Daily quetiapine after severe TBI improves learning and memory.

BACKGROUND: Traumatic brain injury (TBI) induces cognitive deficits driven by neuroinflammation and cerebral edema. The commonly used atypical antipsychotic, quetiapine (QTP), has been recently shown to improve post-TBI outcomes. We hypothesized that QTP would thereby improve animal learning and memory 2 weeks after severe TBI. METHODS: CD1 male mice (n = 35) underwent severe TBI (controlled cortical impact, injury, I) or sham craniotomy (S), followed by BID saline (P, placebo) or QTP (10 or 20 mg/kg, IP) for 2 weeks. Animals underwent Morris Water Maze (MWM) exercises to gauge spatial learning and memory. The distance and time required for swimming animals to reach the platform area (Zone 5, Z5) located in quadrant 1 (Zone 1, Z1) was calculated from digital video recordings analyzed using Ethovision software. Animal bodyweights were recorded daily and on day 14, injured cerebral hemispheres were procured for edema determination (wet-to-dry ratio). Intergroup differences were evaluated with ANOVA/Bonferroni correction (p < 0.05). RESULTS: On day 14, animal weight loss recovery was lowest in I + P compared to I + QTP20 and I + QTP10 (p ≤ 0.01 for either). Cerebral edema was greatest in I + P, and only significantly decreased in I + QTP20 (p < 0.05). Both QTP doses similarly improved spatial learning by significantly reducing latency time and travel distance to target zones (p < 0.05). In probe memory trials, only I + QTP20 and not I + QTP10 significantly favored animal reaching or crossing into target zones (p < 0.05). CONCLUSION: Post-TBI QTP reduces brain edema and improves spatial learning and memory with a potential dose dependence impact benefiting memory up to 14 days. These data suggest an unanticipated QTP benefit following brain injury that should be specifically explored.

What's new in whole blood resuscitation? In the trauma bay and beyond.

PURPOSE OF REVIEW: Transfusion therapy commonly supports patient care during life-threatening injury and critical illness. Herein we examine the recent resurgence of whole blood (WB) resuscitation for patients in hemorrhagic shock following trauma and other causes of severe bleeding. RECENT FINDINGS: A growing body of literature supports the use of various forms of WB for hemostatic resuscitation in military and civilian trauma practice. Different types of WB include warm fresh whole blood (FWB) principally used in the military and low titer O cold stored whole blood (LTOWB) used in a variety of military and civilian settings. Incorporating WB initial resuscitation alongside subsequent component therapy reduces aggregate blood product utilization and improves early mortality without adversely impacting intensive care unit length of stay or infection rate. Applications outside the trauma bay include prehospital WB and use in patients with nontraumatic hemorrhagic shock. SUMMARY: Whole blood may be transfused as FWB or LTOWB to support a hemostatic approach to hemorrhagic shock management. Although the bulk of WB resuscitation literature has appropriately focused on hemorrhagic shock following injury, extension to other etiologies of severe hemorrhage will benefit from focused inquiry to address cost, efficacy, approach, and patient-centered outcomes.

Dose-Dependent Tranexamic Acid Blunting of Penumbral Leukocyte Mobilization and Blood-Brain Barrier Permeability Following Traumatic Brain Injury: An In Vivo Murine Study.

BACKGROUND: Early posttraumatic brain injury (TBI) tranexamic acid (TXA) may reduce blood-brain barrier (BBB) permeability, but it is unclear if this effect is fixed regardless of dose. We hypothesized that post-TBI TXA demonstrates a dose-dependent reduction of in vivo penumbral leukocyte mobilization, BBB microvascular permeability, and enhancement of neuroclinical recovery. METHODS: CD1 male mice (n = 40) were randomly assigned to TBI by controlled cortical impact (injury [I]) or sham TBI (S), followed by intravenous bolus of either saline (placebo [P]) or TXA (15, 30, or 60 mg/kg). At 48 h, in vivo pial intravital microscopy visualized live penumbral BBB microvascular leukocytes and albumin leakage. Neuroclinical recovery was assessed by Garcia Neurological Test scores and animal weight changes at 24 h and 48 h after injury. RESULTS: I + TXA60 reduced live penumbral leukocyte rolling compared with I + P (p < 0.001) and both lower TXA doses (p = 0.017 vs. I + TXA15, p = 0.012 vs. I + TXA30). Leukocyte adhesion was infrequent and similar across groups. Only I + TXA60 significantly reduced BBB permeability compared with that in the I + P (p = 0.004) group. All TXA doses improved Garcia Test scores relative to I + P at both 24 h and 48 h (p < 0.001 vs. I + P for all at both time points). Mean 24-h body weight loss was greatest in the I + P (- 8.7 ± 1.3%) group and lowest in the I + TXA15 (- 4.4 ± 1.0%, p = 0.051 vs. I + P) group. CONCLUSIONS: Only higher TXA dosing definitively abrogates penumbral leukocyte mobilization, preserving BBB integrity post TBI. Some neuroclinical recovery is observed, even with lower TXA dosing. Better outcomes with higher dose TXA after TBI may occur secondary to blunting of leukocyte-mediated penumbral cerebrovascular inflammation.

European society for trauma and emergency surgery member-identified research priorities in emergency surgery: a roadmap for future clinical research opportunities.

BACKGROUND: European Society for Trauma and Emergency Surgery (ESTES) is the European community of clinicians providing care to the injured and critically ill surgical patient. ESTES has several interlinked missions - (1) the promotion of optimal emergency surgical care through networked advocacy, (2) promulgation of relevant clinical cognitive and technical skills, and (3) the advancement of scientific inquiry that closes knowledge gaps, iteratively improves upon surgical and perioperative practice, and guides decision-making rooted in scientific evidence. Faced with multitudinous opportunities for clinical research, ESTES undertook an exercise to determine member priorities for surgical research in the short-to-medium term; these research priorities were presented to a panel of experts to inform a 'road map' narrative review which anchored these research priorities in the contemporary surgical literature. METHODS: Individual ESTES members in active emergency surgery practice were polled as a representative sample of end-users and were asked to rank potential areas of future research according to their personal perceptions of priority. Using the modified eDelphi method, an invited panel of ESTES-associated experts in academic emergency surgery then crafted a narrative review highlighting potential research priorities for the Society. RESULTS: Seventy-two responding ESTES members from 23 countries provided feedback to guide the modified eDelphi expert consensus narrative review. Experts then crafted evidence-based mini-reviews highlighting knowledge gaps and areas of interest for future clinical research in emergency surgery: timing of surgery, inter-hospital transfer, diagnostic imaging in emergency surgery, the role of minimally-invasive surgical techniques and Enhanced Recovery After Surgery (ERAS) protocols, patient-reported outcome measures, risk-stratification methods, disparities in access to care, geriatric outcomes, data registry and snapshot audit evaluations, emerging technologies interrogation, and the delivery and benchmarking of emergency surgical training. CONCLUSIONS: This manuscript presents the priorities for future clinical research in academic emergency surgery as determined by a sample of the membership of ESTES. While the precise basis for prioritization was not evident, it may be anchored in disease prevalence, controversy around aspects of current patient care, or indeed the identification of a knowledge gap. These expert-crafted evidence-based mini-reviews provide useful insights that may guide the direction of future academic emergency surgery research efforts.

The American Society of Transplant Surgeons Consensus Statement on Normothermic Regional Perfusion.

On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the ethical tenets of thoracoabdominal normothermic regional perfusion (NRP) and abdominal NRP; (2) provide guidelines for the standards of practice that should govern thoracoabdominal NRP and abdominal NRP; and (3) develop and implement a central database for the collection of NRP donor and recipient data in the United States. National and international leaders in the fields of neuroscience, transplantation, critical care, NRP, Organ Procurement Organizations, transplant centers, and donor families participated. The conference was designed to focus on the controversial issues of neurological flow and function in donation after circulatory death donors during NRP and propose technical standards necessary to ensure that this procedure is performed safely and effectively. This article discusses major topics and conclusions addressed at the meeting.

Gamification in Critical Care Education and Practice.

OBJECTIVES: To explore gamification as an alternative approach to healthcare education and its potential applications to critical care. DATA SOURCES: English language manuscripts addressing: 1) gamification theory and application in healthcare and critical care and 2) implementation science focused on the knowledge-to-practice gap were identified in Medline and PubMed databases (inception to 2023). STUDY SELECTION: Studies delineating gamification underpinnings, application in education or procedural mentoring, utilization for healthcare or critical care education and practice, and analyses of benefits or pitfalls in comparison to other educational or behavioral modification approaches. DATA EXTRACTION: Data indicated the key gamification tenets and the venues within which they were used to enhance knowledge, support continuing medical education, teach procedural skills, enhance decision-making, or modify behavior. DATA SYNTHESIS: Gamification engages learners in a visual and cognitive fashion using competitive approaches to enhance acquiring new knowledge or skills. While gamification may be used in a variety of settings, specific design elements may relate to the learning environment or learner styles. Additionally, solo and group gamification approaches demonstrate success and leverage adult learning theory elements in a low-stress and low-risk setting. The potential for gamification-driven behavioral modification to close the knowledge-to-practice gap and enable guideline and protocol compliance remains underutilized. CONCLUSIONS: Gamification offers the potential to substantially enhance how critical care professionals acquire and then implement new knowledge in a fashion that is more engaging and rewarding than traditional approaches. Accordingly, educational undertakings from courses to offerings at medical professional meetings may benefit from being gamified.

In-Hospital Violence and Its Impact on Critical Care Practitioners.

OBJECTIVES: To provide a narrative review of hospital violence (HV) and its impact on critical care clinicians. DATA SOURCES: Detailed search strategy using PubMed and OVID Medline for English language articles describing HV, risk factors, precipitating events, consequences, and mitigation strategies. STUDY SELECTION: Studies that specifically addressed HV involving critical care medicine clinicians or their practice settings were selected. The time frame was limited to the last 15 years to enhance relevance to current practice. DATA EXTRACTION: Relevant descriptions or studies were reviewed, and abstracted data were parsed by setting, clinician type, location, social media events, impact, outcomes, and responses (agency, facility, health system, individual). DATA SYNTHESIS: HV is globally prevalent, especially in complex care environments, and correlates with a variety of factors including ICU stay duration, conflict, and has recently expanded to out-of-hospital occurrences; online violence as well as stalking is increasingly prevalent. An overlap with violent extremism and terrorism that impacts healthcare facilities and clinicians is similarly relevant. A number of approaches can reduce HV occurrence including, most notably, conflict management training, communication initiatives, and visitor flow and access management practices. Rescue training for HV occurrences seems prudent. CONCLUSIONS: HV is a global problem that impacts clinicians and imperils patient care. Specific initiatives to reduce HV drivers include individual training and system-wide adaptations. Future methods to identify potential perpetrators may leverage machine learning/augmented intelligence approaches.

Teaching Airway Management Using Virtual Reality: A Scoping Review.

Airway management, a defined procedural and cognitive skillset embracing routine tracheal intubation and emergency airway rescue, is most often acquired through an apprenticeship model of opportunistic learning during anesthesia or acute care residency training. This training engages a host of modalities to teach and embed skill sets but is generally time- and location-constrained. Virtual reality (VR)-based simulation training offers the potential for reproducible and asynchronous skill acquisition and maintenance, an advantage that may be important with restricted trainee work hours and low frequency but high-risk events. In the absence of a formal curriculum from training bodies-or expert guidance from medical professional societies-local initiatives have filled the VR training void in an unstructured fashion. We undertook a scoping review to explore current VR-based airway management training programs to assess their approach, outcomes, and technologies to discover programming gaps. English-language publications addressing any aspect of VR simulation training for airway management were identified across PubMed, Embase, and Scopus. Relevant articles were used to craft a scoping review conforming to the Scale for quality Assessment of Narrative Review Articles (SANRA) best-practice guidance. Fifteen studies described VR simulation programs to teach airway management skills, including flexible fibreoptic bronchoscopic intubation (n = 10), direct laryngoscopy (n = 2), and emergency cricothyroidotomy (n = 1). All studies were single institution initiatives and all reported different protocols and end points using bespoke applications of commercial technology or homegrown technologic solutions. VR-based simulation for airway management currently occurs outside of a formal curriculum structure, only for specific skill sets, and without a training pathway for educators. Medical educators with simulation training and medical professional societies with content expertise have the opportunity to develop consensus guidelines that inform training curricula as well as specialty technology use.

Delayed tranexamic acid after traumatic brain injury impedes learning and memory: Early tranexamic acid is favorable but not in sham animals.

BACKGROUND: Early but not late tranexamic acid (TXA) after TBI preserves blood-brain-barrier integrity, but it is unclear if and how dose timing affects cognitive recovery beyond hours postinjury. We hypothesized that early (1 hour post-TBI) but not late (24 hours post-TBI) TXA administration improves cognitive recovery for 14 days. METHODS: CD1 male mice (n = 25) were randomized to severe TBI (injury [I], by controlled cortical impact) or sham craniotomy (S) followed by intravenous saline at 1 hour (placebo [P1]) or 30 mg/kg TXA at 1 hour (TXA1) or 24 hours (TXA24). Daily body weights, Garcia Neurological Test scores, brain/lung water content, and Morris water maze exercises quantifying swimming traffic in the platform quadrant (zone [Z] 1) and platform area (Z5) were recorded for up to 14 days. RESULTS: Among injured groups, I-TXA1 demonstrated fastest weight gain for 14 days and only I-TXA1 showed rapid (day 1) normalization of Garcia Neurological Test ( p = 0.01 vs. I-P1, I-TXA24). In cumulative spatial trials, compared with I-TXA1, I-TXA24 hindered learning (distance to Z5 and % time in Z1, p < 0.05). Compared with I-TXA1, I-TXA24 showed poorer memory with less Z5 time (0.51 vs. 0.16 seconds, p < 0.01) and Z5 crossing frequency. Unexpectedly, TXA in uninjured animals (S-TXA1) displayed faster weight gain but inferior learning and memory. CONCLUSION: Early TXA appears beneficial for cognitive and behavioral outcomes following TBI, although administration 24 hours postinjury consistently impairs cognitive recovery. Tranexamic acid in sham animals may lead to adverse effects on cognition.

Red Blood Cell Transfusion: 2023 AABB International Guidelines.

Importance: Red blood cell transfusion is a common medical intervention with benefits and harms. Objective: To provide recommendations for use of red blood cell transfusion in adults and children. Evidence Review: Standards for trustworthy guidelines were followed, including using Grading of Recommendations Assessment, Development and Evaluation methods, managing conflicts of interest, and making values and preferences explicit. Evidence from systematic reviews of randomized controlled trials was reviewed. Findings: For adults, 45 randomized controlled trials with 20 599 participants compared restrictive hemoglobin-based transfusion thresholds, typically 7 to 8 g/dL, with liberal transfusion thresholds of 9 to 10 g/dL. For pediatric patients, 7 randomized controlled trials with 2730 participants compared a variety of restrictive and liberal transfusion thresholds. For most patient populations, results provided moderate quality evidence that restrictive transfusion thresholds did not adversely affect patient-important outcomes. Recommendation 1: for hospitalized adult patients who are hemodynamically stable, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). In accordance with the restrictive strategy threshold used in most trials, clinicians may choose a threshold of 7.5 g/dL for patients undergoing cardiac surgery and 8 g/dL for those undergoing orthopedic surgery or those with preexisting cardiovascular disease. Recommendation 2: for hospitalized adult patients with hematologic and oncologic disorders, the panel suggests a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (conditional recommendations, low certainty evidence). Recommendation 3: for critically ill children and those at risk of critical illness who are hemodynamically stable and without a hemoglobinopathy, cyanotic cardiac condition, or severe hypoxemia, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). Recommendation 4: for hemodynamically stable children with congenital heart disease, the international panel suggests a transfusion threshold that is based on the cardiac abnormality and stage of surgical repair: 7 g/dL (biventricular repair), 9 g/dL (single-ventricle palliation), or 7 to 9 g/dL (uncorrected congenital heart disease) (conditional recommendation, low certainty evidence). Conclusions and Relevance: It is good practice to consider overall clinical context and alternative therapies to transfusion when making transfusion decisions about an individual patient.

Surgical Emergencies in Patients with Significant Comorbid Diseases.

Emergency surgery in patients with significant comorbidities benefits from a structured approach to preoperative evaluation, intra-operative intervention, and postoperative management. Providing goal concordant care is ideal using shared decision-making. When operation cannot achieve the patient's goal, non-operative therapy including Comfort Care is appropriate. When surgical therapy is offered, preoperative physiology-improving interventions are far fewer than in other phases. Reevaluation of clinical care progress helps define trajectory and inform goals of care. Palliative Care Medicine may be critical in supporting loved ones during a patient's critical illness. Outcome evaluation defines successful strategies and outline opportunities for improvement.

EquiPrEP: An implementation science protocol for promoting equitable access and uptake of long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP).

BACKGROUND: Long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) was approved by the U.S. Food and Drug Administration in December 2021. This initial phase of implementation represents a prime opportunity to ensure equitable LAI-PrEP provision to communities often underrepresented in PrEP care before disparities in access and uptake emerge. Herein, we describe the EquiPrEP Project which utilizes an equity-oriented implementation science framework to optimize LAI-PrEP rollout in an urban safety-net clinic in New York City. METHODS: The primary objectives of this project are to: (1) increase LAI-PrEP initiation overall; (2) increase uptake among groups disproportionately impacted by the HIV epidemic; (3) preserve high PrEP retention while expanding use; and (4) identify barriers and facilitators to LAI-PrEP use. EquiPrEP will enroll 210 PrEP-eligible participants into LAI-PrEP care with planned follow-up for one year. We will recruit from the following priority populations: Black and/or Latine men who have sex with men, Black and/or Latine cisgender women, and transgender women and nonbinary individuals. To evaluate implementation of LAI-PrEP, we will utilize equity-focused iterations of the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework and the Consolidated Framework for Implementation Research (CFIR), in addition to longitudinal surveys and qualitative interviews. DISCUSSION: Novel LAI-PrEP formulations carry tremendous potential to revolutionize the field of HIV prevention. Implementation strategies rooted in equity are needed to ensure that marginalized populations have access to LAI-PrEP and to address the structural factors that hinder initiation and retention in care.

The impact of hypertonic saline on damage control laparotomy after penetrating abdominal trauma.

PURPOSE: The inability to achieve primary fascial closure (PFC) after emergency laparotomy increases the rates of adverse outcomes including fistula formation, incisional hernia, and intraabdominal infection. Hypertonic saline (HTS) infusion improves early PFC rates and decreases time to PFC in patients undergoing damage control laparotomy (DCL) after injury. We hypothesized that in patients undergoing DCL after penetrating abdominal injury, HTS infusion would decrease the time to fascial closure as well as the volume of crystalloid required for resuscitation without inducing clinically relevant acute kidney injury (AKI) or electrolyte derangements. METHODS: We retrospectively analyzed all penetrating abdominal injury patients undergoing DCL within the University of Pennsylvania Health System (January 2015-December 2018). We compared patients who received 3% HTS at 30 mL/h (HTS) to those receiving isotonic fluid (ISO) for resuscitation while the abdominal fascia remained open. Primary outcomes were the rate of early PFC (PFC within 72 h) and time to PFC; secondary outcomes included acute kidney injury, sodium derangement, ventilator-free days, hospital length of stay (LOS), and ICU LOS. Intergroup comparisons occurred by ANOVA and Tukey's comparison, and student's t, and Fischer's exact tests, as appropriate. A Shapiro-Wilk test was performed to determine normality of distribution. RESULTS: Fifty-seven patients underwent DCL after penetrating abdominal injury (ISO n = 41, HTS n = 16). There were no significant intergroup differences in baseline characteristics or injury severity score. Mean time to fascial closure was significantly shorter in HTS (36.37 h ± 14.21 vs 59.05 h ± 50.75, p = 0.02), and the PFC rate was significantly higher in HTS (100% vs 73%, p = 0.01). Mean 24-h fluid and 48-h fluid totals were significantly less in HTS versus ISO (24 h: 5.2L ± 1.7 vs 8.6L ± 2.2, p = 0.01; 48 h: 1.3L ± 1.1 vs 2.6L ± 2.2, p = 0.008). During the first 72 h, peak sodium (Na) concentration (146.2 mEq/L ± 2.94 vs 142.8 mEq/L ± 3.67, p = 0.0017) as well as change in Na from ICU admission (5.1 mEq/L vs 2.3, p = 0.016) were significantly higher in HTS compared to ISO. Patients in the HTS group received significantly more blood in the trauma bay compared to ISO. There were no intergroup differences in intraoperative blood transfusion volume, AKI incidence, change in chloride concentration (△Cl) from ICU admit, Na to Cl gradient (Na:Cl), initial serum creatinine (Cr), peak post-operative Cr, change in creatinine concentration (△Cr) from ICU admission, creatinine clearance (CrCl), initial serum potassium (K), peak ICU K, change in K from ICU admission, initial pH, highest or lowest post-operative pH, mean hospital LOS, ICU LOS, and ventilator-free days. CONCLUSIONS: HTS infusion in patients undergoing DCL after penetrating abdominal injury decreases the time to fascial closure and led to 100% early PFC. HTS infusion also decreased resuscitative fluid volume without causing significant AKI or electrolyte derangement. HTS appears to offer a safe and effective fluid management approach in patients who sustain penetrating abdominal injury and DCL to support early PFC without inducing measurable harm. LEVEL OF EVIDENCE: Level III.

Are trauma surgeons prepared? A survey of trauma surgeons' disaster preparedness before and during the COVID-19 pandemic.

Objective: US trauma centers (TCs) must remain prepared for mass casualty incidents (MCIs). However, trauma surgeons may lack formal MCI training. The recent COVID-19 pandemic drove multiple patient surges, overloaded Emergency Medical Services (EMS) agencies, and stressed TCs. This survey assessed trauma surgeons' MCI training, experience, and system and personal preparedness before the pandemic compared with the pandemic's third year. Methods: Survey invitations were emailed to all 1544 members of the American Association for the Surgery of Trauma in 2019, and then resent in 2022 to 1575 members with additional questions regarding the pandemic. Questions assessed practice type, TC characteristics, training, experience, beliefs about personal and hospital preparedness, likelihood of MCI scenarios, interventions desired from membership organizations, and pandemic experiences. Results: The response rate was 16.7% in 2019 and 12% in 2022. In 2022, surgeons felt better prepared than their hospitals for pandemic care, mass shootings, and active shooters, but remained feeling less well prepared for cyberattack and hazardous material events, compared with 2019. Only 35% of the respondents had unintentional MCI response experience in 2019 or 2022, and even fewer had experience with intentional MCI. 78% had completed a Stop the Bleed (STB) course and 63% own an STB kit. 57% had engaged in family preparedness activities; less than 40% had a family action plan if they could not come home during an MCI. 100% of the respondents witnessed pandemic-related adverse events, including colleague and coworker illness, patient surges, and resource limitations, and 17% faced colleague or coworker death. Conclusions: Trauma surgeons thought that they became better at pandemic care and rated themselves as better prepared than their hospitals for MCI care, which is an opportunity for them to take greater leadership roles. Opportunities remain to improve surgeons' family and personal MCI preparedness. Surgeons' most desired professional organization interventions include advocacy, national standards for TC preparedness, and online training. Level of evidence: VII, survey of expert opinion.

Successful Integration of HIV PrEP in Primary Care and Women's Health Clinical Practice: A Model for Implementation.

Ending the HIV Epidemic is contingent upon the increased utilization of pre-exposure prophylaxis (PrEP). The majority of PrEP in the United States is prescribed in specialty care settings; however, to achieve national implementation goals, it is necessary to expand PrEP services in primary care and women's health clinics. To this end, a prospective cohort study was conducted of health care providers participating in one of three rounds of a virtual program aimed at increasing the number of PrEP prescribers in primary care and women's health clinics within the NYC Health and Hospitals network, the public healthcare system of New York City. Provider prescribing behavior was compared at pre-intervention (August 2018-September 2019) and post-intervention (October 2019-February 2021). Among 104 providers, the number prescribing PrEP increased from 12 (11.5%) to 51 (49%) and the number of individual patients on PrEP increased from 19 to 128. The program utilized clinical integration models centering on existing STI management workflows and was associated with increased numbers of PrEP prescribers and volume of prescriptions in primary care and women's health clinics. The dissemination of similar programs could support national scale-up of PrEP.

Early posttraumatic brain injury tranexamic acid prevents blood-brain barrier hyperpermeability and improves surrogates of neuroclinical recovery.

BACKGROUND: Tranexamic acid (TXA) given early, but not late, after traumatic brain injury (TBI) appears to improve survival. This may be partly related to TXA-driven profibrinolysis and increased leukocyte (LEU)-mediated inflammation when administered late post-injury. We hypothesized that early TXA (1 hour post-TBI), blunts penumbral, blood-brain barrier (BBB) leukocyte-endothelial cell (LEU-EC) interactions and microvascular permeability, in vivo when compared with late administration (24 hours post-TBI). METHODS: CD1 male mice (n = 35) were randomized to severe TBI (injury by controlled cortical impact; injury: velocity, 6 m/s; depth, 1 mm; diameter, 3 mm) or sham craniotomy followed by intravenous saline (placebo) at 1 hour, or TXA (30 mg/kg) at 1 hour or 24 hours. At 48 hours, in vivo pial intravital microscopy visualized live penumbral LEU-EC interactions and BBB microvascular fluorescent albumin leakage. Neuroclinical recovery was assessed by the Garcia Neurological Test (motor, sensory, reflex, and balance assessments) and body weight loss recovery at 1 and 2 days after injury. Analysis of variance with Bonferroni correction assessed intergroup differences ( p < 0.05). RESULTS: One-hour, but not 24-hour, TXA improved Garcia Neurological Test performance on day 1 post-TBI compared with placebo. Both 1 hour and 24 hours TXA similarly improved day 1 weight loss recovery, but only 1 hour TXA significantly improved weight loss recovery on day 2 compared with placebo ( p = 0.04). No intergroup differences were found in LEU rolling or adhesion between injured animal groups. Compared with untreated injured animals, only TXA at 1 hour reduced BBB permeability. CONCLUSION: Only early post-TBI TXA consistently improves murine neurological recovery. Tranexamic acid preserves BBB integrity but only when administered early. This effect appears independent of LEU-EC interactions and demonstrates a time-sensitive effect that supports only early TXA administration.