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.

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.

Association of Neighborhood-Level Socioeconomic Factors With Delay to Hospital Arrival in Patients With Acute Stroke.

BACKGROUND AND OBJECTIVES: Delivery of acute ischemic stroke (AIS) therapies is contingent on the duration from last known well (LKW) to emergency department arrival time (EDAT). One reason for treatment ineligibility is delay in presentation to the hospital. We evaluate patient and neighborhood characteristics associated with time from LKW to EDAT. METHODS: This was a retrospective observational study of patients presenting to the Yale New Haven Hospital in the AIS code pathway from 2010 to 2020. Patients presenting within 4.5 hours from LKW who were recorded in the institutional Get With the Guidelines Stroke registry were classified as early while those presenting beyond 4.5 hours were designated as late. Temporal trends in late presentation were explored by univariate logistic regression. Using variables significant in univariate analysis at p < 0.05, we developed a mixed-effect logistic regression model to estimate the probability of late presentation as a function of patient-level and neighborhood (ZIP)-level characteristics (area deprivation index [ADI] derived from the Health Resources and Services Administration), adjusted for calendar year and geographic distance from the centroid of the ZIP code to the hospital. RESULTS: A total of 2,643 patients with AIS from 2010 to 2020 were included (63.4% presented late and 36.6% presented early). The frequency of late presentation increased significantly from 68% in 2010 to 71% in 2020 (p = 0.002) and only among non-White patients. Patients presenting late were more likely to be non-White (37.1% vs 26.9%, p < 0.0001), arrive by means other than emergency medical services (EMS) (32.7% vs 16.1%, p < 0.0001), have an NIHSS <6 (68.7% vs 55.2%, p < 0.0001), and present from a neighborhood with a higher ADI category (p = 0.0001) that was nearer to the hospital (median 5.8 vs 7.7 miles, p = 0.0032). In the mixed model, the ADI by units of 10 (odds ratio [OR] 1.022, 95% confidence interval [CI] 1.020-1.024), non-White race (OR 1.083, 95% CI 1.039-1.127), arrival by means other than EMS (OR 1.193, 95% CI 1.145-1.124), and an NIHSS <6 (OR 1.085, 95% CI 1.041-1.129) were associated with late presentation. DISCUSSION: In addition to patient-level factors, socioeconomic deprivation of neighborhood of residence contributes to delays in hospital presentation for AIS. These findings may provide opportunities for targeted interventions to improve presentation times in at-risk communities.

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.

Development and validation of a novel score to predict brain death after out-of-hospital cardiac arrest.

BACKGROUND AND OBJECTIVES: Brain death (BD) occurs in 9-24% of successfully resuscitated out-of-hospital cardiac arrests (OHCA). To predict BD after OHCA, we developed a novel brain death risk (BDR) score. METHODS: We identified independent predictors of BD after OHCA in a retrospective, single academic center cohort between 2011 and 2021. The BDR score ranges from 0 to 7 points and includes: non-shockable rhythm (1 point), drug overdose as etiology of arrest (1 point), evidence of grey-white differentiation loss or sulcal effacement on head computed tomography (CT) radiology report within 24 hours of arrest (2 points), Full-Outline-Of-UnResponsiveness (FOUR) score of 0 (2 points), FOUR score 1-5 (1 point), and age <45 years (1 point). We internally validated the BDR score using k-fold cross validation (k = 8) and externally validated the score at an independent academic center. The main outcome was BD. RESULTS: The development cohort included 362OHCA patients, of whom 18% (N = 58) experienced BD. Internal validation provided an area under the receiving operator characteristic curve (AUC) (95% CI) of 0.931 (0.905-0.957). In the validation cohort, 19.8% (N = 17) experienced BD. The AUC (95% CI) was 0.849 (0.765-0.933). In both cohorts, a BDR score >4 was the optimal cut off (sensitivity 0.903 and 0.882, specificity 0.830 and 0.652, in the development and validation cohorts respectively). DISCUSSION: The BDR score identifies those at highest risk for BD after OHCA. Our data suggest that a BDR score >4 is the optimal cut off.

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.

Identification of White Matter Hyperintensities in Routine Emergency Department Visits Using Portable Bedside Magnetic Resonance Imaging.

Background White matter hyperintensity (WMH) on magnetic resonance imaging (MRI) of the brain is associated with vascular cognitive impairment, cardiovascular disease, and stroke. We hypothesized that portable magnetic resonance imaging (pMRI) could successfully identify WMHs and facilitate doing so in an unconventional setting. Methods and Results In a retrospective cohort of patients with both a conventional 1.5 Tesla MRI and pMRI, we report Cohen's kappa (κ) to measure agreement for detection of moderate to severe WMH (Fazekas ≥2). In a subsequent prospective observational study, we enrolled adult patients with a vascular risk factor being evaluated in the emergency department for a nonstroke complaint and measured WMH using pMRI. In the retrospective cohort, we included 33 patients, identifying 16 (49.5%) with WMH on conventional MRI. Between 2 raters evaluating pMRI, the interrater agreement on WMH was strong (κ=0.81), and between 1 rater for conventional MRI and the 2 raters for pMRI, intermodality agreement was moderate (κ=0.66, 0.60). In the prospective cohort we enrolled 91 individuals (mean age, 62.6 years; 53.9% men; 73.6% with hypertension), of which 58.2% had WMHs on pMRI. Among 37 Black and Hispanic individuals, the Area Deprivation Index was higher (versus White, 51.8±12.9 versus 37.9±11.9; P<0.001). Among 81 individuals who did not have a standard-of-care MRI in the preceding year, we identified WMHs in 43 of 81 (53.1%). Conclusions Portable, low-field imaging could be useful for identifying moderate to severe WMHs. These preliminary results introduce a novel role for pMRI outside of acute care and the potential role for pMRI to reduce disparities in neuroimaging.

Validation of the rCAST score and comparison to the PCAC and FOUR scores for prognostication after out-of-hospital cardiac arrest.

AIM: Early, accurate outcome prediction after out-of-hospital cardiac arrest (OHCA) is critical for clinical decision-making and resource allocation. We sought to validate the revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST) score in a United States cohort and compare its prognostic performance to the Pittsburgh Cardiac Arrest Category (PCAC) and Full Outline of UnResponsiveness (FOUR) scores. METHODS: This is a single-center, retrospective study of OHCA patients admitted between January 2014-August 2022. Area under the receiver operating curve (AUC) was computed for each score for predicting poor neurologic outcome at discharge and in-hospital mortality. We compared the scores' predictive abilities via Delong's test. RESULTS: Of 505 OHCA patients with all scores available, the medians [IQR] for rCAST, PCAC, and FOUR scores were 9.5 [6.0, 11.5], 4 [3, 4], and 2 [0, 5], respectively. The AUC [95% confidence interval] of the rCAST, PCAC, and FOUR scores for predicting poor neurologic outcome were 0.815 [0.763-0.867], 0.753 [0.697-0.809], and 0.841 [0.796-0.886], respectively. The AUC [95% confidence interval] of the rCAST, PCAC, and FOUR scores for predicting mortality were 0.799 [0.751-0.847], 0.723 [0.673-0.773], and 0.813 [0.770-0.855], respectively. The rCAST score was superior to the PCAC score for predicting mortality (p = 0.017). The FOUR score was superior to the PCAC score for predicting poor neurological outcome (p < 0.001) and mortality (p < 0.001). CONCLUSION: The rCAST score can reliably predict poor outcome in a United States cohort of OHCA patients regardless of TTM status and outperforms the PCAC score.

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.

Emergency department initiated resuscitative endovascular balloon occlusion of the aorta (REBOA) for out-of-hospital cardiac arrest is feasible and associated with improvements in end-tidal carbon dioxide.

Objectives: Out-of-hospital cardiac arrest (OHCA) claims the lives of approximately 350,000 people in the United States each year. Resuscitative endovascular balloon occlusion of the aorta (REBOA) when used as an adjunct to advanced cardiac life support may improve cardio-cerebral perfusion. Our primary research objective was to determine the feasibility of emergency department (ED)-initiated REBOA for OHCA patients in an academic urban ED. Methods: This was a single-center, single-arm, early feasibility trial that used REBOA as an adjunct to advanced cardiac life support (ACLS) in OHCA. Subjects under 80 years with witnessed OHCA and who received cardiopulmonary rescuitation (CPR) within 6 minutes were eligible. Results: Five patients were enrolled between February 2020 and April 2021. The procedure was successful in all patients and 4 of 5 (80%) patients had transient return of spontaneous circulation (ROSC) after aortic occlusion. Unfortunately, all patients re-arrested soon after intra-aortic balloon deflation and none survived to hospital admission. At 30 seconds post-aortic occlusion, investigators noted a statistically significant increase in end tidal carbon dioxide of 26% (95% confidence interval, 10%, 44%). Conclusion: Initiating REBOA for OHCA patients in an academic urban ED setting is feasible. Aortic occlusion during chest compressions is temporally associated with improvements in end tidal carbon dioxide 30 seconds after aortic occlusion. Four of 5 patients achieved ROSC after aortic occlusion; however, deflation of the intra-aortic balloon quickly led to re-arrest and death in all patients. Future research should focus on the utilization of partial-REBOA to prevent re-arrest after ROSC, as well as the optimal way to incorporate this technique with other endovascular reperfusion strategies.

Prehospital emergency department care activations during the initial COVID-19 pandemic surge.

OBJECTIVE: To describe trends in prehospital presentations of critical medical and trauma conditions during the COVID-19 pandemic using prehospital and emergency department (ED) care activations. METHODS: Observational analysis of ED care activations in a tertiary, urban ED between March 10, 2020 and September 1, 2020 was compared to the same time periods in 2018 and 2019. ED care activations for critical medical conditions were classified based on clinical indication: undifferentiated medical, trauma, or stroke. MAIN OUTCOME: The primary outcomes were the number of patients presenting from the prehospital setting with specified ED activation criteria, total ED volume, ambulance arrival volume, and volume of COVID-19 hospital admissions. Locally weighted scatterplot smoothing curves were used to visually display our results. RESULTS: There were 1,461 undifferentiated medical activations, 905 stroke activations, and 1,478 trauma activations recorded, representing absolute decreases of 11.3, 28.1, and 20.3 percent, respectively, relative to the same period in 2019, coinciding with the declaration of a public health emergency in Connecticut. For all three types of presentation, post-peak spikes in activations were observed in early May, approximately two weeks after our health system in Connecticut reached its peak number of COVID-19 hospitalizations-eg, undifferentiated medical activations: increase in 280 percent, n = 140 from 2019, p < 0.0001-and declined thereafter, reaching a nadir in early June 2020. CONCLUSIONS: After the announcement of public health measures to mitigate COVID-19, ED care activations declined in a large Northeast academic ED, followed by post-peak surges in activations as COVID- 19 cases decreased.

Bedside monitoring of hypoxic ischemic brain injury using low-field, portable brain magnetic resonance imaging after cardiac arrest.

BACKGROUND: Assessment of brain injury severity is critically important after survival from cardiac arrest (CA). Recent advances in low-field MRI technology have permitted the acquisition of clinically useful bedside brain imaging. Our objective was to deploy a novel approach for evaluating brain injury after CA in critically ill patients at high risk for adverse neurological outcome. METHODS: This retrospective, single center study involved review of all consecutive portable MRIs performed as part of clinical care for CA patients between September 2020 and January 2022. Portable MR images were retrospectively reviewed by a blinded board-certified neuroradiologist (S.P.). Fluid-inversion recovery (FLAIR) signal intensities were measured in select regions of interest. RESULTS: We performed 22 low-field MRI examinations in 19 patients resuscitated from CA (68.4% male, mean [standard deviation] age, 51.8 [13.1] years). Twelve patients (63.2%) had findings consistent with HIBI on conventional neuroimaging radiology report. Low-field MRI detected findings consistent with HIBI in all of these patients. Low-field MRI was acquired at a median (interquartile range) of 78 (40-136) hours post-arrest. Quantitatively, we measured FLAIR signal intensity in three regions of interest, which were higher amongst patients with confirmed HIBI. Low-field MRI was completed in all patients without disruption of intensive care unit equipment monitoring and no safety events occurred. CONCLUSION: In a critically ill CA population in whom MR imaging is often not feasible, low-field MRI can be deployed at the bedside to identify HIBI. Low-field MRI provides an opportunity to evaluate the time-dependent nature of MRI findings in CA survivors.

Portable, low-field magnetic resonance imaging enables highly accessible and dynamic bedside evaluation of ischemic stroke.

Brain imaging is essential to the clinical management of patients with ischemic stroke. Timely and accessible neuroimaging, however, can be limited in clinical stroke pathways. Here, portable magnetic resonance imaging (pMRI) acquired at very low magnetic field strength (0.064 T) is used to obtain actionable bedside neuroimaging for 50 confirmed patients with ischemic stroke. Low-field pMRI detected infarcts in 45 (90%) patients across cortical, subcortical, and cerebellar structures. Lesions as small as 4 mm were captured. Infarcts appeared as hyperintense regions on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences. Stroke volume measurements were consistent across pMRI sequences and between low-field pMRI and conventional high-field MRI studies. Low-field pMRI stroke volumes significantly correlated with stroke severity and functional outcome at discharge. These results validate the use of low-field pMRI to obtain clinically useful imaging of stroke, setting the stage for use in resource-limited environments.

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.

Methodology for Low-Field, Portable Magnetic Resonance Neuroimaging at the Bedside.

Neuroimaging is a critical component of triage and treatment for patients who present with neuropathology. Magnetic resonance imaging and non-contrast computed tomography are the gold standard for diagnosis and prognostication of patients with acute brain injuries. However, these modalities require intra-hospital transport to strict, access-controlled environments, which puts critically ill patients at risk for complications and secondary injuries. A novel, portable MRI (pMRI) device that can be deployed at the patient's bedside provides a needed solution. In a dual-center investigation, Yale New Haven Hospital has obtained regular neuroimaging on patients using the pMRI as part of routine clinical care in the Emergency Department and Intensive Care Unit (ICU) since August of 2020. Massachusetts General Hospital has begun using pMRI in the Neuroscience Intensive Care Unit since January 2021. This technology has expanded the population of patients who can receive MRI imaging by increasing accessibility and timeliness for scan completion by eliminating the need for transport and increasing the potential for serial monitoring. Here we describe our methods for screening, coordinating, and executing pMRI exams and provide further detail on how to scan specific patient populations.

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.