Diffusion-Weighted Imaging Fluid-Attenuated Inversion Recovery Mismatch on Portable, Low-Field Magnetic Resonance Imaging Among Acute Stroke Patients.

OBJECTIVE: For stroke patients with unknown time of onset, mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can guide thrombolytic intervention. However, access to MRI for hyperacute stroke is limited. Here, we sought to evaluate whether a portable, low-field (LF)-MRI scanner can identify DWI-FLAIR mismatch in acute ischemic stroke. METHODS: Eligible patients with a diagnosis of acute ischemic stroke underwent LF-MRI acquisition on a 0.064-T scanner within 24 h of last known well. Qualitative and quantitative metrics were evaluated. Two trained assessors determined the visibility of stroke lesions on LF-FLAIR. An image coregistration pipeline was developed, and the LF-FLAIR signal intensity ratio (SIR) was derived. RESULTS: The study included 71 patients aged 71 ± 14 years and a National Institutes of Health Stroke Scale of 6 (interquartile range 3-14). The interobserver agreement for identifying visible FLAIR hyperintensities was high (κ = 0.85, 95% CI 0.70-0.99). Visual DWI-FLAIR mismatch had a 60% sensitivity and 82% specificity for stroke patients <4.5 h, with a negative predictive value of 93%. LF-FLAIR SIR had a mean value of 1.18 ± 0.18 <4.5 h, 1.24 ± 0.39 4.5-6 h, and 1.40 ± 0.23 >6 h of stroke onset. The optimal cut-point for LF-FLAIR SIR was 1.15, with 85% sensitivity and 70% specificity. A cut-point of 6.6 h was established for a FLAIR SIR <1.15, with an 89% sensitivity and 62% specificity. INTERPRETATION: A 0.064-T portable LF-MRI can identify DWI-FLAIR mismatch among patients with acute ischemic stroke. Future research is needed to prospectively validate thresholds and evaluate a role of LF-MRI in guiding thrombolysis among stroke patients with uncertain time of onset. ANN NEUROL 2024;96:321-331.

Considering Adverse Effects of Common Antihypertensive Medications in the ED.

PURPOSE OF REVIEW: To evaluate the adverse effects of common antihypertensive agents utilized or encountered in the Emergency Department. RECENT FINDINGS: All categories of antihypertensive agents may manifest adverse effects, inclusive of adverse drug reactions (ADRs), drug-to-drug interactions, or accidental overdose. Adverse effects, and specifically ADRs, may be stratified into the organ systems affected, might require specific time-sensitive interventions, could pose particular risks to vulnerable populations, and may result in significant morbidity, and potential mortality. Adverse effects of common antihypertensive agents may be encountered in the ED, necessitating that ED systems of care are poised to prevent, recognize, and intervene when adverse effects arise.

Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues.

Women acquire HIV through sexual transmission, with increasing incidence in women >50 years old. Identifying protective mechanisms in the female genital tract (FGT) is important to prevent HIV-acquisition in women as they age. Human genital and blood neutrophils inactivate HIV by releasing neutrophil extracellular traps (NETs), an innate protective mechanism against HIV-infection. However, how NET formation is triggered by HIV in different tissues and whether this mechanism is affected by aging remain unknown. We demonstrate that the mechanisms that trigger NET release in response to HIV are different in blood and genital tissues, and that NET release decreases with aging. In blood neutrophils, HIV stimulation independently activated calcium pathways and endosomal TLR8, but aging reduced calcium responses, resulting in delayed NET release. In contrast, calcium responses were absent in genital neutrophils and NET release was triggered preferentially through TLR8 activation, but aging impaired this pathway. HIV induced NET formation through non-lytic pathways in blood and FGT neutrophils, except for a small subset of NETs that incorporated annexin V and lactoferrin predominantly in blood, suggesting proinflammatory and lytic NET release. Our findings demonstrate that blood neutrophils cannot model genital neutrophil responses which has important implications to understanding protection against HIV acquisition.

Aging modifies endometrial dendritic cell function and unconventional double negative T cells in the human genital mucosa.

BACKGROUND: Immune function in the genital mucosa balances reproduction with protection against pathogens. As women age, genital infections, and gynecological cancer risk increase, however, the mechanisms that regulate cell-mediated immune protection in the female genital tract and how they change with aging remain poorly understood. Unconventional double negative (DN) T cells (TCRαß + CD4-CD8-) are thought to play important roles in reproduction in mice but have yet to be characterized in the human female genital tract. Using genital tissues from women (27-77 years old), here we investigated the impact of aging on the induction, distribution, and function of DN T cells throughout the female genital tract. RESULTS: We discovered a novel site-specific regulation of dendritic cells (DCs) and unconventional DN T cells in the genital tract that changes with age. Human genital DCs, particularly CD1a + DCs, induced proliferation of DN T cells in a TFGß dependent manner. Importantly, induction of DN T cell proliferation, as well as specific changes in cytokine production, was enhanced in DCs from older women, indicating subset-specific regulation of DC function with increasing age. In human genital tissues, DN T cells represented a discrete T cell subset with distinct phenotypical and transcriptional profiles compared to CD4 + and CD8 + T cells. Single-cell RNA and oligo-tag antibody sequencing studies revealed that DN T cells represented a heterogeneous population with unique homeostatic, regulatory, cytotoxic, and antiviral functions. DN T cells showed relative to CD4 + and CD8 + T cells, enhanced expression of inhibitory checkpoint molecules and genes related to immune regulatory as well as innate-like anti-viral pathways. Flow cytometry analysis demonstrated that DN T cells express tissue residency markers and intracellular content of cytotoxic molecules. Interestingly, we demonstrate age-dependent and site-dependent redistribution and functional changes of genital DN T cells, with increased cytotoxic potential of endometrial DN T cells, but decreased cytotoxicity in the ectocervix as women age, with implications for reproductive failure and enhanced susceptibility to infections respectively. CONCLUSIONS: Our deep characterization of DN T cell induction and function in the female genital tract provides novel mechanistic avenues to improve reproductive outcomes, protection against infections and gynecological cancers as women age.

Diagnosis, Workup, Risk Reduction of Transient Ischemic Attack in the Emergency Department Setting: A Scientific Statement From the American Heart Association.

At least 240 000 individuals experience a transient ischemic attack each year in the United States. Transient ischemic attack is a strong predictor of subsequent stroke. The 90-day stroke risk after transient ischemic attack can be as high as 17.8%, with almost half occurring within 2 days of the index event. Diagnosing transient ischemic attack can also be challenging given the transitory nature of symptoms, often reassuring neurological examination at the time of evaluation, and lack of confirmatory testing. Limited resources, such as imaging availability and access to specialists, can further exacerbate this challenge. This scientific statement focuses on the correct clinical diagnosis, risk assessment, and management decisions of patients with suspected transient ischemic attack. Identification of high-risk patients can be achieved through use of comprehensive protocols incorporating acute phase imaging of both the brain and cerebral vasculature, thoughtful use of risk stratification scales, and ancillary testing with the ultimate goal of determining who can be safely discharged home from the emergency department versus admitted to the hospital. We discuss various methods for rapid yet comprehensive evaluations, keeping resource-limited sites in mind. In addition, we discuss strategies for secondary prevention of future cerebrovascular events using maximal medical therapy and patient education.

Aging beyond menopause selectively decreases CD8+ T cell numbers but enhances cytotoxic activity in the human endometrium.

BACKGROUND: Regulation of endometrial (EM) CD8+ T cells, which provide protection through cell-mediated cytotoxicity, is essential for successful reproduction, and protection against sexually transmitted infections and potential tumors. We have previously demonstrated that EM CD8+ T cell cytotoxicity is suppressed directly and indirectly by sex hormones and enhanced after menopause. What remains unclear is whether CD8+ T cell protection and the contribution of tissue-resident (CD103+) and non-resident (CD103-) T cell populations in the EM change as women age following menopause. RESULTS: Using hysterectomy EM tissues, we found that EM CD8+ T cell numbers declined significantly in the years following menopause. Despite an overall decline in CD8+ T cells, cytotoxic activity per cell for both CD103- and CD103 + CD8+ T cells increased with age. Investigation of the underlying mechanisms responsible for cytotoxicity indicated that the percentage of total granzyme A and granzyme B positive CD8+ T cells, but not perforin, increased significantly after menopause and remained high and constant as women aged. Additionally, baseline TNFα production by EM CD8+ T cells increased significantly in the years following menopause, and estradiol suppressed TNFα secretion. Moreover, in response to PMA activation, TNFα and IFNγ were significantly up-regulated, and CD103-CD8+ T cells up-regulation of TNFα, IFNγ and IL-6 increased as women aged. CONCLUSIONS: Understanding the underlying factors involved in regulating cell-mediated protection of the EM by CD8+ T cells will contribute to the foundation of information essential for developing therapeutic tools to protect women against gynecological cancers and infections as they age.

Establishment of SEP-1 national practice guidelines does not impact fluid administration for septic shock patients.

BACKGROUND: The Centers for Medicare and Medicaid Services introduced the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) as a national quality measure in October 2015. The purpose of SEP-1 is to facilitate the efficient, effective, and timely delivery of high-quality care to patients presenting along the spectrum of sepsis severity. OBJECTIVES: The primary aim of this study was to investigate whether provider practice surrounding emergency department (ED) fluid management of suspected septic shock patients was impacted by SEP-1. METHODS: The study was a retrospective observational analysis of 470,558 patient encounters at an urban academic center over a five-year period. The sample of suspected septic shock patients was defined by the following: blood cultures collected, antibiotics administered, and vasopressors initiated. Participants were divided into two cohorts based on date of presentation (Pre-SEP-1: May 1, 2013, - August 30, 2015, and Post-SEP-1: November 1, 2015, - February 28, 2018). The primary outcome was classified as a dichotomous variable based on whether the total volume of fluids administered equaled or exceeded the calculated weight-based (≥30 cc/kg) goal. Segmented logistic regression analyses were used to assess the immediate impact of SEP-1 as well as to compare the long-term trend of fluid volume administered between Pre-SEP-1 and Post-SEP-1 cohorts. RESULTS: A total of 413 and 482 septic shock patients were included in the Pre-SEP-1 and Post-SEP-1 cohorts, respectively. There was no statistically significant change in weight-based fluid management between the cohorts. The odds of compliance with the weight-based goal decreased 22% immediately following dissemination of SEP-1, however, this was not statistically significant (log-odds = -0.25, p = 0.41). A positive trend in compliance was observed during both the Pre-SEP-1 and Post-SEP-1 periods with odds ratios increasing 0.005 and 0.018 each month, respectively, however, these findings were not statistically significant (log-odds = 0.005, p = 0.736, and log-odds = 0.018, p = 0.10, respectively). CONCLUSIONS: Overall, there were no clinically or statistically meaningful changes in fluid volume resuscitation strategies for suspected septic shock patients following SEP-1. Broad mandates may not be effective tools for promoting practice change in the ED setting. Further research investigating barrier to changes in practice patterns surrounding fluid administration and other SEP-1 bundle elements is warranted.

Drip-and-ship versus mothership for endovascular treatment of acute stroke: A comparative effectiveness analysis.

BACKGROUND: Triage for suspected acute stroke has two main options: (1) transport to the closest primary stroke center (PSC) and then to the nearest comprehensive stroke center (CSC) (Drip-and-Ship) or (2) transport the patient to the nearest CSC, bypassing a closer PSC (mothership). The purpose was to evaluate the effectiveness of drip-and-ship versus mothership models for acute stroke patients. METHODS: A Markov decision-analytic model was constructed. All model parameters were derived from recent medical literature. Our target population was adult patient with sudden onset of acute stroke within 8 h of onset over a one-year horizon. The primary outcome was quantified in terms of quality-adjusted-life-years (QALYs). RESULTS: The base case scenario show that the drip-and-ship strategy has a slightly higher expected health benefit, 0.591 QALY, as compared to 0.586 QALY in the mothership strategy when the time to PSC is 30 min and to CSC is 65 min, although the difference in health benefit becomes minimal as the time to PSC increases towards 60 min. Multiple sensitivity analyses show that when both PSC and CSC are far from place of onset (>1.5 h away), drip-and-ship becomes the better strategy. Mothership strategy is favored by smaller difference between distances to PSC and CSC, shorter transfer time from PSC to CSC, and longer delay in reperfusion in CSC for transferred patients. Drip-and-ship is favored by the reverse. CONCLUSION: Drip-and-ship has a slightly higher utility than mothership. This study assesses the complex issue of prehospital triage of acute stroke patients and can provide a framework for real-world data input.

Medroxyprogesterone acetate inhibits wound closure of human endometrial epithelial cells and stromal fibroblasts in vitro.

Mucosal integrity in the endometrium is essential for immune protection. Since breaches or injury to the epithelial barrier exposes underlying tissue and is hypothesized to increase infection risk, we determined whether endogenous progesterone or three exogenous progestins (medroxyprogesterone acetate (MPA), norethindrone (NET), and levonorgestrel (LNG)) used by women as contraceptives interfere with wound closure of endometrial epithelial cells and fibroblasts in vitro. Progesterone and LNG had no inhibitory effect on wound closure by either epithelial cells or fibroblasts. MPA significantly impaired wound closure in both cell types and delayed the reestablishment of transepithelial resistance by epithelial cells. In contrast to MPA, NET selectively decreased wound closure by stromal fibroblasts but not epithelial cells. Following epithelial injury, MPA but not LNG or NET, blocked the injury-induced upregulation of HBD2, a broad-spectrum antimicrobial implicated in wound healing, but had no effect on the secretion of RANTES, CCL20 and SDF-1α. This study demonstrates that, unlike progesterone and LNG, MPA and NET may interfere with wound closure following injury in the endometrium, potentially conferring a higher risk of pathogen transmission. Our findings highlight the importance of evaluating progestins for their impact on wound repair at mucosal surfaces.

Sex Hormones and Aging Modulate Interferon Lambda 1 Production and Signaling by Human Uterine Epithelial Cells and Fibroblasts.

Estradiol (E2) and progesterone (P) have potent effects on immune function in the human uterine endometrium which is essential for creating an environment conducive for successful reproduction. Type III/lambda (λ) interferons (IFN) are implicated in immune defense of the placenta against viral pathogens, which occurs against the backdrop of high E2 and P levels. However, the effect of E2 and P in modulating the expression and function of IFNλ1 in the non-pregnant human uterine endometrium is unknown. We generated purified in vitro cultures of human uterine epithelial cells and stromal fibroblast cells recovered from hysterectomy specimens. Poly (I:C), a viral dsRNA mimic, potently increased secretion of IFNλ1 by both epithelial cells and fibroblasts. The secretion of IFNλ1 by epithelial cells significantly increased with increasing age following poly (I:C) stimulation. Stimulation of either cell type with E2 (5x10-8M) or P (1x10-7M) had no effect on expression or secretion of IFNλ1 either alone or in the presence of poly (I:C). E2 suppressed the IFNλ1-induced upregulation of the antiviral IFN-stimulated genes (ISGs) MxA, OAS2 and ISG15 in epithelial cells, but not fibroblasts. Estrogen receptor alpha (ERα) blockade using Raloxifene indicated that E2 mediated its inhibitory effects on ISG expression via ERα. In contrast to E2, P potentiated the upregulation of ISG15 in response to IFNλ1 but had no effect on MxA and OAS2 in epithelial cells. Our results demonstrate that the effects of E2 and P on IFNλ1-induced ISGs are cell-type specific. E2-mediated suppression, and selective P-mediated stimulation, of IFNλ1-induced ISG expression in uterine epithelial cells suggest that the effects of IFNλ1 varies with menstrual cycle stage, pregnancy, and menopausal status. The suppressive effect of E2 could be a potential mechanism by which ascending pathogens from the lower reproductive tract can infect the pregnant and non-pregnant endometrium.

Sepsis Fluid Metric Compliance and its Impact on Outcomes of Patients with Congestive Heart Failure, End-Stage Renal Disease or Obesity.

BACKGROUND: Emergency physicians express concern administering a 30-cc/kg fluid bolus to septic shock patients with pre-existing congestive heart failure (CHF), end-stage renal disease (ESRD), or obesity, due to the perceived risk of precipitating a fluid overload state. OBJECTIVE: Our aim was to determine whether there is a difference in fluid administration to septic shock patients with these pre-existing conditions in the emergency department (ED). Secondary objectives focused on whether compliance impacts mortality, need for intubation, and length of stay. METHODS: We conducted a retrospective chart review of 470,558 ED patient encounters at a single urban academic center during a 5-year period. RESULTS: Of 847 patients with septic shock, 308 (36.36%) had no pre-existing condition and 199 (23.49%), 17 (2.01%), and 154 (18.18%) had the single pre-existing condition of CHF, ESRD, and obesity, respectively, and 169 (19.95%) had multiple pre-existing conditions. Weight-based fluid compliance was achieved in 460 patients (54.31%). There was a lower likelihood of compliance among patients with CHF (adjusted odds ratio [aOR] 0.35; 95% confidence interval [CI] 0.24-0.52; p < 0.001), ESRD (aOR 0.11, 95% CI 0.04-0.32; p < 0.001), and obesity (aOR 0.29, 95% CI 0.19-0.44; p < 0.001) compared with patients with no pre-existing conditions. Compliance decreased further in patients with multiple pre-existing conditions (aOR 0.49, 95% CI 0.33-0.72; p < 0.001). Compliance was not associated with mortality in patients with CHF and ESRD, but was protective in patients with obesity and those with no pre-existing conditions. CONCLUSIONS: Septic shock patients with pre-existing CHF, ESRD, or obesity are less likely to achieve compliance with a 30-cc/kg weight-based fluid goal compared with those without these pre-existing conditions.

Endometrial Cancer Suppresses CD8+ T Cell-Mediated Cytotoxicity in Postmenopausal Women.

Endometrial cancer is the most common gynecological cancer. To investigate how it suppresses host immune function, we isolated CD8+ T cells from endometrial endometroid carcinomas and adjacent non-cancerous endometrium and determined if the tumor environment regulates cytotoxic capacity. Endometrial carcinomas had increased numbers of CD8+ T cells compared to adjacent non-cancerous endometrium. Tumor CD8+ T cells expressed significantly less granzyme A (GZA), B (GZB), and PD-1 than those in adjacent non-cancerous tissues and also had significantly lower cytotoxic killing of allogeneic target cells. CD103-CD8+ T cells, but not CD103+CD8+ T cells, from both adjacent and tumor tissue were primarily responsible for killing of allogeneic target cells. Secretions recovered from endometrial carcinoma tissues suppressed CD8+ cytotoxic killing and lowered perforin, GZB and PD-1 expression relative to non-tumor CD8+ T cells. Furthermore, tumor secretions contained significantly higher levels of immunosuppressive cytokines including TGFß than non-tumor tissues. Thus, the tumor microenvironment suppresses cytotoxic killing by CD8+ T cells via the secretion of immunosuppressive cytokines leading to decreased expression of intracellular cytolytic molecules. These studies demonstrate the complexity of CD8+ T cell regulation within the endometrial tumor microenvironment and provide a foundation of information essential for the development of therapeutic strategies for gynecological cancers.

The impact of aging on innate and adaptive immunity in the human female genital tract.

Mucosal tissues in the human female reproductive tract (FRT) are primary sites for both gynecological cancers and infections by a spectrum of sexually transmitted pathogens, including human immunodeficiency virus (HIV), that compromise women's health. While the regulation of innate and adaptive immune protection in the FRT by hormonal cyclic changes across the menstrual cycle and pregnancy are being intensely studied, little to nothing is known about the alterations in mucosal immune protection that occur throughout the FRT as women age following menopause. The immune system in the FRT has two key functions: defense against pathogens and reproduction. After menopause, natural reproductive function ends, and therefore, two overlapping processes contribute to alterations in immune protection in aging women: menopause and immunosenescence. The goal of this review is to summarize the multiple immune changes that occur in the FRT with aging, including the impact on the function of epithelial cells, immune cells, and stromal fibroblasts. These studies indicate that major aspects of innate and adaptive immunity in the FRT are compromised in a site-specific manner in the FRT as women age. Further, at some FRT sites, immunological compensation occurs. Overall, alterations in mucosal immune protection contribute to the increased risk of sexually transmitted infections (STI), urogenital infections, and gynecological cancers. Further studies are essential to provide a foundation for the development of novel therapeutic interventions to restore immune protection and reverse conditions that threaten women's lives as they age.

Care of the Patient With Acute Ischemic Stroke (Prehospital and Acute Phase of Care): Update to the 2009 Comprehensive Nursing Care Scientific Statement: A Scientific Statement From the American Heart Association.

The year 2020 was the year of the nurse, celebrating nurse scholarship, innovation, and leadership by promoting scientific nursing research, improving nursing practice, advancing nursing education, and providing leadership to influence health policy. As architects of stroke care, neuroscience nurses play a vital role in collaborating and coordinating care between multiple health professionals. Nurses improve accessibility and equity through telestroke, emergency medical services, and mobile stroke units and are integral to implementing education strategies by advocating and ensuring that patients and caregivers receive stroke education while safely transitioning through the health care system and to home. Stroke care is increasingly complex in the new reperfusion era, requiring nurses to participate in continuing education while attaining levels of competency in both the acute and recovery care process. Advanced practice nurses are taking the lead in many organizations, serving as prehospital providers on mobile stroke units, participating as members of the stroke response team, and directing stroke care protocols in the emergency department. This scientific statement is an update to the 2009 "Comprehensive Overview of Nursing and Interdisciplinary Care of the Acute Ischemic Stroke Patient." The aim is to provide a comprehensive review of the scientific evidence on nursing care in the prehospital and hyperacute emergency hospital setting, arming nurses with the necessary tools to provide evidenced-based high-quality care.

Stroke Code Presentations, Interventions, and Outcomes Before and During the COVID-19 Pandemic.

BACKGROUND: Anecdotal reports suggest fewer patients with stroke symptoms are presenting to hospitals during the coronavirus disease 2019 (COVID-19) pandemic. We quantify trends in stroke code calls and treatments at 3 Connecticut hospitals during the local emergence of COVID-19 and examine patient characteristics and stroke process measures at a Comprehensive Stroke Center (CSC) before and during the pandemic. METHODS: Stroke code activity was analyzed from January 1 to April 28, 2020, and corresponding dates in 2019. Piecewise linear regression and spline models identified when stroke codes in 2020 began to decline and when they fell below 2019 levels. Patient-level data were analyzed in February versus March and April 2020 at the CSC to identify differences in patient characteristics during the pandemic. RESULTS: A total of 822 stroke codes were activated at 3 hospitals from January 1 to April 28, 2020. The number of stroke codes/wk decreased by 12.8/wk from February 18 to March 16 (P=0.0360) with nadir of 39.6% of expected stroke codes called from March 10 to 16 (30% decrease in total stroke codes during the pandemic weeks in 2020 versus 2019). There was no commensurate increase in within-network telestroke utilization. Compared with before the pandemic (n=167), pandemic-epoch stroke code patients at the CSC (n=211) were more likely to have histories of hypertension, dyslipidemia, coronary artery disease, and substance abuse; no or public health insurance; lower median household income; and to live in the CSC city (P<0.05). There was no difference in age, sex, race/ethnicity, stroke severity, time to presentation, door-to-needle/door-to-reperfusion times, or discharge modified Rankin Scale. CONCLUSIONS: Hospital presentation for stroke-like symptoms decreased during the COVID-19 pandemic, without differences in stroke severity or early outcomes. Individuals living outside of the CSC city were less likely to present for stroke codes at the CSC during the pandemic. Public health initiatives to increase awareness of presenting for non-COVID-19 medical emergencies such as stroke during the pandemic are critical.

Crisis Resource Management and High-Performing Teams in Hyperacute Stroke Care.

BACKGROUND AND PURPOSE: Management of stroke patients in the acute setting is a high-stakes task with several challenges including the need for rapid assessment and treatment, maintenance of high-performing team dynamics, management of cognitive load affecting providers, and factors impacting team communication. Crisis resource management (CRM) provides a framework to tackle these challenges and is well established in other resuscitative disciplines. The current Coronavirus Disease 2019 (COVID-19) pandemic has exposed a potential quality gap in emergency preparedness and the ability to adapt to emergency scenarios in real time. METHODS: Available resources in the literature in other disciplines and expert consensus were used to identify key elements of CRM as they apply to acute stroke management. RESULTS: We outline essential ingredients of CRM as a means to mitigate nontechnical challenges providers face during acute stroke care. These strategies include situational awareness, triage and prioritization, mitigation of cognitive load, team member role clarity, communication, and debriefing. Incorporation of CRM along with simulation is an established tool in other resuscitative disciplines and can be incorporated into acute stroke care. CONCLUSIONS: As stroke care processes evolve during these trying times, the importance of consistent, safe, and efficacious care facilitated by CRM principles offers a unique avenue to alleviate human factors and support high-performing teams.

Pandemic Guidance for Stroke Centers Aiding COVID-19 Treatment Teams.

The coronavirus disease 2019 (COVID-19) pandemic has in some regions overwhelmed the capacity and staffing needs of healthcare systems, necessitating the provision of resources and staff from different disciplines to aid COVID treatment teams. Stroke centers have multidisciplinary clinical and procedural expertise to support COVID treatment teams. Staff safety and patient safety are essential, as are open lines of communication between stroke center leaders and hospital leadership in a pandemic where policies and procedures can change or evolve rapidly. Support needs to be allocated in a way that allows for the continued operation of a fully capable stroke center, with the ability to adjust if stroke center volume or staff attrition requires.

Differential Cytotoxic Function of Resident and Non-resident CD8+ T Cells in the Human Female Reproductive Tract Before and After Menopause.

The functional characterization and regulation of tissue resident and non-resident CD8+ T cells in the human female reproductive tract (FRT) as women age remains a gap in our knowledge. Here we characterized the cytotoxic activity and granular contents of CD8+ T cells from the FRT in pre- and postmenopausal women. We found that under steady-state conditions, CD8+ T cells from endometrium (EM), endocervix and ectocervix displayed direct cytotoxic activity, and that cytotoxicity increased in the EM after menopause. Cytotoxic activity was sensitive to suppression by TGFß exclusively in the EM, and sensitivity to TGFß was reduced after menopause. Under steady-state conditions, cytotoxic activity (measured as direct killing activity), cytotoxic potential (measured as content of cytotoxic molecules) and proliferation are enhanced in non-resident CD8+ (CD103-) T cells compared to tissue resident (CD103+) T cells. Upon activation, CD103+ T cells displayed greater degranulation compared to CD103- T cells, however the granular content of perforin, granzyme A (GZA) or granzyme B (GZB) was significantly lower. After menopause, degranulation significantly increased, and granular release switched from predominantly GZB in premenopausal to GZA in postmenopausal women. Postmenopausal changes affected both CD103+ and CD103- subpopulations. Finally, CD103+ T cells displayed reduced proliferation compared to CD103- T cells, but after proliferation, cytotoxic molecules were similar in each population. Our results highlight the complexity of regulation of cytotoxic function in the FRT before and after menopause, and are relevant to the development of protective strategies against genital infections and gynecological cancers as women age.

Guiding Cardiopulmonary Resuscitation with Focused Echocardiography: A Report of Five Cases.

Background: Focused transthoracic echocardiography has been used to determine etiologies of cardiac arrest and evaluate utility of continuing resuscitation after cardiac arrest. Few guidelines exist advising ultrasound timing within the advanced cardiac life support algorithm. Natural timing of echocardiography occurs during the pulse check, when views are unencumbered by stabilization equipment or vigorous movements. However, recent studies suggest that ultrasound performance during pulse checks prolongs the pause duration of cardiopulmonary resuscitation. Transesophageal echocardiography studies have demonstrated benefits in this regard, but there have been no transthoracic echocardiography studies assessing the physical performance of compressions during cardiopulmonary resuscitation. Objective: The purpose of this study was to describe cases where echocardiography performed at the beginning of the cardiac arrest algorithm offers actionable information to cardiopulmonary resuscitation itself without delaying provision of compressions. Conclusion: Providers using focused echocardiography to evaluate cardiac arrest patients should consider initiating scans at the start of compressions to identify the optimal location for compression delivery and to detect inadequate compressions. Subsequent visualization of full left ventricular compression may be seen after a location change, and combined with end tidal carbon dioxide values, gives indication for improved forward circulatory flow. Although it is not possible in all patients, doing so hastens provision of quality compressions that affect hemodynamic parameters without causing prolongations to the pulse check pause. Further research is needed to determine patient outcomes from both out-of-hospital and in-hospital cardiac arrest when cardiopulmonary resuscitation is visually guided by focused echocardiography.