haussen: consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB for Jacobs Institute; stock options in viz AI. Dr Herweh: consultancy for Brainomix; speaker with Stryker. Dr Jadhav: consulting with Basking Biosciences; stock options in Gravity Medical Technology; a patent for a novel stent retriever device licensed to Basking Biosciences; and Editor-in-Chief for the Stroke: Vascular and Interventional Neurology journal. Dr Kaesmacher: grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Kaiser: grants from the Joachim Herz Foundation. Dr Kuramatsu: grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. Dr Marto: consulting and speaker fees from Amicus Therapeutics and Boehringer Ingelheim. Dr Michel: grants from the University of Lausanne and SNF. Dr Möhlenbruch: grants from Medtronic, Stryker, and MicroVention. Dr Mokin: stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology; consulting at MicroVention, Medtronic, and Johnson & Johnson. Dr Nagel: consultancy for Brainomix; speaker at Boehringer Ingelheim and Pfizer. Dr Nguyen: Associate Editor of Stroke, advisory board at Aruna Bio and Brainomix. Dr Nogueira: consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; grants from Cerenovus and Stryker. Dr Nolte: research support and compensation from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen; consultancy for Alexion, Daiichi Sankyo, Novartis, AstraZeneca, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. S. Poli: research grants from BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside of the submitted work). Dr Psychogios: grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; consultancy for Siemens Healthineers. Dr Puetz: lecturer for Daiichi Sankyo. Dr Ribo: consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Ringleb: travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Romoli: research grants from the Italian Stroke Association; consultancy for CSL Behring. Dr Sheth: consultancy for Imperative Care, viz AI, and Penumbra; compensation from Motif Neurosciences (other services); grants from the National Institutes of Health. Dr Siddiqui: ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAid Ltd, Cerevatech Medical, InspireMD, PerFlow Medical; security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Inc, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. Dr Strbian: Assistant Editor of Stroke, Editorial Board of European Stroke Journal, advisory board at Boehringer Ingelheim, Alexion/AstraZeneca, and Bristol Myers Squibb/Janssen; research support from Boehringer Ingelheim; consultancies for Orion, Herantis Pharma, and CSL Behring. The other authors report no conflicts.

Boza, a cereal-based beverage popular in southeast Europe, is fortified with probiotics and is believed to positively impact the composition of the gut microflora. This investigation focused on fermented cereal-based beverage boza to identify strains of probiotic Lactobacillus spp. capable of inhibiting carbohydrate-hydrolysing enzymes α -glucosidase (AG) and α -amylase (AA). The isolated bacterial strains underwent a comprehensive assessment, including biochemical, molecular, and probiotic trait analyses such as tolerance survivability, adhesion, safety, and health-promoting attributes. We evaluated the inhibitory potential of the supernatant, cell lysate, and intact cells of Lactobacillus spp. Molecular analysis has revealed that isolates RAMULAB30 and RAMULAB29 exhibit a significant genetic similarity (>97%) to Lacticaseibacillus paracasei and Limosilactobacillus fermentum , respectively. These findings are documented in the NCBI database. They exhibited significant resistance to gastrointestinal and intestinal fluids, also indicating their potential for adhesion. Additionally, the isolates showed a significant antibacterial activity, particularly against Micrococcus luteus . They showed resistance to vancomycin and methicillin antibiotics but were more susceptible to streptomycin and ampicillin. Furthermore, the strains demonstrated antioxidant properties. To ensure their safety, a haemolytic assay was conducted despite their general recognition as safe (GRAS) status. The study primarily aimed to evaluate the inhibitory effects of the extract on enzymes AG and AA. Bacterial isolates demonstrated a significant inhibitory activity against both enzyme AG (32%-67% inhibition) and enzyme AA (18%-46% inhibition) in different forms, including supernatant (CS), lysed extract (CE), and intact cell (IC). These findings underscore the potential of bacterial isolates to inhibit the enzyme activity effectively. Furthermore, the L. fermentum RAMULAB29 and L. paracasei RAMULAB30 strains exhibit remarkable antidiabetic potential. Food products incorporating these strains have promising prospects as nutraceuticals, providing improved health benefits., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 Chandana Kumari V. B. et al.)

The current study aims to evaluate and characterize the probiotic andantidiabetic properties of lactic acid bacteria (LAB) obtained from milk and other dairy-based products. The strains were tested physiologically, biochemically, and molecularly. Based on biochemical tests and 16S rRNA gene amplification and sequencing, all three isolates RAMULAB18, RAMULAB19, and RAMULAB53 were identified as Lacticaseibacillus paracasei with homology similarity of more than 98%. The inhibitory potential of each isolate against carbohydrate hydrolysis enzymes (α-amylase and α-glucosidase) was assessed using three different preparations of RAMULAB (RL) isolates: the supernatant (RL-CS), intact cells (RL-IC), and cell-free extraction (RL-CE). Additionally, the isolate was evaluated for its antioxidant activity against free radicals (DPPH and ABTS). The strain's RL-CS, RL-CE, and RL-IC inhibited α-amylase (17.25 to 55.42%), α-glucosidase (15.08-59.55%), DPPH (56.42-87.45%), and ABTS (46.35-78.45%) enzymes differently. With the highest survival rate (>98%) toward tolerance to gastrointestinal conditions, hydrophobicity (>42.18%), aggregation (>74.21%), as well as attachment to an individual's colorectal cancer cell line (HT-29) (>64.98%), human buccal and chicken crop epithelial cells, all three isolates exhibited extensive results. All three isolates exhibited high resistance toward antibiotics (methicillin, kanamycin, cefixime, and vancomycin), and other assays such as antibacterial, DNase, hemolytic, and gelatinase were performed for safety assessment. Results suggest that the LAB described are valuable candidates for their significant health benefits and that they can also be utilized as a beginning or bio-preservative tradition in the food, agriculture, and pharmaceutical sectors. The LAB isolates are excellent in vitro probiotic applicants and yet additional in vivo testing is required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huligere, Kumari V B, Desai, Wong, Firdose and Ramu.)

Background: An understanding of global, regional, and national macroeconomic losses caused by stroke is important for allocation of clinical and research resources. The authors investigated the macroeconomic consequences of stroke disease burden in the year 2019 in 173 countries., Methods: Disability-adjusted life year data for overall stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) were collected from the GBD study (Global Burden of Disease) 2019 database. Gross domestic product (GDP, adjusted for purchasing power parity [PPP]) data were collected from the World Bank; GDP and disability-adjusted life year data were combined to estimate macroeconomic losses using a value of lost welfare (VLW) approach. All results are presented in 2017 international US dollars adjusted for PPP., Results: Globally, in 2019, VLW due to stroke was $2059.67 billion or 1.66% of the global GDP. Global VLW/GDP for stroke subtypes was 0.78% (VLW=$964.51 billion) for ischemic stroke, 0.71% (VLW=$882.81 billion) for intracerebral hemorrhage, and 0.17% (VLW=$212.36 billion) for subarachnoid hemorrhage. The Central European, Eastern European, and Central Asian GBD super-region reported the highest VLW/GDP for stroke overall (3.01%), ischemic stroke (1.86%), and for subarachnoid hemorrhage (0.26%). The Southeast Asian, East Asian, and Oceanian GBD super-region reported the highest VLW/GDP for intracerebral hemorrhage (1.48%)., Conclusions: The global macroeconomic consequences related to stroke are vast even when considering stroke subtypes. The present quantification may be leveraged to help justify increased spending of finite resources on stroke in an effort to improve outcomes for patients with stroke globally., Competing Interests: Disclosures Q.R. Qu reports employment by Brigham and Women’s Hospital; Dr Gaude reports stock holdings in Pockit diagnostics; Dr Atchaneeyasakul reports employment by Gravity Medical Technology; Dr Yavagal reports stock options in Rapid Medical, compensation from Vascular Dynamics for consultant services, compensation from Poseydon for consultant services, stock holdings in Athersys, compensation from Johnson & Johnson Health Care Systems, Inc for consultant services, compensation from Stryker Corporation for consultant services, stock options in Poseydon, compensation from Medtronic, United States, Inc for consultant services, compensation from Athersys for consultant services, and compensation from Gravity Medical Technology for consultant services; Dr Aziz-Sultan reports compensation from MicroVention, Inc for other services; Dr Du reports compensation from Grand Rounds for consultant services, employment by Brigham and Women’s Hospital, compensation from Society of Neurological Surgeons for other services, compensation from Oakstone for other services, and compensation from National Institutes of Health for other services; Dr Smith reports stock holdings in Phebe Health; Dr Bernstock has equity positions in POCKiT Diagnostics, which is developing a diagnostic tool for large vessel occlusion detection, he also holds positions/equity in Treovir, NeuroX1, and Centile Bioscience.”

Importance: Medicaid patients with mental illness comprise one of the most high-need and complex patient populations. Value-based reforms aim to improve care, but their efficacy in the Medicaid program is unclear., Objective: To investigate if New York state's Medicaid value-based payment reform was associated with improved utilization patterns for patients with mental illness., Design, Setting, and Participants: This retrospective cohort study used a difference-in-differences analysis to compare changes in utilization between Medicaid beneficiaries whose outpatient practices participated in value-based payment reform and beneficiaries whose practices did not participate from before (July 1, 2013-June 30, 2015) to after reform (July 1, 2015-June 30, 2019). Participants were Medicaid beneficiaries in New York state aged 18 to 64 years with major depression disorder, bipolar disorder, and/or schizophrenia. Data analysis was performed from April 2021 to July 2023., Exposure: Beneficiaries were exposed to value-based payment reforms if their attributed outpatient practice participated in value-based payment reform at baseline (July 1, 2015)., Main Outcomes and Measures: Primary outcomes were the number of outpatient primary care visits and the number of behavioral health visits per year. Secondary outcomes were the number of mental health emergency department visits and hospitalizations per year., Results: The analytic population comprised 306 290 individuals with depression (67.4% female; mean [SD] age, 38.6 [11.9] years), 85 105 patients with bipolar disorder (59.6% female; mean [SD] age, 38.0 [11.6] years), and 71 299 patients with schizophrenia (45.1% female; mean [SD] age, 40.3 [12.2] years). After adjustment, analyses estimated a statistically significant, positive association between value-based payments and behavioral health visits for patients with depression (0.91 visits; 95% CI, 0.51-1.30) and bipolar disorder (1.01 visits; 95% CI, 0.22-1.79). There was no statistically significant changes to primary care visits for patients with depression and bipolar disorder, but value-based payments were associated with reductions in primary care visits for patients with schizophrenia (-1.31 visits; 95% CI, -2.51 to -0.12). In every diagnostic population, value-based payment was associated with significant reductions in mental health emergency department visits (population with depression: -0.01 visits [95% CI, -0.02 to -0.002]; population with bipolar disorder: -0.02 visits [95% CI, -0.05 to -0.001]; population with schizophrenia: -0.04 visits [95% CI, -0.07 to -0.01])., Conclusions and Relevance: In this cohort study, Medicaid value-based payment reform was statistically significantly associated with an increase in behavioral health visits and a reduction in mental health emergency department visits for patients with mental illness. Medicaid value-based payment may be effective at altering health care utilization in patients with mental illness.

Background: Chronological heterogeneity in neurological improvement after endovascular thrombectomy (EVT) for large vessel occlusion (LVO) stroke is commonly observed in clinical practice. Understanding the temporal progression of functional independence after EVT, especially delayed functional independence in patients who do not improve early, is essential for prognostication and rehabilitation. We aim to determine the incidence of early functional independence (EFI) and delayed functional independence (DFI), identify associated predictors after EVT, and develop the Delayed Functional Independence After Neurothrombectomy (DEFIANT) score., Methods: Demographic, clinical, radiological, treatment, and procedural information were analyzed from the Trevo Registry (patients undergoing EVT due to anterior LVO using the Trevo stent retriever). Incidence and predictors of EFI (modified Rankin Scale (mRS) score 0-2 at discharge) and DFI (mRS score 0-2 at 90 days in non-EFI patients) were analyzed., Results: A total of 1623 patients met study criteria. EFI was observed in 45% (730) of patients. Among surviving non-EFI patients (884), DFI was observed in 35% (308). Younger age (p=0.003), lower discharge National Institutes of Health Stroke Scale (NIHSS) score (p<0.0001), and absence of any hemorrhage (p=0.021) were independent predictors of DFI. After age 60, the probability of DFI declines significantly with 5 year age increments (approximately 7% decline for every 5 years; p(DFI)= 1.3559-0.0699, p for slope=0.001). The DEFIANT score is available online (https://bit.ly/3KZRVq5)., Conclusion: Approximately 45% of patients experience EFI. About one-third of non-early improvers experience DFI. Younger age, lower discharge NIHSS score, and absence of any hemorrhage were independent predictors of DFI among non-early improvers., Competing Interests: Competing interests: RG is a Principal Investigator for ASSIST Registry, Stryker Neurovascular, Modest Compensation; Principal Investigator for Tiger Retriever Study, Rapid Medical, Modest Compensation Principal Investigator for Recclaim trial, Zoll Medical, No compensation; Consultant Cerenovous, Modest Compensation. BWB is the SNIS Foundation Chair and sits on the editorial board of JNIS. BWB reports receiving consulting fees and fees for serving on a speakers’ bureau from Penumbra and consulting fees from Medtronic, Route 92 Medical, Viz.ai, 880 Medical, Marblehead Medical, Rapid Medical, Metactive, and holding U.S. Patent 9526863 on devices and methods for perfusion therapy, licensed to Neuronal Protection System. AK is a consultant for Stryker Neurovascular. Dr Nogueira reports potential conflicts with Stryker Neurovascular (DAWN Trial Principal Investigator–no compensation, TREVO Registry Steering Committee–no compensation, Trevo-2 Trial Principal Investigator–modest; Consultant–modest), Medtronic (SWIFT Trial Steering Committee–modest; SWIFT-Prime Trial Steering Committee–no compensation; STAR Trial Angiographic Core Lab–significant), Penumbra (3D Separator Trial Executive Committee–no compensation), Cerenovus/ Neuravi (ENDOLOW Trial Principal Investigator, EXCELLENT Registry Principal Investigator, ARISE-2 trial Steering Committee–no compensation, Physician Advisory Board, modest), Phenox (Physician Advisory Board, modest), Anaconda (Physician Advisory Board, modest), Genentech (Physician Advisory Board–modest), Biogen (Physician Advisory Board–modest), Prolong Pharmaceuticals (Physician Advisory Board–modest), Allm Inc (Physician Advisory Board–no compensation), IschemaView (Speaker, modest), Brainomix (Research Software Use–no compensation), Sensome (Research Device Use–no compensation), Viz-AI (Physician Advisory Board, stock options), Philips (Research Software Use–no compensation, Speaker–modest), and Corindus Vascular Robotics (Physician Advisory Board, stock options). DSL is a consultant as an imaging core lab for Cerenovus, Genentech, Medtronic, Rapid Medical, Stryker, Vesalio. EV reports being a co-Principal Investigator for the Trevo Registry., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In the realm of oncology, the development of TIVAD (chemoport) has been a blessing for cancer patients, freeing them from having to undergo numerous recurrent venepunctures throughout their treatment. The External Jugular Vein cut-down has been the standard procedure for administering chemotherapy to cancer patients at our institution. Here, we discuss our experience with the External Jugular Vein cut-down Chemoport Insertion Technique and the outcomes it produced., Materials and Methods: We performed a prospective observational study and included all patients who underwent the open External Jugular Vein cut-down technique of Chemoport Insertion from January 2019 to January 2022 in the Department of Surgical Oncology at our hospital., Results: Out of 136 patients, 3 (2.2%) had failed external jugular vein (EJV) cannulation, and alternative access (Internal Jugular Vein) was chosen for cannulation. The most common indication for chemoport insertion in our study was carcinoma of the breast, around 72.93% (97/133), and hence the majority of patients were females, about 84.21% (112/133). Only 18.04% (24/133) were male patients. The age distribution ranged from 2 years to 84 years. Out of 133 patients, complications were observed in 14 patients (10.52%). Around 6 patients (4.5%) had problems with catheter blockage after one cycle of chemotherapy. 4 patients (3%) had port infections at the chamber region (pectoral region). 3 patients (2.2%) had catheter tip displacement into the brachiocephalic vein. 1 patient (0.75%) had extravasation of chemotherapy., Conclusion: In conclusion, our study demonstrates that the External Jugular Vein cut-down technique offers several advantages in the realm of oncology, as it is a safe, efficient, and straightforward technique for chemoport insertion. With its minimal learning curve and simplicity, this technique represents a favorable initial option for successfully implanting chemoports in cancer patients. Further research and comparative studies are needed to validate and further explore the benefits of this technique in diverse patient populations and healthcare settings.

Background Oral cavity cancer ranks sixth among all cancers worldwide. India has the most oral cancer cases and accounts for one-third of the global oral cancer burden. Oral cavity cancer is known to be associated with an elevated likelihood of locoregional recurrences, which account for the bulk of post-surgery and radiotherapy treatment failures. Mitomycin C (MMC) is an antineoplastic and antibiotic agent that is administered topically rather than intravenously to treat bladder and intraperitoneal tumors to avoid recurrences. This study aimed to investigate the use of injection MMC as a local application on surgical resection beds for patients undergoing surgery for oral cancer and to assess its efficacy in preventing regional recurrences. Methodology In this prospective, interventional, pilot study, patients were assigned randomly to two groups using simple randomization. Group A involved the application of two gauze pieces soaked with MMC injection. Group B involved the application of two gauze pieces soaked with a 10% betadine solution. During the pectoralis major myocutaneous flap harvest procedure for reconstruction, two gauze pieces soaked with either injection MMC solution (20 mg MMC in 20 mL of 0.9% normal saline) or 10% betadine solution were placed on the surgical resection bed for a 45-minute contact period. Patients were evaluated daily in the postoperative period for local complications. Regular follow-up visits were scheduled for 15 months of follow-up. Results After exclusions at various phases, the final analysis included 50 patients in Group A and 50 patients in Group B. Minor complications, specifically blackening of the skin flap in the neck resulting in surgical site infections, were observed in 16% (eight patients) of the MMC group and in 6% (three patients) of the betadine group (p = 0.1997) patients. In the MMC group, two (4%) patients experienced locoregional recurrences at three months, four (8%) patients at six months, six (12%) patients at nine months, eight (16%) patients at 12 months, and 10 (20%) patients at 15 months of follow-up. In contrast, locoregional recurrences occurred in two (4%) patients in the betadine group at three months, six (12%) patients at six months, nine (18%) patients at nine months, 12 (24%) patients at 12 months, and 15 (30%) patients at 15 months. Although the difference in locoregional recurrences between the two groups was not statistically significant, there was a trend of decreasing locoregional recurrences in the MMC group relative to the betadine group as the duration of follow-up increased. In the subgroup analysis of patients with pathological extranodal extension (ENE), only 10 of 18 patients with ENE in Group A (55.55%) experienced a recurrence, whereas all 12 patients with ENE in Group B (100%) experienced a recurrence within the same time frame. This difference in locoregional recurrence rates between the two groups was statistically significant, with a p-value of 0.0100. Conclusions Our study demonstrated that the local administration of MMC on surgical resection beds may lower the risk of locoregional recurrences in patients with oral cancer, especially those with ENE. These findings contribute to the ongoing efforts to enhance treatment strategies and patient outcomes for this challenging malignancy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ghosh et al.)

Objective: To evaluate clinical outcomes of endovascular thrombectomy (EVT) for acute basilar artery occlusion (BAO) using population-level data from the United States., Methods: Weighted discharge data from the National Inpatient Sample were queried to identify adult patients with acute BAO during the period of 2015 to 2019 treated with EVT or medical management only. Complex samples statistical methods and propensity-score adjustment using inverse probability of treatment weighting (IPTW) were performed to assess clinical endpoints., Results: Among 3,950 BAO patients identified, 1,425 (36.1%) were treated with EVT [mean age 66.7 years, median National Institute of Health Stroke Scale (NIHSS) score 22]. On unadjusted analysis, 155 (10.9%) EVT patients achieved favorable functional outcomes (discharge disposition to home without services), while 515 (36.1%) experienced in-hospital mortality, and 20 (1.4%) developed symptomatic intracranial hemorrhage (sICH). Following propensity-score adjustment by IPTW accounting for age, stroke severity, and comorbidity burden, EVT was independently associated with favorable functional outcome [adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07, 1.46; p = 0.004], but not with in-hospital mortality or sICH. In an IPTW-adjusted sub-group analysis of patients with NIHSS scores >20, EVT was associated with both favorable functional outcome (discharge disposition to home or to acute rehabilitation) (aOR 1.55, 95% CI 1.24, 1.94; p < 0.001) and decreased mortality (aOR 0.78, 95% CI 0.69, 0.89; p < 0.001), but not with sICH., Interpretation: This retrospective population-based analysis using a large national registry provides real-world evidence of a potential benefit of EVT in acute BAO patients. ANN NEUROL 2023;94:55-60., (© 2023 American Neurological Association.)

Background: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion., Methods: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale., Results: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P =0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P =0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P =0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P =0.0001; mortality, 10.1% versus 5.0%; P =0.002)., Conclusions: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted., Competing Interests: Disclosures Dr Asdaghi reported employment by the American Heart Association. Dr Dabus reported consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker and stock holdings in RIST and InNeuroCo. Dr Fifi reported consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; and stock holdings in Imperative Care and Sim&Cure. Dr Fischer reported research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; and is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. Dr Finitsis reports patent US11166738B2. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB from Jacobs Institute; and stock options in Viz AI. Dr Herweh reported consultancy for Brainomix and Speaker with Stryker. Dr Jadhav reports consulting with Basking Biosciences; stock options in Gravity Medical Technology; and a patent for a novel stent retriever device licensed to Basking Biosciences. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Kuramatsu reports grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. Dr Pedro Marto reported consulting from Amicus Therapeutics and Boehringer Ingelheim and Speaker with Boehringer Ingelheim. Dr Michel reported grants from the University of Lausanne and Swiss National Science Foundation (SNF). Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Mokin reported stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology and consulting from MicroVention, Medtronic, and Johnson & Johnson. Dr Nagel reported consultancy for Brainomix and is a speaker with Boehringer Ingelheim and Pfizer. Dr Nguyen reported research support from Society of Vascular and Interventional Neurology (SVIN) and Medtronic and is on the advisory board with Idorsia. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; and grants from Cerenovus and Stryker. Dr Nolte reported compensation (other services) from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen and consultancy for Daiichi Sankyo, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. Dr Psychogios reported grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; and consultancy for Siemens Healthineers. Dr Puetz reported being a lecturer for Daiichi Sankyo. Dr Ribo reported consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips and stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb and consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Sheth reported consultancy for Imperative Care, Viz AI, and Penumbra; compensation from Motif Neurosciences (other services); and grants from the National Institutes of Health. Dr Siddiqui reported an ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and Viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in Viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAID, Cerevatech Medical, InspireMD, and PerFlow Medical; and security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. The other authors report no conflicts.

While a large body of evidence has examined hospital concentration, its effects on health care for low-income populations are less explored. We use comprehensive discharge data from New York State to measure the effects of changes in market concentration on hospital-level inpatient Medicaid volumes. Holding fixed hospital factors constant, a one percent increase in HHI leads to a 0.6% (s.e. = 0.28%) decrease in the number of Medicaid admissions for the average hospital. The strongest effects are on admissions for birth (-1.3%, s.e. = 0.58%). These average hospital-level decreases largely reflect redistribution of Medicaid patients across hospitals, rather than overall reductions in hospitalizations for Medicaid patients. In particular, hospital concentration leads to a redistribution of admissions from non-profit hospitals to public hospitals. We find evidence that for births, physicians serving high shares of Medicaid beneficiaries in particular experience reduced admissions as concentration increased. These reductions may reflect preferences among these physicians or reduced admitting privileges by hospitals as a means to screen out Medicaid patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.

The therapeutic focus in acute ischemic stroke over the last 2.5 decades has been to balance the benefits of rapid reperfusion therapy with the risks of treatment-related complications. Both intravenous thrombolytics and endovascular thrombectomy are proven to substantially improve outcomes in a time-dependent manner. Each minute saved in achieving successful reperfusion grants an additional week of healthy life and may salvage up to 27 million neurons. The current approach to patient triage is inherited from the preendovascular thrombectomy era of stroke care. Current workflow concentrates on stabilization, diagnosis, and decision-making in the emergency department, followed by thrombolysis if eligible and subsequent transfer to the angiography suite as needed for further treatment. Multiple efforts have been directed toward minimizing the time from first medical contact to reperfusion therapy including prehospital triage and intrahospital workflow. Novel approaches for stroke patient triage such as the direct to angio approach, (also referred to as One Stop Management) are currently in development. The concept was initially introduced as several single-center experiences. In this narrative review article, we will consider various definitions of direct to angio and its variants, discuss its rationale, review its safety and efficacy, assess its feasibility, and delineate its limitations. Further, we will address methods to overcome these limitations and the potential impact of emerging data and new technologies on the direct-to-angio approach., Competing Interests: Disclosures Dr Psychogios reports grants from Medtronic; grants from Stryker Neurovascular, Inc; compensation from Siemens Healthineers AG for consultant services; travel support from Stryker Neurovascular, Inc; grants from Rapid Medical, Ltd; travel support from Medtronic; travel support from Siemens Healthineers AG; travel support from Phenox, Inc; grants from Penumbra, Inc; travel support from Penumbra, Inc; grants from Phenox, Inc; grants from Bangerter-Rhyner Stiftung; grants from the Swiss National Science Foundation; and grants from Siemens Healthineers AG. Dr Khatri reports grants from the National Institutes of Health; grants from Johnson & Johnson Health Care Systems, Inc; compensation from Basking Biosciences for consultant services; compensation from Lumosa for consultant services; compensation from Bayer for consultant services; and royalties from UptoDate, Inc, for online publication. Dr Jovin reports stock options in Viz.ai; stock options in Methinks; stock options in Route92; stock options in Galaxy; compensation from Contego Medical, Inc, for consultant services; stock options in Freeox Biotech; grants from Stryker Corporation; compensation from Johnson & Johnson Cerenovus for data and safety monitoring services; stock options in Anaconda; and grants from Medtronic USA, Inc. Dr Jadhav reports employment by Barrow Brain and Spine; a patent issued for novel stent retriever device licensed to Gravity Medical Technology; compensation from Basking Biosciences for consultant services; and stock options in Gravity Medical Technology. The other author reports no conflicts.

Biosimilar drugs-lower-cost alternatives to expensive biologic drugs-have the potential to slow the growth of US drug spending. However, rates of biosimilar uptake have varied across hospital outpatient providers. We investigated whether the 340B Drug Pricing Program, which offers eligible hospitals substantial discounts on drug purchases, inhibits biosimilar uptake. Almost one-third of US hospitals participate in the 340B program. Using a regression discontinuity design and two high-volume biologics with biosimilar competitors, filgrastim and infliximab, we estimated that 340B program eligibility was associated with a 22.9-percentage-point reduction in biosimilar adoption. In addition, 340B program eligibility was associated with 13.3 more biologic administrations annually per hospital and $17,919 more biologic revenue per hospital. Our findings suggest that the program inhibited biosimilar uptake, possibly as a result of financial incentives making reference drugs more profitable than biosimilar medications.

Background: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale., Methods: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA., Results: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70-11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower-middle versus high: odds ratio, 0.08 [95% CI, 0.04-0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07-5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84-4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70-9.42]) were significantly associated with increased odds of MTA., Conclusions: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country's per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

Objective: The objective of this study was to identify factors that lead to a prolonged hospital stay or 30-day readmission after minimally invasive surgery (MIS) for transforaminal lumbar interbody fusion (TLIF) at a single institution., Methods: Consecutive patients who underwent MIS TLIF from January 1, 2016, to March 31, 2018, were retrospectively analyzed. Demographic data, including age, sex, ethnicity, smoking status, and body mass index, were collected along with operative details, indications, affected spinal levels, estimated blood loss, and operative duration. The effects of these data were evaluated relative to the hospital length of stay (LOS) and 30-day readmission., Results: The authors identified 174 consecutive patients who underwent MIS TLIF at 1 or 2 levels from a prospectively collected database. The mean (range) patient age was 64.1 (31-81) years, 97 were women (56%), and 77 were men (44%). Of 182 levels fused, 127 were done at L4-5 (70%), 32 at L3-4 (18%), 13 at L5-S1 (7%), and 10 at L2-3 (5%). Patients underwent 166 (95%) single-level procedures and 8 (5%) 2-level procedures. The mean (range) procedural duration, defined as the time from incision to closure, was 164.6 (90-529) minutes. The mean (range) LOS was 1.8 (0-8) days. Eleven patients (6%) were readmitted within 30 days; the most frequent causes were urinary retention, constipation, and persistent or contralateral symptoms. Seventeen patients had LOS greater than 3 days. Six of those patients (35%) were identified as widows, widowers, or divorced, and 5 of them lived alone. Six patients with prolonged LOS (35%) required placement in either skilled nursing or acute inpatient rehabilitation. Regression analyses showed living alone (p = 0.04) and diabetes (p = 0.04) as predictors of readmission. Regression analyses revealed female sex (p = 0.03), diabetes (p = 0.03), and multilevel surgery (p = 0.006) as predictors of LOS > 3 days., Conclusions: Urinary retention, constipation, and persistent radicular symptoms were the leading causes of readmission within 30 days of surgery in this series, which is distinct from data from the American College of Surgeons National Surgical Quality Improvement Program. The inability to discharge a patient home for social reasons led to prolonged inpatient hospital stays. Identifying these risk factors and proactively addressing them could lower readmission rates and decrease LOS among patients undergoing MIS TLIF.

Objectives: Addressing traumatic brain injury (TBI) heterogeneity is increasingly recognized as essential for therapy translation given the long history of failed clinical trials. We evaluated differential effects of a promising treatment (glibenclamide) based on dose, TBI type (patient selection), and imaging endophenotype (outcome selection). Our goal to inform TBI precision medicine is contextually timely given ongoing phase 2/planned phase 3 trials of glibenclamide in brain contusion., Design: Blinded randomized controlled preclinical trial of glibenclamide on MRI endophenotypes in two established severe TBI models: controlled cortical impact (CCI, isolated brain contusion) and CCI+hemorrhagic shock (HS, clinically common second insult)., Setting: Preclinical laboratory., Subjects: Adult male C57BL/6J mice (n = 54)., Interventions: Mice were randomized to naïve, CCI±HS with vehicle/low-dose (20 μg/kg)/high-dose glibenclamide (10 μg/mouse). Seven-day subcutaneous infusions (0.4 μg/hr) were continued., Measurements and Main Results: Serial MRI (3 hr, 6 hr, 24 hr, and 7 d) measured hematoma and edema volumes, T2 relaxation (vasogenic edema), apparent diffusion coefficient (ADC, cellular/cytotoxic edema), and 7-day T1-post gadolinium values (blood-brain-barrier [BBB] integrity). Linear mixed models assessed temporal changes. Marked heterogeneity was observed between CCI versus CCI+HS in terms of different MRI edema endophenotypes generated (all p < 0.05). Glibenclamide had variable impact. High-dose glibenclamide reduced hematoma volume ~60% after CCI (p = 0.0001) and ~48% after CCI+HS (p = 4.1 × 10-6) versus vehicle. Antiedema benefits were primarily in CCI: high-dose glibenclamide normalized several MRI endophenotypes in ipsilateral cortex (all p < 0.05, hematoma volume, T2, ADC, and T1-post contrast). Acute effects (3 hr) were specific to hematoma (p = 0.001) and cytotoxic edema reduction (p = 0.0045). High-dose glibenclamide reduced hematoma volume after TBI with concomitant HS, but antiedema effects were not robust. Low-dose glibenclamide was not beneficial., Conclusions: High-dose glibenclamide benefitted hematoma volume, vasogenic edema, cytotoxic edema, and BBB integrity after isolated brain contusion. Hematoma and cytotoxic edema effects were acute; longer treatment windows may be possible for vasogenic edema. Our findings provide new insights to inform interpretation of ongoing trials as well as precision design (dose, sample size estimation, patient selection, outcome selection, and Bayesian analysis) of future TBI trials of glibenclamide., Competing Interests: Dr. Kochanek’s institution received funding from the National Institutes of Health (NIH). Drs. Kochanek’s and Jha’s institutions received funding from The Chuck Noll Foundation. Drs. Kochanek, Simard, Karahalios, and Jha received support for article research from the NIH. Dr. Simard’s institution received funding from the National Institutes of Neurological Disorders and Stroke (NINDS) (R01NS102589); he received funding from Remedy Pharmaceuticals. Drs. Simard and Jha received funding from Biogen. Dr. Jha’s institution received funding from NINDS (K23NS101036 and R01NS115815) and the Barrow Neurological Foundation; she disclosed the off-label product use of BIIB093. Dr. Kochanek is supported by the Ake Grenvik Endowment. Dr. Jha is a paid consultant and on the advisory board for Biogen. Dr. Simard holds a U.S. patent (7,285,574), “A novel non-selective cation channel in neural cells and methods for treating brain swelling.” Dr. Simard is a member of the Board of Directors and holds shares in Remedy Pharmaceuticals and is a paid consultant for Biogen. This study was not funded, reviewed, edited, or influenced in any way by Biogen. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: Intravenous tissue plasminogen activator (IV-tPA) remains part of the guidelines for acute ischemic stroke treatment, yet internal carotid artery occlusions (ICAO) are known to be poorly responsive to IV-tPA. It is unknown whether bridging thrombolysis (BT) is beneficial in such cases., Purpose: We sought to evaluate whether the use of IV-tPA improved overall clinical outcomes in patients undergoing endovascular thrombectomy (EVT) for ICA occlusions., Methods: Data from 1367 consecutive stroke cases treated with EVT from 2012-2019 were prospectively collected from a single center. Univariate and multivariate logistic regression were used to assess the relationship between IV-tPA administration and clinical outcome., Results: 153 patients were found to have carotid terminus and tandem ICAO who received EVT and presented within 4.5h of last seen well. 50% (n = 82) received IV tPA. There were no differences between the groups with respect to age, NIHSS, time to EVT and ASPECTS score. 53% had tandem ICA-MCA occlusions. Rate of recanalization (≥ TICI 2B) and sICH did not significantly differ between the two groups. Regression analysis demonstrated no effect of IV-tPA on modified Rankin Score (mRS) at 90 days and overall mortality. Factors significantly associated with reduced mortality included lower age, lower NIHSS, and better rate of recanalization., Conclusions: There was no significant difference in clinical outcomes in those receiving BT vs. direct EVT for ICAO. For centers with optimal door-to-puncture times, bypassing IV-tPA may expedite recanalization times and potentially yield more favorable outcomes. Patients with higher NIHSS and tandem lesions may have better outcomes with BT., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Gross: consultant for Medtronic and Microvention, (© The Author(s) 2022.)

Purpose and background: Isocitrate dehydrogenase (IDH) mutation and O-6 methyl guanine methyl transferase (MGMT) methylation are surrogate biomarkers of improved survival in gliomas. This study aims at studying the ability of semantic magnetic resonance imaging (MRI) features to predict the IDH mutation status confirmed by the gold standard molecular tests. Methods: The MRI of 148 patients were reviewed for various imaging parameters based on the Visually AcceSAble Rembrandt Images (VASARI) study. Their IDH status was determined using immunohistochemistry (IHC). Fisher’s exact or chi-square tests for univariate and logistic regression for multivariate analysis were used. Results: Parameters such as mild and patchy enhancement, minimal edema, necrosis < 25%, presence of cysts, and less rCBV (relative cerebral blood volume) correlated with IDH mutation. The median age of IDH-mutant and IDH-wild patients were 34 years (IQR: 29−43) and 52 years (IQR: 45−59), respectively. Mild to moderate enhancement was observed in 15/19 IDH-mutant patients (79%), while 99/129 IDH-wildtype (77%) had severe enhancement (p-value <0.001). The volume of edema with respect to tumor volume distinguished IDH-mutants from wild phenotypes (peritumoral edema volume < tumor volume was associated with higher IDH-mutant phenotypes; p-value < 0.025). IDH-mutant patients had a median rCBV value of 1.8 (IQR: 1.4−2.0), while for IDH-wild phenotypes, it was 2.6 (IQR: 1.9−3.5) {p-value = 0.001}. On multivariate analysis, a cut-off of 25% necrosis was able to differentiate IDH-mutant from IDH-wildtype (p-value < 0.001), and a cut-off rCBV of 2.0 could differentiate IDH-mutant from IDH-wild phenotypes (p-value < 0.007). Conclusion: Semantic imaging features could reliably predict the IDH mutation status in high-grade gliomas. Presurgical prediction of IDH mutation status could help the treating oncologist to tailor the adjuvant therapy or use novel IDH inhibitors.

Importance: Rising drug costs contribute to medication nonadherence and adverse health outcomes. Real-time prescription benefit (RTPB) systems present prescribers with patient-specific out-of-pocket cost estimates and recommend lower-cost, clinically appropriate alternatives at the point of prescribing., Objective: To investigate whether RTPB recommendations lead to reduced patient out-of-pocket costs for medications., Design, Setting, and Participants: In this cluster randomized trial, medical practices in a large, urban academic health system were randomly assigned to RTPB recommendations from January 13 to July 31, 2021. Participants were adult patients receiving outpatient prescriptions during the study period. The analysis was limited to prescriptions for which RTPB could recommend an available alternative. Electronic health record data were used to analyze the intervention's effects on prescribing. Data analyses were performed from August 20, 2021, to June 8, 2022., Interventions: When a prescription was initiated in the electronic health record, the RTPB system recommended available lower-cost, clinically appropriate alternatives for a different medication, length of prescription, and/or choice of pharmacy. The prescriber could select either the initiated order or one of the recommended options., Main Outcomes and Measures: Patient out-of-pocket cost for a prescription. Secondary outcomes were whether a mail-order prescription and a 90-day supply were ordered., Results: Of 867 757 outpatient prescriptions at randomized practices, 36 419 (4.2%) met the inclusion criteria of having an available alternative. Out-of-pocket costs were $39.90 for a 30-day supply in the intervention group and $67.80 for a 30-day supply in the control group. The intervention led to an adjusted 11.2%; (95% CI, -15.7% to -6.4%) reduction in out-of-pocket costs. Mail-order pharmacy use was 9.6% and 7.6% in the intervention and control groups, respectively (adjusted 1.9 percentage point increase; 95% CI, 0.9 to 3.0). Rates of 90-day supply were not different. In high-cost drug classes, the intervention reduced out-of-pocket costs by 38.9%; 95% CI, -47.6% to -28.7%., Conclusions and Relevance: This cluster randomized clinical trial showed that RTPB recommendations led to lower patient out-of-pocket costs, with the largest savings occurring for high-cost medications. However, RTPB recommendations were made for only a small percentage of prescriptions., Trial Registration: ClinicalTrials.gov Identifier: NCT04940988; American Economic Association Registry: AEARCTR-0006909.

Importance: Randomized clinical trials have shown the efficacy of endovascular therapy (EVT) for acute large vessel occlusion strokes. The benefit of EVT in acute stroke with distal, medium vessel occlusion (DMVO) remains unclear., Objective: To examine the efficacy and safety outcomes associated with EVT in patients with primary DMVO stroke when compared with a control cohort treated with medical management (MM) alone., Design, Setting, and Participants: This multicenter, retrospective cohort study pooled data from patients who had an acute stroke and a primary anterior circulation emergency DMVO, defined as any segment of the anterior cerebral artery (ACA) or distal middle cerebral artery, between January 1, 2015, and December 31, 2019. Those with a concomitant proximal occlusion were excluded. Outcomes were compared between the 2 treatment groups using propensity score methods. Data analysis was performed from March to June 2021., Exposures: Patients were divided into EVT and MM groups., Main Outcomes and Measures: Main efficacy outcomes included 3-month functional independence (modified Rankin Scale [mRS] scores, 0-2) and 3-month excellent outcome (mRS scores, 0-1). Safety outcomes included 3-month mortality and symptomatic intracranial hemorrhage., Results: A total of 286 patients with DMVO were evaluated, including 156 treated with EVT (mean [SD] age, 66.7 [13.7] years; 90 men [57.6%]; median National Institute of Health Stroke Scale [NIHSS] score, 13.5 [IQR, 8.5-18.5]; intravenous tissue plasminogen activator [IV tPA] use, 75 [49.7%]; ACA involvement, 49 [31.4%]) and 130 treated with medical management (mean [SD] age, 69.8 [14.9] years; 62 men [47.7%]; median NIHSS score, 7.0 [IQR, 4.0-14.0], IV tPA use, 58 [44.6%]; ACA involvement, 31 [24.0%]). There was no difference in the unadjusted rate of 3-month functional independence in the EVT vs MM groups (151 [51.7%] vs 124 [50.0%]; P = .78), excellent outcome (151 [38.4%] vs 123 [31.7%]; P = .25), or mortality (139 [18.7%] vs 106 [11.3%]; P = .15). The rate of symptomatic intracranial hemorrhage was similar in the EVT vs MM groups (weighted: 4.0% vs 3.1%; P = .90). In inverse probability of treatment weighting propensity analyses, there was no significant difference between groups for functional independence (adjusted odds ratio [aOR], 1.36; 95% CI, 0.84-2.19; P = .20) or mortality (aOR, 1.24; 95% CI, 0.63-2.43; P = .53), whereas the EVT group had higher odds of an excellent outcome (mRS scores, 0-1) at 3 months (aOR, 1.71; 95% CI, 1.02-2.87; P = .04)., Conclusions and Relevance: The findings of this multicenter cohort study suggest that EVT may be considered for selected patients with ACA or distal middle cerebral artery strokes. Further larger randomized investigation regarding the risk-benefit ratio for DMVO treatment is indicated.

Low grade laryngeal chondrosarcomas are rare, slow growing tumors. Surgical removal of the tumor along with preservation of laryngeal function is the preferred modality of treatment. We report a case of a large low grade chondrosarcoma removed by transoral CO 2 LASER surgery which had avoided an open surgery., Competing Interests: Conflict of interestNo conflicts of interests., (© Association of Otolaryngologists of India 2020.)

Importance: Given higher reimbursement rates, hospitals primarily serving privately insured patients may invest more in intensive coding than hospitals serving publicly insured patients. This may lead these hospitals to code more diagnoses for all patients., Objective: To estimate whether, for the same Medicaid enrollee with multiple hospitalizations, a hospital's share of privately insured patients is associated with the number of diagnoses on claims., Design, Setting, and Participants: This cross-sectional study used patient-level fixed effects regression models on inpatient Medicaid claims from Medicaid enrollees with at least 2 admissions in at least 2 different hospitals in New York State between 2010 and 2017. Analyses were conducted from 2019 to 2021., Exposures: The annual share of privately insured patients at the admitting hospital., Main Outcomes and Measures: Number of diagnostic codes per admission. Probability of diagnoses being from a list of conditions shown to be intensely coded in response to payment incentives., Results: This analysis included 1 614 630 hospitalizations for Medicaid-insured patients (mean [SD] age, 48.2 [20.1] years; 829 684 [51.4%] women and 784 946 [48.6%] men). Overall, 74 998 were Asian (4.6%), 462 259 Black (28.6%), 375 591 Hispanic (23.3%), 486 313 White (30.1%), 128 896 unknown (8.0%), and 86 573 other (5.4%). When the same patient was seen in a hospital with a higher share of privately insured patients, more diagnoses were recorded (0.03 diagnoses per percentage point [pp] increase in share of privately insured; 95% CI, 0.02-0.05; P < .001). Patients discharged from hospitals in the bottom quartile of privately insured patient share received 1.37 more diagnoses when they were subsequently discharged from hospitals in the top quartile, relative to patients whose admissions were both in the bottom quartile (95% CI, 1.21-1.53; P < .001). Those going from hospitals in the top quartile to the bottom had 1.67 fewer diagnoses (95% CI, -1.84 to -1.50; P < .001). Diagnoses in hospitals with a higher private payer share were more likely to be for conditions sensitive to payment incentives (0.08 pp increase for each pp increase in private share; 95% CI, 0.06-0.10; P < .001). These findings were replicated in 2016 to 2017 data., Conclusions and Relevance: In this cross-sectional study of Medicaid enrollees, admission to a hospital with a higher private payer share was associated with more diagnoses on Medicaid claims. This suggests payment policy may drive differential investments in infrastructure to document diagnoses. This may create a feedback loop that exacerbates resource inequity.

Sanjay M. Desai Objectives  Epithelial ovarian cancer (EOC) is a heterogeneous, essentially peritoneal disease. Standard treatment consists of staging, cytoreductive surgery (CRS), and adjuvant chemotherapy. In this study, we intended to assess the effectiveness of single-dose intraperitoneal (IP) chemotherapy in optimally debulked advanced EOC patients. Materials and Methods  A prospective randomized study of 87 patients with advanced EOC was done from January 2017 to May 2021 in a tertiary care center. Patients who underwent primary and interval cytoreduction received a single dose of IP chemotherapy for 24 hours after being divided into four groups: group A, IP cisplatin; group B, IP paclitaxel; group C, IP paclitaxel and cisplatin; and group D, saline. Pre- and postperitoneal IP cytology was assessed along with possible complications. Statistical Analysis  Logistic regression analysis was used to assess for intergroup significance in cytology and complications. Kaplan-Meir analysis was done to assess disease-free survival (DFS). Results  Of 87 patients, 17.2% of patients had FIGO stage IIIA, 47.2% had IIIB, and 35.6% had IIIC. Also, 22 (25.3%) patients were in group A (cisplatin), 22 (25.3%) patients in group B (paclitaxel), 23 (26.4%) in group C (cisplatin and paclitaxel), and 20 (23%) in group D (saline). Cytology samples taken during staging laparotomy were positive, and 48 hours post-IP chemotherapy, 2 (9%) of 22 samples in cisplatin group and 14 (70%) of 20 samples in saline group were positive; all of the post-IP samples in groups B and C were negative. No major morbidity was noted. In our study, DFS in saline group was 15 months, while in IP chemotherapy group it was 28 months and was statistically significant based log-rank test. However, there was no significant difference in DFS between different IP chemotherapy groups. Conclusion  Complete or optimal CRS in advanced EOC does have a possibility of microscopic peritoneal residue. Adjuvant locoregional strategies should be considered to prolong DFS. Single-dose normothermic IP chemotherapy can be offered to the patients with minimal morbidity, and its prognostic benefits are comparable to hyperthermic IP chemotherapy. Future clinical trials are required to validate these protocols., Competing Interests: Conflict of Interest The authors declare no conflicts of interest and no external funding was received for the study., (MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Cerebral edema and intracranial hypertension are major contributors to unfavorable prognosis in traumatic brain injury (TBI). Local epigenetic changes, particularly in DNA methylation, may influence gene expression and thus host response/secondary injury after TBI. It remains unknown whether DNA methylation in the central nervous system is associated with cerebral edema severity or intracranial hypertension post TBI. We sought to identify epigenome-wide DNA methylation patterns associated with these forms of secondary injury after TBI., Methods: We obtained genome-wide DNA methylation profiles of DNA extracted from ventricular cerebrospinal fluid samples at three different postinjury time points from a prospective cohort of patients with severe TBI (n = 89 patients, 254 samples). Cerebral edema and intracranial pressure (ICP) measures were clustered to generate composite end points of cerebral edema and ICP severity. We performed an unbiased epigenome-wide association study (EWAS) to test associations between DNA methylation at 419,895 cytosine-phosphate-guanine (CpG) sites and cerebral edema/ICP severity categories. Given inflated p values, we conducted permutation tests for top CpG sites to filter out potential false discoveries., Results: Our data-driven hierarchical clustering across six cerebral edema and ICP measures identified two groups differing significantly in ICP based on the EWAS-identified CpG site cg22111818 in RGMA (Repulsive guidance molecule A, permutation p = 4.20 × 10 -8 ). At 3-4 days post TBI, patients with severe intracranial hypertension had significantly lower levels of methylation at cg22111818., Conclusions: We report a novel potential relationship between intracranial hypertension after TBI and an acute, nonsustained reduction in DNA methylation at cg22111818 in the RGMA gene. To our knowledge, this is the largest EWAS in severe TBI. Our findings are further strengthened by previous findings that RGMA modulates axonal repair in other central nervous system disorders, but a role in intracranial hypertension or TBI has not been previously identified. Additional work is warranted to validate and extend these findings, including assessment of its possible role in risk stratification, identification of novel druggable targets, and ultimately our ability to personalize therapy in TBI., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objectives: Transient ischemic attack (TIA) serves a precursor for an acute ischemic stroke (AIS); however, not all TIA patients harbor the same risk for subsequent AIS. We aimed to investigate expediting outpatient management of low-risk TIA patients (ABCD: Giles and Rothwell, 2007 score ≤ 3) via our "Fast-Track" TIA Protocol (FTTP)., Materials and Methods: A retrospective analysis was performed on patients who presented to our academic network 04/2020 - 2/2021. Patients who presented with ABCD: Giles and Rothwell, 2007 scores ≤ 3 without large vessel occlusion or flow limiting stenosis were eligible for the FTTP. These patients were discharged on dual antiplatelet therapy and statin and received prescriptions for transthoracic echo, holter monitor, LDL, and A1c along with a scheduled follow-up appointment 30 days from presentation., Results: 182 consecutive patients were evaluated during this period, 21 (11%) were excluded from analysis due to NIHSS > 0 and/or infarct present on MRI. 35 (22%) patients qualified for FTTP and were directly discharged from the ED. Median ABCD 2 score was 2 for the discharge group and 4 for the admitted group. There was a significant difference with respect to age and hypertension. Additionally, the FTTP patient population were more likely to be smokers than the admitted patient population. 3 FTTP patients re-presented to the ED, but none of them suffered a symptomatic stroke., Conclusions: A FTTP demonstrated feasibility and safety with low rates of re-presentation and ischemic stroke. Further research is warranted to determine an optimal patient population that can be safely managed in an outpatient setting., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: For patients undergoing endovascular thrombectomy (EVT), those who are recanalized with a successful single pass (first pass effect, FPE) have better functional outcomes than those who do not. There is a scarcity of data regarding predictors of FPE in basilar artery occlusion (BAO). We aim to determine what characteristics may predict FPE for posterior circulation thrombectomies in a cohort of patients undergoing EVT for BAO., Methods: We reviewed prospectively-collected data for patients presenting to a comprehensive stroke center with BAO between December 2015 and April 2019. Patients were included in this study if they underwent manual aspiration thrombectomy for BAO. Patients were excluded if they had occlusions of the posterior cerebral or vertebral arteries or if they had tandem lesions. Patients were stratified by whether FPE or modified FPE (mFPE) was achieved, and multivariate logistic regression analyses were performed to identify predictors of FPE and the effect of FPE on clinical outcome., Results: 100 patients with BAO underwent thrombectomy. Mean age was 64.7 ± 16.7, 42% were female, and median NIHSS was 20 (IQR 11-27). 33% met criteria for FPE and 60% for mFPE. Univariate analysis identified female gender, lack of IV-tPA use, pcASPECTS, atrial fibrillation, and hyperlipidemia as possible predictors of FPE. On multivariate analysis, age, pcASPECTs, atrial fibrillation, hyperlipidemia and IV-tPA use were not independent predictors of FPE or mFPE. Female gender was an independent predictor of mFPE (p = 0.02), but not FPE (p = 0.18). FPE was a predictor of mRS 0-2 at 90 days (p = 0.04). Predictors of mortality were age (p < 0.01), baseline NIHSS (p < 0.01) and mFPE (p = 0.01)., Conclusion: In this cohort analysis of 100 patients with basilar artery occlusion undergoing manual aspiration thrombectomy, female gender was associated with mFPE but not FPE. Previously-reported anterior circulation FPE predictors including age, ASPECTS and atrial fibrillation were not predictors of FPE in this cohort of patients with BAO., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This cross-sectional study assesses pharmacy participation in the 340B Drug Pricing Program following the 2010 expansion and the extent to which growth has occurred in socioeconomically disadvantaged neighborhoods., Competing Interests: Conflict of Interest Disclosures: Dr Li reported personal fees from HealthStatistics LLC and Covia Health Solutions outside the submitted work. Dr Doshi reported grants from Humana, Janssen, Merck, Novartis, PAN Foundation, Regeneron, and Sanofi, and personal fees from AbbVie, Acadia, Boehringer Ingelheim, Catabasis, Janssen, MeiraGTx, Merck, Otsuka, SAGE Therapeutics, Takeda, and The Medicines Company, all unrelated to and outside the submitted work. No other disclosures were reported., (Copyright 2022 Lin JK et al. JAMA Health Forum.)

Introduction: Research shows autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage lesions. In this study, we assessed mid-term efficacy and safety of gel-based ACI or autologous adult live cultured chondrocytes (CARTIGROW®) implantation in patients with cartilage defects of the knee joint., Methods: In this prospective, open-label study, patients (19-38 years) with focal, international cartilage repair society grade III or IV articular cartilage defects of the knee joint were enroled at four centres across India from April 2015 to September 2015. Punch biopsy was conducted to harvest cartilage, from which chondrocytes were isolated and cultured, and the characterised chondrocytes were implanted into the cartilage defect. Key efficacy outcomes were assessed by quantitative changes in international knee documentation committee (IKDC), visual analogue scale (VAS) scores, and qualitative changes in magnetic resonance imaging at six months and four years from baseline., Results: Of the14 patients enroled in the study, all patients completed the six month follow-up and 11 completed the four year follow-up. The IKDC score improved significantly from 32.84 ± 9.25 at baseline to 67.49 ± 13.03 at six months (mean difference [MD] 34.66 ± 13.00, p < 0.0001) and to 60.18 ± 10.33 at four years (MD 28.21 ± 15.14, p = 0.0001). The VAS score reduced from 72.00 ± 14.40 at baseline to 16.64 ± 17.03 at six months (MD 55.36 ± 24.50, p < 0.0001) and further to 12.72 ± 9.05 at four years (MD 62.09 ± 10.66, p < 0.0001). All patients showed improvement on MRI of the knee joint. No adverse events were reported., Conclusion: Autologous adult live cultured chondrocytes (CARTIGROW®) implantation showed good mid-term efficacy in patients with cartilage defects of the knee joint with no side-effects., (© 2022. The Author(s).)

Background: The optimal imaging paradigm for endovascular thrombectomy (EVT) patient selection in early time window (0-6 hours) treated acute ischemic stroke patients remains uncertain. We aimed to compare post-EVT outcomes between patients who underwent prerandomization basic (noncontrast computed tomography [CT], CT angiography only) versus additional advanced imaging (computed tomography perfusion [CTP] imaging) and to determine the association of performance of prerandomization CTP imaging with clinical outcomes., Methods: The HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) pooled patient-level data from randomized controlled trials comparing EVT with usual care for acute ischemic stroke due to anterior circulation large vessel occlusion. Good functional outcome, defined as modified Rankin Scale score 0 to 2 at 90 days, was compared between randomized patients with and without CTP baseline imaging. Univariable and multivariable binary logistic regression analysis was performed to determine the association of baseline CTP imaging and good functional outcome., Results: We analyzed 1348 patients 610 (45.3%) of whom underwent CTP prerandomization. The benefit of EVT compared with best medical management was maintained irrespective of the baseline imaging paradigm (90-day modified Rankin Scale score 0-2 in EVT versus control patients: with CTP: 46.0% (137/298) versus 28.9% (88/305), without CTP: 44.1% (162/367) versus 27.3% (100/366). Performance of CTP baseline imaging compared with baseline noncontrast CT and CT angiography only yielded similar rates of good outcome (odds ratio, 1.05 [95% CI, 0.82-1.33], adjusted odds ratio, 1.04, [95% CI, 0.80-1.35])., Conclusions: Rates of good functional outcome were similar among patients in whom CTP was or was not performed, and EVT treatment effect in the 0- to 6-hour time window was similar in patients with and without baseline CTP imaging.

Objectives: High-value care is providing high quality care at low cost; we sought to define hospital value and identify the characteristics of hospitals which provide high-value care., Design: Retrospective observational study., Setting: Acute care hospitals in the USA., Participants: All Medicare beneficiaries with claims included in Center for Medicare & Medicaid Services Overall Star Ratings or in publicly available Medicare spending per beneficiary data., Primary and Secondary Outcome Measures: Our primary outcome was value defined as the difference between Star Ratings quality score and Medicare spending; the secondary outcome was classification as a 4 or 5 star hospital with lowest quintile Medicare spending ('high value') or 1 or 2 star hospital with highest quintile spending ('low value')., Results: Two thousand nine hundred and fourteen hospitals had both quality and spending data, and were included. The value score had a mean (SD) of 0.58 (1.79). A total of 286 hospitals were classified as high value; these represented 28.6% of 999 4 and 5 star hospitals and 46.8% of 611 low cost hospitals. A total of 258 hospitals were classified as low value; these represented 26.6% of 970 1 and 2 star hospitals and 49.3% of 523 high cost hospitals. In regression models ownership, non-teaching status, beds, urbanity, nurse to bed ratio, percentage of dual eligible Medicare patients and percentage of disproportionate share hospital payments were associated with the primary value score., Conclusions: There are high quality hospitals that are not high value, and a number of factors are strongly associated with being low or high value. These findings can inform efforts of policymakers and hospitals to increase the value of care., Competing Interests: Competing interests: SMB, JH, ZL and AKV recieve salary support from the Centers for Medicare and Medicaid Services to develop, implement and maintain hospital performance outcome measures, including the methodology for the Overall Hospital Star Ratings, that are publicly reported. LIH and HY have worked under contract to the Centers for Medicare and Medicaid Services to develop quality measures, including some used in the Overall Hospital Star Ratings program., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The data regarding patients eligible for endovascular thrombectomy (EVT), especially in the developing world is lacking., Objective: To determine the proportion of patients with acute ischemic stroke (AIS) who are eligible for EVT in the 0-24-h time window., Materials and Methods: We performed a retrospective cohort study using prospectively collected AIS data between July 2017 and September 2019. Demographic, clinical, and management information were analyzed. EVT eligibility was explored using the following criteria: National Institutes of Health Stroke Scale (NIHSS) score ≥6, presence of anterior circulation large-vessel occlusion (ACLVO), Alberta stroke program early Computerized Tomography score (ASPECTS) ≥6, baseline modified Rankin Scale (mRS) score 0-2, and within 24 h of time last seen well (TLSW). EVT-eligible patients were further evaluated for in-hospital course and outcomes., Results: In the study period of 27 months, there were 221 patients with AIS who presented within 24 h. The mean age of the patients was 54.4 (16.0) years and 66.1% (146) were males. A majority (61.5% [136/221]) arrived within 6 h of TLSW. Of these, 81.6% (111/136) presented in the time window for thrombolysis (0-4.5 h). The patients with NIHSS ≥6 and ACLVO constituted 41.2% (91/221) of the patients. AIS eligible for EVT constituted 19.5% (43/221) of the patients., Conclusion: In our study, the proportion of AIS eligible for endovascular thrombectomy was comparable to the developed world. These data predict a large potential for the late-window EVT in India., Competing Interests: None

This cross-sectional study describes the price differences between capsule and tablet or ointment and cream forms of prescription drugs for insured patients., Competing Interests: Conflict of Interest Disclosures: Dr Bhargava reported receiving a research excellence gift from Google Inc outside the submitted work. No other disclosures were reported., (Copyright 2022 Desai SM et al. JAMA Health Forum.)

Background and Purpose: Achieving complete revascularization after a single pass of a mechanical thrombectomy device (first pass effect [FPE]) is associated with good clinical outcomes in patients with acute ischemic stroke due to large vessel occlusion. We assessed patient characteristics, outcomes, and predictors of FPE among a large real-world cohort of patients (Systematic Evaluation of Patients Treated with Stroke Devices for Acute Ischemic Stroke registry)., Methods: Demographics, clinical outcomes, and procedural characteristics were analyzed among patients in whom FPE (modified Thrombolysis in Cerebral Infarction 2c/3 after first pass) was achieved versus those requiring multiple passes (MP). Modified FPE and modified MP included patients achieving modified Thrombolysis in Cerebral Infarction 2B-3. Primary outcomes included 90-day modified Rankin Scale (mRS) score and mortality., Results: Among 984 Systematic Evaluation of Patients Treated with Stroke Devices for Acute Ischemic Stroke patients, 930 had complete 90-day follow-up. FPE was achieved in 40.5% (377/930) of patients and MP in 20.0% (186/930). Baseline characteristics were similar across all groups. The FPE group had fewer internal carotid artery occlusions compared with MP ( P =0.029). The FPE group had faster puncture to recanalization time ( P ≤0.001), higher rates of 90-day mRS score of 0 to 1 (52.6% versus 38.6%, P =0.003), mRS score of 0 to 2 (65.4% versus 52.0%, P =0.003), and lower 90-day mortality compared with the MP group (12.0% versus 18.7%, P =0.038). Similarly, compared with modified MP patients, the modified FPE group had fewer internal carotid artery occlusions ( P =0.004), faster puncture to recanalization time ( P ≤0.001), and higher rates of 90-day mRS score of 0 to 1 ( P =0.002) and mRS score of 0 to 2 ( P =0.003)., Conclusions: Our findings demonstrate that FPE and modified FPE are associated with superior clinical outcomes.

Background: Acute ischemic stroke (AIS) is a major contributor toward healthcare-associated costs and services. Symptomatic intracranial hemorrhage (sICH) and early neurologic decline (END), defined as a National Health Institute Stroke Scale score decline of ≥ 4 within 24 h (with or without sICH), remain major concerns when administering intravenous tissue plasminogen activator (IV tPA) despite improved functional neurologic outcomes with its use. Given these risks, current guidelines recommend comprehensive stroke care (most often in an intensive care unit setting) for 24 h posttreatment. However, a number of patients may remain stable after IV tPA and thus not require such intensive resources. We sought to determine causes of END, along with timing and predictors of both sICH and END, to identify patients at lower risk of neurological deterioration and those suitable for earlier transition to a lower level of care., Methods: This present study analyzed patients with AIS that presented within 4.5 h of being last seen well and received IV tPA. Baseline demographic, clinical, and radiographic findings were collected. Outcomes included END from any cause, parenchymal hemorrhage (PH1 or PH2), sICH, and mortality at 90 days., Results: A total of 1238 patients with AIS without acute treatment of large vessel occlusion received IV tPA. 9.4% (116) had presence of any degree of ICH on noncontrast computed tomography head and 7.4% (91) experienced associated END. 2.7% (33) of patients experienced sICH, while 6.7% (83) experienced asymptomatic ICH. Of the patients with END, 63.7% did not have ICH. Predictive factors at presentation for END included an older age (72.6 ± 16.1 vs. 69.1 ± 14.8, p = 0.03), history of tobacco use (odds ratio [OR] 2.1 [1.1-4.3], p = 0.04), and hyperlipidemia (OR 1.7 [1.1-2.8], p = 0.02), along with the presence of an untreated large vessel occlusion (OR 2.1 [1.4-3.1], p = 0.02). Most END occurred within a mean time of 242 ± 251 min (4 ± 4 h). Because of the small proportion of patients suffering from sICH (33), predictors could not be determined; however, for patients with any ICH, predictive factors included an older age (74.6 ± 12.4 vs. 68.8 ± 15.1, p = 0.001), higher baseline National Health Institute Stroke Scale score (14.6 ± 7.3 vs. 10.8 ± 7.9, p = 0.002), and higher baseline glucose levels (155.1 ± 87.5 vs. 140.4 ± 70.5, p = 0.04)., Conclusions: In this study, only a small proportion suffered from either sICH and/or END, typically within 12 h of tPA administration. These findings may support earlier deescalation of higher acuity monitoring in clinically stable post-IV tPA patients without large vessel occlusion., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Glaucoma is an ocular condition characterized by elevated intraocular pressure (IOP). Conventional treatments of glaucoma face poor corneal permeability and bioavailability. To address these issues, a nanoemulsion in situ gel of Timolol maleate was developed in this study by adding the polymer Carbopol 934p. Using Carbopol 934p, a novel ophthalmic pH-induced nanoemulsion in situ gel was formulated. The formulation was liquid at pH 4 and quickly gelled when the pH was raised to 7.4 (Lacrimal pH). The pH-triggered in situ gelling mechanism demonstrated continuous drug release over a 24 h cycle. A total of nine trial formulations were prepared (NEI 1 -NEI 9 ) and subjected to various physicochemical and in vitro evaluations. According to the in vitro release kinetics, the drug release of Timolol maleate nanoemulsion in situ gel NEI 5 followed zero-order kinetics, with a release exponent value of 0.902, indicating that the mechanism of release was non-Fickian diffusion regulated. In vivo results showed that Timolol maleate nanoemulsion in situ gel NEI 5 provided a better-sustained release of the drug, compared with the Timolet OD eye drops. The formulation is stable in storage, with no distinguishable change in appearance, physical properties, quality, and percentage drug release. NEI 5 also reduces drug administration frequency, which improves patient compliance. Timolol maleate nanoemulsion in situ gel NEI 5 achieved the goal of controlled drug delivery with extended-release and cost-effectiveness, lowering the dosage and frequency of drug administration, and thus may improve patient compliance. In conclusion, the stable nanoemulsion in situ gel of Timolol maleate NEI 5 decreases intraocular pressure (IOP) over a prolonged period.

Background: Unprecedented workflow shifts during the coronavirus disease 2019 (COVID-19) pandemic have contributed to delays in acute care delivery, but whether it adversely affected endovascular thrombectomy metrics in acute large vessel occlusion (LVO) is unknown., Methods: We performed a retrospective review of observational data from 14 comprehensive stroke centers in nine US states with acute LVO. EVT metrics were compared between March to July 2019 against March to July 2020 (primary analysis), and between state-specific pre-peak and peak COVID-19 months (secondary analysis), with multivariable adjustment., Results: Of the 1364 patients included in the primary analysis (51% female, median NIHSS 14 [IQR 7-21], and 74% of whom underwent EVT), there was no difference in the primary outcome of door-to-puncture (DTP) time between the 2019 control period and the COVID-19 period (median 71 vs 67 min, P=0.10). After adjustment for variables associated with faster DTP, and clustering by site, there remained a trend toward shorter DTP during the pandemic (β adj =-73.2, 95% CI -153.8-7.4, Pp=0.07). There was no difference in DTP times according to local COVID-19 peaks vs pre-peak months in unadjusted or adjusted multivariable regression (β adj =-3.85, 95% CI -36.9-29.2, P=0.80). In this final multivariable model (secondary analysis), faster DTP times were significantly associated with transfer from an outside institution (β adj =-46.44, 95% CI -62.8 to - -30.0, P<0.01) and higher NIHSS (β adj =-2.15, 95% CI -4.2to - -0.1, P=0.05)., Conclusions: In this multi-center study, there was no delay in EVT among patients treated for intracranial occlusion during the COVID-19 era compared with the pre-COVID era., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Patients with advanced carcinoma tongue end up with near-total/total glossectomy (NTG/TG). We intended to compare functional, oncological, and survival outcomes of patients undergoing pedicled and microsurgical flap reconstruction in NTG/TG patients at our hospital., Methodology: A prospective study was conducted for 7 years on 91 patients with carcinoma tongue who underwent NTG/TG at our institute. Patients underwent anterolateral thigh (ALT), free radial artery forearm flap (FRAFF), and pectoralis major myocutaneous (PMMC) flap reconstruction and were followed up for immediate complications and functional outcomes for speech, swallowing, and decannulation after completion of adjuvant treatment and then for survival rates for a period of 60 months and statistically analysed with log rank test and Fisher's exact test for correlation., Results: Ninety-one (42.85%) patients underwent NTG, while 57.14% underwent TG. 85% of patients had >5 mm margin, 14% had ≤ of 5 mm, and none were positive. 57% of patients did not have postoperative complications and 10% underwent re-exploration. During follow-up, 85.7% of patients were able to take orally: 52% soft diet and 32% liquid diet. Multivariate analysis of individual flaps, swallowing, and speech intelligibility values were significant. After 5 years of postadjuvant therapy, there was 76% overall survival, 11% local recurrence and 12% had regional recurrence., Discussion: Morbidity and functional outcome depends on the extent of resection. PMMC flaps can be done on lack of expertise. FRAFF has better functional outcomes owing to pliability of flap. ALT and other bulky flaps require expertise and are prone to flap-related complications. Planning of reconstruction should be based on the defect size together with counseling of patients regarding the risk of complications and delay in adjuvant therapy., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Maxillofacial Surgery.)

Background: Heterogeneity in the infarct growth rate among anterior circulation large vessel occlusion (LVO) strokes has triage and treatment implications. Such data are lacking for basilar artery occlusion (BAO) strokes. We aim to describe the variability in brainstem infarct volume at presentation and compute the distribution of the infarct growth rate (IGR) and rate of loss of neurons during BAO strokes., Methods: A retrospective review of consecutive patients with BAO stroke with pretreatment MRI was performed. Ischemic core volume was manually calculated (product of slice thickness and sum of area of region of interests) for the brainstem lesion. The distribution of various brainstem infarct volume groups was analyzed and the IGR (including rate of loss of neurons) was computed., Results: Fifty-nine patients were included. Mean age was 64±13 and 34% were men. Mean National Institutes of Health Stroke Scale score was 20±11 and time to MRI was 9±5 hours. Mean brainstem ischemic core volume was 4.5±4.6 mL. According to predefined thresholds, 13% and 6% of patients with BAO stroke in the 0-6 hour time window were fast (5-10 mL) and ultra-fast progressors (>10 mL), respectively, and 14% of patients in the 6-24 hour time window were slow progressors (<1 mL). Median and mean rate of loss of neurons was 146 300 neurons/min and 261 300 (±400 000) neurons/min, respectively, and ranged from <19 400 to >2.12 million., Conclusion: Approximately 14% of BAO strokes are slow progressors and 19% are fast/ultra-fast progressors, with the rate of loss of neurons ranging from <19 000 to >2.1 million/min. Large heterogeneity exists in brainstem infarct volume at presentation and IGR among patients with BAO stroke., Competing Interests: Competing interests: TGJ: Consultant: Stryker Neurovascular (PI DAWN unpaid), Biogen (modest); Ownership interest: Anaconda (modest); Advisory Board/Investor: FreeOx Biotech (modest); Advisory Board/Investor: Route92 (modest); Advisory Board/Investor: Blockade Medical (modest), Silk Road (modest), Consultant; Honoraria: Cerenovus (modest), DSMB., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with advanced carcinoma tongue in the Indian subcontinent have an additional component of submucosal fibrosis (SMF) due to chewing of betel. We intend to evaluate  mandibular pull-through approach for total or near-total glossectomy and assessed its functional and survival outcome. Prospective study of 77 patients with carcinoma tongue, who underwent total or near-total glossectomy at our institute, were assessed retrospectively. All the patients who underwent glossecomy through mandibular pull through approach with pedicled or free flap reconstruction were assessed for functional and survival outcomes. Of the 77 patients, 45 (58.44%) patients underwent total glossectomy, while 32 (41.55%) patients near-total glossectomy, 61 (79.22%) cases had operative time ≤ 30 min, 69 (89.61%) patients had margins of > 5 mm, and none of the margins were involved. Flaps were reconstructed with 42 (54.54%) PMMC, 24 (31.16%) FRAFF, and 11 (14.28%) ALT. Five (6.49%) patients had surgical site infections, 6 patients each had to undergo re-explorations and partial flap loss, 7 patients had oro-cutaneous fistula, while 53 (68.83%) patients had no complications/osteoradionecrosis. A total of 94% of patients underwent decannulation, 92% of patients got discharged, and 89% got NG tube removed within 21 POD. Forty patients had reasonably good speech. On the long-term follow-up, 9% of the patients developed local recurrence and 11% of patients had regional/lymph node recurrence. Mandibular pull-through approach had the advantages of good accessibility to the tumour with the least mutilating techniques with shorter operation time, lower rates of postoperative complications, and better aesthetics and based on available data, it is superior to the mandibular lip-spilt surgery for advanced tongue involving BOT and floor of mouth cancers when coupled with SMF surgeries for the Indian scenario., (© Indian Association of Surgical Oncology 2021.)

Purpose of the Review: This article reviews recent breakthroughs in the treatment of acute ischemic stroke, mainly focusing on the evolution of endovascular thrombectomy, its impact on guidelines, and the need for and implications of next-generation randomized controlled trials., Recent Findings: Endovascular thrombectomy is a powerful tool to treat large vessel occlusion strokes and multiple trials over the past 5 years have established its safety and efficacy in the treatment of anterior circulation large vessel occlusion strokes up to 24 hours from stroke onset., Summary: In 2015, multiple landmark trials (MR CLEAN, ESCAPE, SWIFT PRIME, REVASCAT, and EXTEND IA) established the superiority of endovascular thrombectomy over medical management for the treatment of anterior circulation large vessel occlusion strokes. Endovascular thrombectomy has a strong treatment effect with a number needed to treat ranging from 3 to 10. These trials selected patients based on occlusion location (proximal anterior occlusion: internal carotid or middle cerebral artery), time from stroke onset (early window: up to 6-12 hours), and acceptable infarct burden (Alberta Stroke Program Early CT Score [ASPECTS] ≥6 or infarct volume <50 mL). In 2017, the DAWN and DEFUSE-3 trials successfully extended the time window up to 24 hours in appropriately selected patients. Societal and national thrombectomy guidelines have incorporated these findings and offer Class 1A recommendation to a subset of well-selected patients. Thrombectomy ineligible stroke subpopulations are being studied in ongoing randomized controlled trials. These trials, built on encouraging data from pooled analysis of early trials (HERMES collaboration) and emerging retrospective data, are studying large vessel occlusion strokes with mild deficits (National Institutes of Health Stroke Scale <6) and large infarct burden (core volume >70 mL)., (© 2021 American Academy of Neurology.)

Purpose of the Review: Mechanical thrombectomy (MT)-mediated endovascular recanalization has dramatically transformed treatment and outcomes after acute ischemic stroke caused by a large vessel occlusion (LVO). Current guidelines recommend MT up to 24 hours from stroke onset in carefully selected patients based on favorable clinical and imaging parameters. Despite optimal patient selection and low complication rates with current recanalization technology, approximately 1 in 2 patients with LVO stroke do not achieve functional independence at 3 months. This ceiling effect of MT efficacy may be explained by ischemic core expansion into the ischemic penumbra before recanalization and neuronal loss occurring after recanalization. Factors affecting the efficacy of MT, or the degree of irreversible injury, include time from symptom onset to recanalization, collateral circulation status, and differences in neuronal vulnerability. The purpose of this brief review is to discuss potential targets for neuroprotection, present and future potential pharmacologic and nonpharmacologic agents, and the data available in the literature., Recent Findings: In experimental ischemia models, several authors reported that pharmacologic and nonpharmacologic agents are able to slow the progression of ischemic core expansion. However, in the era of unsuccessful recanalization of the occluded artery, several neuroprotective agents that were promising in the preclinical stage failed phase II/III clinical trials., Summary: Providing neuroprotection before and after recanalization of an LVO may play an important role in improving outcomes in the era of MT. Neuroprotection is classically defined as a process that results in the salvage, recovery, or regeneration of neuronal (and other supporting CNS cell) structure or function. The advent of successful recanalization of acute LVO by MT in the majority of patients may spur the growth of effective neuroprotection., (© 2021 American Academy of Neurology.)