Periprosthetic Fractures: A Rising Tide of Hip Arthroplasty Failure Noted in the American Joint Replacement Registry and the Preventative Role of Cemented Stems.

BACKGROUND: This investigation examined cemented femoral component use in total hip arthroplasty (THA) and its impact on the incidence of periprosthetic fractures (PPFx), a common failure mode in THA. The study leverages data from the American Joint Replacement Registry (AJRR) to assess trends in cemented femoral component usage over time, its association with PPFx rates, and compares the survivorship and 90-day complication rates between cemented and cementless femoral component THAs. METHODS: Primary THAs, captured in the AJRR, in patients aged 65 years and older from 2012 to 2021 were analyzed. Variables considered included age, sex, race, region, teaching status, year, Charlson Comorbidity Index (CCI), and institution bed size. Analysis compared fixation types for THA on all-cause linked revision and PPFx. Logistic regression models analyzed the odds ratios for all-cause linked revision and PPFx for any follow-up time as well as for 90-day revision. The models were adjusted for the listed variables. RESULTS: During the study period, the rate of cement utilization as a percentage of primary THAs performed and reported to the AJRR increased from 4.4 to 8.3%. The rate of THA failure from PPFx increased from 11.4 to 33.3%. When both fixation groups were compared in the univariate analysis, there was a statistically significant difference in all demographic variables (P < 0.001). To account for this, multivariable logistic regression models were applied. In our models, cemented stems showed a 54.4% (OR [odds ratio]: 0.456, 95% CI [confidence interval]: 0.347 to 0.599, P < 0.0001) and 65.8% (OR: 0.342, 95% CI: 0.237 to 0.493, P < 0.0001) lower risk of PPFx linked and PPFx early linked revision, respectively. CONCLUSION: Periprosthetic fractures are becoming a leading failure mode for THAs in the AJRR. Given cemented fixation's relative resistance to this failure mode compared to cementless fixation, we should consider increasing the utilization of this technique.

Reference Interval Creation for Symmetric Dimethylarginine (SDMA) in Healthy Hispaniolan Amazon Parrots (Amazona ventralis) and Quaker Parrots (Myiopsitta monachus).

Renal disease is often identified as a cause of morbidity and mortality in avian patients. However, currently, early antemortem detection of renal disease in avian patients is difficult. Anatomical and physiological differences between mammals and birds mean the use of commonly employed diagnostic testing (ie, measurement of blood urea nitrogen [BUN] and serum creatinine, urinalysis, and ultrasonography) are either nondiagnostic or difficult to achieve. Symmetric dimethylarginine (SDMA) is considered a more sensitive marker for renal disease in humans, dogs, and cats. However, SDMA has not yet been assessed for diagnostic use in any psittacine species. In this study, we establish reference ranges for SDMA in both Hispaniolan Amazon parrots (Amazona ventralis, HAP) and Quaker parrots (Myiopsitta monachus, QP). Blood was collected from 23 Amazon parrots and 32 Quaker parrots maintained in research facilities. Measurement of SDMA through a commercially available immunoassay (IA-SDMA) as well as creatinine, BUN, uric acid, phosphorus, calcium, sodium, potassium, and chloride were determined through IDEXX Laboratories. Plasma SDMA concentrations ranged from 6 to 15 µg/dL and 3 to 15 µg/dL for the HAP and QP, respectively. Sex was a confounding factor for the QP population, but sex did not have a significant effect on SDMA for the HAP population. No significant correlations were identified between SDMA concentrations and other parameters in either psittacine species. Our results show proof of concept for the IA-SDMA and provide reference intervals for SDMA in HAP and QP. Further investigation is required to determine the validity of this assay and the predictive power of SDMA in the detection of renal impairment for parrots and other common companion birds.

Sleep disorder experienced by healthcare nurses after terminating Zero-COVID-19 policy.

OBJECTIVE: Medical staff, especially nurses, suffered great anxiety and stress from the COVID-19 pandemic, which negatively affected their sleep quality. In this study, we aimed to analyze the sleep quality of nursing staff after terminating the Zero-COVID-19 policy in China. METHODS: 506 participants were involved in our study. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep status of the participants. Binary regression was performed to evaluate the impact factors related to sleep difficulty. RESULTS: The majority of participants (96.44%) suffered from sleep disturbances. There were significant differences in age, education level and front-line activity between participants with good sleep quality and sleep difficulty. Younger age (16-25 years old) was independently associated with less sleep difficulty, while front-line activity was independently associated with severe sleep difficulty. CONCLUSION: Sleep disorder was very common among nurses after ending the Zero-COVID-19 policy in China. More front-line nurses suffered severe sleep difficulty in particular, which should be worthy of attention.

Correction: Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment.

[This corrects the article DOI: 10.1371/journal.pone.0140310.].

Endovascular thrombectomy for ischemic stroke with large infarct, short- and long-term outcomes: a meta-analysis of 6 randomised control trials.

Endovascular Thrombectomy (EVT) as first-line treatment of patients with large core ischemic infarct is a subject of debate. A systematic literature search was conducted in four electronic databases for randomized control trials (RCTs) comparing EVT to best medical treatment (BMT) for large core infarcts (ASPECTS ≤ 5). Relevant studies were added after screening for titles, abstracts, and complete text. Meta-analysis was performed. The continuous outcomes were analyzed using the standardized mean difference (SMD) and 95% CI, while the binary outcomes were analyzed using the risk ratio (RR) and 95% confidence interval (CI). A funnel plot was used to visually evaluate publication bias, and if feasible, Egger's test was used to validate. We included 1918 patients from six RCTs that compared EVT plus BMT and BMT alone in patients with large core infarct due to large vessel occlusion in the anterior circulation. There were 946 patients in the EVT group and 972 patients in the BMT group. The one-year outcomes are available for 314 patients in the EVT group and 292 patents in the BMT group from two RCTs. EVT group had statistically significant higher rate of 90-day mRS 0-1 (RR = 3.1, P-value < 0.0001), mRS 0-2 (RR = 2.64, P-value < 0.0001), mRS 0-3 (RR = 1.80, P-value < 0.0001), lower 90-day mean mRS score (SMD = -0.29, P-value < 0.0001), lower 90-day mortality rate (RR = 0.85, P-value = 0.015), and greater early neurological improvement (RR = 2.16, P-value < 0.00001) compared to the BMT group. However, the rates of symptomatic intracerebral hemorrhage (sICH) (RR = 1.76, P-value = 0.01) and any ICH (RR = 2.18, P-value < 0.00001) were higher in EVT group. Our finding showed that EVT plus BMT led to in an absolute improvement of 5%, 12%, and 16% in 90-day mRS 0-1, 0-2, and 0-3, respectively. In addition, patients in EVT plus BMT group had a 3% increased probability of experiencing sICH and were 32% more susceptible to any ICH. Moreover, the one-year mRS 0-2 (RR = 2.16, P-value < 0.00001) and mRS 0-3 (RR = 1.80, P-value < 0.0001) was significantly favor the EVT plus BMT over BMT alone. Although, the one-year mortality rate was not significantly differed between two groups (RR = 0.91, P-value = 0.31). There was no statistically significant difference observed between the EVT plus BMT group and the BMT group concerning new stroke, decompressive craniectomy, and serious adverse events. Combined data from six RCTs shows that EVT plus BMT provides significantly better short- and long-term functional outcomes with minimal increase in symptomatic hemorrhage over BMT in patient with large core infarcts.

Urinary polycyclic aromatic hydrocarbon (PAH) metabolite concentrations in three pregnancy cohorts from 7 U.S. study sites.

OBJECTIVE: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH exposures in a large, multisite U.S. consortium. METHODS: We measured 12 mono-hydroxylated metabolites (OH-PAHs) of 7 PAHs (naphthalene, fluorene, phenanthrene, pyrene, benzo(c)phenanthrene, chrysene, benz(a)anthracene) in mid-pregnancy urine of 1,892 pregnant individuals from the ECHO PATHWAYS consortium cohorts: CANDLE (n = 988; Memphis), TIDES (n = 664; Minneapolis, Rochester, San Francisco, Seattle) and GAPPS (n = 240; Seattle and Yakima, WA). We described concentrations of 8 OH-PAHs of non-smoking participants (n = 1,695) by site, socioeconomic characteristics, and pregnancy stage (we report intraclass correlation coefficients (ICC) for n = 677 TIDES participants). RESULTS: Exposure to the selected PAHs was ubiquitous at all sites. 2-hydroxynaphthalene had the highest average concentrations at all sites. CANDLE had the highest average concentrations of most metabolites. Among non-smoking participants, we observed some patterns by income, education, and race but these were not consistent and varied by site and metabolite. ICCs of repeated OH-PAH measures from TIDES participants were ≤ 0.51. CONCLUSION: In this geographically-diverse descriptive analysis of U.S. pregnancies, we observed ubiquitous exposure to low molecular weight PAHs, highlighting the importance of better understanding PAH sources and their pediatric health outcomes attributed to early life PAH exposure.

Carotid revascularisation versus medical treatment for asymptomatic carotid artery stenosis.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compare the safety and efficacy of carotid revascularisation plus best medical treatment with best medical treatment alone in people with asymptomatic carotid artery stenosis.

Main and interactive effects of discrimination, parent racial/ethnic socialization, and internalizing symptomology on BIPOC teens' ethnic-racial identity.

Research suggests that BIPOC (Black, Indigenous, People of Color) adolescents have the best developmental outcomes when strong, positive ethnic-racial identity (ERI) is acknowledged and embraced. This study investigated whether discrimination, internalizing symptomology, parent socialization, and/or interactions of these variables were associated with adolescent ERI, specifically in exploration, resolution, and affirmation, to illuminate nuanced ways BIPOC youth can achieve positive ERI. Recruited from third-party research panels, surveyed participants were adolescents (Mage = 15.28; 51.6% male) of diverse ethnic/racial groups and socioeconomic backgrounds from all regions of the United States. Overall, results showed that there were four significant main effects on ERI: a negative relation between internalizing symptomology and exploration, a positive relation between parent socialization and exploration, a positive relation between parent socialization and resolution, and a negative relation between internalizing symptomology and affirmation. There were also two significant interactive effects such that (1) discrimination had a stronger negative relation with affirmation under condition of high internalizing, and (2) parent socialization had a stronger positive relation with affirmation under condition of high internalizing. Results show development of ERI in adolescence is subject to multiple, interactive influences. Main and interactive effects highlight the contextual role that mental health implicates for youth of color. Implications for parents and practitioners are discussed.

Sellar hemangiopericytoma masquerading as pituitary adenoma: an overlooked intriguing case study unveiling a rare surgical conundrum.

Hemangiopericytoma (HPC) constitutes less than 1% of all primary central nervous system tumors. It is a vascular neoplasm with potential malignancy that, in rare instances, manifests as a primary lesion within the brain. Typically, it originates from the meninges. Here, we describe an exceptionally uncommon sellar region solitary fibrous tumor/hemangiopericytoma (SFT/HPC) that mimicked a nonfunctional pituitary adenoma. Case presentation: A 54-year-old male was referred to our hospital due to progressive blurred vision in the left eye over the past year. A homogeneous iso-dense extra-axial intrasellar round mass with extension into the suprasellar region, mainly on the left side, along with bony erosion and osteolysis around the sellar region, was observed on a brain computed tomography (CT) scan. Brain magnetic resonance imaging (MRI) revealed a well-defined 251,713 mm mass with iso-signal on T1-weighted images and hypersignal on T2-weighted images, originating from the pituitary gland within the sella turcica. The mass avidly enhanced following Gadolinium injection and adhered to both carotid arteries without vascular compression or invasion. It extended to the suprasellar cistern and compressed the optic chiasm. The diagnosis was nonfunctional pituitary macroadenoma, leading to the decision for Endoscopic Trans-Sphenoidal Surgery (ETSS). A non-sustainable, soft, grayish mass was grossly and totally resected during the operation. Subsequently, there was a significant improvement in visual acuity during the early postoperative period. Histopathologic examination confirmed hemangiopericytoma (WHO grade II). Conclusion: Due to its malignant nature, hemangiopericytoma should be included in the differential diagnosis of a sellar mass, both from a clinical and morphological perspective.

Estimating the Effect of COVID-19 Pandemic Restrictions on Self-reported Antiretroviral Therapy Use and Late Refill Visits Among People Living With HIV in Rural South Africa.

BACKGROUND: People living with HIV require reliable access to and adequate supply of antiretroviral therapy (ART) for viral suppression. The Deliver Health Study, a randomized trial conducted during the COVID-19 pandemic, found that home-delivered ART significantly increased viral suppression compared with clinic-based care. The effect of changing COVID-19 alert levels on self-reported ART use has not been quantified. SETTING: KwaZulu-Natal, South Africa. METHODS: Adults living with HIV were followed in the Deliver Health Study during October 2019-December 2020. We used difference-in-differences (DiD) to estimate the effect of changing COVID-19 alert levels during 3 distinct periods on self-reported missed ART doses (missed 0 vs. ≥1 doses in past week) for participants receiving home-delivered vs. clinic-based refills. We additionally estimated the effect of changing COVID-19 alert levels on late clinic ART refill visits (late vs. on-time). We used relative risk regression for both binary outcomes. RESULTS: Of 155 participants, 46% were women and the median age was 36 years. The mean number of missed weekly doses was 0.11, 0, and 0.12 in the home-delivery group and 0.09, 0.08, and 0.18 in the clinic group during periods 1, 2, and 3, respectively. There were no differences in relative risk of self-reported daily ART use between refill groups when comparing across periods [DiDperiod 2 vs. 1 = 1.05; 95% confidence interval: 0.97, 1.13 and DiDperiod 3 vs. 2 = 0.99; 95% confidence interval (CI): 0.91, 1.08]. In the clinic group, the risk of late refill visits was significantly higher during COVID-19 restrictions (vs. before alert level 5 implementation) and even after the COVID-19 alert level was downgraded to level 1 (RRperiod 2 vs. 1 = 1.83, 95% CI: 1.34, 2.51 and RRperiod 3 vs. 2 = 1.71; 95% CI: 1.43, 2.04). CONCLUSION: The COVID-19 pandemic did not differentially impact self-reported ART adherence by the method of ART refills, but the risk of late clinic refill visits was significantly higher during COVID-19 restrictions and sustained after restrictions were loosened.

Prenatal exposure to polycyclic aromatic hydrocarbons and executive functions at school age: Results from a combined cohort study.

BACKGROUND: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited. METHODS: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture. RESULTS: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident. CONCLUSION: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.

Magnetoencephalography for the pediatric population, indications, acquisition and interpretation for the clinician.

Magnetoencephalography (MEG) is an imaging technique that enables the assessment of cortical activity via direct measures of neurophysiology. It is a non-invasive and passive technique that is completely painless. MEG has gained increasing prominence in the field of pediatric neuroimaging. This dedicated review article for the pediatric population summarizes the fundamental technical and clinical aspects of MEG for the clinician. We discuss methods tailored for children to improve data quality, including child-friendly MEG facility environments and strategies to mitigate motion artifacts. We provide an in-depth overview on accurate localization of neural sources and different analysis methods, as well as data interpretation. The contemporary platforms and approaches of two quaternary pediatric referral centers are illustrated, shedding light on practical implementations in clinical settings. Finally, we describe the expanding clinical applications of MEG, including its pivotal role in presurgical evaluation of epilepsy patients, presurgical mapping of eloquent cortices (somatosensory and motor cortices, visual and auditory cortices, lateralization of language), its emerging relevance in autism spectrum disorder research and potential future clinical applications, and its utility in assessing mild traumatic brain injury. In conclusion, this review serves as a comprehensive resource of clinicians as well as researchers, offering insights into the evolving landscape of pediatric MEG. It discusses the importance of technical advancements, data acquisition strategies, and expanding clinical applications in harnessing the full potential of MEG to study neurological conditions in the pediatric population.

Tuning energetic properties through co-crystallisation - a high-pressure experimental and computational study of nitrotriazolone: 4,4'-bipyridine.

We report the preparation of a co-crystal formed between the energetic molecule 3-nitro-1,2,4-triazol-5-one (NTO) and 4,4'-bipyridine (BIPY), that has been structurally characterised by high-pressure single crystal and neutron powder diffraction data up to 5.93 GPa. No phase transitions or proton transfer were observed up to this pressure. At higher pressures the crystal quality degraded and the X-ray diffraction patterns showed severe twinning, with the appearance of multiple crystalline domains. Computational modelling indicates that the colour changes observed on application of pressure can be attributed to compression of the unit cell that cause heightened band dispersion and band gap narrowing that coincides with a shortening of the BIPY π⋯π stacking distance. Modelling also suggests that the application of pressure induces proton migration along an N-H⋯N intermolecular hydrogen bond. Impact-sensitivity measurements show that the co-crystal is less sensitive to initiation than NTO, whereas computational modelling suggests that the impact sensitivities of NTO and the co-crystal are broadly similar.

Lower Associated Risk of Revision with All-Polyethylene Tibial Components in Total Knee Arthroplasty: An Analysis of the American Joint Replacement Registry.

BACKGROUND: Despite the potential advantage of all-polyethylene tibial components, modular metal-backed component use predominates the market in the United States for total knee arthroplasty (TKA). This is partially driven by concerns about the associated revision risk due to the lack of modularity with all-polyethylene components. This study utilized the American Joint Replacement Registry (AJRR) to compare the associated risk of all-cause revision and revision for infection for all-polyethylene versus modular metal-backed tibial components. METHODS: An analysis of primary TKA cases in patients aged 65 years and older was performed with AJRR data linked to Centers for Medicare and Medicaid Services data from 2012 to 2019. Analyses compared all-polyethylene to modular metal-backed tibial components. We identified 485,024 primary TKA cases, consisting of 479,465 (98.9%) metal-backed and 5,559 (1.1%) all-polyethylene. Cox proportional hazard regression analyses created hazard ratios (HRs) to evaluate the association of design and the risk of all-cause revision while adjusting for sex, age and the competing risk of mortality. Event-free survival curves evaluate time to revision. RESULTS: The all-polyethylene tibia group demonstrated a decreased risk for all-cause revision (HR = 0.37, 95% CI [confidence interval]: 0.24 to 0.55, P < 0.0001) and revision for infection (HR = 0.41, 95% CI: 0.22 to 0.77, P < 0.0001). Event-free survival curves demonstrated a decreased risk of all-cause revision that persisted across time points until 8 years post-TKA. CONCLUSION: In the United States, all-polyethylene tibial component use for TKA remains low compared to modular metal-backed designs. A decreased associated risk for revision should ease concerns about the use of all-polyethylene components in patients aged 65 years or older, and future investigations should investigate the potential cost and value savings associated with expanded use in this population.

DNA Delivery by Virus-Like Nanocarriers in Plant Cells.

Tobacco mild green mosaic virus (TMGMV)-like nanocarriers were designed for gene delivery to plant cells. High aspect ratio TMGMVs were coated with a polycationic biopolymer, poly(allylamine) hydrochloride (PAH), to generate highly charged nanomaterials (TMGMV-PAH; 56.20 ± 4.7 mV) that efficiently load (1:6 TMGMV:DNA mass ratio) and deliver single-stranded and plasmid DNA to plant cells. The TMGMV-PAH were taken up through energy-independent mechanisms in Arabidopsis protoplasts. TMGMV-PAH delivered a plasmid DNA encoding a green fluorescent protein (GFP) to the protoplast nucleus (70% viability), as evidenced by GFP expression using confocal microscopy and Western blot analysis. TMGMV-PAH were inactivated (iTMGMV-PAH) using UV cross-linking to prevent systemic infection in intact plants. Inactivated iTMGMV-PAH-mediated pDNA delivery and gene expression of GFP in vivo was determined using confocal microscopy and RT-qPCR. Virus-like nanocarrier-mediated gene delivery can act as a facile and biocompatible tool for advancing genetic engineering in plants.

Crystal Growth of Quaternary AkRE2Si2S8 (Ak = Ca and Sr; RE = La-Tb) Thiosilicates Using Flux-Assisted Boron Chalcogen Mixture Method: Exploring X-ray Scintillation, Luminescence, and Magnetic Properties.

We report on the detailed structural analysis of a series of 11 new quaternary rare earths containing thiosilicates, AkRE2Si2S8 (Ak = Ca and Sr; RE = La, Ce, Pr, Nd, Sm, Gd, and Tb), synthesized using the flux-assisted boron chalcogen mixture method. High quality crystals were grown and used to determine their crystal structures by single crystal X-ray diffraction. All members of the AkRE2Si2S8 series crystallize in the trigonal crystal system with space group R3̅c (space group no. 167). Polycrystalline powders were used for physical property measurements, including magnetic susceptibility, diffuse reflectance in the UV-visible range, and scintillation. Magnetic measurements indicated that CaRE2Si2S8 (RE = Nd and Tb) exhibits paramagnetic behavior with a slightly negative Weiss constant. The band gaps of the materials were determined from diffuse reflectance data, and optical band gaps were estimated to be 2.5(1) and 2.9(1) eV for CaCe2Si2S8 and CaGd2Si2S8, respectively. CaCe2Si2S8, CaTb2Si2S8, and SrCe2Si2S8 exhibited intense green luminescence upon irradiation with 375 nm ultraviolet light and, furthermore, scintillated when exposed to X-rays. Radioluminescence measurements of CaCe2Si2S8 powder revealed green emission with an intensity approximately 14% of that emitted by bismuth germanium oxide powder.

Air Pollution Exposures and Child Executive Function: A U.S. Multi-Cohort Study.

BACKGROUND: Executive function, which develops rapidly in childhood, enables problem solving, focused attention, and planning. Animal models describe executive function decrements associated with ambient air pollution exposure, but epidemiologic studies are limited. METHODS: We examined associations between early childhood air pollution exposure and school-aged executive function in 1,235 children from three U.S. pregnancy cohorts in the ECHO-PATHWAYS Consortium. We derived point-based residential exposures to ambient particulate matter ≤2.5µm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2), and ozone (O3) at ages 0-4 years from spatiotemporal models with a 2-week resolution. We assessed executive function across three domains -- cognitive flexibility, working memory, and inhibitory control -- using performance-based measures and calculated a composite score quantifying overall performance. We fitted linear regressions to assess air pollution - child executive function associations, adjusting for sociodemographic characteristics, maternal mental health, and health behaviors, and examined modification by child sex, maternal education, and neighborhood educational opportunity. RESULTS: In the overall sample, we found hypothesized inverse associations in crude but not adjusted models. Modified associations between NO2 exposure and working memory by neighborhood education opportunity were present (P interaction = 0.05), with inverse associations more pronounced in the "High" and "Very high" categories. Associations of interest did not differ by child sex or maternal education. CONCLUSIONS: This work contributes to the evolving science regarding early-life environmental exposures and child development. There remains a need for continued exploration in future research endeavors, to elucidate the complex interplay between natural environment and social determinants influencing child neurodevelopment.

Impact and determinants of door in-door out time for stroke thrombectomy transfers in a large hub-and-spoke network.

INTRODUCTION: The mantra "time is brain" cannot be overstated for patients suffering from acute ischemic stroke. This is especially true for those with large vessel occlusions (LVOs) requiring transfer to an endovascular thrombectomy (EVT) capable center. We sought to evaluate the spoke hospital door in-door out (DIDO) times for patients transferred to our hub center for EVT. METHODS: Individuals who first presented with LVO to a spoke hospital and were then transferred to the hub for EVT were retrospectively identified from a prospectively maintained database from January 2019 to November 2022. DIDO was defined as the time between spoke hospital door in arrival and door out exit. Baseline characteristics, treatments, and outcomes were compared, dichotomizing DIDO at 90 minutes based in the American Heart Association goal for DIDO ≤90 minutes for 50% of transfers. Multivariable regression analyses were performed for determinants of the 90-day ordinal modified Rankin Scale (mRS) and DIDO. RESULTS: We identified 194 patients transferred for EVT with available DIDO. The median age was 67 years (IQR 57-80), and 46% were female. The median National Institutes of Health Stroke Scale (NIHSS) was 16 (10-20), 50% were treated with intravenous thrombolysis at a spoke, and TICI 2B-3 reperfusion was achieved in 87% at the hub. The median DIDO was 120 minutes (97-149), with DIDO ≤90 minutes achieved in 18%. DIDO was a significant determinant of 90-day ordinal mRS (B = 0.007, 95% CI = 0.001-0.012, p = 0.013), even when accounting for the last known well-to-spoke door in, spoke door out-to-hub arrival, hub arrival-to-puncture, puncture-to-first pass, age, NIHSS, intravenous thrombolysis, TICI 2B-3, and symptomatic intracranial hemorrhage. Importantly, determinants of DIDO included Black race or Hispanic ethnicity (B = 0.918, 95% CI = 0.010-1.826, p = 0.048), atrial fibrillation or heart failure (B = 0.793, 95% CI = 0.257-1.329, p = 0.004), and basilar LVO location (B = 2.528, 95% CI = 1.154-3.901, p < 0.001). CONCLUSION: Spoke DIDO was the most important period of time for long-term outcomes of LVO stroke patients treated with EVT. Targets were identified to reduce DIDO and improve patient outcomes.