Cryo-EM analysis provides new mechanistic insight into ATP binding to Ca2+ -ATPase SERCA2b.

Sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) 2b is a ubiquitous SERCA family member that conducts Ca2+ uptake from the cytosol to the ER. Herein, we present a 3.3 Å resolution cryo-electron microscopy (cryo-EM) structure of human SERCA2b in the E1·2Ca2+ state, revealing a new conformation for Ca2+ -bound SERCA2b with a much closer arrangement of cytosolic domains than in the previously reported crystal structure of Ca2+ -bound SERCA1a. Multiple conformations generated by 3D classification of cryo-EM maps reflect the intrinsically dynamic nature of the cytosolic domains in this state. Notably, ATP binding residues of SERCA2b in the E1·2Ca2+ state are located at similar positions to those in the E1·2Ca2+ -ATP state; hence, the cryo-EM structure likely represents a preformed state immediately prior to ATP binding. Consistently, a SERCA2b mutant with an interdomain disulfide bridge that locks the closed cytosolic domain arrangement displayed significant autophosphorylation activity in the presence of Ca2+ . We propose a novel mechanism of ATP binding to SERCA2b.

Mechanistic characterization of disulfide bond reduction of an ERAD substrate mediated by cooperation between ERdj5 and BiP.

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a protein quality control process that eliminates misfolded proteins from the ER. DnaJ homolog subfamily C member 10 (ERdj5) is a protein disulfide isomerase family member that accelerates ERAD by reducing disulfide bonds of aberrant proteins with the help of an ER-resident chaperone BiP. However, the detailed mechanisms by which ERdj5 acts in concert with BiP are poorly understood. In this study, we reconstituted an in vitro system that monitors ERdj5-mediated reduction of disulfide-linked J-chain oligomers, known to be physiological ERAD substrates. Biochemical analyses using purified proteins revealed that J-chain oligomers were reduced to monomers by ERdj5 in a stepwise manner via trimeric and dimeric intermediates, and BiP synergistically enhanced this action in an ATP-dependent manner. Single-molecule observations of ERdj5-catalyzed J-chain disaggregation using high-speed atomic force microscopy, demonstrated the stochastic release of small J-chain oligomers through repeated actions of ERdj5 on peripheral and flexible regions of large J-chain aggregates. Using systematic mutational analyses, ERAD substrate disaggregation mediated by ERdj5 and BiP was dissected at the molecular level.

Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared to standard care resuscitation in patients with hemorrhagic shock. SUMMARY BACKGROUND DATA: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at five U.S. trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days vs. standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared to 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P=0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences.

Risk factors for stroke in penetrating cerebrovascular injuries.

OBJECTIVE: Penetrating cerebrovascular injuries (PCVI) are associated with a high incidence of mortality and neurological events. The optimal treatment strategy of PCVI, especially when damage control measures are required, remains controversial. The aim of this study was to describe the management of PCVI and patient outcomes at a level 1 trauma center where vascular injuries are managed predominantly by trauma surgeons. METHODS: An institutional trauma registry was queried for patients with PCVI from 2011 to 2021. Patients with common carotid artery (CCA), internal carotid artery (ICA), or vertebral artery injuries were included for analysis. The primary outcome was in-hospital stroke. The secondary outcomes were in-hospital mortality and in-hospital stroke or death. A subgroup analysis was completed of arterial repair (primary repair or interposition graft) vs ligation or embolization vs temporary intravascular shunting at the index procedure. RESULTS: We analyzed 54 patients with PCVI. Overall, the in-hospital stroke rate was 17% and in-hospital mortality was 26%. Twenty-one patients (39%) underwent arterial interventions for PCVI. Ten patients underwent arterial repair, six patients underwent ligation or embolization, and five patients underwent intravascular shunting as a damage control strategy with a plan for delayed repair. The rate of in-hospital stroke was 30% after arterial repair, 0% after arterial ligation or embolization, and 80% after temporary intravascular shunting. There was a significant difference in the stroke rate between the three subgroups (P = .015). Of the 32 patients who did not have an intervention to the CCA, ICA, or vertebral artery, 1 patient with ICA occlusion and 1 patient with CCA intimal injury developed in-hospital stroke. The mortality rate was 0% after arterial repair, 50% after ligation or embolization, and 60% after intravascular shunting. The rate of stroke or death was 30% in the arterial repair group, 50% in the ligation or embolization group, and 100% in the temporary intravascular shunting group. CONCLUSIONS: High rates of stroke and mortality were seen in patients requiring damage control after PCVI. In particular, temporary intravascular shunting was associated with a high incidence of in-hospital stroke and a 100% rate of stroke or death. Further investigation is needed into the factors related to these finding and whether the use of temporary intravascular shunting in PCVI is an advisable strategy.

Resuscitative Thoracotomy for Traumatic Cardiac Arrest: Potential Impact of Resource Constraint on Outcomes and Blood Product Utilization.

INTRODUCTION: Resuscitative thoracotomy (RT) in the setting of traumatic arrest serves as a vital but resource-intensive intervention. The COVID-19 pandemic has created critical shortages, sharpening the focus on efficient resource utilization. This study aims to compare RT performance and blood product utilization before and after the onset of the COVID-19 pandemic for patients in traumatic cardiac arrest. METHODS: All patients undergoing RT for traumatic cardiac arrest in the emergency department at our American College of Surgeons-verified Level 1 trauma center (August 01, 2017-July 31, 2022) were included in this retrospective observational study. Study groups were dichotomized into pre-COVID (before October 03, 2020) versus COVID (from October 03, 2020 on) based on patient arrival date demographics, clinical/injury data, and outcomes were collected. The primary outcome was blood product transfusion <4 h after presentation. RESULTS: 445 RTs (2% of 23,488 trauma encounters) were performed over the study period: Pre-COVID, n = 209 (2%) versus COVID, n = 236 (2%) (P = 0.697). Survival to discharge was equivalent Pre-COVID versus COVID (n = 22, 11% versus n = 21, 9%, P = 0.562). RT patients during COVID consumed a median of 1 unit less packed red blood cells at the 4 h measurement (3.0 [1.8-7.0] versus 3.9 [2.0-10.0] units, P = 0.012) and 1 unit less of platelets at the 4 h measurement (4.3 [2.6-10.0] versus 5.7 [2.9-14.4] units, P = 0.012) compared to Pre-COVID. These findings were persistent after performing multivariable negative binomial regression. CONCLUSIONS: Rates of RT and survival after RT remained consistent during the pandemic. Despite comparable RT frequency, packed red blood cells and platelet transfusions were reduced, likely reflecting resource expenditure minimization during the severe blood shortages that occurred during the pandemic. RT performance for patients in traumatic arrest may, therefore, be feasible during global pandemics at prepandemic frequencies as long as particular attention is paid to resource expenditure.

Outcomes Associated With Aortic Balloon Occlusion Time in Patients With Zone 1 Resuscitative Endovascular Balloon Occlusion of the Aorta.

INTRODUCTION: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has the potential to cause clinically relevant systemic ischemic burden with long durations of aortic occlusion (AO). We aimed to examine the association between balloon occlusion time and clinical complications and mortality outcomes in patients undergoing zone 1 REBOA. METHODS: A retrospective cohort analysis of American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acuteregistry patients with Zone 1 REBOA between 2013 and 2022 was performed. Patients with cardiopulmonary resuscitation on arrival or who did not survive past the emergency department were excluded. Total AO times were categorized as follows: <15 min, 15-30 min, 31-60 min, and >60 min. Clinical and procedural variables and in-hospital outcomes were compared across groups using bivariate and multivariate regression analyses. RESULTS: There were 327 cases meeting inclusion criteria (n = 51 < 15 min, 83 15-30 min, 98 31-60 min, and 95 > 60 min, respectively). AO >60 min had higher admission lactate (8 ± 6; P = 0.004) compared to all other time groups, but injury severity score, heart rate, and systolic blood pressure were similar. Group average times from admission to definitive hemorrhage control ranged from 82 to 103 min and were similar across groups (85 min in AO >60 group). Longer AO times were associated with greater red blood cell, fresh frozen plasma transfusions (P < 0.001), and vasopressor use (P = 0.001). Mortality was greatest in the >60 min group (73%) versus the <15 min, 15-30 min, and 31-60 min groups (53%, 43%, and 45%, P < 0.001). With adjustment for injury severity score, systolic blood pressure, and lactate, AO >60 min had greater mortality (OR 3.7, 95% CI 1.6-9.4; P < 0.001) than other AO duration groups. Among 153 survivors, AO >60 min had a higher rate of multiple organ failure (15.4%) compared to the other AO durations (0%, 0%, and 4%, P = 0.02). There were no differences in amputation rates (0.7%) or spinal cord ischemia (1.4%). acute kidney injury was seen in 41% of >60 min versus 21%, 27%, and 33%, P = 0.42. CONCLUSIONS: Though greater preocclusion physiologic injury may have been present, REBOA-induced ischemic insult was correlated with poor patient outcomes, specifically, REBOA inflation time >60 min had higher rates of mortality and multiple organ failure. Minimizing AO duration should be prioritized, and AO should not delay achieving definitive hemostasis. Partial REBOA may be a solution to extend safe AO time and deserves further study.

Structural basis of the conformational and functional regulation of human SERCA2b, the ubiquitous endoplasmic reticulum calcium pump.

Sarco/endoplasmic reticulum Ca2+ ATPase 2b (SERCA2b), a member of the SERCA family, is expressed ubiquitously and transports Ca2+ into the sarco/endoplasmic reticulum using the energy provided by ATP binding and hydrolysis. The crystal structure of SERCA2b in its Ca2+ - and ATP-bound (E1∙2Ca2+ -ATP) state and cryo-electron microscopy (cryo-EM) structures of the protein in its E1∙2Ca2+ -ATP and Ca2+ -unbound phosphorylated (E2P) states have provided essential insights into how the overall conformation and ATPase activity of SERCA2b is regulated by the transmembrane helix 11 and the subsequent luminal extension loop, both of which are specific to this isoform. More recently, our cryo-EM analysis has revealed that SERCA2b likely adopts open and closed conformations of the cytosolic domains in the Ca2+ -bound but ATP-free (E1∙2Ca2+ ) state, and that the closed conformation represents a state immediately prior to ATP binding. This review article summarizes the unique mechanisms underlying the conformational and functional regulation of SERCA2b.

Safety/booster seats in pediatric motor vehicle crashes: Public health concern.

INTRODUCTION: The American Academy of Pediatrics (AAP) guidelines recommend that children ≤12-years-old with height < 145 cm should use safety/booster seats. However, national adherence and clinical outcomes for eligible children involved in motor vehicle collisions (MVCs) are unknown. We hypothesized that children recommended to use safety/booster seats involved in MVCs have a lower rate of serious injuries if a safety/booster seat is used, compared to children without safety/booster seat. METHODS: This retrospective cohort study queried the 2017-2019 Trauma Quality Improvement Program database for patients ≤12-years-old and <145 cm (recommendation for use of safety/booster seat per American Academy of Pediatrics) presenting after MVC. Serious injury was defined by abbreviated injury scale grade ≥3 for any body-region. High-risk MVC was defined by authors in conjunction with definitions provided by the Centers for Disease Control and Prevention and the American College of Surgeons Committee on Trauma. RESULTS: From 8259 cases, 41% used a safety/booster seat. There was no difference in overall rate of serious traumatic injuries or mortality (both p > 0.05) between the safety/booster seat and no safety/booster seat groups. In a subset analysis of high-risk MVCs, the overall use of safety/booster seats was 56%. The rate of serious traumatic injury (53.6% vs. 62.1%, p = 0.017) and operative intervention (15.8% vs. 21.6%, p = 0.039) was lower in the safety/booster seat group compared to the no safety/booster seat group. CONCLUSIONS: Despite AAP guidelines, less than half of recommended children in our study population presenting to a trauma center after MVC used safety/booster seats. Pediatric patients involved in a high-risk MVC suffered more serious injuries and were more likely to require surgical intervention without a safety/booster seat. A public health program to increase adherence to safety/booster seat use within this population appears warranted.

Significant variation in computed tomography imaging of pregnant trauma patients: a retrospective multicenter study.

PURPOSE: Following motor vehicle collisions (MVCs), patients often undergo extensive computed tomography (CT) imaging. However, pregnant trauma patients (PTPs) represent a unique population where the risk of fetal radiation may supersede the benefits of liberal CT imaging. This study sought to evaluate imaging practices for PTPs, hypothesizing variability in CT imaging among trauma centers. If demonstrated, this might suggest the need to develop specific guidelines to standardize practice. METHODS: A multicenter retrospective study (2016-2021) was performed at 12 Level-I/II trauma centers. Adult (≥18 years old) PTPs involved in MVCs were included, with no patients excluded. The primary outcome was the frequency of CT. Chi-square tests were used to compare categorical variables, and ANOVA was used to compare the means of normally distributed continuous variables. RESULTS: A total of 729 PTPs sustained MVCs (73% at high speed of ≥ 25 miles per hour). Most patients were mildly injured but a small variation of injury severity score (range 1.1-4.6, p < 0.001) among centers was observed. There was a variation of imaging rates for CT head (range 11.8-62.5%, p < 0.001), cervical spine (11.8-75%, p < 0.001), chest (4.4-50.2%, p < 0.001), and abdomen/pelvis (0-57.3%, p < 0.001). In high-speed MVCs, there was variation for CT head (12.5-64.3%, p < 0.001), cervical spine (16.7-75%, p < 0.001), chest (5.9-83.3%, p < 0.001), and abdomen/pelvis (0-60%, p < 0.001). There was no difference in mortality (0-2.9%, p =0.19). CONCLUSION: Significant variability of CT imaging in PTPs after MVCs was demonstrated across 12 trauma centers, supporting the need for standardization of CT imaging for PTPs to reduce unnecessary radiation exposure while ensuring optimal injury identification is achieved.

Structures, Mechanisms, and Physiological Functions of Zinc Transporters in Different Biological Kingdoms.

Zinc transporters take up/release zinc ions (Zn2+) across biological membranes and maintain intracellular and intra-organellar Zn2+ homeostasis. Since this process requires a series of conformational changes in the transporters, detailed information about the structures of different reaction intermediates is required for a comprehensive understanding of their Zn2+ transport mechanisms. Recently, various Zn2+ transport systems have been identified in bacteria, yeasts, plants, and humans. Based on structural analyses of human ZnT7, human ZnT8, and bacterial YiiP, we propose updated models explaining their mechanisms of action to ensure efficient Zn2+ transport. We place particular focus on the mechanistic roles of the histidine-rich loop shared by several zinc transporters, which facilitates Zn2+ recruitment to the transmembrane Zn2+-binding site. This review provides an extensive overview of the structures, mechanisms, and physiological functions of zinc transporters in different biological kingdoms.

Management for Acute Uncomplicated Appendicitis During Pregnancy: National Trends and Patient Outcomes.

OBJECTIVE: This study analyzes national trends in the management of uncomplicated appendicitis during pregnancy, comparing outcomes for nonoperative management (NOM) and appendectomy. BACKGROUND: In the nonpregnant population, several randomized controlled trials demonstrated noninferiority of NOM compared with appendectomy for acute uncomplicated appendicitis. However, it remains unclear whether these findings are generalizable to pregnant patients. METHODS: The National Inpatient Sample was queried for pregnant women diagnosed with acute uncomplicated appendicitis from January 2003 to September 2015. Patients were categorized by treatment: NOM, laparoscopic appendectomy (LA), and open appendectomy. A quasi-experimental analysis with interrupted time series examined the relationship between the year of admission and the likelihood of receiving NOM. Multivariable logistic regression analyses were used to evaluate the association between treatment strategy and patient outcomes. RESULTS: A total of 33,120 women satisfied the inclusion criteria. Respectively, 1070 (3.2%), 18,736 (56.6%), and 13,314 (40.2%) underwent NOM, LA, and open appendectomy. The NOM rate significantly increased between 2006 and 2015, with an annual increase of 13.9% (95% CI, 8.5-19.4, P <0.001). Compared with LA, NOM was significantly associated with higher rates of preterm abortion (odds ratio [OR]: 3.057, 95% CI, 2.210-4.229, P <0.001) and preterm labor/delivery (OR: 3.186, 95% CI, 2.326-4.365, P <0.001). Each day of delay to appendectomy was associated with significantly greater rates of preterm abortion (OR: 1.210, 95% CI, 1.123-1.303, P <0.001). CONCLUSIONS: Although NOM has been increasing as a treatment for pregnant patients with uncomplicated appendicitis, compared with LA, it is associated with worse clinical outcomes.

Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-Analysis.

PURPOSE: Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients. METHODS: We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology. RESULTS: We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared to fixed LMWH dosing, anti-Xa-guided dosing may reduce deep vein thrombosis [adjusted odds ratio (aOR); 0.52, 95% CI: 0.40-0.69], pulmonary embolism (aOR: 0.48, 95% CI: 0.30-0.78) or any VTE (aOR: 0.54, 95% CI: 0.42-0.69), though all estimates are based on low certainty evidence. There was an uncertain effect on mortality (aOR: 1.06, 95% CI: 0.85-1.32) and bleeding events (aOR: 0.84, 95% CI: 0.50-1.39), limited by serious imprecision. We used several sensitivity and subgroup analyses to confirm the validity of our assumptions. CONCLUSION: Anti-Xa-guided dosing may be more effective than fixed dosing for prevention of deep vein thrombosis, pulmonary embolism, and VTE for adult trauma patients. These promising findings justify the need for a high-quality randomized study with the potential to deliver practice changing results.

Epidemiology, repair technique, and predictors of stroke and mortality in penetrating carotid artery injuries.

OBJECTIVE: Penetrating carotid artery injuries (PCAI) are significantly morbid and deadly, often presenting in extremis with associated injuries and central nervous system deficit. Repair may be challenging with arterial reconstruction vs ligation role poorly defined. This study evaluated contemporary outcomes and management of PCAI. METHODS: PCAI patients in the National Trauma Data Bank from 2007 to 2018 were analyzed. Outcomes were compared between repair and ligation groups after additionally excluding external carotid injuries, concomitant jugular vein injuries, and head/spine Abbreviated Injury Severity score of ≥3. Primary end points were in-hospital mortality and stroke. Secondary end points were associated injury frequency and operative management. RESULTS: There were 4723 PCAI (55.7% gunshot wounds, 44.1% stab wounds). Gunshot wounds more frequently had associated brain (73.8% vs 19.7%; P < .001) and spinal cord (7.6% vs 1.2%; P < .001) injuries; stab wounds more frequently had jugular vein injuries (19.7% vs 29.3%; P < .001). The overall in-hospital mortality was 21.9% and the stroke rate was 6.2%. After exclusion criteria, 239 patients underwent ligation and 483 surgical repair. Ligation patients had lower presenting Glasgow Coma Scale (GCS) than repair patients (13 vs 15; P = .010). Stroke rates were equivalent (10.9% vs 9.3%; P = .507); however, in-hospital mortality was higher after ligation (19.7% vs 8.7%; P < .001). In-hospital mortality was higher in ligated common carotid artery injuries (21.3% vs 11.6%; P = .028) and internal carotid artery injuries (24.5% vs 7.3%; P = .005) compared with repair. On multivariable analysis, ligation was associated with in-hospital mortality, but not with stroke. A history of neurological deficit before injury lower GCS, and higher Injury Severity Score (ISS) were associated with stroke; ligation, hypotension, higher ISS, lower GCS, and cardiac arrest were associated with in-hospital mortality. CONCLUSIONS: PCAI are associated with a 22% rate of in-hospital mortality and a 6% rate of stroke. In this study, carotid repair was not associated with a decreased stroke rate, but did have improved mortality outcomes compared with ligation. The only factors associated with postoperative stroke were low GCS, high ISS, and a history of neurological deficit before injury. Beside ligation, low GCS, high ISS, and postoperative cardiac arrest were associated with in-hospital mortality.

Outcomes of vascular trauma associated with an evolution in the use of endovascular management.

OBJECTIVE: The availability of endovascular techniques has led to a paradigm shift in the management of vascular injury. Although previous reports showed trends towards the increased use of catheter-based techniques, there have been no contemporary studies of practice patterns and how these approaches differ by anatomic distributions of injury. The objective of this study is to provide a temporal assessment of the use of endovascular techniques in the management of torso, junctional (subclavian, axillary, iliac), and extremity injury and to evaluate any association with survival and length of stay. METHODS: The American Association for the Surgery of Trauma (AAST) Prospective Observational Vascular Injury Treatment registry (PROOVIT) is the only large multicenter database focusing specifically on the management of vascular trauma. Patients in the AAST PROOVIT registry from 2013 to 2019 with arterial injuries were queried, and radial/ulnar, and tibial artery injuries were excluded. The primary aim was to evaluate the frequency in use of endovascular techniques over time and by body region. A secondary analysis evaluated the trends for junctional injuries and compared the mortality between those treated with open vs endovascular repair. RESULTS: Of the 3249 patients included, 76% were male, and overall treatment type was 42% nonoperative, 44% open, and 14% endovascular. Endovascular treatment increased an average of 2% per year from 2013 to 2019 (range, 17%-35%; R2 = .61). The use of endovascular techniques for junctional injuries increased by 5% per year (range, 33%-63%; R2 = .89). Endovascular treatment was more common for thoracic, abdominal, and cerebrovascular injuries, and least likely in upper and lower extremity injuries. Injury severity score was higher for patients receiving endovascular repair in every vascular bed except lower extremity. Endovascular repair was associated with significantly lower mortality than open repair for thoracic (5% vs 46%; P < .001) and abdominal injuries (15% vs 38%; P < .001). For junctional injuries, endovascular repair was associated with a non-statistically significant lower mortality (19% vs 29%; P = .099), despite higher injury severity score (25 vs 21; P = .003) compared with open repair. CONCLUSIONS: The reported use of endovascular techniques within the PROOVIT registry increased more than 10% over a 6-year period. This increase was associated with improved survival, especially for patients with junctional vascular injuries. Practices and training programs should account for these changes by providing access to endovascular technologies and instruction in the catheter-based skill sets to optimize outcomes in the future.

Nationwide Analysis of Penetrating Thoracic Aortic Injury: Injury Patterns, Management, and Outcomes.

INTRODUCTION: Penetrating thoracic aortic injuries (PTAI) represent a rare form of thoracic trauma. Unlike blunt thoracic aortic injuries (BTAI), only scarce data, included in small case series, are currently available for PTAI. The purpose of this study was to describe injury patterns, surgical management, and outcomes of patients with PTAI and compare to those with BTAI. MATERIALS AND METHODS: A 9-y retrospective cohort study (2007-2015) was conducted using the National Trauma Data Bank. Patient demographics, injury profile, procedures performed, and patient outcomes were compared between the PTAI and BTAI group. RESULTS: A total of 2714 patients with PTAI and 14,037 patients with BTAI were identified. Compared to BTAI, PTAI patients were younger (28 versus 42 y, P < 0.001), more often male (89.1% versus 71.7%, P < 0.001), and more likely to arrive without signs of life (27.6% versus 7.5%, P < 0.001). PTAI patients had less associated injuries, overall, compared to those with BTAI; however, were more likely to have injuries to the esophagus, diaphragm, and heart. Patients with PTAI were less likely to undergo endovascular (5.8% versus 30.5%, P < 0.001) or open surgical repair (3.0% versus 4.2%, P < 0.001) compared to BTAI. While the large majority of PTAI patients expired before their hospital arrival or in the emergency department, the in-hospital mortality rate among those who survivedemergency department stay was 43.1%. CONCLUSIONS: Most patients with PTAI present to the hospital without any signs of life, and their overall mortality rate is extremely high. Only a small portion of PTAI patients who survived the initial resuscitation period underwent surgical interventions for thoracic aortic injuries. Further studies are still warranted to clarify the indications and types of surgical interventions for PTAI.

Disparities in Care Among Gunshot Victims: A Nationwide Analysis.

INTRODUCTION: Given the well-known healthcare disparities most pronounced in racial and ethnic minorities, trauma healthcare in underrepresented patients should be examined, as in-hospital bias may influence the care rendered to patients. This study seeks to examine racial differences in outcomes and resource utilization among victims of gunshot wounds in the United States. METHODS: This is a retrospective review of the National Trauma Data Bank (NTDB) conducted from 2007 to 2017. The NTDB was queried for patients who suffered a gunshot wound not related to accidental injury or suicide. Patients were stratified according to race. The primary outcome for this study was mortality. Secondary outcomes included racial differences in resource utilization including air transport and discharge to rehabilitation centers. Univariate and multivariate analyses were used to compare differences in outcomes between the groups. RESULTS: A total of 250,675 patients were included in the analysis. After regression analysis, Black patients were noted to have greater odds of death compared to White patients (odds ratio [OR] 1.14, confidence interval [CI] 1.037-1.244; P = 0.006) and decreased odds of admission to the intensive care unit (ICU) (OR 0.76, CI 0.732-0.794; P < 0.001). Hispanic patients were significantly less likely to be discharged to rehabilitation centers (Hispanic: 0.78, CI 0.715-0.856; P < 0.001). Black patients had the shortest time to death (median time in minutes: White 49 interquartile range [IQR] [9-437] versus Black 24 IQR [7-205] versus Hispanic 39 IQR [8-379] versus Asian 60 [9-753], P < 0.001). CONCLUSIONS: As society carefully examines major institutions for implicit bias, healthcare should not be exempt. Greater mortality among Black patients, along with differences in other important outcome measures, demonstrate disparities that encourage further analysis of causes and solutions to these issues.

Arterial Access Complications Following Percutaneous Femoral Access in 24-Hour Resuscitative Endovascular Balloon Occlusion of the Aorta Survivors.

INTRODUCTION: With the use of resuscitative endovascular balloon occlusion of the aorta (REBOA) comes the potential for vascular access site complications (VASCs) and limb ischemic sequelae. We aimed to determine the prevalence of VASC and associated clinical and technical factors. METHODS: A retrospective cohort analysis of 24-h survivors undergoing percutaneous REBOA via the femoral artery in the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute care surgery registry between Oct 2013 and Sep 2021 was performed. The primary outcome was VASC, defined as at least one of the following: hematoma, pseudoaneurysm, arteriovenous fistula, arterial stenosis, or the use of patch angioplasty for arterial closure. Associated clinical and procedural variables were examined. Data were analyzed using Fisher exact test, Mann-Whitney-U tests, and linear regression. RESULTS: There were 34 (7%) cases with VASC among 485 meeting inclusion criteria. Hematoma (40%) was the most common, followed by pseudoaneurysm (26%) and patch angioplasty (21%). No differences in demographics or injury/shock severity were noted between cases with and without VASC. The use of ultrasound (US) was protective (VASC, 35% versus no VASC, 51%; P = 0.05). The VASC rate in US cases was 12/242 (5%) versus 22/240 (9.2%) without US. Arterial sheath size >7 Fr was not associated with VASC. US use increased over time (R2 = 0.94, P < 0.001) with a stable rate of VASC (R2 = 0.78, P = 0.61). VASC were associated with limb ischemia (VASC, 15% versus no VASC, 4%; P = 0.006) and arterial bypass procedures (VASC 3% versus no VASC 0%; P < 0.001) but amputation was uncommon (VASC, 3% versus no VASC, 0.4%; P = 0.07). CONCLUSIONS: Percutaneous femoral REBOA had a 7% VASC rate which was stable over time. VASC are associated with limb ischemia but need for surgical intervention and/or amputation is rare. The use of US-guided access appears to be protective against VASC and is recommended for use in all percutaneous femoral REBOA procedures.

Narrative Review: Is There a Transfusion Cutoff Value After Which Nonsurvivability Is Inevitable in Trauma Patients Receiving Ultramassive Transfusion?

The institution of massive transfusion protocols (MTPs) has improved the timely delivery of large quantities of blood products and improves patient outcomes. In recent years, the cost of blood products has increased, compounded by significant blood product shortages. There is practical need for identification of a transfusion volume in trauma patients that is associated with increased mortality, or a threshold after which additional transfusion is futile and associated with nonsurvivability. This transfusion threshold is often described in the setting of an ultramassive transfusion (UMT). There are few studies defining what constitutes amount or outcomes associated with such large volume transfusion. The purpose of this narrative review is to provide an analysis of existing literature examining the effects of UMT on outcomes including survival in adult trauma patients and to determine whether there is a threshold transfusion limit after which mortality is inevitable. Fourteen studies were included in this review. The data examining the utility of UMT in trauma are of poor quality, and with the variability inherent in trauma patients, and the surgeons caring for them, no universally accepted cutoff for transfusion exists. Not surprisingly, there is a trend toward increasing mortality with increasing transfusions. The decision to continue transfusing is multifactorial and must be individualized, taking into consideration patient characteristics, institution factors, blood bank supply, and most importantly, constant reevaluation of the need for ongoing transfusion rather than blind continuous transfusion until the heart stops.

Observing the nonvectorial yet cotranslational folding of a multidomain protein, LDL receptor, in the ER of mammalian cells.

Proteins have evolved by incorporating several structural units within a single polypeptide. As a result, multidomain proteins constitute a large fraction of all proteomes. Their domains often fold to their native structures individually and vectorially as each domain emerges from the ribosome or the protein translocation channel, leading to the decreased risk of interdomain misfolding. However, some multidomain proteins fold in the endoplasmic reticulum (ER) nonvectorially via intermediates with nonnative disulfide bonds, which were believed to be shuffled to native ones slowly after synthesis. Yet, the mechanism by which they fold nonvectorially remains unclear. Using two-dimensional (2D) gel electrophoresis and a conformation-specific antibody that recognizes a correctly folded domain, we show here that shuffling of nonnative disulfide bonds to native ones in the most N-terminal region of LDL receptor (LDLR) started at a specific timing during synthesis. Deletion analysis identified a region on LDLR that assisted with disulfide shuffling in the upstream domain, thereby promoting its cotranslational folding. Thus, a plasma membrane-bound multidomain protein has evolved a sequence that promotes the nonvectorial folding of its upstream domains. These findings demonstrate that nonvectorial folding of a multidomain protein in the ER of mammalian cells is more coordinated and elaborated than previously thought. Thus, our findings alter our current view of how a multidomain protein folds nonvectorially in the ER of living cells.

Does mortality after trauma team activation peak at shift change?

BACKGROUND: Prior institutional data have demonstrated trauma mortality to be highest between 06:00-07:59 at our center, which is also when providers change shifts (07:00-07:30). The objective was definition of patient, provider, and systems variables associated with trauma mortality at shift change among patients arriving as trauma team activations (TTA). METHODS: All TTA patients at our ACS-verified Level I trauma center were included (01/2008-07/2019), excluding those with undocumented arrival time. Study groups were defined by arrival time: shift change (SC) (06:00-07:59) vs. non-shift change (NSC) (all other times). Univariable/multivariable analyses compared key variables. Propensity score analysis compared outcomes after matching. RESULTS: After exclusions, 6020 patients remained: 229 (4%) SC and 5791 (96%) NSC. SC mortality was 25% vs. 16% during NSC (p < 0.001). More SC patients arrived with SBP <90 (19% vs. 11%, p < 0.001) or GCS <9 (35% vs. 24%, p < 0.001). ISS was higher during SC (43[32-50] vs. 34[27-50], p < 0.001). Time to CT scan (36[23-66] vs. 38[23-61] minutes, p = 0.638) and emergent surgery (94[35-141] vs. 63[34-107] minutes, p = 0.071) were comparable. Older age (p < 0.001), SBP <90 (p < 0.001), GCS <9 (p < 0.001), need for emergent operative intervention (p = 0.044), and higher ISS (p < 0.001) were independently associated with mortality. After propensity score matching, mortality was no different between SC and NSC (p = 0.764). CONCLUSIONS: Early morning is a low-volume, high-mortality time for TTAs. Increased mortality at shift change was independently associated with patient/injury factors but not provider/systems factors. Ensuring ample clinical resource allocation during this high acuity time may be prudent to streamline patient care at shift change.