Removing the barriers to prehospital blood: a roadmap to success.

ABSTRACT: This review describes the necessity, evolution, and current state of prehospital blood programs in the United States. Less than 1% of 9-1-1 Ground Emergency Medical Service agencies have been able to successfully implement prehospital blood transfusions as part of a resuscitation strategy for patients in hemorrhagic shock despite estimates that annually between 54,000 and 900,000 patients may benefit from its use. The use of prehospital blood transfusions as a tool for managing hemorrhagic shock has barriers to overcome to ensure it becomes widely available to patients throughout the United States. Barriers include 1) current state Emergency Medical Services clinicians' scope of practice limitations, 2) program costs and reimbursement of blood products, 3) no centralized data collection process for prehospital hemorrhagic shock and patient outcomes, 4) collaboration between prehospital agencies, blood suppliers, and hospital clinicians and transfusion service activities. The following paper identifies barriers and a proposed roadmap to reduce death due to prehospital hemorrhage.

A comparison of computed tomography angiography and digital subtraction angiography for the diagnosis of penetrating cerebrovascular injury: a prospective multicenter study.

OBJECTIVE: In this research, the authors sought to characterize the incidence and extent of cerebrovascular lesions after penetrating brain injury in a civilian population and to compare the diagnostic value of head computed tomography angiography (CTA) and digital subtraction angiography (DSA) in their diagnosis. METHODS: This was a prospective multicenter cohort study of patients with penetrating brain injury due to any mechanism presenting at two academic medical centers over a 3-year period (May 2020 to May 2023). All patients underwent both CTA and DSA. The sensitivity and specificity of CTA was calculated, with DSA considered the gold standard. The number of DSA studies needed to identify a lesion requiring treatment that had not been identified on CTA was also calculated. RESULTS: A total of 73 patients were included in the study, 33 of whom had at least 1 penetrating cerebrovascular injury, for an incidence of 45.2%. The injuries included 13 pseudoaneurysms, 11 major arterial occlusions, 9 dural venous sinus occlusions, 8 dural arteriovenous fistulas, and 6 carotid cavernous fistulas. The sensitivity of CTA was 36.4%, and the specificity was 85.0%. Overall, 5.6 DSA studies were needed to identify a lesion requiring treatment that had not been identified with CTA. CONCLUSIONS: Cerebrovascular injury is common after penetrating brain injury, and CTA alone is insufficient to diagnosis these injuries. Patients with penetrating brain injuries should routinely undergo DSA.

Incidence and Risk Model of Post-Traumatic Hydrocephalus in Patients with Traumatic Brain Injury.

OBJECTIVE: Post-traumatic hydrocephalus (PTH) is a complication following traumatic brain injury (TBI). Early diagnosis and treatment are essential to improving outcomes. We report the incidence and risk factors of PTH in a large TBI population while considering death as a competing risk. METHODS: We conducted a retrospective cohort study on consecutive TBI patients with radiographic intracranial abnormalities admitted to our academic medical center from 2009 to 2015. We assessed patient demographics, perioperative data, and in-hospital data as risk factors for PTH using survival analysis with death as a competing risk. RESULTS: Among 7,473 patients, the overall incidence of PTH requiring shunt surgery was 0.94%. The adjusted cumulative incidence was 0.99%. The all-cause cumulative hazard for death was 32.6%, which was considered a competing risk during analysis. Craniectomy (HR 11.53, P < 0.001, 95% CI 5.57-223.85), venous sinus injury (HR 4.13, P = 0.01, 95% CI 1.53-11.16), and age ≤5 (P < 0.001) were significant risk factors for PTH. Glasgow Coma Score (GCS) > 13 was protective against shunt placement (HR 0.50, P = 0.04, 95% CI 0.26-0.97). Shunt surgery occurred after hospital discharge in 60% of patients. CONCLUSIONS: We describe the incidence and risk factors for PTH in a large traumatic brain injury (TBI) population. Most cases of PTH were diagnosed after hospital discharge, suggesting that close follow-up and multidisciplinary diagnostic vigilance for PTH are needed to prevent morbidity and disability.

Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model.

Multiple vaccines have been developed and licensed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While these vaccines reduce disease severity, they do not prevent infection. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor-binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4 A using cryogenicelectron microscopy. Using this RBD-grafted SpyCage scaffold (RBD + SpyCage), we performed two intranasal vaccination studies in the "gold-standard" pre-clinical Syrian hamster model. The initial study focused on assessing the immunogenicity of RBD + SpyCage combined with the LTA1 intranasal adjuvant. These studies showed RBD + SpyCage vaccination induced an antibody response that promoted viral clearance but did not prevent infection. Inclusion of the LTA1 adjuvant enhanced the magnitude of the antibody response but did not enhance protection. Thus, in an expanded study, in the absence of an intranasal adjuvant, we evaluated if covalent bonding of RBD to the scaffold was required to induce an antibody response. Covalent grafting of RBD was required for the vaccine to be immunogenic, and animals vaccinated with RBD + SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.IMPORTANCEDespite the availability of efficacious COVID vaccines that reduce disease severity, SARS-CoV-2 continues to spread. To limit SARS-CoV-2 transmission, the next generation of vaccines must induce immunity in the mucosa of the upper respiratory tract. Therefore, we performed proof-of-principle, intranasal vaccination studies with a recombinant protein nanoparticle scaffold, SpyCage, decorated with the RBD of the S protein (SpyCage + RBD). We show that SpyCage + RBD was immunogenic and enhanced SARS-CoV-2 clearance from the nose and lungs of Syrian hamsters. Moreover, covalent grafting of the RBD to the scaffold was required to induce an immune response when given via the intranasal route. These proof-of-concept findings indicate that with further enhancements to immunogenicity (e.g., adjuvant incorporation and antigen optimization), the SpyCage scaffold has potential as a versatile, intranasal vaccine platform for respiratory pathogens.

The Simons Observatory: Cryogenic half wave plate rotation mechanism for the small aperture telescopes.

We present the requirements, design, and evaluation of the cryogenic continuously rotating half-wave plate (CHWP) for the Simons Observatory (SO). SO is a cosmic microwave background polarization experiment at Parque Astronómico de Atacama in northern Chile that covers a wide range of angular scales using both small (⌀0.42 m) and large (⌀6 m) aperture telescopes. In particular, the small aperture telescopes (SATs) focus on large angular scales for primordial B-mode polarization. To this end, the SATs employ a CHWP to modulate the polarization of the incident light at 8 Hz, suppressing atmospheric 1/f noise and mitigating systematic uncertainties that would otherwise arise due to the differential response of detectors sensitive to orthogonal polarizations. The CHWP consists of a 505 mm diameter achromatic sapphire HWP and a cryogenic rotation mechanism, both of which are cooled down to ∼50 K to reduce detector thermal loading. Under normal operation, the HWP is suspended by a superconducting magnetic bearing and rotates with a constant 2 Hz frequency, controlled by an electromagnetic synchronous motor. We find that the number of superconductors and the number of magnets that make up the superconducting magnetic bearing are important design parameters, especially for the rotation mechanism's vibration performance. The rotation angle is detected through an angular encoder with a noise level of 0.07 µrad s. During a cooldown process, the rotor is held in place by a grip-and-release mechanism that serves as both an alignment device and a thermal path. In this paper, we provide an overview of the SO SAT CHWP: its requirements, hardware design, and laboratory performance.

The Chief Wellness Officer: A long overdue catalyst for systemic change in Emergency Medicine.

GOALS: The American healthcare system is amid a burnout epidemic, worsened by COVID, that must be addressed expeditiously and with high priority. The burden Emergency Physicians encountered before and during the pandemic is well known, with countless healthcare workers exiting the work force. A Chief Wellness Officer (CWO) is a senior leader who works primarily to cultivate organisational wellness and to foster and promote a culture of well-being throughout an institution. Specifically, the CWO assists the health system leadership promote clinician engagement and address clinician burnout. This paper explores the status of existing CWOs, and cites the benefits, impacts, and barriers to implementation of a CWO, with focus on the field of Emergency Medicine (EM). METHODS: A steering committee of wellness experts was formed from a national EM organisation. A purposive search and literature review using search terms relating to CWOs was completed. Publications were examined for relevance and recency. The committee created an online questionnaire surveying current US CWOs, conducted personal interviews, and met through regular focused meetings. A framework delineating the role of a CWO as an organisation evolves from instituting novice wellness interventions to expert organisational innovations was created. PRINCIPLE FINDINGS: Despite their title, CWOs are not regularly included in c-suite decisions. Barriers to instituting a CWO include perceived financial cost, the medical system itself, and physician resistance. Defining and measuring objective return on investment may be a solution to overcoming barriers. CWOs who create comprehensive institutional wellness innovations bring organisations to the highest proficient and expert levels of wellness practices, positively affecting physician engagement and deflecting burnout. CWOs instituting novice and beginner levels of wellness interventions, especially in EM, only modestly impact individual wellness practices. PRACTICAL APPLICATIONS: A CWO and team with an organisational voice and a C-suite stakeholder's seat are essential to centralising and leading effective wellness efforts and innovations in EM and other specialities. This team will improve the work environment and culture and begin to fix our broken healthcare system and providers.

The Roles of Protocols and Protocolization in Improving Outcome From Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Our Phase-I parallel-cohort study suggested that managing severe traumatic brain injury (sTBI) in the absence of intracranial pressure (ICP) monitoring using an ad hoc Imaging and Clinical Examination (ICE) treatment protocol was associated with superior outcome vs nonprotocolized management but could not differentiate the influence of protocolization from that of the specific protocol. Phase II investigates whether adopting the Consensus REVised Imaging and Clinical Examination (CREVICE) protocol improved outcome directly or indirectly via protocolization. METHODS: We performed a Phase-II sequential parallel-cohort study examining adoption of the CREVICE protocol from no protocol vs a previous protocol in patients with sTBI older than 13 years presenting ≤24 hours after injury. Primary outcome was prespecified 6-month recovery. The study was done mostly at public South American centers managing sTBI without ICP monitoring. Fourteen Phase-I nonprotocol centers and 5 Phase-I protocol centers adopted CREVICE. Data were analyzed using generalized estimating equation regression adjusting for demographic imbalances. RESULTS: A total of 501 patients (86% male, mean age 35.4 years) enrolled; 81% had 6 months of follow-up. Adopting CREVICE from no protocol was associated with significantly superior results for overall 6-month extended Glasgow Outcome Score (GOSE) (protocol effect = 0.53 [0.11, 0.95], P = .013), mortality (36% vs 21%, HR = 0.59 [0.46, 0.76], P < .001), and orientation (Galveston Orientation and Amnesia Test discharge protocol effect = 10.9 [6.0, 15.8], P < .001, 6-month protocol effect = 11.4 [4.1, 18.6], P < .005). Adopting CREVICE from ICE was associated with significant benefits to GOSE (protocol effect = 0.51 [0.04, 0.98], P = .033), 6-month mortality (25% vs 18%, HR = 0.55 [0.39, 0.77], P < .001), and orientation (Galveston Orientation and Amnesia Test 6-month protocol effect = 9.2 [3.6, 14.7], P = .004). Comparing both groups using CREVICE, those who had used ICE previously had significantly better GOSE (protocol effect = 1.15 [0.09, 2.20], P = .033). CONCLUSION: Centers managing adult sTBI without ICP monitoring should strongly consider protocolization through adopting/adapting the CREVICE protocol. Protocolization is indirectly supported at sTBI centers regardless of resource availability.

Stakeholder endorsement advancing the implementation of a patient-reported domain for harms in rheumatology clinical trials: Outcome of the OMERACT Safety Working Group.

OBJECTIVES: To develop an understanding of the concept of safety/harms experienced by patients involved in clinical trials for their rheumatic and musculoskeletal diseases (RMDs) and to seek input from the OMERACT community before moving forward to developing or selecting an outcome measurement instrument. METHODS: OMERACT 2023 presented and discussed interview results from 34 patients indicating that up to 171 items might be important for patients' harm-reporting. RESULTS: Domain was defined in detail and supported by qualitative work. Participants in the Special-Interest-Group endorsed (96 %) that enough qualitative data are available to start Delphi survey(s). CONCLUSION: We present a definition of safety/harms that represents the patient voice (i.e., patients' perception of safety) evaluating the symptomatic treatment-related adverse events for people with RMDs enrolled in clinical trials.

Acute Extra-Arachnoid Subdural Hematomas in Patients 50 Years and Older: When Subdurals Act Like Epidurals.

BACKGROUND: Some patients with subdural hematoma (SDH) with acute extra-arachnoid lesions and without concomitant subarachnoid blood or contusions may present in similarly grave neurological condition compared with the general population of patients with SDH. However, these patients often make an impressive neurological recovery. This study compared neurological outcomes in patients with extra-arachnoid SDH with all other SDH patients. METHODS: We compared a prospective series of extra-arachnoid SDH patients without subarachnoid hemorrhage or other concomitant intracranial injury with a Transforming Research and Clinical Knowledge in TBI control group with SDH only. We performed inverse probability weighting for key characteristics and ordinal regression with and without controlling for midline shift comparing neurological outcomes (Extended Glasgow Outcome Scale score) at 2 weeks. We used the Corticosteroid Randomization After Significant Head Injury prognostic model to predict mortality based on age, Glasgow Coma Scale score, pupil reactivity, and major extracranial injury. RESULTS: Mean midline shift was significantly different between extra-arachnoid SDH and control groups (7.2 mm vs. 2.7 mm, P < 0.001). After weighting for group allocation and controlling for midline shift, extra-arachnoid SDH patients had 5.68 greater odds (P < 0.001) of a better 2-week Extended Glasgow Outcome Scale score than control patients. Mortality in the extra-arachnoid SDH group was less than predicted by the Corticosteroid Randomization After Significant Head Injury prognostic model (10% vs. 21% predicted). CONCLUSIONS: Patients with extra-arachnoid SDH have significantly better 2-week neurological outcomes and lower mortality than predicted by the Corticosteroid Randomization After Significant Head Injury model. Neurosurgeons should consider surgery for this patient subset even in cases of poor neurological examination, older age, and large hematoma with high degree of midline shift.

Advanced practice nursing in France: Social capital assessment.

ABSTRACT: France is in the initial stage of development of the advanced practice nursing role. Social capital is essential to move this development forward, as evidenced by similar global movements resulting in the establishment of the advanced practice role of nurses. A pilot project examined the general response of French citizens (social capital) to the idea of advanced nursing practice in their country. The overwhelming majority of participants were in support of advanced nursing practice, with 90% of the participants answering "Yes" to the question "Would you trust and feel safe having a Nurse Practitioner (APRN) provide your primary care instead of a physician?" Social capital is needed in many areas of health care and may be enhanced by strong social capital within the citizenry.

The Neurological Pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study.

BACKGROUND: Improving the prognostication of acute brain injury is a key element of critical care. Standard assessment includes pupillary light reactivity testing with a hand-held light source, but findings are interpreted subjectively; automated pupillometry might be more precise and reproducible. We aimed to assess the association of the Neurological Pupil index (NPi)-a quantitative measure of pupillary reactivity computed by automated pupillometry-with outcomes of patients with severe non-anoxic acute brain injury. METHODS: ORANGE is a multicentre, prospective, observational cohort study at 13 hospitals in eight countries in Europe and North America. Patients admitted to the intensive care unit after traumatic brain injury, aneurysmal subarachnoid haemorrhage, or intracerebral haemorrhage were eligible for the study. Patients underwent automated infrared pupillometry assessment every 4 h during the first 7 days after admission to compute NPi, with values ranging from 0 to 5 (with abnormal NPi being <3). The co-primary outcomes of the study were neurological outcome (assessed with the extended Glasgow Outcome Scale [GOSE]) and mortality at 6 months. We used logistic regression to model the association between NPi and poor neurological outcome (GOSE ≤4) at 6 months and Cox regression to model the relation of NPi with 6-month mortality. This study is registered with ClinicalTrials.gov, NCT04490005. FINDINGS: Between Nov 1, 2020, and May 3, 2022, 514 patients (224 with traumatic brain injury, 139 with aneurysmal subarachnoid haemorrhage, and 151 with intracerebral haemorrhage) were enrolled. The median age of patients was 61 years (IQR 46-71), and the median Glasgow Coma Scale score on admission was 8 (5-11). 40 071 NPi measurements were taken (median 40 per patient [20-50]). The 6-month outcome was assessed in 497 (97%) patients, of whom 160 (32%) patients died, and 241 (47%) patients had at least one recording of abnormal NPi, which was associated with poor neurological outcome (for each 10% increase in the frequency of abnormal NPi, adjusted odds ratio 1·42 [95% CI 1·27-1·64]; p<0·0001) and in-hospital mortality (adjusted hazard ratio 5·58 [95% CI 3·92-7·95]; p<0·0001). INTERPRETATION: NPi has clinically and statistically significant prognostic value for neurological outcome and mortality after acute brain injury. Simple, automatic, repeat automated pupillometry assessment could improve the continuous monitoring of disease progression and the dynamics of outcome prediction at the bedside. FUNDING: NeurOptics.

Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations.

BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion. METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression. RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations. CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.

Multiorganizational consensus to define guiding principles for perioperative pain management in patients with chronic pain, preoperative opioid tolerance, or substance use disorder.

Significant knowledge gaps exist in the perioperative pain management of patients with a history of chronic pain, substance use disorder, and/or opioid tolerance as highlighted in the US Health and Human Services Pain Management Best Practices Inter-Agency Task Force 2019 report. The report emphasized the challenges of caring for these populations and the need for multidisciplinary care and a comprehensive approach. Such care requires stakeholder alignment across multiple specialties and care settings. With the intention of codifying this alignment into a reliable and efficient processes, a consortium of 15 professional healthcare societies was convened in a year-long modified Delphi consensus process and summit. This process produced seven guiding principles for the perioperative care of patients with chronic pain, substance use disorder, and/or preoperative opioid tolerance. These principles provide a framework and direction for future improvement in the optimization and care of 'complex' patients as they undergo surgical procedures.

Understanding hydrodynamic wear in self-similar superhydrophobic coatings subjected to rapid droplet impacts.

Superhydrophobic materials rely on both chemical apolarity and surface roughness to achieve the high contact angles and the low roll-off angles that lead to self-cleaning and antibacterial properties. Current superhydrophobic coatings tend to be delicate and lose their properties easily when subjected to droplet impact. Such impact deteriorates these coatings through hydrodynamic wear; changing structure, eroding hydrophobic chemistry, and quickly leading to full wet out of the substrate. In fact, hydrodynamic wear is more detrimental to coatings than seemingly more aggressive mechanical wear including scratching with sandpaper - a common approach used to claim both self-similarity of a material and extreme robustness against wear. What makes certain coatings more robust against hydrodynamic wear? To understand this answer, we systematically study ten disparate self-similar superhydrophobic coating approaches from academia to industry by subjecting them to hydrodynamic wear with rapid droplet impacts. We offer an iteration of a spinning disk methodology that enables parallel testing of multiple coatings simultaneously. We have developed an analytical model that accurately estimates the average size and velocity of droplets created from the spinning disk. We find rapid droplet impacts that simulate a medium rain can deteriorate most coatings within seconds or minutes, with certain exceptions lasting up to 22 days. The more resilient coatings share common attributes including robust apolar chemistry, hierarchal topography, and a slow loss of sacrificial material. The best performing coatings can be characterized using power-law relationships that parallel mechanical fatigue functions and provide a predictive quantitative metric for the performance of hydrophobic coatings. Overall, this paper offers a quantitative approach to hydrodynamic wear of self-similar superhydrophobic coatings.

Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair.

Selenoprotein W (Selenow) is a ~9 kDa selenoprotein suggested to play a beneficial role in resolving inflammation. However, the underlying mechanisms are poorly understood. SELENOW expression in the human GI tract using ScRNAseq Gut Cell Atlas and Gene Expression Omnibus (GEO) databases revealed its expression in the small intestine and colonic epithelial, endothelial, mesenchymal, and stem cells and correlated with a protective effect in ulcerative colitis patients. Selenow KO mice treated with 4% dextran sodium sulfate (DSS) showed exacerbated acute colitis, with greater weight loss, shorter colons, and increased fecal occult blood compared to the WT counterparts. Selenow KO mice expressed higher colonic Tnfα, increased Tnfα+ macrophages in the colonic lamina propria, and exhibited loss in epithelial barrier integrity and decreased zonula occludens 1 (Zo-1) expression following DSS treatment. Expression of epithelial cellular adhesion marker (EpCam), yes-associated protein 1 (Yap1), and epidermal growth factor receptor (Egfr) were decreased along with CD24lo cycling epithelial cells in Selenow KO mice. Colonic lysates and organoids confirmed a crosstalk between Egfr and Yap1 that was regulated by Selenow. Overall, our findings suggest Selenow expression is key for efficient resolution of inflammation in experimental colitis that is mediated through the regulation of Egfr and Yap1.