BACKGROUND:Penetrating traumatic brain injury (pTBI) affects civilian and military populations resulting in significant morbidity, mortality, and health care costs. No up-to-date and evidence-based guidelines exist to assist modern medical and surgical management of these complex injuries. METHODS:A preliminary literature search informed a need for updated guidelines. Methodologists experienced in TBI guidelines supported 2 co-chairs, a diverse steering committee and three expert working groups. Over half of our panelists were active service military or military veterans and they addressed twenty-six Key Questions (KQs). We searched Ovid MEDLINE®, EMBASE, and Cochrane CENTRAL from inception to August 31, 2022, reference lists, and clinical trial registries. Penetrating, perforating and tangential penetrating brain injuries were included. Predefined criteria were used to identify studies; pre-specified methods were used to assess study quality and strength of evidence for key outcomes. Effects were analyzed qualitatively and quantitatively where appropriate. RESULTS:125 studies provided evidence and another 80 studies provided contextual data for these guidelines. In general there was a paucity of literature and most of the identified evidence was judged to be high risk of bias due to study design. We did not identify any studies meeting inclusion criteria for 12 KQs. The highest quality evidence, rated moderate in strength, was identified for four KQs that covered: cerebral angiography vs computed tomography angiography, the relationship between bihemispheric injury in adult pTBI and mortality, the ability of the Surviving Penetrating Injury to the Brain (SPIN) score to predict mortality, and the relationship between infection and cerebrospinal fluid fistula. Evidence for most KQs came from case series. CONCLUSIONS:The development of up-to-date evidence and consensus based clinical care guidelines and algorithms for pTBI provide guidance to care providers in the prehospital and emergency medicine, surgical and intensive care settings. Few moderately strong conclusions on the benefit of specific management strategies for penetrating brain injury could be made. Detailed reporting of patient outcomes in future studies could advance the field by providing greater evidence for specific treatments by patient population, mechanism of injury, severity of injury, and specific interventions employed.

The accelerometer has become an almost ubiquitous device, providing enormous opportunities in healthcare monitoring beyond step counting or other average energy estimates in 15-60 second epochs. Objective: To develop an open data set with associated open-source code for processing 50 Hz tri-axial accelerometry-based to classify patient activity levels and natural types of movement. Approach: Data were collected from 23 healthy subjects (16 males and seven females) aged between 23 and 62 years using an ambulatory device, which included a triaxial accelerometer and synchronous lead II equivalent ECG for an average of 26 minutes each. Participants followed a standardized activity routine involving five distinct activities: lying, sitting, standing, walking, and jogging. Two classifiers were constructed: a signal processing technique to distinguish between high and low activity levels and a convolutional neural network (CNN)-based approach to classify each of the five activities. Main results: The binary (high/low) activity classifier exhibited an F1 score of 0.79. The multi-class CNN-based classifier provided an F1 score of 0.83. The code for this analysis has been made available under an open-source license together with the data on which the classifiers were trained and tested. Significance: The classification of behavioral activity, as demonstrated in this study, offers valuable context for interpreting traditional health metrics and may provide contextual information to support the future development of clinical decision-making tools for patient monitoring, predictive analytics, and personalized health interventions.

BACKGROUND:Penetrating traumatic brain injury (pTBI) is an important wounding mechanism which is seen increasingly as a result of violent crime and armed conflicts. pTBI is very challenging to manage as it is often highly complex yet requires expeditious treatment. Treatment algorithms thus can assist even experienced clinicians to avoid pitfalls while caring for these patients. METHODS:To supplement the evidence-based recommendations produced in conjunction with the Brain Trauma Foundation Guidelines for the Management of Penetrating Brain Injury, Second Edition, we developed protocols for care to help bridge limitations of published evidence with care decisions required at the bedside. Our working group of over 30 diverse expert panelists identified care, care pathways and key decisions relevant to pTBI care through discussion. A rigorous, blinded Delphi consensus process was then applied. Items achieving at least an 80% consensus vote were incorporated into the treatment algorithms. Consensus voting also approved the final versions of the care pathways. RESULTS:To meet the needs of diverse pTBI patients we created a Master Care Pathway relevant to all patients. We also created 'Toolkits' designed to address care issues that only some patients will have. Toolkits for surgical management, protruding foreign bodies, severe injury, skull base injury and vascular injury were developed. In addition, a futility assessment is provided to assist with delineating the small proportion of patients for whom initial non-aggressive care might be considered with the recognition that avoidance of nihilism is critical to achieving best outcomes in pTBI victims. CONCLUSIONS:Care pathways are presented which reflect suggestions for care that aim to inspire thoughtful management. The algorithms also aim to avoids potential pitfalls in management to help achieve best possible outcomes for pTBI patients.

INTRODUCTION: Minimally invasive evacuation of intracerebral hemorrhage (ICH) was recently investigated in the Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) trial, which showed a clinical benefit over medical treatment. METHODS: We performed a post-hoc analysis of the surgical arm of the ENRICH trial. Surgeons' experience was categorized as novice, intermediate, and expert per trial design and also computed in months of practice since licensing. Institutions were classified as comprehensive stroke centers(CSC) or not and teaching or non-teaching facilities. Bayesian mixed-effect regression models were used to predict absolute end-of-treatment volume (EOTV), EOTV-to-preoperative volume ratio, utility-weighted Modified Rankin Scale (uwMRS), and mortality. RESULTS: Average pre- and post-operative ICH volumes(ml) were 54.39[39.44-72.42] and 7.18[1.93-17.53]. Optimal target EOTV was obtained in all surgical categories (novice: 8.76[1.83-22.54], intermediate: 5.37[1.93-13.51], expert: 6.95[2.20-21.13]). Higher preoperative volume (B:1.01 [1.002-1.02]) and admission to non-teaching hospitals (B:0.31[0.14-0.94]) but not surgical experience were independent predictors of lower EOTV. Moreover, hemorrhage location (B:0.22[0.1-0.33]), preoperative volume (B:-0.003[-0.01-(-0.001)], preoperative GCS (B:0.03[0.01-0.05]) and age(B:-0.01[-0.01-(-0.003)] but not surgical experience were predictors of higher uw-mRS scores. Age (OR:1.07[1.03-1.13]) and preoperative GCS (OR:0.78[0.64-0.94]) were the major predictors of mortality at 180 days. CONCLUSIONS: These findings showed consistent rates of hematoma evacuation and functional outcome through a reproducible minimally invasive surgical technique. Technical proficiency using this standardized approach as determined by EOTV remained high regardless of surgical experience or institutional setting.

INTRODUCTION: The Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) trial has recently established a milestone for surgical intervention in lobar ICHs compared to medical management. METHODS: We conducted a post-hoc study on the ENRICH trial surgical arm, with sub-analyses for lobar and anterior basal ganglia (ABG) ICHs. Interval from last known normal (LKN) to surgery, surgeon’s experience, ICH volume before and after treatment, percentage of hematoma evacuated, target end-of-treatment volume (EOTV) < 15 mL were analyzed, and outcomes were determined as dichotomized modified Rankin scale (mRS; 0-3 vs 4-6) and mortality at 180-day. RESULTS: Median LKN to surgery times were 17.78, 18.72 and 14.92 hours for the overall, lobar, and ABG groups, with an optimal intervention cut-off at 12.78 hours [AUROC: 0.549 (0.456-0.642)] for mRS 0-3. Average preoperative ICH volumes were 54.39, 54.40 and 50.96 mL, a threshold of 62.49 mL predicted a better outcome [AUROC: 0.656 (0.569-0.744)]. EOTV analysis (7.18, 6.90 and 7.72 mL for the groups investigated) revealed a significant threshold at 2.47 mL overall [AUROC: 0.642 (0.554-0.730)] for mRS 0-3 and at 30.42 mL [AUROC: 0.635 (0.516-0.754)] for improved mortality – with a slightly inferior mortality threshold for the ABG group at 21.78 mL (AUROC: 0.601 [0.391-0.811],). Multivariable ordinal regression identified age, preoperative GCS, preoperative and EOTVs as independent predictors of favorable mRS. LKN to surgery time did not show a significant effect in the adjusted model. Finally, EOTV (OR: 1.02 [1.004-1.04]) was also an independent predictor of mortality, other than age (OR: 1.06 [1.01-1.10]) and preoperative GCS (OR:0.82[0.68-0.98]). CONCLUSIONS: Optimal thresholds impacting functional outcome and mortality were established regarding time-to-intervention, preoperative ICH volume, and EOTV. These findings might aid in optimizing patient selection and have significant implications for designing future clinical trials.

Non-neurological organ dysfunction (NNOD) is a prevalent complication and contributes to poor outcome after traumatic brain injury (TBI). Contributing factors to NNOD may include initial TBI severity, but this relationship has not been rigorously studied. The objectives of this study were to describe the frequency and timing of NNOD after TBI, evaluate the association between NNOD and outcome (mortality and Glasgow Outcome Score-Extended [GOSE] at 6 months post-injury), and examine the relationship between multimodal markers of initial TBI severity and NNOD. We performed a secondary analysis of data from participants in both the ProTECT III clinical trial (progesterone vs. placebo in participants with moderate-to-severe TBI) and the embedded Bio-ProTECT blood biomarker study (N = 536 individuals). We reviewed laboratory and clinical data to determine the prevalence of NNOD in renal, hematological, hepatic, cardiovascular, and respiratory systems, based on the sequential organ failure assessment system. TBI severity was assessed using index Glasgow coma scale score (iGCS-first GCS post-primary resuscitation), Rotterdam computed tomography (CT) score, head-region abbreviated injury scale scores, and baseline TBI biomarkers (S100 calcium binding protein B [S100b], glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCHL1], and spectrin breakdown products [SBDP]). NNOD frequencies by organ system were 72% (respiratory), 52% (cardiovascular), 45% (hematological), 8% (renal), and 2% (hepatic). All TBI severity markers were positively correlated (using Spearman coefficients) with the number of systems in dysfunction. To examine effects of NNOD on outcome independent of TBI severity, we used logistic regression and adjusted for age, sex, iGCS, Rotterdam CT score, and biomarker load score (mean biomarker quartile), wherein each additional system of dysfunction resulted in a 1.30× higher odds of unfavorable GOSE (95% confidence interval [CI]: [1.01-1.67], p = 0.04). Stratification analyses revealed the relationship between greater NNOD and worse outcome was most pronounced among individuals with more severe Rotterdam CT and lower GCS scores. In conclusion, NNOD occurs frequently after moderate-to-severe TBI, is associated with higher odds of unfavorable GOSE at 6 months, and is positively associated with multimodal biomarkers of baseline TBI severity. This is the first study to demonstrate a relationship between TBI blood biomarker levels and NNOD. Future study is needed to determine mechanisms of NNOD and their relationships to subsequent neurological injury. While TBI research has historically focused on brain-centric measures and outcomes, this study builds on mounting evidence that non-neurological organ systems play an important role in injury response after TBI.

OBJECTIVE:This post hoc study of the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (ProTECT) III trial investigates whether improving traumatic brain injury (TBI) classification, using serum biomarkers (glial fibrillary acidic protein [GFAP] and ubiquitin carboxyl-terminal esterase L1 [UCH-L1]) and algorithmically assessed total lesion volume, could identify a subset of responders to progesterone treatment, beyond broad measures like the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale-Extended (GOS-E), which may fail to capture subtle changes in TBI recovery. DESIGN:Brain lesion volumes on CT scans were quantified using Brain Lesion Analysis and Segmentation Tool for CT. Patients were classified into true-positive and true-negative groups based on an optimization scheme to determine a threshold that maximizes agreement between radiological assessment and objectively measured lesion volume. True-positives were further categorized into low (> 0.2-10 mL), medium (> 10-50 mL), and high (> 50 mL) lesion volumes for analysis with protein biomarkers and injury severity. Correlation analyses linked Rotterdam scores (RSs) with biomarker levels and lesion volumes, whereas Welch's t-test evaluated biomarker differences between groups and progesterone's effects. SETTING:Forty-nine level 1 trauma centers in the United States. PATIENT:Patients with moderate-to-severe TBI. INTERVENTIONS:Progesterone. MEASUREMENTS AND MAIN RESULTS:GFAP and UCH-L1 levels were significantly higher in true-positive cases with low to medium lesion volume. Only UCH-L1 differed between progesterone and placebo groups at 48 hours. Both biomarkers and lesion volume in the true-positive group correlated with the RS. No sex-specific or treatment differences were found. CONCLUSIONS:This study reaffirms elevated levels of GFAP and UCH-L1 as biomarkers for detecting TBI in patients with brain lesions and for predicting clinical outcomes. Despite improved classification using CT-imaging segmentation and serum biomarkers, we did not identify a subset of progesterone responders within 24 or 48 hours of progesterone treatment. More rigorous and quantifiable measures for classifying the nature of injury may be needed to enable development of therapeutics as neither serum markers nor algorithmic CT analysis performed better than the older metrics of Rotterdam or GCS metrics.

The Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) trial, which recently explored minimally invasive evacuation of intracerebral hemorrhage (ICH), demonstrated a relevant clinical improvement in functional outcomes and mortality compared to standard medical care particularly for lobar haemorrhages. We included all patients from the ENRICH surgical cohort (n=150), assessed several variables, including the interval from last known normal (LKN) to surgery, surgeon’s experience, ICH volume before (preop ICH volume) and after treatment (EOTV) and the rate of target EOTV < 15 mL for predicting 180-day mortality. AUROC analysis and multivariable regression models were employed to determine relevant thresholds and significant predictors. Median LKN to surgery intervals were 17.78, 18.72 and 14.92 hours for the entire cohort, lobar, and ABG ICHs respectively, with a cut-off at 11.73 hours of LKN to surgery being associated with better outcomes and a 0.538 (0.427-0.649) AUROC. Mean preoperative ICH volumes were 54.39, 54.40 and 50.96 mL respectively, with a 0.678 (0.575-0.782) AUROC and a 62.75 mL threshold for better outcomes in the overall and lobar ICH cohorts and a 35.25 mL threshold for the ABG group. EOTVs (7.18, 6.90 and 7.72 mL, respectively) showed a 0.635(0.516-0.754) AUROC with a threshold of 30.42 mL overall, and a slightly inferior result for the ABG group (AUROC: 0.601[0.391-0.811]; threshold: 21.78 mL). Among these, only EOTV (OR: 1.02[1.004-1.04]) represented an independent predictor of mortality, other than age (OR: 1.06[1.01-1.10]) and preoperative GCS (OR: 0.82[0.68-0.98]); surgical experience was not predictive of mortality. Within ENRICH surgical participants optimal thresholds impacting mortality were established with regards to time-to-intervention, preoperative ICH volume, and EOTV. These findings might aid in optimizing patient selection and have significant implications for designing future clinical trials.

Introduction: Several transcriptomic signatures for sepsis have been proposed but none have translated into clinical practice. How these signatures relate to each other is unclear and this lack of consensus remains a barrier to implementation. We investigated whether these signatures could be leveraged to develop a consensus immune dysregulation framework with prognostic and therapeutic relevance. Methods: The SUBSPACE consortium is an international group of sepsis investigators who have shared whole blood bulk RNA sequencing data. We co-normalized 3,013 samples across 10 SUBSPACE sepsis cohorts and applied seven transcriptomic signatures.We performed network analysis on scaled scores using Spearman correlation to identify edges. We integrated 254 samples (602,338 cells) from 4 publicly available sepsis peripheral blood single cell RNA-seq (scRNA-seq) datasets inclusive of the neutrophil compartment to identify the cellular origin of these consensus clusters. We applied these biologic insights to develop a framework for quantifying myeloid and lymphoid dysregulation in sepsis. The association of dysregulation with 30-day mortality was evaluated using Fisher's exact test. The association of dysregulation with treatment response was evaluated in two randomized controlled trials: (1) the SAVE-MORE trial (anakinra in COVID-19); and (2) the VICTAS trial (hydrocortisone, thiamine, and vitamin C in sepsis). Patients in VICTAS who received open-label steroids were excluded. Outcomes were assessed using Fisher's exact test and interaction terms were generated using logistic regression. Results: Network analysis identified four clusters of scores: two clusters associated with high-risk and two with low risk. Using scRNA-seq data, we found that these score clusters separate along myeloid and lymphoid lineages. We derived myeloid and lymphoid dysregulation scores by combining applied signatures and defined dysregulation as a z-score >1.65 relative to healthy controls. Dysregulation was associated with an odds ratio of 1.9 for 30-day mortality (95% CI 1.4-2.7, p = 4.7e-5, Figure 1A,B). In SAVE-MORE (n = 391), anakinra therapy in COVID-19 patients with lymphoid dysregulation was associated with reduced mortality (OR = 0.02, Fisher p=0.02, p(interaction) = 0.05, Figure 1C). In VICTAS (n = 89), hydrocortisone, vitamin C, and thiamine therapy in sepsis patients with lymphoid dysregulation was associated with reduced 30-day mortality (OR = 0.19, Fisher p = 0.05, p(interaction) = 0.05, Figure 1D). Neither treatment improved mortality in patients without lymphoid dysregulation in either trial. Conclusion: The consensus immune dysregulation framework quantifies myeloid and lymphoid dysregulation in sepsis. Dysregulation is associated with increased mortality and differential response to treatment with anakinra and hydrocortisone.

BACKGROUND:Evidence shows that patients identified as Black experience worse emergency department (ED) care compared to patients identified as White. Clinical interactions (CI) are thought to affect racial disparities, but no systematic reviews to date have synthesized the evidence on the effects of patient race on CI processes and experiences. OBJECTIVE:We synthesized evidence from published studies comparing observed and/or patient-reported CI processes and experiences between patients identified as Black and White in US EDs. METHODS:This was a mixed-methods systematic review following the Joanna Briggs Institute guidelines and registered a priori with PROSPERO (CRD42021281653). We used a broad search strategy to query six databases. Peer-reviewed original research reports comparing processes or experiences of CIs between Black and White patients in US EDs from 2004 to 2024 were eligible for inclusion. RESULTS:Nine studies met inclusion criteria. Of these, three focused on observational CI processes and six focused on patient-reported CI experiences. Evidence of differences in CI processes and patient-reported experiences between Black and White patients was inconclusive. We identified four themes across measures used in studies of patient reported CI experiences, however, including responsive nonverbal behavior, effective verbal communication, person centeredness, and patient satisfaction. DISCUSSION:Research on the effects of patient race on ED CIs is lacking, especially research with observed real-world CI processes. Psychometrically robust instruments and conceptual clarity in the study of racial disparities in CI experiences are needed. We provide groundwork for future research development on racial disparities in ED CIs.

Critical care syndromes such as sepsis, acute respiratory distress syndrome (ARDS) and trauma continue to have unacceptably high morbidity and mortality, with progress limited by the inherent heterogeneity within syndromic illnesses. Although numerous immune endotypes have been proposed for sepsis and critical care, the similarities and differences between these endotypes remain unclear, hindering clinical translation. The SUBSPACE consortium is an international consortium that aims to advance precision medicine in critical care through the sharing of transcriptomic data. Here, evaluating the overlap of existing immune endotypes in sepsis across >7,074 samples from 37 independent cohorts, we developed cell-type-specific gene expression signatures to quantify dysregulation within immune compartments. Myeloid and lymphoid dysregulation were associated with disease severity and mortality across all cohorts. Importantly, this dysregulation was also observed in patients with ARDS, trauma and burns, suggesting a conserved mechanism across various critical illness syndromes. Moreover, analysis of randomized controlled trial data revealed that myeloid and lymphoid dysregulation are associated with differential mortality in patients treated with anakinra in the SAVE-MORE trial (n = 452) and corticosteroids in the VICTAS (n = 89) and VANISH (n = 117) trials, underscoring their prognostic and therapeutic implications. In conclusion, our proposed immunology-based framework for quantifying cellular compartment dysregulation offers a potentially valuable tool for understanding immune dysregulation in critical illness with prognostic and therapeutic significance.

Lack of reliable diagnostics for the presence, type and severity of infection in patients presenting to emergency departments with non-specific symptoms poses considerable challenges. We developed TriVerity, which uses isothermal amplification of 29 mRNAs and machine learning algorithms on the Myrna instrument to determine likelihoods of bacterial infection, viral infection and need for critical care interventions within 7 days. To validate TriVerity, the SEPSIS-SHIELD study enrolled 1,222 patients with clinically adjudicated infection status and need for critical care intervention within 7 days as endpoints. The TriVerity Bacterial and Viral scores had higher accuracy than C-reactive protein, procalcitonin or white blood cell count for the diagnosis of bacterial infection with area under the receiver operating characteristic (AUROC) of 0.83, and viral infection (AUROC = 0.91). The TriVerity Severity score had an AUROC of 0.78 for predicting illness severity and allowed reclassification of risk for critical care interventions compared to clinical assessment (quick Sequential Organ Failure Assessment) alone. Each of the three scores had rule-in specificity >92% and rule-out sensitivity >95%. Comparison of antibiotics administration at presentation with post-follow-up adjudication found that TriVerity could potentially reduce false positives and false negatives for inappropriate antibiotics use by 60-70%. Further clinical testing in an interventional setting is needed to prove actionability and clinical benefit of TriVerity.

Despite evidence that non-mydriatic fundus cameras are beneficial in non-ophthalmic settings, they are only available in a minority of hospitals in the US. The lag from research-based evidence to change in clinical practice highlights the complexities of implementation of new technology and practice. We describe the steps used to implement successfully a non-mydriatic ocular fundus camera combined with optical coherence tomography (OCT) in a general emergency department (ED) using Kotter's 8-Step Change Model. We prospectively collected the number of trained personnel in the ED, the number of imaging studies obtained each week during the first year following implementation, and we documented major achievements each month, as well as outcome measures, barriers to implementation and possible solutions. Between 12 and 42 patients were imaged per week, resulting in a total of 1274 patients imaged demonstrating sustained usage of non-mydriatic fundus camera/OCT in the ED one year after implementation. The implementation process was contingent upon multidisciplinary collaboration, extensive communication, coordinated training of staff, and continuous motivation. The future will likely include the use of artificial intelligence deep learning systems for automated interpretation of ocular imaging as an immediate diagnostic aid for ED or other non-eye care providers.

Progress in the management of critical care syndromes such as sepsis, Acute Respiratory Distress Syndrome (ARDS), and trauma has slowed over the last two decades, limited by the inherent heterogeneity within syndromic illnesses. Numerous immune endotypes have been proposed in sepsis and critical care, however the overlap of the endotypes is unclear, limiting clinical translation. The SUBSPACE consortium is an international consortium that aims to advance precision medicine through the sharing of transcriptomic data. By evaluating the overlap of existing immune endotypes in sepsis across over 6,000 samples, we developed cell-type specific signatures to quantify dysregulation in these immune compartments. Myeloid and lymphoid dysregulation were associated with disease severity and mortality across all cohorts. This dysregulation was not only observed in sepsis but also in ARDS, trauma, and burn patients, indicating a conserved mechanism across various critical illness syndromes. Moreover, analysis of randomized controlled trial data revealed that myeloid and lymphoid dysregulation is linked to differential mortality in patients treated with anakinra or corticosteroids, underscoring its prognostic and therapeutic significance. In conclusion, this novel immunology-based framework for quantifying cellular compartment dysregulation offers a valuable tool for prognosis and therapeutic decision-making in critical illness.

Background: Central retinal artery occlusion (CRAO) is a retinal infarction with causes/management similar to cerebral infarction. However, CRAO diagnosis is often delayed, resulting in missed opportunities for rapid treatment. Diagnosis by ophthalmologists is essential prior to management by stroke neurologists and may be challenging within a few hours of vision loss. Our goal is to provide a new paradigm in the emergency department (ED) with the implementation of a nonmydriatic ocular fundus camera (NMFP) combined with optical coherence tomography (OCT) to allow for ultrarapid remote diagnosis and stroke alert as soon as patients present to the ED. Methods: Prospective collection of data from consecutive patients who had NMFP-OCT for acute monocular vision loss in our general ED affiliated with a comprehensive stroke center. We collected timing of photographs; final diagnosis (CRAO/other causes of vision loss); time between vision loss onset and CRAO diagnosis; NMFP-OCT findings. Results: Over 9 weeks, 27 patients had NMFP-OCT obtained for acute monocular visual loss, including 9 CRAO [others included 7 retinal detachments; 8 vitreous hemorrhages; 3 temporal arteritis]. Diagnosis of acute CRAO was made remotely on NMFP-OCT obtained 30, 33, 36 min after arriving in ED in 3 patients presenting to ED within 3.5 hrs of vision loss. In all 3 patients, the ocular color photographs were almost normal and acute CRAO diagnosis was made primarily from the OCT showing inner retinal edema/hyperreflectivity. Conclusion: Incorporating NMFP-OCT into the ED workflow can be used as a substitute for funduscopic examination/pupillary dilation, allowing for remote diagnosis of CRAO by ophthalmologists who can provide real time recommendations before in person visit. These positive preliminary results suggest that this strategy accelerates the diagnosis of urgent vision loss, resulting in improved patient outcomes. Results of the first 6 months will be presented at the conference.

OBJECTIVE:Sepsis is a leading cause of mortality. Predicting outcomes is challenging and few biomarkers perform well. Defects in the renin-angiotensin system (RAS) can predict clinical outcomes in sepsis and may outperform traditional biomarkers. We postulated that RAS dysfunction (elevated active renin, angiotensin 1-7 [Ang-(1-7)], and angiotensin-converting enzyme 2 (ACE2) activity with depressed Ang-II and ACE activity) would be associated with mortality in a cohort of septic patients.DESIGN:Post hoc analysis of patients enrolled in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized controlled trial.SETTING:Forty-three hospitals across the United States.PATIENTS:Biorepository samples of 103 patients.INTERVENTIONS:We analyzed day 0 (within 24 hr of respiratory failure, septic shock, or both) and day 3 samples ( n = 103 and 95, respectively) for assessment of the RAS. The association of RAS values with 30-day mortality was determined using Cox proportional hazards regression with multivariable adjustments for age, sex, VICTAS treatment arm, systolic blood pressure, Sequential Organ Failure Assessment Score, and vasopressor use.MEASUREMENTS AND MAIN RESULTS:High baseline active renin values were associated with higher 30-day mortality when dichotomized to the median of 188.7 pg/mL (hazard ratio [HR] = 2.84 [95% CI, 1.10-7.33], p = 0.031) or stratified into quartiles (Q1 = ref, HR Q2 = 2.01 [0.37-11.04], HR Q3 = 3.22 [0.64-16.28], HR Q4 = 5.58 [1.18-26.32], p for linear trend = 0.023). A 1- sd (593.6 pg/mL) increase in renin from day 0 to day 3 was associated with increased mortality (HR = 3.75 [95% CI, 1.94-7.22], p < 0.001), and patients whose renin decreased had improved survival compared with those whose renin increased (HR 0.22 [95% CI, 0.08-0.60], p = 0.003). Ang-(1-7), ACE2 activity, Ang-II and ACE activity did not show this association. Mortality was attenuated in patients with renin over the median on day 0 who received the VICTAS intervention, but not on day 3 ( p interaction 0.020 and 0.137, respectively). There were no additional consistent patterns of mortality on the RAS from the VICTAS intervention.CONCLUSIONS:Baseline serum active renin levels were strongly associated with mortality in critically ill patients with sepsis. Furthermore, a greater relative activation in circulating renin from day 0 to day 3 was associated with a higher risk of death.