How and why do species break a developmental trade-off? Elucidating the association of trichomes and stomata across species.

PREMISE: Previous studies have suggested a trade-off between trichome density (Dt) and stomatal density (Ds) due to shared cell precursors. We clarified how, when, and why this developmental trade-off may be overcome across species. METHODS: We derived equations to determine the developmental basis for Dt and Ds in trichome and stomatal indices (it and is) and the sizes of epidermal pavement cells (e), trichome bases (t), and stomata (s) and quantified the importance of these determinants of Dt and Ds for 78 California species. We compiled 17 previous studies of Dt-Ds relationships to determine the commonness of Dt-Ds associations. We modeled the consequences of different Dt-Ds associations for plant carbon balance. RESULTS: Our analyses showed that higher Dt was determined by higher it and lower e, and higher Ds by higher is and lower e. Across California species, positive Dt-Ds coordination arose due to it-is coordination and impacts of the variation in e. A Dt-Ds trade-off was found in only 30% of studies. Heuristic modeling showed that species sets would have the highest carbon balance with a positive or negative relationship or decoupling of Dt and Ds, depending on environmental conditions. CONCLUSIONS: Shared precursor cells of trichomes and stomata do not limit higher numbers of both cell types or drive a general Dt-Ds trade-off across species. This developmental flexibility across diverse species enables different Dt-Ds associations according to environmental pressures. Developmental trait analysis can clarify how contrasting trait associations would arise within and across species.

The partnership between statisticians and the Institutional Animal Care and Use Committee (IACUC).

In this tutorial we explore the valuable partnership between statisticians and Institutional Animal Care and Use Committees (IACUCs) in the context of animal research, shedding light on the critical role statisticians play in ensuring the ethical and scientifically rigorous use of animals in research. Pharmaceutical statisticians have increasingly become vital members of these committees, contributing expertise in study design, data analysis, and interpretation, and working more generally to facilitate the integration of good statistical practices into experimental procedures. We review the "3Rs" principles (Replacement, Reduction, and Refinement) which are the foundation for the humane use of animals in scientific research, and how statisticians can partner with IACUC to help ensure robust and reproducible research while adhering to the 3Rs principles. We also highlight emerging areas of interest, such as the use of virtual control groups.

Similar Survival Among All Subtypes of Mucinous Appendiceal Adenocarcinoma Except the Intermediate Subtype, Which Shows an Improved Survival.

BACKGROUND: Limited success in the management of mucinous appendiceal adenocarcinoma (MACA) has been reported. METHODS: Cytoreductive surgery with perioperative intraperitoneal chemotherapy was used to treat a cohort of patients with peritoneal dissemination of MACA. The clinical and histopathologic variables were assessed for their impact on overall survival. RESULTS: The study analyzed 196 patients during a median follow-up period of 8 years. The patients had a median age was 46 years, a median survival of 12 years, and a mean survival of 12.4 years. Preoperative systemic chemotherapy and a high prior surgical score had a negative impact on prognosis. Survival was better for 37 patients (18.9%) with mucinous appendiceal adenocarcinoma-Intermediate (MACA-Int) histology than for 159 patients (81.1%) with MACA grade 1, 2, or 3, or signet ring cells (S) (p = 0.0004). Although MACA-1 and MACA-2 versus MACA-3 and MACA-S had a difference in survival of 63.9 versus 43.2 years at 5 years, with long-term follow-up evaluation, the differences in survival became insignificant (p = 0.5841). CONCLUSION: The histologic subtype of MACA-Int had a 10-year survival of 81.1%, which was markedly superior to that of MACA-1, -2, -3, or -S (32.7%). With long-term follow-up evaluation, MACA-1, -2, -3, and -S did not differ significantly in survival.

Cerebral vasospasm following arteriovenous malformation rupture: a population-based cross-sectional study.

OBJECTIVE: Studies examining the risk factors and clinical outcomes of arterial vasospasm secondary to cerebral arteriovenous malformation (cAVM) rupture are scarce in the literature. The authors used a population-based national registry to investigate this largely unexamined clinical entity. METHODS: Admissions for adult patients with cAVM ruptures were identified in the National Inpatient Sample during the period from 2015 to 2019. Complex samples multivariable logistic regression and chi-square automatic interaction detection (CHAID) decision tree analyses were performed to identify significant associations between clinical covariates and the development of vasospasm, and a cAVM-vasospasm predictive model (cAVM-VPM) was generated based on the effect sizes of these parameters. RESULTS: Among 7215 cAVM patients identified, 935 developed vasospasm, corresponding to an incidence rate of 13.0%; 110 of these patients (11.8%) subsequently progressed to delayed cerebral ischemia (DCI). Multivariable adjusted modeling identified the following baseline clinical covariates: decreasing age by decade (adjusted odds ratio [aOR] 0.87, 95% CI 0.83-0.92; p < 0.001), female sex (aOR 1.68, 95% CI 1.45-1.95; p < 0.001), admission Glasgow Coma Scale score < 9 (aOR 1.34, 95% CI 1.01-1.79; p = 0.045), intraventricular hemorrhage (aOR 1.87, 95% CI 1.17-2.98; p = 0.009), hypertension (aOR 1.77, 95% CI 1.50-2.08; p < 0.001), obesity (aOR 0.68, 95% CI 0.55-0.84; p < 0.001), congestive heart failure (aOR 1.34, 95% CI 1.01-1.78; p = 0.043), tobacco smoking (aOR 1.48, 95% CI 1.23-1.78; p < 0.019), and hospitalization events (leukocytosis [aOR 1.64, 95% CI 1.32-2.04; p < 0.001], hyponatremia [aOR 1.66, 95% CI 1.39-1.98; p < 0.001], and acute hypotension [aOR 1.67, 95% CI 1.31-2.11; p < 0.001]) independently associated with the development of vasospasm. Intraparenchymal and subarachnoid hemorrhage were not associated with the development of vasospasm following multivariable adjustment. Among significant associations, a CHAID decision tree algorithm identified age 50-59 years (parent node), hyponatremia, and leukocytosis as important determinants of vasospasm development. The cAVM-VPM achieved an area under the curve of 0.65 (sensitivity 0.70, specificity 0.53). Progression to DCI, but not vasospasm alone, was independently associated with in-hospital mortality (aOR 2.35, 95% CI 1.29-4.31; p = 0.016) and lower likelihood of routine discharge (aOR 0.62, 95% CI 0.41-0.96; p = 0.031). CONCLUSIONS: This large-scale assessment of vasospasm in cAVM identifies common clinical risk factors and establishes progression to DCI as a predictor of poor neurological outcomes.

Portable stroke detection devices: a systematic scoping review of prehospital applications.

BACKGROUND: The worldwide burden of stroke remains high, with increasing time-to-treatment correlated with worse outcomes. Yet stroke subtype determination, most importantly between stroke/non-stroke and ischemic/hemorrhagic stroke, is not confirmed until hospital CT diagnosis, resulting in suboptimal prehospital triage and delayed treatment. In this study, we survey portable, non-invasive diagnostic technologies that could streamline triage by making this initial determination of stroke type, thereby reducing time-to-treatment. METHODS: Following PRISMA guidelines, we performed a scoping review of portable stroke diagnostic devices. The search was executed in PubMed and Scopus, and all studies testing technology for the detection of stroke or intracranial hemorrhage were eligible for inclusion. Extracted data included type of technology, location, feasibility, time to results, and diagnostic accuracy. RESULTS: After a screening of 296 studies, 16 papers were selected for inclusion. Studied devices utilized various types of diagnostic technology, including near-infrared spectroscopy (6), ultrasound (4), electroencephalography (4), microwave technology (1), and volumetric impedance spectroscopy (1). Three devices were tested prior to hospital arrival, 6 were tested in the emergency department, and 7 were tested in unspecified hospital settings. Median measurement time was 3 minutes (IQR: 3 minutes to 5.6 minutes). Several technologies showed high diagnostic accuracy in severe stroke and intracranial hematoma detection. CONCLUSION: Numerous emerging portable technologies have been reported to detect and stratify stroke to potentially improve prehospital triage. However, the majority of these current technologies are still in development and utilize a variety of accuracy metrics, making inter-technology comparisons difficult. Standardizing evaluation of diagnostic accuracy may be helpful in further optimizing portable stroke detection technology for clinical use.

Time to Evacuation and Functional Outcome After Minimally Invasive Endoscopic Intracerebral Hemorrhage Evacuation.

BACKGROUND AND PURPOSE: We present a retrospective analysis of patients who underwent minimally invasive endoscopic intracerebral hemorrhage (ICH) evacuation to identify variables that were associated with long-term outcome. METHODS: Minimally invasive endoscopic ICH evacuation was performed on patients with supratentorial ICH who fit prespecified clinical inclusion and exclusion criteria. Demographic, clinical, and radiographic factors previously demonstrated to impact functional outcome in ICH were included in a univariate analysis to identify factors associated with favorable outcome (modified Rankin Scale score, 0-3) at 6 months. Factors associated with a favorable outcome in the univariate analysis (P≤0.20) were included in a multivariate logistic regression analysis with the same dependent variable. RESULTS: Ninety patients underwent MIS endoscopic ICH evacuation within 72 hours of ictus. In a multivariate analysis, factors associated with good long-term functional outcome included time to evacuation (per hour; OR, 0.95 [95% CI, 0.92-0.98], P=0.004), age (per decade, odds ratio [OR], 0.49 [95% CI, 0.28-0.77], P=0.005), presence of intraventricular hemorrhage (OR, 0.15 [95% CI, 0.04-0.47], P=0.002), and lobar location (OR, 18.5 [95% CI, 4.5-103], P=0.0005). Early evacuation was not associated with an increased risk of rebleeding. CONCLUSIONS: Young age, lack of intraventricular hemorrhage, lobar location, and time to evacuation were independently associated with good long-term functional outcome in patients undergoing minimally invasive endoscopic ICH evacuation. The OR for time to evacuation suggests that for each additional hour, there was a 5% reduction in the odds of achieving a favorable outcome.

Ultra-Early Venous Thromboembolism (VTE) Prophylaxis in Spontaneous Intracerebral Hemorrhage (sICH).

OBJECTIVE: To determine if ultra-early (<24 h) venous thromboembolism (VTE) prophylaxis was associated with hematoma growth in spontaneous intracerebral hemorrhage (ICH). BACKGROUND: Patients with ICH have a high risk of VTE. Pharmacological prophylaxis such as unfractionated heparin (UFH) have been demonstrated to reduce VTE. However, published datasets exclude patients with recent ICH out of concern for hematoma enlargement. American Heart/Stroke Association guidelines recommend UFH 1-4 days after hematoma stabilization while the European Stroke Organization has no recommendations on when to begin UFH. Our institutional practice is to obtain stability CT scans at 6 to 24 h and to begin UFH following documented clinical and radiologic stability. We examined the impact of this practice on hematoma expansion. METHODS: We performed a retrospective cohort analysis of consecutive ICH patients treated at a single tertiary academic referral center in the US. Demographic and clinical characteristics were abstracted. ICH volume was measured via 3D volumetrics for a CT head done on admission, follow-up stability, and prior to discharge. The primary outcome was analyzed as ≥3 mL hematoma enlargement. Secondary outcomes include hematoma expansion of ≥6mL and ≥ 33%, length of stay (LOS), discharge disposition and mortality. RESULTS: A total of 163 ICH patients were analyzed. There were 58 (35.6%) patients in the ultra-early UFH group and UFH was initiated on average at 13.8 h from initial scan. There were 105 (64.6%) patients in the standard group who initiated UFH at an average of 46.6 h. The primary outcome of hematoma enlargement ≥3 mL was observed in 2/58(3.4%) patients with ultra-early initiation of UFH and in 7/105(6.7%) in the standard group (p=0.49). Secondary outcomes were not significant including hematoma expansion in the ultra-early group ≥ 6 mL 3/58 (5.2%) and ≥33% 7/58 (12.1%) (p=0.91, 0.61, respectively) as well as mortality or LOS. CONCLUSION: Venous thromboembolism prophylaxis started ultra-early (≤24 h) after ICH was not associated with hematoma expansion.

COVID-19 and Decompressive Hemicraniectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Young patients with malignant cerebral edema have been shown to benefit from early decompressive hemicraniectomy. The impact of concomitant infection with coronavirus disease 2019 (COVID-19) and how this should weigh in on the decision for surgery is unclear. METHODS: We retrospectively reviewed all COVID-19-positive patients admitted to the neuroscience intensive care unit for malignant edema monitoring. Patients with >50% of middle cerebral artery involvement on computed tomography imaging were considered at risk for malignant edema. RESULTS: Seven patients were admitted for monitoring of whom 4 died. Cause of death was related to COVID-19 complications, and these were either seen both very early and several days into the intensive care unit course after the typical window of malignant cerebral swelling. Three cases underwent surgery, and 1 patient died postoperatively from cardiac failure. A good outcome was attained in the other 2 cases. CONCLUSIONS: COVID-19-positive patients with large hemispheric stroke can have a good outcome with decompressive hemicraniectomy. A positive test for COVID-19 should not be used in isolation to exclude patients from a potentially lifesaving procedure.

Use of direct-acting antivirals for hepatitis C viral infection and association with intrahepatic cholangiocarcinoma: Is there a linkage?

Hepatitis C viral infection is recognized worldwide as a leading cause of cirrhosis and hepatocellular carcinoma. The goal of hepatitis C viral antiviral therapy is the permanent eradication of hepatitis C viral RNA, commonly referred to as a sustained virologic response - defined as "undetectable" RNA at 12 weeks following the completion of therapy. Hepatitis C viral treatment has dramatically advanced with the FDA approval of several new agents known as direct-acting antivirals. These drugs target specific nonstructural proteins of the virus, which disrupt viral replication, and therefore halt infection. However, recently, there has been a concern for increased risk of recurrence of treated hepatocellular carcinoma or denovo occurrence of hepatocellular carcinoma after treatment with direct-acting antivirals. We are now reporting three cases of intrahepatic cholangiocarcinoma that developed after sustained virologic response following hepatitis C viral treatment with direct-acting antivirals.

Impact of Aura and Status Migrainosus on Readmissions for Vascular Events After Migraine Admission.

OBJECTIVE: -To estimate readmission rates for acute ischemic stroke (AIS), transient ischemic attack (TIA), subarachnoid hemorrhage, and intracerebral hemorrhage after an index admission for migraine, using nationally representative data. METHODS: -The Nationwide Readmissions Database was designed to analyze readmissions for all payers and uninsured, with data on >14 million US admissions in 2013. We used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify index migraine admissions with and without aura or status migrainosus, and readmissions for cerebrovascular events. Cox proportional hazards regression was performed for each outcome with aura and status migrainosus as main predictors, adjusting for age and vascular risk factors. RESULTS: -Out of 12,448 index admissions for migraine, 9972 (80.1%) were women, mean age was 45.5 ± 14.8 years, aura was present in 3038 (24.41%), and status migrainosus in 1798 (14.44%). The 30-day readmission rate (per 100,000 index admissions) was 154 for ischemic stroke, 86 for TIA, 42 for subarachnoid hemorrhage, and 17 for intracranial hemorrhage. In unadjusted models, aura was significantly associated with TIA (hazard ratio 2.43, 95% CI 1.39-4.24), but not AIS (1.26, 0.73-2.18), intracranial hemorrhage (1.86, 0.45-7.79) or subarachnoid hemorrhage (1.85, 0.44-7.75). When adjusting for age and vascular risk factors, aura remained significantly associated with TIA (2.13, 1.22-3.74). Status, in adjusted models, was significantly associated with subarachnoid hemorrhage readmission (4.83, 1.09-21.42). CONCLUSIONS: -In this large, nationally representative retrospective cohort study, migraine admission with aura was independently associated with TIA readmission, and status migrainosus was independently associated with subarachnoid hemorrhage. Further research would clarify the role of misdiagnosis and causal relationships underlying these strong associations.

Preventable Readmissions and Predictors of Readmission After Subarachnoid Hemorrhage.

OBJECTIVE: To estimate rates of all-cause and potentially preventable readmissions up to 90 days after discharge for aneurysmal subarachnoid hemorrhage (SAH) and medical comorbidities associated with readmissions BACKGROUND: Readmission rate is a common metric linked to compensation and used as a proxy to quality of care. Prior studies in SAH have reported 30-day readmission rates of 7-17% with a higher readmission risk among those with the higher SAH severity, ≥ 3 comorbidities, and non-home discharge. Intermediate-term rates, up to 90-days, and the proportion of these readmissions that are potentially preventable are unknown. Furthermore, the specific medical comorbidities associated with readmissions are unknown. METHODS: Index SAH admissions were identified from the 2013 Nationwide Readmissions Database. All-cause readmissions were defined as any readmission during the 30-, 60-, and 90-day post-discharge period. Potentially preventable readmissions were identified using Prevention Quality Indicators developed by the US Agency for Healthcare Research and Quality. Unadjusted and adjusted Poisson models were used to identify factors associated with increased readmission rates. RESULTS: Out of 9987 index admissions for SAH, 7949 (79%) survived to discharge. The percentage of 30-, 60-, and 90-day all-cause readmissions were 7.8, 16.6, and 26%, respectively. Up to 14% of readmissions in the first 30 days were considered potentially preventable and acute conditions (dehydration, bacterial pneumonia, and urinary tract infections) accounted for over half, whereas acute cerebrovascular disease was the most common cause for neurological return. In multivariable analysis, significant predictors of a higher readmission rate included diabetes (rate ratio [RR] 1.09, 95% confidence interval [CI] 1.03-1.15), congestive heart failure (RR 1.09, 1.003-1.18), and renal impairment (RR 1.35, 1.13-1.61). Only discharge home was associated with a lower readmission rate (RR 0.89, 0.85-0.93). CONCLUSIONS: SAH has a 30-day readmission rate of 7.8% which continues to rise into the intermediate-term. A low but constant proportion of readmissions are potentially preventable. Several chronic medical comorbidities were associated with readmissions. Prospective studies are warranted to clarify causal relationships.

Sex Differences in Outcomes after Stroke in Patients with Diabetes in Ontario, Canada.

BACKGROUND: Outcomes after stroke in those with diabetes are not well characterized, especially by sex and age. We sought to calculate the sex- and age-specific risk of cardiovascular outcomes after ischemic stroke among those with diabetes. METHODS: Using population-based demographic and administrative health-care databases in Ontario, Canada, all patients with diabetes hospitalized with index ischemic stroke between April 1, 2002, and March 31, 2012, were followed for death, stroke, and myocardial infarction (MI). The Kaplan-Meier survival analysis and Fine-Gray competing risk models estimated hazards of outcomes by sex and age, unadjusted and adjusted for demographics and vascular risk factors. RESULTS: Among 25,495 diabetic patients with index ischemic stroke, the incidence of death was higher in women than in men (14.08 per 100 person-years [95% confidence interval [CI], 13.73-14.44] versus 11.89 [11.60-12.19]) but was lower after adjustment for age and other risk factors (adjusted hazard ratio [HR], .95 [.92-.99]). Recurrent stroke incidence was similar by sex, but men were more likely to be readmitted for MI (1.99 per 100 person-years [1.89-2.10] versus 1.58 [1.49-1.68] among females). In multivariable models, females had a lower risk of readmission for any event (HR, .96 [95% CI, .93-.99]). CONCLUSIONS: In this large, population-based, retrospective study among diabetic patients with index stroke, women had a higher unadjusted death rate but lower unadjusted incidence of MI. In adjusted models, females had a lower death rate compared with males, although the increased risk of MI among males persisted. These findings confirm and quantify sex differences in outcomes after stroke in patients with diabetes.

Mobile Interventional Stroke Teams Lead to Faster Treatment Times for Thrombectomy in Large Vessel Occlusion.

BACKGROUND AND PURPOSE: Endovascular recanalization treatment for acute ischemic stroke is a complex, time-sensitive intervention. Trip-and-treat is an interhospital service delivery model that has not previously been evaluated in the literature and consists of a shared mobile interventional stroke team that travels to primary stroke centers to provide on-site interventional capability. We compared treatment times between the trip-and-treat model and the traditional drip-and-ship model. METHODS: We performed a retrospective analysis on 86 consecutive eligible patients with acute ischemic stroke secondary to large vessel occlusion who received endovascular treatment at 4 hospitals in Manhattan. Patients were divided into 2 cohorts: trip-and-treat (n=39) and drip-and-ship (n=47). The primary outcome was initial door-to-puncture time, defined as the time between arrival at any hospital and arterial puncture. We also recorded and analyzed the times of last known well, IV-tPA (intravenous tissue-type plasminogen activator) administration, transfer, and reperfusion. RESULTS: Mean initial door-to-puncture time was 143 minutes for trip-and-treat and 222 minutes for drip-and-ship (P<0.0001). Although there was a trend in longer puncture-to-recanalization times for trip-and-treat (P=0.0887), initial door-to-recanalization was nonetheless 79 minutes faster for trip-and-treat (P<0.0001). There was a trend in improved admission-to-discharge change in National Institutes of Health Stroke Scale for trip-and-treat compared with drip-and-ship (P=0.0704). CONCLUSIONS: Compared with drip-and-ship, the trip-and-treat model demonstrated shorter treatment times for endovascular therapy in our series. The trip-and-treat model offers a valid alternative to current interhospital stroke transfers in urban environments.

Quality of life independently predicts long-term mortality but not vascular events: the Northern Manhattan Study.

PURPOSE: Cardiovascular disease is a major contributor to morbidity and mortality, and prevention relies on accurate identification of those at risk. Studies of the association between quality of life (QOL) and mortality and vascular events incompletely accounted for depression, cognitive status, social support, and functional status, all of which have an impact on vascular outcomes. We hypothesized that baseline QOL is independently associated with long-term mortality in a large, multi-ethnic urban cohort. METHODS: In the prospective, population-based Northern Manhattan Study, Spitzer QOL index (SQI, range 0-10, with ten signifying the highest QOL) was assessed at baseline. Participants were followed over a median 11 years for stroke, myocardial infarction (MI), and vascular and non-vascular death. Multivariable Cox proportional hazards regression estimated hazard ratio and 95% confidence interval (HR, 95% CI) for each outcome, with SQI as the main predictor, dichotomized at 10, adjusting for baseline demographics, vascular risk factors, history of cancer, social support, cognitive status, depression, and functional status. RESULTS: Among 3298 participants, mean age was 69.7 + 10.3 years; 1795 (54.5%) had SQI of 10. In fully adjusted models, SQI of 10 (compared to SQI <10) was associated with reduced risk of all-cause mortality (HR 0.80, 95% CI 0.72-0.90), vascular death (0.81, 0.69-0.97), non-vascular death (0.78, 0.67-0.91), and stroke or MI or death (0.82, 0.74-0.91). In fully adjusted competing risk models, there was no association with stroke (0.93, 0.74-1.17), MI (0.98, 0.75-1.28), and stroke or MI (1.03, 0.86-1.24). Results were consistent when SQI was analyzed continuously. CONCLUSION: In this large population-based cohort, highest QOL was inversely associated with long-term mortality, vascular and non-vascular, independently of baseline primary vascular risk factors, social support, cognition, depression, and functional status. QOL was not associated with non-fatal vascular events.

Utility of Carotid Ultrasonography in Management of an Atypical High Vascular-Risk Patient with Recurrent Calcified Cerebral Embolic Stroke.

OBJECTIVE: To describe a case of recurrent calcified cerebral emboli (CCE)-related acute ischemic stroke (AIS) and the diagnostic utility of plaque morphology characterization on carotid ultrasound. BACKGROUND: CCE are a rare cause of AIS. CCE-related AIS has been previously reported only in high vascular-risk patients such as those with severe carotid stenosis, widespread atheromatous disease, or cardiac valvular disease. CCE-related AIS from a carotid origin has not been reported in patients without carotid stenosis. CASE: A 69-year-old man with no known medical history presented with hemiparesis and aphasia was found to have a curvilinear calcification in the left sylvian fissure on brain imaging, consistent with CCE. Two months later, he developed a second episode of CCE-related AIS. Standard workup, as well as advanced imaging with digital subtraction angiography, revealed no carotid stenosis or valvular disease. Carotid ultrasound demonstrated normal flow velocities but a left carotid heterogeneous plaque with multiple ulcerative craters and lucencies, suggestive of an active thromboembolic source. CONCLUSION: To our knowledge, this is the first case reporting CCE-AIS from carotid origin in a patient with no carotid stenosis. Carotid ultrasound serves a diagnostic role in these patients.

More Time Is Taken to Administer Tissue Plasminogen Activator in Ischemic Stroke Patients with Earlier Presentations.

BACKGROUND: In ischemic stroke, administration of tissue plasminogen activator (tPA) within 4.5 hours from the time last known well (LKW) improves outcomes, with better outcomes seen with earlier administration. However, for patients presenting early, a perception of significant remaining time within this window may lead to delayed tPA administration. We hypothesized that cases with a shorter LKW-to-stroke team activation (code) time will have a longer "code-to-tPA" administration time. METHODS: In the Mount Sinai Hospital Stroke Registry (2009-2015), 122 patients received tPA. The patients were divided by "LKW-to-code" time into 3 groups: 0-59 minutes (n = 38), 60-119 minutes (n = 49), and 120 minutes or more (n = 35). The code-to-tPA time was compared among these groups, adjusting for age, sex, National Institutes of Health Stroke Scale (NIHSS) score, and race-ethnicity. RESULTS: The average code-to-tPA time was 80 minutes in the 0-59 minutes group, 67 minutes in the 60-119 minutes group, and 52 minutes in the 120 minutes or more group (analysis of variance P < .0001). There was an average 28-minute difference (P = .021) between the 0-59 and 120 minutes or more groups. CONCLUSION: There was a significant negative correlation between the LKW-to-code time and the code-to-tPA time that was independent of age, sex, NIHSS score, and race-ethnicity.