The thin red line: Blood planning factors and the enduring need for a robust military blood system to support combat operations.

ABSTRACT: Battlefield lessons learned are forgotten; the current name for this is the Walker Dip. Blood transfusion and the need for a Department of Defense Blood Program are lessons that have cycled through being learned during wartime, forgotten, and then relearned during the next war. The military will always need a blood program to support combat and contingency operations. Also, blood supply to the battlefield has planning factors that have been consistent over a century. In 2024, it is imperative that we codify these lessons learned. The linchpins of modern combat casualty care are optimal prehospital care, early whole blood transfusion, and forward surgical care. This current opinion comprised of authors from all three military Services, the Joint Trauma System, the Armed Services Blood Program, blood SMEs and the CCC Research Program discuss two vital necessities for a successful military trauma system: (1) the need for an Armed Services Blood Program and (2) Planning factors for current and future deployed military ere is no effective care for wounded soldiers, and by extension there is no effective military medicine.

Complexities of autonomy in military medical ethics: A brief report.

ABSTRACT: The first Fallen Surgeons Military Educational Symposium was convened in conjunction with the the American Association for the Surgery of Trauma (AAST) 23 meeting, under the guidance of the AAST Military Liaison Committee. The daylong session included a 1.5-hour segment on military medical ethics in combat and its unique challenges. Medical ethical issues arise frequently within the military across a range of varied circumstances, from the day-to-day operations of stateside forces to the complexities of deployed troops in theaters of conflict. Given the scope of these circumstances, preparation and advanced planning are the key to addressing and resolving the ethical issues that occur. The goal of this session was to present illustrative cases, not to prescribe solutions, and to make the attendees aware of some of the challenges they may encounter when deployed.

Immunonutrition with Omega-3 Fatty Acid Supplementation in Severe TBI: Retrospective Analysis of Patient Characteristics and Outcomes.

Early evidence-based medical interventions to improve patient outcomes after traumatic brain injury (TBI) are lacking. In patients admitted to the ICU after TBI, optimization of nutrition is an emerging field of interest. Specialized enteral nutrition (EN) formulas that include immunonutrition containing omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been developed and are used for their proposed anti-inflammatory and proimmune properties; however, their use has not been rigorously studied in human TBI populations. A single-center, retrospective, descriptive observational study was conducted at the LAC + USC Medical Center. Patients with severe TBI (sTBI, Glasgow Coma Scale score ≤ 8) who remained in the ICU for ≥2 weeks and received EN were identified between 2017 and 2022 using the institutional trauma registry. Those who received immunonutrition formulas containing n-3 PUFAs were compared with those who received standard, polymeric EN with regard to baseline characteristics, clinical markers of inflammation and immune function, and short-term clinical outcomes. A total of 151 patients with sTBI were analyzed. Those who received immunonutrition with n-3 PUFA supplementation were more likely to be male, younger, Hispanic/Latinx, and have polytrauma needing non-central nervous system surgery. No differences in clinical markers of inflammation or infection rate were found. In multivariate regression analysis, immunonutrition was associated with reduced hospital length of stay (LOS). ICU LOS was also reduced in the subgroup of patients with polytrauma and TBI. This study identifies important differences in patient characteristics and outcomes associated with the EN formula prescribed. Study results can directly inform a prospective pragmatic study of immunonutrition with n-3 PUFA supplementation aimed to confirm the biomechanistic and clinical benefits of the intervention.

Novel Textbook Outcomes following emergency laparotomy: Delphi exercise.

BACKGROUND: Textbook outcomes are composite outcome measures that reflect the ideal overall experience for patients. There are many of these in the elective surgery literature but no textbook outcomes have been proposed for patients following emergency laparotomy. The aim was to achieve international consensus amongst experts and patients for the best Textbook Outcomes for non-trauma and trauma emergency laparotomy. METHODS: A modified Delphi exercise was undertaken with three planned rounds to achieve consensus regarding the best Textbook Outcomes based on the category, number and importance (Likert scale of 1-5) of individual outcome measures. There were separate questions for non-trauma and trauma. A patient engagement exercise was undertaken after round 2 to inform the final round. RESULTS: A total of 337 participants from 53 countries participated in all three rounds of the exercise. The final Textbook Outcomes were divided into 'early' and 'longer-term'. For non-trauma patients the proposed early Textbook Outcome was 'Discharged from hospital without serious postoperative complications (Clavien-Dindo ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation or death). For trauma patients it was 'Discharged from hospital without unexpected transfusion after haemostasis, and no serious postoperative complications (adapted Clavien-Dindo for trauma ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation on or death)'. The longer-term Textbook Outcome for both non-trauma and trauma was 'Achieved the early Textbook Outcome, and restoration of baseline quality of life at 1 year'. CONCLUSION: Early and longer-term Textbook Outcomes have been agreed by an international consensus of experts for non-trauma and trauma emergency laparotomy. These now require clinical validation with patient data.

Unhoused and Injured: Injury Characteristics and Outcomes in Unhoused Trauma Patients.

INTRODUCTION: The unhoused population is known to be at high risk for traumatic injury. However, there are scarce data regarding injury patterns and outcomes for this patient group. This study aims to investigate any differences in injury characteristics and hospital outcomes between unhoused and housed patients presenting with traumatic injuries. METHODS: We conducted a 3-y retrospective cohort study at a level 1 trauma center in a metropolitan area with a large unhoused population. All adult trauma patients who were identified as unhoused or housed underinsured (HUI) were included in the study. Injury characteristics, comorbidities, and hospital outcomes were compared between the two groups. RESULTS: A total of 8450 patients were identified, of which 7.5% were unhoused. Compared to HUI patients, unhoused patients were more likely to sustain minor injuries (65.2% versus 59.1%, P = 0.003) and more likely to be injured by assault (17.9% versus 12.4%, P < 0.001), stab wound (17.7% versus 10.8%, P < 0.001), and automobile versus pedestrian or bike (21.0% versus 15.8% P < 0.001). We found that unhoused patients had higher odds of mortality (adjusted odds ratio [AOR]: 1.93, 95% confidence interval [CI]: 1.10-3.36, P = 0.021), brain death (AOR: 5.40, 95% CI: 2.11-13.83, P < 0.001), bacteremia/sepsis (AOR: 4.36, 95% CI: 1.20-15.81, P = 0.025), and increased hospital length of stay (regression coefficient: 0.08, 95% CI: 0.03-0.12, P = 0.003). CONCLUSIONS: This study observed significant disparities in injury characteristics and hospital outcomes between the unhoused and HUI groups. Our results suggest that these disparities are impacted by social determinants of health unique to the unhoused population.

Safety of redo sleeve gastrectomy as a primary revisional procedure.

BACKGROUND: Insufficient weight loss after primary laparoscopic sleeve gastrectomy (LSG) occasionally requires revisional surgery. A few single-institution studies have examined the safety of redo LSG (RSG) and have shown mixed results. OBJECTIVES: The aim of this study was to evaluate the safety of RSG compared with LSG over a period of 30 days. SETTING: University of Southern California, United States; Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. METHODS: The 2020-2021 MBSAQIP registry was used to evaluate patients who underwent RSG. Thirty-day outcomes were evaluated using univariable analysis and multivariable logistic and linear regression. RESULTS: A total of 226,029 patients were reviewed, of whom 1454 (.7%) underwent RSG and 224,575 (99.3%) underwent initial LSG. Patients who underwent RSG were older (45 versus 42 yr), predominantly female (86.2% versus 81.3%), had a lower body mass index (40.0 versus 43.4), fewer co-morbidities, and greater rates of gastroesophageal reflux (38.7% versus 25.1%). They demonstrated increased overall complications (3.6% versus 2.1%, P < .001) and a longer operative time (81 versus 62 min, P < .001), but there was no difference in mortality. On multivariable analysis, patients who underwent RSG were independently associated with an increased risk of overall postoperative complications (odds ratio [OR]: 1.493, P = .018), organ space infection (OR: 6.231, P < .001), staple line leak (OR: 12.838, P < .001), pneumonia (OR: 3.85, P = .013), ventilator requirement over 48 hours (OR: 6.404, P = .035), sepsis (OR: 4.397, P = .010), septic shock (OR: 8.669, P < .001), reoperation (OR: 1.808, P = .013), readmission (OR: 2.104, P < .001), reintervention (OR: 4.435, P < .001), and longer operative times (ß = 12.790, P < .001). CONCLUSIONS: In this national database study, RSG was associated with increased rates of postoperative complications and a longer operative time. Although these results are concerning, further studies are required to examine long-term outcomes.

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.

Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants.

Epilepsy is a common neurological disorder characterized by abnormal activity of neuronal networks, leading to seizures. The racetam class of anti-seizure medications bind specifically to a membrane protein found in the synaptic vesicles of neurons called synaptic vesicle protein 2 (SV2) A (SV2A). SV2A belongs to an orphan subfamily of the solute carrier 22 organic ion transporter family that also includes SV2B and SV2C. The molecular basis for how anti-seizure medications act on SV2s remains unknown. Here we report cryo-electron microscopy structures of SV2A and SV2B captured in a luminal-occluded conformation complexed with anticonvulsant ligands. The conformation bound by anticonvulsants resembles an inhibited transporter with closed luminal and intracellular gates. Anticonvulsants bind to a highly conserved central site in SV2s. These structures provide blueprints for future drug design and will facilitate future investigations into the biological function of SV2s.

Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension.

Background: Hypertension (HTN) involves genetic variability in the renin-angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen (AGT) messenger RNA (mRNA) is endogenously bound by miR-122-5p and rs699 A > G decreases reporter mRNA in the microRNA functional-assay PASSPORT-seq. The AGT promoter variant rs5051 C > T is in linkage disequilibrium (LD) with rs699 A > G and increases AGT transcription. The independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C > T counterbalances AGT decreased by rs699 A > G, and when these variants occur independently, it translates to HTN-related phenotypes. Methods: We used in silico, in vitro, in vivo, and retrospective models to test this hypothesis. Results: In silico, rs699 A > G is predicted to increase miR-122-5p binding affinity by 3%. Mir-eCLIP results show rs699 is 40-45 nucleotides from the strongest microRNA-binding site in the AGT mRNA. Unexpectedly, rs699 A > G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression model. Genotype-Tissue Expression (GTEx) and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A > G occurs independently from rs5051 C > T. However, GTEx and the in vitro experiments suggest rs699 A > G confers cell-type-specific effects on AGT mRNA abundance, and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A > G associations with HTN. Conclusions: We found that rs5051 C > T and rs699 A > G significantly associate with systolic blood pressure in Black participants in the UK Biobank, demonstrating a fourfold larger effect than in White participants. Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C > T or rs699 A > G. Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.

Mechanism Matters: Differential benefits of cold-stored whole blood for trauma resuscitation from a prospective multicenter study.

BACKGROUND: Resuscitation with cold-stored low-titre whole blood (LTOWB) has increased despite the paucity of robust civilian data. Most studies are in predominately blunt trauma and lack analysis of specific subgroups or mechanism of injury. We sought to compare outcomes between patients receiving LTOWB vs. balanced component therapy (BCT) after blunt (BL) and penetrating (PN) trauma. METHODS: Secondary analysis of a prospective multicenter study of patients receiving either LTWOB-containing or BCT resuscitation was performed. Patients were grouped by mechanism of injury (BL vs PN). A generalized estimated equations model using inverse probability of treatment weighting was employed. Primary outcome was mortality and secondary outcomes were acute kidney injury, venous thromboembolism, pulmonary complications, and bleeding complications. Additional analyses were performed on non-traumatic brain injury (TBI), severe torso injury, and LTOWB-only resuscitation patients. RESULTS: 1617 patients (BL 47% vs PN 54%) were identified; 1175 (73%) of which received LTOWB. PN trauma patients receiving LTOWB demonstrated improved survival compared to BCT (77% vs. 56%; p<0.01). Interval survival was higher at 6 hrs (95% vs. 88%), 12 hrs (93% vs. 80%) and 24 hrs (88% vs. 57%) (all p<0.05). The survival benefit following LTOWB was also seen across PN non-TBI (83% vs. 52%), and severe torso injuries (75% vs. 43%) (all p <0.05). After controlling for age, sex, injury severity, and trauma center, LTWOB was associated with decreased odds of death (OR .31, p<.05) in PN trauma. However, no difference in overall mortality was seen across the BL groups. Both PN and BL patients receiving LTOWB had more frequent AKI compared to BCT (19% vs. 7% and 12% vs 6%, respectively; p<0.05). CONCLUSIONS: LTOWB resuscitation was independently associated with decreased mortality following PN trauma, but not BL trauma. Further analysis in BL trauma is required to identify subgroups that may demonstrate survival benefit. LEVEL OF EVIDENCE: Therapeutic/Care Management, III.

Deriving acceptable limits for non-mutagenic impurities in medicinal products - Durational adjustments.

ICH Q3A/B guidelines are not intended for application during the clinical research phase of development and durationally adjusted qualification thresholds are not included. A central tenet of ICH Q3A is that lifetime exposure to 1 mg/day of an unqualified non-mutagenic impurity (NMI) is not a safety concern. An analysis of in vivo toxicology data from 4878 unique chemicals with established NO(A)ELs was conducted to determine whether durationally adjusted qualification limits can be supported. Although not recommended in ICH Q3A/B, a conservative approach was taken by using allometric scaling in the analysis. Following allometric scaling of the 5th percentile of the distribution of NO(A)ELs from available chronic toxicology studies, it was reconfirmed that there is a safety basis for the 1 mg/day qualification threshold in ICH Q3A. Additionally, allometric scaling of the 5th percentile of the distribution of NO(A)ELs from sub-acute and sub-chronic toxicology studies could support acceptable limits of 20 and 5 mg/day for an unqualified NMI for dosing durations of less than or greater than one month, respectively. This analysis supports durationally adjusted NMI qualification thresholds for pharmaceuticals that protect patient safety and contribute to 3Rs efforts for qualifying impurities using new approach methods.

Non-Binary Trauma Patients: Delineating a Vulnerable, At-Risk Population.

INTRODUCTION: An increasing proportion of the population identifies as non-binary. This marginalized group may be at differential risk for trauma compared to those who identify as male or female, but physical trauma among non-binary patients has not yet been examined at a national level. METHODS: All patients aged ≥ 16 years in the National Trauma Data Bank were included (2021-2022). Demographics, injury characteristics, and outcomes after trauma among non-binary patients were compared to males and females. The goal was to delineate differences between groups to inform the care and future study of non-binary trauma patients. RESULTS: In total, 1,012,348 patients were included: 283 (<1%) non-binary, 610,904 (60%) male, and 403,161 (40%) female patients. Non-binary patients were younger than males or females (median age 44 vs 49 vs 67 years, P < .001) and less likely to be White race/ethnicity (58% vs 60% vs 74%, P < .001). Despite non-binary patients having a lower median Injury Severity Score (5 vs 9 vs 9, P < .001), mortality was highest among non-binary and male patients than females (5% vs 5% vs 3%, P < .001). DISCUSSION: In this study, non-binary trauma patients were younger and more likely minority races/ethnicities than males or females. Despite having a lower injury severity, non-binary patient mortality rates were comparable to those of males and greater than for females. These disparities identify non-binary trauma patients as doubly marginalized, by gender and race/ethnicity, who experience worse outcomes after trauma than expected based on injury severity. This vulnerable patient population deserves further study to identify areas for improved trauma delivery care.

The Great Debate: Robotic vs Traditional Surgical Approach in the Acute Care Setting.

Robotic surgery was first introduced in the 1980s as a system to aid patients in the battlefield. Since then, robotic surgery has become an important minimally invasive tool and plays an important role in elective surgery among various surgical specialties. However, the role for robotic surgery in the emergent setting is not well established or studied. Robotic surgery has been shown to be advantageous to both patients and operating surgeons. Though limited, studies have found robotic surgery in the acute setting to be safe for patients. These studies found robotic surgery to have improved perioperative outcomes when compared to an open or laparoscopic approach. Additionally, the robotic platform is thought to be an effective tool to prevent conversion to open procedures in emergent settings. Although some studies demonstrate advantages to robotic acute surgery, others have shown increased complications with robotic acute surgery or no distinct advantage when comparing robotic to laparoscopic surgery. Additionally, some of the published papers supporting the use of robotic surgery in the emergent setting may have a degree of bias favoring the robotic platform. Robotic surgery is a mainstay in minimally invasive elective surgery and gaining popularity among patients and surgeons. There are pros and cons to the adaptation of the robotic platform in the acute care setting. Additional large population studies are indicated to determine the true role of the robotic platform in the emergent setting.

Back on the Streets: Examining Emergency Department Return Rates for Unhoused Patients Discharged After Trauma.

BACKGROUND: The unhoused population is at high risk for traumatic injuries and faces unique challenges in accessing follow-up care. However, there is scarce data regarding differences in Emergency Department (ED) return rates and reasons for return between unhoused and housed patients. METHODS: We conducted a 3-year retrospective cohort study at a level-1 trauma center in a large metropolitan area. All patients who presented to the ED with traumatic injuries and were discharged without hospital admission were included in the study. The primary outcome was ED returns for trauma-related complications or new traumatic events <6 months after discharge. Patient characteristics and study outcomes were compared between housed and unhoused groups. RESULTS: A total of 4184 patients were identified, of which 20.3% were unhoused. Compared to housed, unhoused patients were more likely to return to the ED (18.8% vs 13.9%, P < .001), more likely to return for trauma-related complications (4.6% vs 3.1%, P = .045), more likely to return with new trauma (7.1% vs 2.8%, P < .001), and less likely to return for scheduled wound checks (2.5% vs 4.3%, P = .012). Of the patients who returned with trauma-related complications, unhoused patients had a higher proportion of wound infection (20.5% vs 5.7%, P = .008). In the regression analysis, unhoused status was associated with increased odds of ED return with new trauma and decreased odds of return for scheduled wound checks. CONCLUSIONS: This study observed significant disparities between unhoused and housed patients after trauma. Our results suggest that inadequate follow-up in unhoused patients may contribute to further ED return.

Bile Duct Injuries During Urgent Cholecystectomy at a Safety Net Teaching Hospital: Attending Experience and Time of Day May Matter.

Background: Bile duct injury (BDI) is one of the most severe complications during cholecystectomy. Early identification of risk factors for BDI may permit risk reduction strategies and inform patient consent.Objective: This study aimed to define patient, provider, and systemic factors associated with BDI; BDI incidence; and short-term outcomes of BDI after urgent cholecystectomy.Methods: Patients who underwent urgent cholecystectomy for acute cholecystitis were retrospectively screened (2020-2022). All patients who sustained BDI were included without exclusions. Demographics, clinical data, and outcomes were collected and compared with descriptive statistics.Results: During the study period, BDI occurred in 4 (0.5%) of 728 patients who underwent urgent cholecystectomy for acute cholecystitis. Most BDI cases (75%) took place overnight or during the weekend. The attending surgeon was almost exclusively (75%) in their first year of practice. BDI was recognized during index operation in 2 cases (50%). Hepatobiliary surgery performed the bile duct repair in all 4 cases. Two complications occurred (50%). All patients were followed by hepatobiliary surgery in the outpatient setting and returned to their baseline level of function within 2 months of hospital discharge.Conclusion: Most BDI occurred in procedures attended by first-year faculty during after hours cholecystectomies, suggesting a role for increased proctorship in early career attendings in addition to in-hours cholecystectomy for acute cholecystitis. The timely return to baseline function experienced by these patients emphasizes the favorable outcomes associated with early recognition of BDI and involvement of hepatobiliary surgery. Further examination with multicenter evaluation would be beneficial to validate these study findings.

Ethics in disaster, mass casualty care, and critical care.

The primary ethical principle guiding general medical practice is autonomy. However, in mass casualty (MASCAL) or disaster scenarios, the principles of beneficence and justice become of foremost concern. Despite multiple reviews, publications, and training courses available to prepare for a MASCAL incident, a minority of physicians and healthcare providers are abreast of these. In this review, we describe several MASCAL scenarios and their associated ethical, moral, and medicolegal quandaries in attempts to curb potential future misadventures.