Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials.

PURPOSE: We aimed to perform a systematic review and meta-analysis addressing the efficacy of levothyroxine therapy in pregnant women with subclinical hypothyroidism considering most recent evidence and subgroups of interest for clinical practice. METHODS: PubMed, Embase, and Cochrane Central were searched from inception for randomized controlled trials (RCTs) comparing levothyroxine with placebo or no intervention in pregnant women with subclinical hypothyroidism. We used a random-effects model and conducted subgroup analyses based on thyroid peroxidase antibody status, thyroid stimulating hormone levels, fertility treatment, and recurrent miscarriage. RESULTS: We included 11 RCTs comprising 2,749 pregnant women with subclinical hypothyroidism. Patients treated with levothyroxine (1,439; 52.3%) had significantly lower risk of pregnancy loss (risk ratio 0.69; 95% confidence interval 0.52-0.91; p < 0.01; 6 studies). However, there was no significant association between levothyroxine and live birth (risk ratio 1.01; 95% confidence interval 0.99-1.03; p = 0.29; 8 studies). No statistically significant interaction was observed across subgroups (p > 0.05). CONCLUSION: Levothyroxine replacement therapy for subclinical hypothyroidism during pregnancy may decrease pregnancy loss when early prescribed. Nevertheless, further investigation is needed in patients with thyroid stimulating hormone above four milliunits per liter, especially when associated with recurrent miscarriage or infertility.

Percutaneous closure of patent ductus arteriosus versus surgical treatment in low-birth-weight preterms: a systematic review and meta-analysis.

INTRODUCTION: The optimal management of a patent ductus arteriosus in a population of preterm infants is controversial. Traditionally, when the patent ductus arteriosus does not close either with conservative treatment or in response to pharmacological therapy, the only option is surgical closure. However, transcatheter occlusion might provide a therapeutic alternative. METHODS: We searched PubMed, Embase, and Cochrane databases for non-randomised and randomised controlled trials that compared transcatheter percutaneous closure of patent ductus arteriosus with surgical ligation in low-birth-weight preterm infants (<2,500 g). A random-effects model was used for outcomes with high heterogeneity. RESULTS: We included twelve studies comprising 4,668 low-birth-weight preterm infants, of whom 966 (20.7%) were in the transcatheter percutaneous closure group, and 3,702 (79.3%) patients were included in the surgical group. All-cause mortality (OR 0.28; 95% confidence interval 0.18-0.423; p < 0.00001; I2 = 0%) and haemodynamic instability (OR 0.10; 95% confidence interval 0.05-0.21; p < 0.001; I2 = 14%) were significantly lower in the transcatheter percutaneous closure group. There was no significant difference between transcatheter and surgical patent ductus arteriosus closure for the outcomes of bronchopulmonary dysplasia (0.93; 95% confidence interval 0.46-1.87; p = 0.83; I2 = 0%) and major complications (OR 0.76; 95% confidence interval 0.34-1.69; p = 0.51; I2 = 43%). CONCLUSION: These findings suggest that transcatheter patent ductus arteriosus closure in preterm infants under 2,500 g is a safe and effective alternative to surgical treatment. There was a substantial reduction in all-cause mortality and haemodynamic instability with transcatheter intervention compared to surgical closure.

Using an artificial intelligence software improves emergency medicine physician intracranial haemorrhage detection to radiologist levels.

BACKGROUND: Tools to increase the turnaround speed and accuracy of imaging reports could positively influence ED logistics. The Caire ICH is an artificial intelligence (AI) software developed for ED physicians to recognise intracranial haemorrhages (ICHs) on non-contrast enhanced cranial CT scans to manage the clinical care of these patients in a timelier fashion. METHODS: A dataset of 532 non-contrast cranial CT scans was reviewed by five board-certified emergency physicians (EPs) with an average of 14.8 years of practice experience. The scans were labelled in random order for the presence or absence of an ICH. If an ICH was detected, the reader further labelled all subtypes present (ie, epidural, subdural, subarachnoid, intraparenchymal and/or intraventricular haemorrhage). After a washout period, the five EPs reviewed again the scans individually with the assistance of Caire ICH. The mean accuracy of the EP readings with AI assistance was compared with the mean accuracy of three general radiologists reading the films individually. The final diagnosis (ie, ground truth) was adjudicated by a consensus of the radiologists after their individual readings. RESULTS: Mean EP reader accuracy significantly increased by 6.20% (95% CI for the difference 5.10%-7.29%; p=0.0092) when using Caire ICH to detect an ICH. Mean accuracy of the EP cohort in detecting an ICH using Caire ICH was found to be more accurate than the radiologist cohort prior to discussion; this difference, however, was not statistically significant. CONCLUSION: The Caire ICH software significantly improved the accuracy and sensitivity of detecting an ICH by the EP to a level comparable to general radiologists. Further prospective research with larger numbers will be needed to understand the impact of Caire ICH on ED logistics and patient outcomes.

An analysis of racial inequities in emergency department triage among patients with stroke-like symptoms in the United States.

BACKGROUND: Racial inequities exist in treatment and outcomes in patients with acute stroke. OBJECTIVES: Our objective was to determine if racial inequities exist in the time-lapse between patient presentation and provider assessment in patients with stroke-like symptoms in Emergency Departments (ED) across the U.S. METHODS: This study is a retrospective, observational study of the National Hospital Ambulatory Medical Care Survey (NHAMCS) 2014-2018. We identified visits with stroke-like symptoms and stratified the proportion of door-to-provider (DTP) times by racial groups. We used broad and narrow definitions of stroke-like symptoms. We performed bivariate and multivariate analyses using race and clinical and demographic characteristics as covariates. RESULTS: Between 2014-2018, there were an average of 138.58 million annual ED visits. Of the total ED visits, 0.36% to 7.39% of the ED visits presented with stroke-like symptoms, and the average DTP time ranged from 39 to 49 min. The proportion of the visits with a triage level of 1 (immediate) or 2 (emergent) ranged from 16.03% to 23.27% for stroke-like symptoms. We did not find statistically significant racial inequities in DTP or ED triage level. We found significantly longer DTP times in non-Hispanic blacks (15.88 min, 95% CI: 4.29-27.48) and Hispanics (by 14.77 min, 95% CI: 3.37-26.16) than non-Hispanic whites that presented with atypical stroke-like symptoms. We observed that non-Hispanic whites were significantly more diagnosed with a stroke/TIA than other racial minority groups (p = 0.045) for atypical stroke-like symptoms. CONCLUSION: In our population-based analysis, we did not identify systemic racial inequities in the DTP times or ED triage level at ED triage for stroke-like symptoms.

Identification of successful cerebral reperfusions (mTICI ≥2b) using an artificial intelligence strategy.

BACKGROUND: The modified thrombolysis in cerebral infarction (mTICI) scale is a widely used and validated qualitative tool to evaluate angiographic intracerebral inflow following endovascular thrombectomy (EVT). We validated a machine-learning (ML) algorithm to grade digital subtraction angiograms (DSA) using the mTICI scale. MATERIALS AND METHODS: We included angiograms of identified middle cerebral artery (MCA) occlusions who underwent EVT. The complete DSA sequences were preprocessed and normalized. We created three convolutional neural networks to classify DSA into two outcomes, low- (mTICI 0,1,2a) and high-grade (mTICI 2b,2c,3). RESULTS: We included a total of 234 angiograms in this study. The area under the receiver operating characteristic was 0.863 (95% CI 0.816-0.909), 0.914 (95% CI 0.876-0.951), and 0.890 (95% CI 0.848-0.932) for the anteroposterior (AP), lateral (L), and combined models, respectively, when dichotomizing outcomes into low and high grade. The models' area under the precision-recall curve was 0.879 (95% CI 0.829-0.930), 0.906 (95% CI 0.844-0.968), and 0.887 (95% CI 0.834-0.941) for the AP, L, and combined models. CONCLUSION: In complete cerebral DSA, our angiography-based ML strategy was able to predict mTICI scores following EVT rapidly and reliably for MCA occlusions.

The sulci of the inferior surface of the temporal lobe: An anatomical study.

Understanding the anatomy of temporal lobe sulci and their variations can allow for safer neurosurgical approaches. Although the inferior temporal sulci and their relations to each other has been described by several authors, the nomenclature used has not been universal. The aim of this study was to investigate the anatomic features of the three main sulci of the inferior temporal lobe and provide a simple description of complex patterns among these sulci. Sulcal variations and their relations were examined in seventy formalin-fixed, adult cadaveric cerebral hemispheres. We recommend a simple but modified classification specifically for anatomic variations of the rhinal and collateral sulci. Furthermore, we describe the frequency of occipitotemporal sulci that contain 5 and 6 segments, not previously mentioned. The length and depth of all sulci were measured in all samples. Additionally, more detailed results regarding the patterns, courses, connections, relationships and measurements were given. Understanding of the complex anatomy of this clinically important region is of benefit to neurosurgeons, providing necessary guidance for neurosurgical approaches to the inferior surface of the temporal lobe. Clin. Anat. 29:932-942, 2016. © 2016 Wiley Periodicals, Inc.

A deep learning method to identify and localize large-vessel occlusions from cerebral digital subtraction angiography.

BACKGROUND AND PURPOSE: An essential step during endovascular thrombectomy is identifying the occluded arterial vessel on a cerebral digital subtraction angiogram (DSA). We developed an algorithm that can detect and localize the position of occlusions in cerebral DSA. METHODS: We retrospectively collected cerebral DSAs from a single institution between 2018 and 2020 from 188 patients, 86 of whom suffered occlusions of the M1 and proximal M2 segments. We trained an ensemble of deep-learning models on fewer than 60 large-vessel occlusion (LVO)-positive patients. We evaluated the model on an independent test set and evaluated the truth of its predicted localizations using Intersection over Union and expert review. RESULTS: On an independent test set of 166 cerebral DSA frames with an LVO prevalence of 0.19, the model achieved a specificity of 0.95 (95% confidence interval [CI]: 0.90, 0.99), a precision of 0.7450 (95% CI: 0.64, 0.88), and a sensitivity of 0.76 (95% CI: 0.66, 0.91). The model correctly localized the LVO in at least one frame in 13 of the 14 LVO-positive patients in the test set. The model achieved a precision of 0.67 (95% CI: 0.52, 0.79), recall of 0.69 (95% CI: 0.46, 0.81), and a mean average precision of 0.75 (95% CI: 0.56, 0.91). CONCLUSION: This work demonstrates that a deep learning strategy using a limited dataset can generate effective representations used to identify LVOs. Generating an expanded and more complete dataset of LVOs with obstructed LVOs is likely the best way to improve the model's ability to localize LVOs.

The subparietal and parietooccipital sulci: an anatomical study.

The subparietal and parietooccipital sulci are both located on the medial surface of the brain. Both of these sulci reveal significant variability in pattern and complexity. Both subparietal and parietooccipital sulci play an important role as surgical landmarks using posterior interhemispheric parietooccipital approach to lesions located adjacent to the ventricular trigon deep to the cingulate gyrus. The aim of this study is to analyze variations in the patterns of the subparietal and parietooccipital sulci and to emphasize their surgical importance. Fifty-six formalin-fixed cadaveric cerebral hemispheres from 28 adult humans are examined. Subparietal and parietal sulci patterns, variations and their relationship with the cingulate sulcus are studied according to the terminology introduced by Ono et al. The H-pattern was observed in 50% (n = 28) of all hemispheres, being the most common pattern of the subparietal sulcus. The Straight pattern was observed in the 30.4% (n = 17) of all hemispheres, being the most common pattern of the parietooccipital sulcus. Furthermore, more detailed results among the patterns, connections, side branches and the relationship with the adjacent sulci are given. Our study further confirms the complexities in the patterns of the subparietal and parietooccipital sulci and demonstrates that these sulci fall within an expected range of variations. Better knowledge of these variations will further help neurosurgeons to navigate easily during approaches involving the medial surface of the parietal lobe. Clin. Anat. 26:667-674, 2013. © 2013 Wiley Periodicals, Inc.

Mechanical Venous Thrombectomy Using Indigo Aspiration System: A Case Report.

We present a case of successful endovascular thrombectomy of cerebral venous sinus thrombosis utilizing Penumbra's Indigo Aspiration System (Penumbra Inc., Place Alameda, CA), a minimally invasive system with a large-lumen (Indigo System CAT7, 7F) catheter predominantly used for the removal of thromboembolism involving the peripheral arterial and venous systems. A 30-year-old female presented with a seizure and focal neurological deficits and was found to have a left posterior temporal lobe hemorrhagic infarct secondary to an extensive cerebral venous sinus thrombosis extending from the left transverse sinus to the ipsilateral internal jugular bulb. We considered the combination of seizure, motor deficit, and hemorrhagic infarct high-risk features for poor response to standard medical therapy with therapeutic anticoagulation. Therefore, we performed a mechanical venous thrombectomy with the above device in addition to anticoagulation treatment with heparin infusion. This combination therapy resulted in a technically successful radiographic recanalization of the involved sinuses and an excellent functional outcome at follow-up. This case demonstrates that this trackable, atraumatic, large-bore system was safe and efficacious in the cerebral venous system, permitting near-complete thrombus removal.

External Validation of an Artificial Intelligence Device for Intracranial Hemorrhage Detection.

BACKGROUND: Artificial intelligence applications have gained traction in the field of cerebrovascular disease by assisting in the triage, classification, and prognostication of both ischemic and hemorrhagic stroke. The Caire ICH system aims to be the first device to move into the realm of assisted diagnosis for intracranial hemorrhage (ICH) and its subtypes. METHODS: A single-center retrospective dataset of 402 head noncontrast CT scans (NCCT) with an intracranial hemorrhage were retrospectively collected from January 2012 to July 2020; an additional 108 NCCT scans with no intracranial hemorrhage findings were also included. The presence of an ICH and its subtype were determined from the International Classification of Diseases-10 code associated with the scan and validated by an expert panel. We used the Caire ICH vR1 to analyze these scans, and we evaluated its performance in terms of accuracy, sensitivity, and specificity. RESULTS: We found the Caire ICH system to have an accuracy of 98.05% (95% confidence interval [CI]: 96.44%-99.06%), a sensitivity of 97.52% (95% CI: 95.50%-98.81%), and a specificity of 100% (95% CI: 96.67%-100.00%) in the detection of ICH. Experts reviewed the 10 incorrectly classified scans. CONCLUSIONS: The Caire ICH vR1 algorithm was highly accurate, sensitive, and specific in detecting the presence or absence of an ICH and its subtypes in NCCTs. This work suggests that the Caire ICH device has potential to minimize clinical errors in ICH diagnosis that could improve patient outcomes and current workflows as both a point-of-care tool for diagnostics and as a safety net for radiologists.

Microsurgical anatomy of the dorsal thoracic rootlets and dorsal root entry zones.

BACKGROUND: For successful DREZ (dorsal root entry zone) surgery, optimal neuroanatomical orientation and precise microsurgical dissection are required. Although cervical, lumbar, and sacral spinal segments have been studied in detail, such information is not available for thoracic segments. The objective of this anatomical study is to comprehensively illustrate the microanatomical features of the thoracic DREZs and their variations. METHODS: Fifteen formalin-fixed adult cadaveric spinal cords from T1 to T12 were used. The dorsal rootlet numbers, distance between the posteromedial and posterolateral sulcus, length of each DREZ, length of each segment, and mean length of the dorsal rootlets were measured under a surgical microscope. RESULTS: The longest DREZs were observed at the T6, T7, and T8 segments with mean values of 15.3 mm, 15.6 mm, and 15.4 mm, respectively. The longest segment was observed at the T10 segment with a mean value of 21.0 mm, and the shortest segment was observed at the T1 segment with a mean value of 13.5 mm. CONCLUSIONS: The highest dorsal rootlet density is at the T1 segment of the spinal cord, can be easily distinguished visually, and may be a useful surgical landmark. The DREZs in T6-7 segments are longest, while these two segments have the least number of rootlets. Because the dorsolateral tract is remarkably narrow and the dorsal horn is exceedingly deep, DREZ surgery at the thoracic level may be difficult and risky for the dorsal column and corticospinal tract. Acquaintance with the microanatomy of the DREZ in the thoracic spinal cord is crucial to DREZ surgery.

Predicting poor response to anti-coagulation therapy in cerebral venous thrombosis using a simple clinical-radiological score.

BACKGROUND: Multiple studies have attempted to determine predictors of poor clinical outcomes in cerebral venous thrombosis (CVT). Fewer studies target to identify predictors of poor response to anticoagulation therapy in CVT. OBJECTIVE: We aimed to determine the predictors of poor clinical response to therapeutic anticoagulation in patients with acute CVT. METHODS: We performed a retrospective analysis of patients therapeutically anticoagulated for acute CVT. We defined poor clinical outcomes as death, need for mechanical thrombectomy during the hospitalization, or a modified Rankin Scale (mRS) > 3 at clinical follow-up. Bivariate and multivariate analyses identified factors associated with poor outcomes in anticoagulated patients for acute CVT, and we used the identified factors to create the PRACT-CVT (Poor Response to Anticoagulation Therapy in CVT) score. RESULTS: We included 109 patients anticoagulated with acute CVT. The mean patient age was 37 years old (SD 19); nine patients were > 65 years, ten patients were < 10 years, and 64 (59%) were female. Twenty-one (19%) patients had poor clinical outcomes. Age > 65 or < 10 years (OR: 3.16, 95% CI: 1.06-9.44), a GCS ≤ 12 upon presentation (OR: 19.2, 95% CI: 4.05-91.4), focal motor deficits at admission (OR: 5.03, 95% CI: 1.64-15.44), clinical deterioration following admission (OR: 28.18, CI: 4.81-164.86), seizures following admission (OR: 5.59, 95% CI: 1.27-24.51), evidence of brain bleeding/ischemia on admission (OR: 4.67, 95% CI: 1.42-15.34), involvement of the superior sagittal sinus (OR: 3.88, CI: 1.33-11.32), or involvement of both transverse sinuses (OR: 3.87, 95% CI: 1.01-14.90) predicted poor clinical outcome despite therapeutic anticoagulation. A PRACT-CVT score (0-22 points) of ≥ 7 points provided a sensitivity of 71% and a specificity of 95% for predicting poor clinical outcomes with anticoagulation alone. CONCLUSION: Patients with acute CVT aged > 65 or < 10 years old, presenting with a GCS ≤ 12, with focal motor deficits, showing clinical deterioration after admission, having clinical seizures during hospitalization, with brain bleeding/ischemia on initial neuroimaging, involvement of the superior sagittal sinus, or involvement of both transverse sinuses had poor response to anticoagulation. Clinicians may employ the PRACT-CVT score to predict poor response to anticoagulation for acute CVT.

Demographic and institutional predictors of stroke hospitalization mortality among adults in the United States.

INTRODUCTION: Stroke remains a primary source of functional disability and inpatient mortality in the United States (US). Recent evidence reveals declining mortality associated with stroke hospitalizations in the US. However, data updating trends in inpatient mortality is lacking. This study aims to provide a renewed inpatient stroke mortality rate in a national sample and identify common predictors of inpatient stroke mortality. METHODS: In this cross-sectional study, we analyzed data from a nationwide database between 2010 and 2017. We included patient encounters for both ischemic (ICD9 433-434, ICD10 I630-I639) and hemorrhagic stroke (ICD9 430-432, ICD10 I600-I629). We performed an annual comparison of in-hospital stroke mortality rates, and a cross-sectional analytic approach of multiple variables identified common predictors of inpatient stroke mortality. RESULTS: Between 2010 and 2017, we identified 518,185 total stroke admissions (86.6% ischemic stroke and 13.4% hemorrhagic strokes). Stroke admissions steadily increased during the studied period, whereas we observed a steady decline in in-hospital mortality during the same time. The inpatient stroke mortality rate gradually declined from 4.8% in 2010 (95% CI 4.6-5.1) to 2.1% in 2017 (95% CI 2.0-2.1). Predictors of higher odds of dying from ischemic stroke were female (OR 1.059, 95% CI 1.015-1.105, p = 0.008), older age (OR 1.028, 95% CI 1.026-1.029, p < 0.001), and sicker patients (OR 1.091, 95% CI 1.089-1.093, p < 0.001). Predictors of higher odds of dying from hemorrhagic stroke were Hispanic ethnicity (OR 1.459, 95% CI 1.084-1.926, p < 0.001), older age (OR 1.021, 95% CI 1.019-1.023, p < 0.001), and sicker patients (OR 1.042, 95% CI 1.039-1.045, p < 0.001). All census regions and hospital types demonstrated improvements in in-hospital mortality. CONCLUSION: This study identified a continuous declining rate in in-hospital mortality due to stroke in the United States, and it also identified demographic and hospital predictors of inpatient stroke mortality.

Calcium and Boron Fertilization Improves Soybean Photosynthetic Efficiency and Grain Yield.

Foliar fertilization with calcium (Ca) and boron (B) at flowering can promote flower retention and pod fixation, thereby increasing the number of pods per plant and, in turn, crop productivity. The objective of this work was to investigate the effects of Ca + B fertilization during flowering on the nutritional, metabolic and yield performance of soybean (Glycine max L.) The treatments consisted of the presence and the absence of Ca + B fertilization in two growing seasons. Crop nutritional status, gas exchange parameters, photosynthetic enzyme activity (Rubisco), total soluble sugar content, total leaf protein concentration, agronomic parameters, and grain yield were evaluated. Foliar Ca + B fertilization increased water use efficiency and carboxylation efficiency, and the improvement in photosynthesis led to higher leaf sugar and protein concentrations. The improvement in metabolic activity promoted a greater number of pods and grains plant-1, culminating in higher yields. These results indicate that foliar fertilization with Ca + B can efficiently improve carbon metabolism, resulting in better yields in soybean.

Deep Learning System Boosts Radiologist Detection of Intracranial Hemorrhage.

BACKGROUND: Intracranial hemorrhage (ICH) requires emergent medical treatment for positive outcomes. While previous artificial intelligence (AI) solutions achieved rapid diagnostics, none were shown to improve the performance of radiologists in detecting ICHs. Here, we show that the Caire ICH artificial intelligence system enhances a radiologist's ICH diagnosis performance. METHODS: A dataset of non-contrast-enhanced axial cranial computed tomography (CT) scans (n=532) were labeled for the presence or absence of an ICH. If an ICH was detected, its ICH subtype was identified. After a washout period, the three radiologists reviewed the same dataset with the assistance of the Caire ICH system. Performance was measured with respect to reader agreement, accuracy, sensitivity, and specificity when compared to the ground truth, defined as reader consensus. RESULTS: Caire ICH improved the inter-reader agreement on average by 5.76% in a dataset with an ICH prevalence of 74.3%. Further, radiologists using Caire ICH detected an average of 18 more ICHs and significantly increased their accuracy by 6.15%, their sensitivity by 4.6%, and their specificity by 10.62%. The Caire ICH system also improved the radiologist's ability to accurately identify the ICH subtypes present. CONCLUSION: The Caire ICH device significantly improves the performance of a cohort of radiologists. Such a device has the potential to be a tool that can improve patient outcomes and reduce misdiagnosis of ICH.

Bilateral carotid dissection due to Eagle syndrome in a young female.

Eagle syndrome (ES) is a rare clinical syndrome characterized by the elongation of the temporal bone's styloid process, or calcification of stylohyoid ligament, compressing surrounding structures causing pharyngalgia. One of its variants, the styloid-carotid artery syndrome, produces symptoms by compression of the external or internal carotid arteries (ICA). Here, we present a case of a 43-year-old woman with ES and bilateral ICA dissections. The patient underwent staged bilateral angioplasty and covered stent placement, followed by styloidectomy. A computerized tomography angiogram revealed patency of both stents at a two-year follow-up.

Intravenous thrombolysis for the management of acute ischemic stroke in patients therapeutically anticoagulated with heparin: A review.

BACKGROUND: Intravenous thrombolysis (IVT) with alteplase is effective in acute ischemic stroke (AIS). However, its use rate remains low due to the many exclusion criteria. Recent guidelines recommend excluding patients suffering AIS with an elevated aPTT secondary to heparin exposure from receiving IVT. The purpose of this review is to explore the safety and efficacy of IVT in patients therapeutically anticoagulated with heparin. We also propose a treatment algorithm for IVT in patients with AIS that are therapeutically anticoagulated with heparin. METHODS: We performed a systematic review of PubMed and Embase through March 2020 to identify the literature regarding AIS in patients exposed to heparin, followed by IVT treatment, emphasizing safety, efficacy, and clinical outcome using PRISMA guidelines. RESULTS: We included thirteen articles in the final analysis, including three retrospective studies, two observational studies, one randomized trial, five case reports, and two case series. CONCLUSION: There is limited information about the off-label use of IVT in patients with elevated aPTT. Patients with AIS are excluded from IVT if they have recent exposure to heparin. Our review indicates that this population of patients may benefit from IVT as the cases of active bleeding after IVT are few, and functional outcomes are favorable in the long term suggesting that IVT in therapeutically anticoagulated patients may be safe and efficacious.

Perioperative mortality in older patients: a systematic review with a meta-regression analysis and meta-analysis of observational studies.

STUDY OBJECTIVE: Older patients have a higher probability of developing major complications during the perioperative period than other adult patients. Perioperative mortality depends on not only on a patient condition but also on the quality of perioperative care provided. We tested the hypothesis that the perioperative mortality rate among older patients has decreased over time and is related to a country's Human Development Index (HDI) status. DESIGN: A systematic review with a meta-regression and meta-analysis of observational studies that reported perioperative mortality rates in patients aged ≥60 years was performed. We searched the PubMed, EMBASE, LILACS and SciELO databases from inception to December 30, 2019. SETTING: Mortality rates up to the seventh postoperative day were evaluated. MEASUREMENTS: We evaluated the quality of the included studies. Perioperative mortality rates were analysed by time, country HDI status and baseline American Society of Anesthesiologists (ASA) physical status using meta-regression. Perioperative mortality and ASA status were analysed in low- and high-HDI countries during two time periods using proportion meta-analysis. MAIN RESULTS: We included 25 studies, which reported 4,412,100 anaesthesia procedures and 3568 perioperative deaths from 12 countries. Perioperative mortality rates in high-HDI countries decreased over time (P = 0.042). When comparing pre-1990 to 1990-2019, in high-HDI countries, the perioperative mortality rates per 10,000 anaesthesia procedures decreased 7.8-fold from 100.85 (95% CI 43.36 to 181.72) in pre-1990 to 12.98 (95% CI 6.47 to 21.70) in 1990-2019 (P < 0.0001). There were no studies from low-HDI countries pre-1990. In the period from 1990 to 2019, perioperative mortality rates did not differ between low- and high-HDI countries (P = 0.395) but the limited number of patients in low-HDI countries impaired the result. Perioperative mortality rates increased with increasing ASA status (P < 0.0001). There were more ASA III-V patients in high-HDI countries than in low-HDI countries (P < 0.0001), and the perioperative mortality rate increased 24-fold in ASA III-V patients compared with ASA I-II patients (P < 0.0001). CONCLUSION: The perioperative mortality rates in older patients have declined over the past 60 years in high-DHI countries, highlighting that perioperative safety in this population is increasing in these countries. Since data prior to 1990 were lacking in low-HDI countries, the evolution of their mortality rates could not be analysed. The perioperative mortality rate was similar in low- and high-HDI countries in the post-1990 period, but the low number of patients in the low-HDI countries does not allow a definitive conclusion.

Antihypertensive use for stroke in United States emergency departments.

OBJECTIVE: Timely emergency department (ED) control of hypertension in the acute phase of stroke is associated with improved outcomes. It is unclear how emergency physicians use antihypertensive medications to treat severe hypertension associated with stroke. We sought to determine national patterns of antihypertensive use associated with ED visits for stroke in the United States. METHODS: We analyzed data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) 2008-2017. We included ED visits associated with ischemic stroke (ICD9 433-434, ICD10 I630-I639) or hemorrhagic stroke (ICD9 430-432, ICD10 I600-I629). We estimated the number and proportions of stroke ED visits with triage blood pressure meeting treatment thresholds (triage systolic blood pressure [SBP] ≥180 mm Hg). We identified the frequency of antihypertensive use, as well as the most commonly used agents. RESULTS: Between 2008-2017, of a total 135,012,819 ED visits, 619,791 were associated with stroke (78.3% ischemic strokes and 21.7% hemorrhage strokes). Of all stroke visits, 21.8% received antihypertensive medications. Of the identified visits, 9.0% (95% confidence interval [CI] = 6.0%, 13.1%) ischemic stroke visits and 58.2% (95% CI = 49.0%, 66.9%) hemorrhagic stroke visits met criteria for BP reduction. A total of 47.6% (95% CI = 29.1%, 66.7%) of eligible ischemic stroke visits and 41.5% (95% CI = 30.5%, 53.3%) of eligible hemorrhagic strokes visits received antihypertensives. The most common agents used in ischemic stroke were beta-blockers, calcium-channel blockers, and ACE inhibitors. The most common agents used in hemorrhagic stroke included calcium-channel blockers, beta-blockers, and vasodilators. CONCLUSION: In this national sample, less than half of strokes presenting to the ED with hypertension received antihypertensive therapy.

EGFR Signaling Termination via Numb Trafficking in Ependymal Progenitors Controls Postnatal Neurogenic Niche Differentiation.

Specialized microenvironments, called niches, control adult stem cell proliferation and differentiation. The brain lateral ventricular (LV) neurogenic niche is generated from distinct postnatal radial glial progenitors (pRGPs), giving rise to adult neural stem cells (NSCs) and niche ependymal cells (ECs). Cellular-intrinsic programs govern stem versus supporting cell maturation during adult niche assembly, but how they are differentially initiated within a similar microenvironment remains unknown. Using chemical approaches, we discovered that EGFR signaling powerfully inhibits EC differentiation by suppressing multiciliogenesis. We found that EC pRGPs actively terminated EGF activation through receptor redistribution away from CSF-contacting apical domains and that randomized EGFR membrane targeting blocked EC differentiation. Mechanistically, we uncovered spatiotemporal interactions between EGFR and endocytic adaptor protein Numb. Ca2+-dependent basolateral targeting of Numb is necessary and sufficient for proper EGFR redistribution. These results reveal a previously unknown cellular mechanism for neighboring progenitors to differentially engage environmental signals, initiating adult stem cell niche assembly.