"They Have Shown Me It Is Possible to Thrive within STEM": Incorporating Learning Assistants in General Chemistry Enhances Student Belonging and Confidence.

Students often experience social and psychological barriers to success in General Chemistry, which is a key gateway to many students' science pathways. Learning assistants (LAs) have the potential to reduce these barriers and to strengthen students' sense of belonging in General Chemistry and STEM more broadly. Here, we used a 17-item Likert scale to determine whether incorporating LAs into General Chemistry I and II enhances students' sense of belonging in these courses. The incorporation of LAs into General Chemistry I had a significant positive effect and a medium to large effect size for students in all student groups examined: women and men; students in both racially and ethnically underrepresented and well-represented groups; first- and continuing-generation students. In General Chemistry II, similar results were observed for women and men; students in well-represented racial and ethnic groups; continuing-generation students. Further, we asked students to reflect on the impact that working with LAs had on their sense of belonging in STEM and confidence in talking about science. Sixty percent of students indicated that working with LAs had a positive impact on their STEM belonging, with five themes describing LA impacts: reducing isolation, serving as inspirational role models, providing mentoring, increasing opportunities for engagement and confidence building, and serving as accessible and approachable sources of support. Sixty-one percent of students also indicated that working with LAs increased their confidence in talking about science, with three themes emerging: fostering an environment with a lower risk of negative judgment, providing increased opportunities for feedback, and supporting students as they practiced their growing skills. Together, these results indicate that LAs can be an important means to reduce social and psychological barriers for students in gateway science courses, increasing their sense that they belong to the class and STEM more broadly.

The eyes of Tullimonstrum reveal a vertebrate affinity.

Tullimonstrum gregarium is an iconic soft-bodied fossil from the Carboniferous Mazon Creek Lagerstätte (Illinois, USA). Despite a large number of specimens and distinct anatomy, various analyses over the past five decades have failed to determine the phylogenetic affinities of the 'Tully monster', and although it has been allied to such disparate phyla as the Mollusca, Annelida or Chordata, it remains enigmatic. The nature and phylogenetic affinities of Tullimonstrum have defied confident systematic placement because none of its preserved anatomy provides unequivocal evidence of homology, without which comparative analysis fails. Here we show that the eyes of Tullimonstrum possess ultrastructural details indicating homology with vertebrate eyes. Anatomical analysis using scanning electron microscopy reveals that the eyes of Tullimonstrum preserve a retina defined by a thick sheet comprising distinct layers of spheroidal and cylindrical melanosomes. Time-of-flight secondary ion mass spectrometry and multivariate statistics provide further evidence that these microbodies are melanosomes. A range of animals have melanin in their eyes, but the possession of melanosomes of two distinct morphologies arranged in layers, forming retinal pigment epithelium, is a synapomorphy of vertebrates. Our analysis indicates that in addition to evidence of colour patterning, ecology and thermoregulation, fossil melanosomes can also carry a phylogenetic signal. Identification in Tullimonstrum of spheroidal and cylindrical melanosomes forming the remains of retinal pigment epithelium indicates that it is a vertebrate; considering its body parts in this new light suggests it was an anatomically unusual member of total group Vertebrata.

Simultaneous versus rapid serial interventions in a hybrid operating suite for severely injured patients: a prospective evaluation of differences in RAPTOR techniques and outcomes.

BACKGROUND: Open surgical and percutaneous endovascular procedures aimed at arresting traumatic life-threatening hemorrhage are usually performed in rapid serial fashion by surgeons and interventional radiologists; truly simultaneous procedures require modifications in technique, workflow and team collaboration. The primary objective of this study was to prospectively audit outcomes in patients with ongoing hemorrhage who underwent truly simultaneous open and percutaneous procedures. METHODS: We prospectively evaluated the cases of all severely injured patients who required an open and percutaneous procedure within the hybrid RAPTOR (resuscitation with angiography, percutaneous techniques and operative repair) suite at the Foothills Medical Centre, Calgary, Alberta, Canada, between Apr. 4, 2013, and Dec. 5, 2019. We compared outcomes between the truly simultaneous and rapid serial cases. RESULTS: Thirty-five patients (31 [89%] male, median age 46 yr, median Injury Severity Score 30, blunt mechanism in 26 cases [74%]) underwent a hybrid intervention in the RAPTOR suite to stop ongoing hemorrhage during the study period. Twenty-three patients (66%) had a rapid serial procedure, and 12 (34%) had a truly simultaneous procedure. Demographic characteristics were similar between the 2 groups. Compared to the rapid serial group, a higher proportion of patients in the truly simultaneous group were hemodynamically unstable (11 [92%] v. 13 [56%], p = 0.03) and required damage-control procedures (10 [83%] v. 12 [52%], p = 0.03). The time from hospital arrival to procedure initiation was shorter for the truly simultaneous group (mean 31 min v. 59 min, p = 0.02), and a lower proportion had initial radiologic studies (3 [25%] v. 16 [70%], p = 0.01). The median hospital length of stay, intensive care unit stay and mortality rate were similar between the 2 groups. CONCLUSION: Truly simultaneous open and percutaneous procedures to stop ongoing hemorrhage were unique in both patient and procedural details. For the most severely injured patients, the provision of truly simultaneous modalities is necessary to achieve clinical outcomes equivalent to those of less ill patients.

Is the Pringle manoeuvre becoming a lost art? Contemporary use for both severe liver trauma with ongoing hemorrhage and elective partial hepatectomy.

The Pringle manoeuvre (vascular inflow occlusion) has been a mainstay technique in trauma surgery and hepato-pancreato-biliary surgery since it was first described in the early 1900s. We sought to determine how frequently the manoeuvre is used today for both elective and emergent cases in these disciplines. To reflect on its evolution, we evaluated the Pringle manoeuvre over a recent 10-year period (2010-2020). We found it is used less frequently owing to more frequent nonoperative management and more advanced elective hepatic resection techniques. Continuing educational collaboration is critical to ensure continued insight into the impact of hepatic vascular inflow occlusion among trainees who observe this procedure less frequently.

Topography of occult pneumothoraces: its importance for efficiency in diagnosis and avoiding sono-paralysis during POCUS.

Traumatic pneumothoraces remain a life-threatening problem that may be resolved quickly with timely diagnosis. Unfortunately, they are still not optimally managed. The most critically injured patients with hemodynamic instability require immediate diagnoses of potentially correctible conditions in the primary survey. Point-of-care ultrasonography (POCUS) performed by the responsible physician can be a tremendous adjunct to expediting diagnoses in the primary surgery and can typically be done in seconds rather than minutes. If more detailed sonographic examination is required, the secondary survey of the hemodynamically unstable patient is more appropriate. All involved in bedside care need to be conscious to efficiently integrate POCUS into resuscitation with the right intentions and goals to avoid sono-paralysis of the resuscitation sequence. Sono-paralysis has recently been described as critical situations wherein action is delayed through unnecessary imaging after a critical diagnosis has been made or unnecessary imaging details are sought despite an urgent diagnosis being made.

Inviting a friend to evaluate potential grade III pancreatic injuries: Are they truly occult, or simply missed on CT?

Traumatic inuries to the pancreas are notoriously challenging to diagnose and treat. Detecting a main pancreatic ductal injury can be particularly difficult on screening computed tomography (CT). Twenty-four blinded faculty clinicians from 4 differing specialties and 6 institutions reviewed 9 video CT cases of potential pancreatic ductal injuries. Clinician performance in detection of confirmed grade III pancreatic injuries varied widely among specialties. This heterogeneity confirms the critical need for multidisciplinary care and image interpretation for even "minor" (i.e., not grade IV or V) potential pancreatic injuries to optimize outcomes for injured patients. The ubiquitous availability of electronic devices allows real-time collegial second opinions to be easily available.

Neuropilin 1 balances ß8 integrin-activated TGFß signaling to control sprouting angiogenesis in the brain.

Angiogenesis in the developing central nervous system (CNS) is regulated by neuroepithelial cells, although the genes and pathways that couple these cells to blood vessels remain largely uncharacterized. Here, we have used biochemical, cell biological and molecular genetic approaches to demonstrate that ß8 integrin (Itgb8) and neuropilin 1 (Nrp1) cooperatively promote CNS angiogenesis by mediating adhesion and signaling events between neuroepithelial cells and vascular endothelial cells. ß8 integrin in the neuroepithelium promotes the activation of extracellular matrix (ECM)-bound latent transforming growth factor ß (TGFß) ligands and stimulates TGFß receptor signaling in endothelial cells. Nrp1 in endothelial cells suppresses TGFß activation and signaling by forming intercellular protein complexes with ß8 integrin. Cell type-specific ablation of ß8 integrin, Nrp1, or canonical TGFß receptors results in pathological angiogenesis caused by defective neuroepithelial cell-endothelial cell adhesion and imbalances in canonical TGFß signaling. Collectively, these data identify a paracrine signaling pathway that links the neuroepithelium to blood vessels and precisely balances TGFß signaling during cerebral angiogenesis.

RICE CRISPR: Rapidly increased cut ends by an exonuclease Cas9 fusion in zebrafish.

Application of CRISPR-Cas9 technology in diverse organisms has resulted in an explosion of genome modification efforts. To expand the toolbox of applications, we have created an E. coli Exonuclease I (sbcB)-Cas9 fusion that has altered enzymatic activity in zebrafish embryos. This Cas9 variant has increased mutation efficiency and favors longer deletions relative to wild-type Cas9. We anticipate that this variant will allow for more efficient screening for F0 phenotypes and mutation of a larger spectrum of genomic targets including deletion of regulatory regions and creating loss of function mutations in transcription units with poor sequence conservation such as lncRNAs where larger deletions may be required for loss of function.

Does increased prehospital time lead to a "trial of life" effect for patients with blunt trauma?

BACKGROUND: Variance in prehospital time among severely injured blunt trauma patients is dependent upon numerous factors. Effects on subsequent mortality and trauma team activation (TTA) rates are also unclear. The primary aim of this study was to evaluate the relationship between prehospital time and mortality at level I trauma referral centers amongst critically blunt injured patients. MATERIALS AND METHODS: This multiinstitutional study from three geographically distinct level I trauma centers analyzed all severely blunt injured patients (Injury Severity Score [ISS] ≥12). The relationship between prehospital time and survival was evaluated. Secondary outcomes included the association between prehospital time and TTA. Standard statistical methodology was used (P < 0.05 = significance). RESULTS: Between January 1, 2011, and January 1, 2016, 5375 severely blunt injured patients (mean ISS = 25; mean length of stay = 16.3 d) were analyzed (center 1 = 3376; center 2 = 2401; and center 3 = 1104). As prehospital time interval increased, overall mortality decreased (0-30 min = 24.1%; 31-60 min = 14.7%; 61-90 min = 10.3%; 91-120 min = 10.4%; 121-150 min = 10.2%; P < 0.05). This pattern was especially strong for patients with an arrival measurement of hypotension, despite corrections for ISS (P < 0.05). TTA and patient outcomes were extremely variable across intervals and centers (P < 0.05). CONCLUSIONS: A trial of life effect is present for severely blunt injured patients who arrive with vital signs. Despite arrival measurements of hypotension, patients with prolonged prehospital times have a substantially lower risk of subsequent mortality. This concept should contribute to decision-making with regard to TTA.

The ribosomal S10 protein is a general target for decreased tigecycline susceptibility.

Tigecycline is a translational inhibitor with efficacy against a wide range of pathogens. Using experimental evolution, we adapted Acinetobacter baumannii, Enterococcus faecium, Escherichia coli, and Staphylococcus aureus to growth in elevated tigecycline concentrations. At the end of adaptation, 35 out of 47 replicate populations had clones with a mutation in rpsJ, the gene that encodes the ribosomal S10 protein. To validate the role of mutations in rpsJ in conferring tigecycline resistance, we showed that mutation of rpsJ alone in Enterococcus faecalis was sufficient to increase the tigecycline MIC to the clinical breakpoint of 0.5 µg/ml. Importantly, we also report the first identification of rpsJ mutations associated with decreased tigecycline susceptibility in A. baumannii, E. coli, and S. aureus. The identified S10 mutations across both Gram-positive and -negative species cluster in the vertex of an extended loop that is located near the tigecycline-binding pocket within the 16S rRNA. These data indicate that S10 is a general target of tigecycline adaptation and a relevant marker for detecting reduced susceptibility in both Gram-positive and -negative pathogens.

Resuscitation and Care in the Trauma Bay.

Start balanced resuscitation early (pre-hospital if possible), either in the form of whole blood or 1:1:1 ratio. Minimize resuscitation with crystalloid to minimize patient morbidity and mortality. Trauma-induced coagulopathy can be largely avoided with the use of balanced resuscitation, permissive hypotension, and minimized time to hemostasis. Using protocolized "triggers" for massive and ultramassive transfusion will assist in minimizing delays in transfusion of products, achieving balanced ratios, and avoiding trauma induced coagulopathy. Once "audible" bleeding has been addressed, further blood product resuscitation and adjunct replacement should be guided by viscoelastic testing. Early transfusion of whole blood can reduce patient morbidity, mortality, decreases donor exposure, and reduces nursing logistics during transfusions. Adjuncts to resuscitation should be guided by laboratory testing and carefully developed, institution-specific guidelines. These include empiric calcium replacement, tranexamic acid (or other anti-fibrinolytics), and fibrinogen supplementation.

Use of Low-Titer O-Positive Whole Blood in Female Trauma Patients: A Literature Review, Qualitative Multidisciplinary Analysis of Risk/Benefit, and Guidelines for Its Use as a Universal Product in Hemorrhagic Shock.

BACKGROUND: Whole blood transfusion is associated with benefits including improved survival, coagulopathy, and decreased transfusion requirements. The majority of whole blood transfusion is in the form of low-titer O-positive whole blood (LTOWB). Practice at many trauma centers withholds the use of LTOWB in women of childbearing potential due to concerns of alloimmunization. The purpose of this article is to review the evidence for LTOWB transfusion in female trauma patients and generate guidelines for its application. STUDY DESIGN: Literature and evidence for LTOWB transfusion in hemorrhagic shock are reviewed. The rates of alloimmunization and subsequent obstetrical outcomes are compared to the reported outcomes of LTOWB vs other resuscitation media. Literature regarding patient experiences and preferences in regards to the risk of alloimmunization is compared to current trauma practices. RESULTS: LTOWB has shown improved outcomes in both military and civilian settings. The overall risk of alloimmunization for Rhesus factor (Rh) - female patients in hemorrhagic shock exposed to Rh + blood is low (3% to 20%). Fetal outcomes in Rh-sensitized patients are excellent compared to historical standards, and treatment options continue to expand. The majority of female patients surveyed on the risk of alloimmunization favor receiving Rh + blood products to improve trauma outcomes. Obstetrical transfusion practices have incorporated LTOWB with excellent results. CONCLUSIONS: The use of whole blood resuscitation in trauma is associated with benefits in the resuscitation of severely injured patients. The rate at which severely injured, Rh-negative patients develop anti-D antibodies is low. Treatments for alloimmunized pregnancies have advanced, with excellent results. Fears of alloimmunization in female patients are likely overstated and may not warrant the withholding of whole blood resuscitation. The benefits of whole blood resuscitation likely outweigh the risks of alloimmunization.

Are trauma centers penalized for improved prehospital resuscitation?: The effect of prehospital transfusion on arrival vitals and predicted mortality.

BACKGROUND: Prediction models for survival in trauma rely on arrival vital signs to generate survival probabilities. Hospitals are benchmarked on expected and observed outcomes. Prehospital blood (PB) transfusion has been shown to improve mortality, which may affect survival prediction modeling. We hypothesize that the use of PB increases the predicted survival derived from probability models compared with non-blood-based resuscitation. METHODS: All adult trauma patients presenting to a level 1 trauma center requiring emergency release blood transfusion from January 2017 to December 2021 were reviewed. Patients were grouped into those receiving PB or those who did not (no PB). Prehospital Trauma and Injury Severity Score (TRISS) and shock index were compared with those at presentation to hospital. Univariate and multivariate regressions were performed to identify factors associated with changes in survival probability at presentation. RESULTS: In total, 2117 patients were reviewed (PB, 1,011; no PB, 1,106). Patients receiving PB were younger (35 vs. 40 years, p < 0.001), more likely to have blunt mechanism (71% vs. 65%, p = 0.002), and more severely injured (Injury Severity Score, 27 vs. 25; p < 0.001) and had higher rates of prehospital hypotension (44% vs. 19%, p < 0.001) and shock index (1.10 vs. 0.87, p < 0.001). Upon arrival, PB patients had lower rates of ED hypotension (34% vs. 39%, p = 0.01), and significant improvements in arrival TRISS scores (+0.09 vs. -0.02, p < 0.001) and shock index (+0.10 vs. -0.07, p < 0.001) compared with prehospital. On multivariate analysis, PB was associated with a threefold increase in unexpected survivors (odds ratio, 3.28; 95% confidence interval, 2.23-4.60). CONCLUSION: The use of PB was associated with improved probability of survival and an increase in unexpected survivors. Applying TRISS and shock index at hospital arrival does not account for en route hemostatic resuscitation, causing patients to arrive with improved vitals despite severity of injury. Caution should be used when implementing survival probability calculations using arrival vitals in centers with prehospital transfusion capability. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

'Door-to-prophylaxis' as a novel quality improvement metric in prevention of venous thromboembolism following traumatic injury.

Objective: Venous thromboembolism (VTE) risk reduction strategies include early initiation of chemoprophylaxis, reducing missed doses, weight-based dosing and dose adjustment using anti-Xa levels. We hypothesized that time to initiation of chemoprophylaxis would be the strongest modifiable risk for VTE, even after adjusting for competing risk factors. Methods: A prospectively maintained trauma registry was queried for patients admitted July 2017-October 2021 who were 18 years and older and received emergency release blood products. Patients with deep vein thrombosis or pulmonary embolism (VTE) were compared to those without (no VTE). Door-to-prophylaxis was defined as time from hospital arrival to first dose of VTE chemoprophylaxis (hours). Univariate and multivariate analyses were then performed between the two groups. Results: 2047 patients met inclusion (106 VTE, 1941 no VTE). There were no differences in baseline or demographic data. VTE patients had higher injury severity score (29 vs 24), more evidence of shock by arrival lactate (4.6 vs 3.9) and received more post-ED transfusions (8 vs 2 units); all p<0.05. While there was no difference in need for enoxaparin dose adjustment or missed doses, door-to-prophylaxis time was longer in the VTE group (35 vs 25 hours; p=0.009). On multivariate logistic regression analysis, every hour delay from time of arrival increased likelihood of VTE by 1.5% (OR 1.015, 95% CI 1.004 to 1.023, p=0.004). Conclusion: The current retrospective study of severely injured patients with trauma who required emergency release blood products found that increased door-to-prophylaxis time was significantly associated with an increased likelihood for VTE. Chemoprophylaxis initiation is one of the few modifiable risk factors available to combat VTE, therefore early initiation is paramount. Similar to door-to-balloon time in treating myocardial infarction and door-to-tPA time in stroke, "door-to-prophylaxis time" should be considered as a hospital metric for prevention of VTE in trauma. Level of evidence: Level III, retrospective study with up to two negative criteria.

Empiric Cryoprecipitate Transfusion in Patients with Severe Hemorrhage: Results from the US Experience in the International CRYOSTAT-2 Trial.

BACKGROUND: Hypofibrinogenemia has been shown to predict massive transfusion and is associated with higher mortality in severely injured patients. However, the role of empiric fibrinogen replacement in bleeding trauma patients remains controversial. We sought to determine the effect of empiric cryoprecipitate as an adjunct to a balanced transfusion strategy (1:1:1). STUDY DESIGN: This study is a subanalysis of patients treated at the single US trauma center in a multicenter randomized controlled trial. Trauma patients (more than 15 years) were eligible if they had evidence of active hemorrhage requiring emergent surgery or interventional radiology, massive transfusion protocol (MTP) activation, and received at least 1 unit of blood. Transfer patients, those with injuries incompatible with life, or those injured more than 3 hours earlier were excluded. Patients were randomized to standard MTP (STANDARD) or MTP plus 3 pools of cryoprecipitate (CRYO). Primary outcomes included all-cause mortality at 28 days. Secondary outcomes were transfusion requirements, intraoperative and postoperative coagulation laboratory values, and quality-of-life measures (Glasgow outcome score-extended). RESULTS: Forty-nine patients (23 in the CRYO group and 26 in the STANDARD group) were enrolled between May 2021 and October 2021. Time to randomization was similar between groups (14 vs 24 minutes, p = 0.676). Median time to cryoprecipitate was 41 minutes (interquartile range 37 to 48). There were no differences in demographics, arrival physiology, laboratory values, or injury severity. Intraoperative and ICU thrombelastography values, including functional fibrinogen, were similar between groups. There was no benefit to CRYO with respect to post-emergency department transfusions (intraoperative and ICU through 24 hours), complications, Glasgow outcome score, or mortality. CONCLUSIONS: In this study of severely injured, bleeding trauma patients, empiric cryoprecipitate did not improve survival or reduce transfusion requirements. Cryoprecipitate should continue as an "on-demand" addition to a balanced transfusion strategy, guided by laboratory values and should not be given empirically.

AP-4 loss in CRISPR-edited zebrafish affects early embryo development.

Mutations in the heterotetrametric adaptor protein 4 (AP-4; ε/ß4/µ4/σ4 subunits) membrane trafficking coat complex lead to complex neurological disorders characterized by spastic paraplegia, microcephaly, and intellectual disabilities. Understanding molecular mechanisms underlying these disorders continues to emerge with recent identification of an essential autophagy protein, ATG9A, as an AP-4 cargo. Significant progress has been made uncovering AP-4 function in cell culture and patient-derived cell lines, and ATG9A trafficking by AP-4 is considered a potential target for gene therapy approaches. In contrast, understanding how AP-4 trafficking affects development and function at the organismal level has long been hindered by loss of conserved AP-4 genes in key model systems (S. cerevisiae, C. elegans, D. melanogaster). However, zebrafish (Danio rerio) have retained AP-4 and can serve as an important model system for studying both the nervous system and overall development. We undertook gene editing in zebrafish using a CRISPR-ExoCas9 knockout system to determine how loss of single AP-4, or its accessory protein tepsin, genes affect embryo development 24 h post-fertilization (hpf). Single gene-edited embryos display abnormal head morphology and neural necrosis. We further conducted the first exploration of how AP-4 single gene knockouts in zebrafish embryos affect expression levels and patterns of two autophagy genes, atg9a and map1lc3b. This work suggests zebrafish may be further adapted and developed as a tool to uncover AP-4 function in membrane trafficking and autophagy in the context of a model organism.

A rare case of survival after traumatic blunt ventricular rupture.

A male in his 40s presented to the trauma center via air ambulance after colliding with a cement wall at highway speeds. Cross-sectional imaging revealed a right ventricular pseudoaneurysm, confirmed by echocardiography. He was taken emergently to the operating room where he was found to have a pericardial laceration, hemopericardium and a right ventricular rupture, which was primarily repaired. Postoperatively, the patient was transferred to intensive care and after 34 days in the hospital was ultimately discharged home.

Variations in preservation of exceptional fossils within concretions.

Concretions are an interesting mode of preservation that can occasionally yield fossils with soft tissues. To properly interpret these fossils, an understanding of their fossilization is required. Probabilistic models are useful tools to identify variations between different Konservat-Lagerstätten that are separated spatially and temporally. However, the application of probabilistic modeling has been limited to Early Paleozoic Konservat-Lagerstätten preserved in shales. In this paper, the patterns of preservation of three concretionary Konservat-Lagerstätten-the Carboniferous Mazon Creek (USA) and Montceau-les-Mines (France), and the Silurian Herefordshire Lagerstätte (UK)-are analyzed using a statistical approach. It is demonstrated that the degree of biotic involvement, i.e., the degree to which a carcass dictates its own preservation, is connected to internal organ conditional probabilities-the probabilities of finding an internal organ associated with another structure such as biomineralized, sclerotized, cuticularized, or cellular body walls. In concretions that are externally forced with little biological mediation (e.g., Herefordshire), all internal organ conditional probabilities are uniform. As biological mediation in concretion formation becomes more pronounced, heterogeneities in conditional probabilities are introduced (e.g., Montceau-les-Mines and Mazon Creek). The three concretionary sites were also compared with previously investigated Konservat-Lagerstätten preserving fossils in shales to demonstrate how the developed probability framework aids in understanding the broad-scale functioning of preservation in Konservat-Lagerstätten. Supplementary Information: The online version contains supplementary material available at 10.1186/s13358-023-00284-4.

Predicting Futility in Severely Injured Patients: Using Arrival Lab Values and Physiology to Support Evidence-Based Resource Stewardship.

BACKGROUND: The recent pandemic exposed a largely unrecognized threat to medical resources, including daily available blood products. Some of the most severely injured patients who arrive in extremis consume tremendous resources yet succumb shortly after arrival. We sought to identify cut points available early in the patient's resuscitation that predicted 100% mortality. STUDY DESIGN: Cut points were developed from a previously collected data set of all level 1 trauma patients admitted January 2010 to December 2016. Objective values available on or shortly after arrival were evaluated. Once generated, we then validated these variables against (1) a prospective data set November 2017 to October 2021 of severely injured patients and (2) a multicenter, randomized trial of hemorrhagic shock patients. Analyses were conducted using STATA 17.0 (College Station, TX), generating positive predictive value (PPV), negative predictive value, sensitivity, and specificity. RESULTS: The development data set consisted of 9,509 patients (17% mortality), with 2,137 (24%) and 680 (24%) in the two validation data sets. Several combinations of arrival vitals and labs had 100% PPV. Patients undergoing CPR in the field or on arrival (with subsequent return of spontaneous circulation) required lower fibrinolysis LY-30 (30%) than those with systolic blood pressures of ≤50 (30 to 50%), ≤70 (80 to 90%), and ≤90 mmHg (90%). Using a combination of these validated variables, the Suspension of Transfusions and Other Procedures (STOP) criteria were developed, with each element predicting 100% mortality, allowing physicians to cease further resuscitative efforts. CONCLUSIONS: The use of evidence-based STOP criteria provides cut points of futility to help guide early decisions for discontinuing aggressive treatment of severely injured patients arriving in extremis.