Development and Validation of Futility of Resuscitation Measure in Older Adult Trauma Patients.

INTRODUCTION: This study aimed to develop and validate Futility of Resuscitation Measure (FoRM) for predicting the futility of resuscitation among older adult trauma patients. METHODS: This is a retrospective analysis of the American College of Surgeons-Trauma Quality Improvement Program database (2017-2018) (derivation cohort) and American College of Surgeons level I trauma center database (2017-2022) (validation cohort). We included all severely injured (injury severity score >15) older adult (aged ≥60 y) trauma patients. Patients were stratified into decades of age. Injury characteristics (severe traumatic brain injury [Glasgow Coma Scale ≤ 8], traumatic brain injury midline shift), physiologic parameters (lowest in-hospital systolic blood pressure [≤1 h], prehospital cardiac arrest), and interventions employed (4-h packed red blood cell transfusions, emergency department resuscitative thoracotomy, resuscitative endovascular balloon occlusion of the aorta, emergency laparotomy [≤2 h], early vasopressor requirement [≤6 h], and craniectomy) were identified. Regression coefficient-based weighted scoring system was developed using the Schneeweiss method and subsequently validated using institutional database. RESULTS: A total of 5562 patients in derivation cohort and 873 in validation cohort were identified. Mortality was 31% in the derivation cohort and FoRM had excellent discriminative power to predict mortality (area under the receiver operator characteristic = 0.860; 95% confidence interval [0.847-0.872], P < 0.001). Patients with a FoRM score of >16 had a less than 10% chance of survival, while those with a FoRM score of >20 had a less than 5% chance of survival. In validation cohort, mortality rate was 17% and FoRM had good discriminative power (area under the receiver operator characteristic = 0.76; 95% confidence interval [0.71-0.80], P < 0.001). CONCLUSIONS: FoRM can reliably identify the risk of futile resuscitation among older adult patients admitted to our level I trauma center.

The Synergy Factor: Trauma and Cancer.

INTRODUCTION: Trauma and cancer are the leading causes of death in the US. There is a paucity of data describing the impact of cancer on trauma patients. We aimed to determine the influence of cancer on outcomes of trauma patients. METHODS: In this retrospective analysis of American College of Surgeons-Trauma Quality Improvement Program 2019-2021, we included all adult trauma patients (≥18 y) and excluded patients with severe head injuries and nonmelanomatous skin cancers. Patients were stratified into cancer (C), and no cancer (No-C). Propensity score matching (1:3) was performed. Outcomes were complications and mortality. RESULTS: A matched cohort of 3236 patients (C, 809; No-C, 2427) was analyzed. The mean age was 70 y, 50.5% were males, and the median injury severity score was 8 (4-10). There were no differences in terms of receiving thromboprophylaxis (C 51%: No-C 50%, P = 0.516). Compared to No-C group, the C group had higher rates of deep vein thrombosis (C 1.1% versus No-C 0.3%, P = 0.004), but there was no difference in terms of overall complications. Patients in the C group had higher mortality (C 7.5% versus No-C 2.7%, P < 0.001). CONCLUSIONS: Trauma patients with cancer have nearly 4 times higher odds of deep vein thrombosis and 3 times higher odds of mortality. Developing pathways specific to cancer patients might be necessary to improve the outcomes of trauma patients with cancer.

Endovascular Versus Open Repair in Adolescent Patients With Difficult-to-Access Vascular Injuries.

INTRODUCTION: Management of subclavian artery injuries (SAI) and iliac artery injuries (IAI) in adolescent trauma patients poses a considerable challenge due to their complex anatomical locations. The aim of our study was to determine the association between the injury mechanism and type of repair with the outcomes of patients with traumatic SAI and IAI. METHODS: In this retrospective analysis of the American College of Surgeons Trauma Quality Improvement Program database2017-2020, adolescent (<18 y) patients with SAI and IAI undergoing either endovascular or open repair were included. Patients were stratified by mechanism (blunt versus penetrating) and type of repair (endovascular [E] versus open [O]) and compared. Outcomes measured were mortality and major complications. Multivariable logistic regression analyses were performed. RESULTS: Over 4 y, 170 pediatric patients were identified, of which 73 (43%) sustained an SAI and 97 (57%) had IAI. The mean age was 15 and 79% were male. Overall, 39% were managed endovascularly. Both groups had comparable median injury severity score (E: 23 versus O: 25, P = 0.278). For patients with blunt injury (n = 60), the type of repair was neither associated with major complications (E: 39% versus O: 33%, P = 0.694) nor mortality (E: 2.6% versus O: 4.8%, P = 0.651). For patients with penetrating injuries (n = 110), the endovascular repair had significantly lower morbidity (19% versus 41%, P = 0.034) and mortality (3.7% versus 21%, P = 0.041). On multivariable logistic regression, endovascular repair was identified as the only modifiable risk factor associated with reduced mortality (adjusted odds ratio: 0.201, 95% confidence interval [0.14-0.76], P = 0.038). CONCLUSIONS: Difficult-to-access vascular injuries result in significant morbidity and mortality. Endovascular repair was found to be the only modifiable factor associated with decreased mortality of patients with penetrating injury, whereas the type of repair was not associated with mortality in those with blunt injury.

When Every Minute Counts: REBOA Before Surgery Is Independently Associated With a 15-Minute Delay in Time to Definitive Hemorrhage Control.

INTRODUCTION: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a temporizing hemorrhage control intervention, but its inevitable effect on time to operating room (OR) has not been assessed. The aim of our study is to assess the impact of undergoing REBOA before surgery (RBS) on time to definitive hemorrhage control surgery. METHODS: In this retrospective analysis of 2017-2021 ACS-TQIP database, all adult (≥18 years) patients who underwent emergency hemorrhage control laparotomy (≤4 hours of admission) and received early blood products (≤4 hours) were included, and patients with severe head injury (Head-abbreviated injury score > 2) were excluded. Patients were stratified into those who did (RBS) vs those who did not undergo REBOA before surgery (No-RBS). Primary outcome was time to laparotomy. Secondary outcomes were complications and mortality. Multivariable linear and binary logistic regression analyses were performed to identify the independent associations between RBS and outcomes. RESULTS: A total of 32,683 patients who underwent emergency laparotomy were identified (RBS: 342; No-RBS: 32,341). The mean age was 39 (16) years, 78% were male, mean SBP was 107 (34) mmHg, and the median injury severity score was 21 [14-29]. The median time to emergency hemorrhage control surgery was 50 [32-85] minutes. Overall complication rate was 16% and mortality was 19%. On univariate analysis, RBS group had longer time to surgery (RBS 56 [41-89] vs No-RBS 50 [32-85] minutes, P < 0.001). On multivariable analysis, RBS was independently associated with a longer time to hemorrhage control surgery (ß + 14.5 [95%CI 7.8-21.3], P < 0.001), higher odds of complications (aOR = 1.72, 95%CI = 1.27-2.34, P < 0.001), and mortality (aOR = 3.42, 95%CI = 2.57-4.55, P < 0.001). CONCLUSION: REBOA is independently associated with longer time to OR for hemorrhaging trauma patients with an average delay of 15 minutes. Further research evaluating center-specific REBOA volume and utilization practices, and other pertinent system factors, may help improve both time to REBOA as well as time to definitive hemorrhage control across US trauma centers. LEVEL OF EVIDENCE: III. STUDY TYPE: Epidemiologic.

Clonal Hematopoiesis of Indeterminate Potential in Crohn's Disease and Ulcerative Colitis.

Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of somatic mutations in myeloid and lymphoid malignancy genes in the blood cells of individuals without a hematologic malignancy. Inflammation is hypothesized to be a key mediator in the progression of CHIP to hematologic malignancy and patients with CHIP have a high prevalence of inflammatory diseases. This study aimed to identify the prevalence and characteristics of CHIP in patients with inflammatory bowel disease (IBD). We analyzed whole exome sequencing data from 587 Crohn's disease (CD), 441 ulcerative colitis (UC), and 293 non-IBD controls to assess CHIP prevalence and used logistic regression to study associations with clinical outcomes. Older UC patients (age>45) harbored increased myeloid-CHIP mutations compared to younger patients (age≤45) (p=0.01). Lymphoid-CHIP was more prevalent in older IBD patients (p=0.007). Young CD patients were found to have myeloid-CHIP with high-risk features. IBD patients with CHIP exhibited unique mutational profiles compared to controls. Steroid use was associated with increased CHIP (p=0.05), while anti-TNF therapy was associated with decreased myeloid-CHIP (p=0.03). Pathway enrichment analyses indicated overlap between CHIP genes, IBD phenotypes, and inflammatory pathways. Our findings underscore a connection between IBD and CHIP pathophysiology. Patients with IBD and CHIP had unique risk profiles especially among older UC patients and younger CD patients. These findings suggest distinct evolutionary pathways for CHIP in IBD and necessitate awareness among IBD providers and hematologists to identify patients potentially at risk for CHIP-related complications including malignancy, cardiovascular disease and acceleration of their inflammatory disease.

Complete Blood Count Values Over Time in Young Children During the Dengue Virus Epidemic in the Dominican Republic From 2018 to 2020.

Background: Dengue fever (DF) is a mosquito-borne illness with substantial economic and societal impact. Understanding laboratory trends of hospitalized Dominican Republic (DR) pediatric patients could help develop screening procedures in low-resourced settings. We sought to describe laboratory findings over time in DR children with DF and DF severity from 2018 to 2020. Methods: Clinical information was obtained prospectively from recruited children with DF. Complete blood count (CBC) laboratory measures were assessed across Days 1-10 of fever. Participants were classified as DF-negative and DF-positive and grouped by severity. We assessed associations of DF severity with demographics, clinical characteristics, and peripheral blood studies. Using linear mixed-models, we assessed if hematologic values/trajectories differed by DF status/severity. Results: A total of 597 of 1101 with a DF clinical diagnosis were serologically evaluated, and 574 (471 DF-positive) met inclusion criteria. In DF, platelet count and hemoglobin were higher on earlier days of fever (p < = 0.0017). Eighty had severe DF. Severe DF risk was associated with thrombocytopenia, intraillness anemia, and leukocytosis, differing by fever day (p < = 0.001). Conclusions: In a pediatric hospitalized DR cohort, we found marked anemia in late stages of severe DF, unlike the typically seen hemoconcentration. These findings, paired with clinical symptom changes over time, may help guide risk-stratified screenings for resource-limited settings.

Navigating the Predictive Landscape: DiaRem's Role in Unveiling Outcomes for Diabetes Remission following ESG.

PURPOSE: Rising obesity and type 2 diabetes mellitus (T2DM) rates can be mitigated by various strategies, with a 10% total body weight loss (TBWL) threshold often required for T2DM remission. T2DM remission rates after bariatric surgery like Roux-en-Y gastric bypass (RYGB) are well established; endoscopic sleeve gastroplasty (ESG) is a less invasive option that averages 15% TBWL and allows for T2DM remission. This study explores the DiaRem (Diabetes Remission post-RYGB) score's ability to predict T2DM remission 1-year post-ESG. MATERIALS AND METHODS: We conducted a retrospective cohort study on 39 individuals with T2DM who underwent ESG. Age, utilization of diabetes medications, insulin administration, and hemoglobin A1c levels were used to calculate the DiaRem score. The area under the receiver operating characteristic curve (AUC) was employed to evaluate the discriminative ability of DiaRem in distinguishing diabetes remission. RESULTS: Among the 39 patients with a median hemoglobin A1c of 6.7, 12.8% required insulin, and 43.6% used diabetes medication. At 1-year post-ESG, 69.2% of patients experienced diabetes remission with a median %TWBL of 12.7. The DiaRem score's ability to detect diabetes resolution for ESG patients had a sensitivity of 100% and a specificity of 58.3%, at the optimal cutoff value of 10. The AUC was 0.779 (95% CI 0.546-0.959). CONCLUSION: Our study demonstrated the DiaRem score's predictive value for T2DM remission post-ESG, highlighting its utility in clinical decision-making for ESG-related outcomes. Further investigation is needed to identify alternative indicators that may enhance predictive accuracy, thus refining personalized decision-making for this patient group.

Local synthesis of estradiol in the rostral ventromedial medulla protects against widespread muscle pain in male mice.

Animal studies consistently demonstrate that testosterone is protective against pain in multiple models, including an animal model of activity-induced muscle pain. In this model, females develop widespread muscle hyperalgesia, and reducing testosterone levels in males results in widespread muscle hyperalgesia. Widespread pain is believed to be mediated by changes in the central nervous system, including the rostral ventromedial medulla (RVM). The enzyme that converts testosterone to estradiol, aromatase, is highly expressed in the RVM. Therefore, we hypothesized that testosterone is converted by aromatase to estradiol locally in the RVM to prevent development of widespread muscle hyperalgesia in male mice. This was tested through pharmacological inhibition of estrogen receptors (ER), aromatase, or ER-α in the RVM which resulted in contralateral hyperalgesia in male mice (C57BL/6J). ER inhibition in the RVM had no effect on hyperalgesia in female mice. As prior studies show modulation of estradiol signaling alters GABA receptor and transporter expression, we examined if removal of testosterone in males would decrease mRNA expression of GABA receptor subunits and vesicular GABA transporter (VGAT). However, there were no differences in mRNA expression of GABA receptor subunits of VGAT between gonadectomized and sham control males. Lastly, we used RNAscope to determine expression of ER-α in the RVM and show expression in inhibitory (VGAT+), serotonergic (tryptophan hydroxylase 2+), and µ-opioid receptor expressing (MOR+) cells. In conclusion, testosterone protects males from development of widespread hyperalgesia through aromatization to estradiol and activation of ER-α which is widely expressed in multiple cell types in the RVM.Significance Statement This study's findings reveal, for the first time, that testosterone protects males from development of widespread muscle hyperalgesia through aromatization to estradiol and activation of ER-α within the RVM. The findings also show, for the first time, ER-α expression in the RVM in male mice, and the distribution patterns of this expression among multiple cell types. Thus, together our data suggest a unique endogenous mechanism in the RVM for protection against widespread pain in males only.

Endothelial Cell Transcription Modulation in Cerebral Aneurysms After Endovascular Flow Diversion.

PURPOSE: Flow diverting stents (FDS) are used to treat cerebral aneurysms, by promoting thrombosis and occlusion of the aneurysm sac. However, retreatment is required in some cases, and the biologic basis behind treatment outcome is not known. The goal of this study was to understand how changes in hemodynamic flow after FDS placement affect aneurysmal endothelial cell (EC) activity. METHODS: Three-dimensional models of patient-specific aneurysms were created to quantify the EC response to FDS placement. Computational fluid dynamic simulations were used to determine the hemodynamic impact of FDS. Two identical models were created for each patient; into one a FDS was inserted. Each model was then populated with human carotid ECs and subjected to patient-specific pulsatile flow for 24 h. ECs were isolated from aneurysm dome from each model and bulk RNA sequencing was performed. RESULTS: Paired untreated and treated models were created for four patients. Aneurysm dome EC analysis revealed 366 (2.6%) significant gene changes between the untreated and FDS conditions, out of 13909 total expressed genes. Gene set enrichment analysis of the untreated models demonstrated enriched gene ontology terms related to cell adhesion, growth/tensile activity, cytoskeletal organization, and calcium ion binding. In the FDS models, enriched terms were related to cellular proliferation, ribosomal activity, RNA splicing, and protein folding. CONCLUSION: Treatment of cerebral aneurysms with FDS induces significant EC gene transcription changes related to aneurysm hemodynamics in patient-specific in vitro 3D-printed models subjected to pulsatile flow. Further investigation is needed into the relationship between transcriptional change and treatment outcome.

Thyroid Fine-Needle Aspiration: The Current and Future Landscape of Cytopathology.

Thyroid cytology is a rapidly evolving field that has seen significant advances in recent years. Its main goal is to accurately diagnose thyroid nodules, differentiate between benign and malignant lesions, and risk stratify nodules when a definitive diagnosis is not possible. The current landscape of thyroid cytology includes the use of fine-needle aspiration for the diagnosis of thyroid nodules with the use of uniform, tiered reporting systems such as the Bethesda System for Reporting Thyroid Cytopathology. In recent years, molecular testing has emerged as a reliable preoperative diagnostic tool that stratifies patients into different risk categories (low, intermediate, or high) with varying probabilities of malignancy and helps guide patient treatment.

Artificial Intelligence Applications in Cytopathology: Current State of the Art.

The practice of cytopathology has been significantly refined in recent years, largely through the creation of consensus rule sets for the diagnosis of particular specimens (Bethesda, Milan, Paris, and so forth). In general, these diagnostic systems have focused on reducing intraobserver variance, removing nebulous/redundant categories, reducing the use of "atypical" diagnoses, and promoting the use of quantitative scoring systems while providing a uniform language to communicate these results. Computational pathology is a natural offshoot of this process in that it promises 100% reproducible diagnoses rendered by quantitative processes that are free from many of the biases of human practitioners.

Viral escape mutations do not account for non-protection from SIVmac239 challenge in RhCMV/SIV vaccinated rhesus macaques.

Simian immunodeficiency virus (SIV) vaccines based upon 68-1 Rhesus Cytomegalovirus (RhCMV) vectors show remarkable protection against pathogenic SIVmac239 challenge. Across multiple independent rhesus macaque (RM) challenge studies, nearly 60% of vaccinated RM show early, complete arrest of SIVmac239 replication after effective challenge, whereas the remainder show progressive infection similar to controls. Here, we performed viral sequencing to determine whether the failure to control viral replication in non-protected RMs is associated with the acquisition of viral escape mutations. While low level viral mutations accumulated in all animals by 28 days-post-challenge, which is after the establishment of viral control in protected animals, the dominant circulating virus in virtually all unprotected RMs was nearly identical to the challenge stock, and there was no difference in mutation patterns between this cohort and unvaccinated controls. These data definitively demonstrate that viral mutation does not explain lack of viral control in RMs not protected by RhCMV/SIV vaccination. We further demonstrate that during chronic infection RhCMV/SIV vaccinated RMs do not acquire escape mutation in epitopes targeted by RhCMV/SIV, but instead display mutation in canonical MHC-Ia epitopes similar to unvaccinated RMs. This suggests that after the initial failure of viral control, unconventional T cell responses induced by 68-1 RhCMV/SIV vaccination do not exert strong selective pressure on systemically replicating SIV.

Chymase Activity in Plasma and Urine Extracellular Vesicles in Primary Hypertension.

BACKGROUND: Circulating extracellular vesicles (EVs) carry protected cargoes of nucleic acids, proteins, and metabolites. Here we identified and validated the surface proteins and enzymatic activity of chymase, angiotensin converting enzymes 1 (ACE) and 2 (ACE2), and neprilysin (NEP) in EVs isolated from the blood and urine of primary hypertensive patients. METHODS: Peripheral venous blood and spot urine from 34 hypertensive patients were processed to isolate plasma and urinary EVs. Immuno-gold labeling and transmission electron microscopy validated the presence of the exosomal marker protein CD63 on the surface of plasma and urinary EVs. Flow cytometry characterized plasma and urinary EVs for CD63, CD9, and CD81 surface markers. In addition, exosomal CD63, TSG101, and Alix were analyzed in urine by Western blotting. Urinary EVs did not express the endoplasmic reticulum protein calnexin and Golgi protein GM130. Chymase, ACE, ACE2, and NEP activities on 125I substrates ─ angiotensin-(1-12) [Ang-(1‒12)] and angiotensin II (Ang II) ─ [1 nmol/L each] were quantified by HPLC. Data were analyzed based on whether the patient's blood pressure was controlled (Group I: <140/80 mm Hg) or not controlled (Group II: ≥ 140/80 mm Hg). RESULTS: Chymase activity on Ang-(1‒12) was significantly higher in plasma and urinary EVs than in ACE, ACE2, and NEP. In addition, chymase activity in urine EVs was more than 3-fold higher than in plasma EVs. Chymase activity increased in plasma and urine EVs retrieved from Group II patients. No comparable differences were found in the enzymatic activities of ACE, ACE2, and NEP urinary EVs between Group I and Group II. CONCLUSION: These studies reveal a differential enzymatic activity of renin angiotensin system enzymes in plasma and urine EVs isolated from hypertensive patients. Demonstrating a comparatively high chymase enzymatic activity in EVs expands a previously documented finding of increased plasma Ang-(1‒12) in hypertensive patients.

Impact of alemtuzumab-mediated lymphocyte depletion on SIV reservoir establishment and persistence.

Persistence of the rebound-competent viral reservoir (RCVR) within the CD4+ T cell compartment of people living with HIV remains a major barrier to HIV cure. Here, we determined the effects of the pan-lymphocyte-depleting monoclonal antibody (mAb) alemtuzumab on the RCVR in SIVmac239-infected rhesus macaques (RM) receiving antiretroviral therapy (ART). Alemtuzumab administered during chronic ART or at the time of ART initiation induced >95% depletion of circulating CD4+ T cells in peripheral blood and substantial CD4+ T cell depletion in lymph nodes. However, treatment was followed by proliferation and reconstitution of CD4+ T cells in blood, and despite ongoing ART, levels of cell-associated SIV DNA in blood and lymphoid tissues were not substantially different between alemtuzumab-treated and control RM after immune cell reconstitution, irrespective of the time of alemtuzumab treatment. Upon ART cessation, 19 of 22 alemtuzumab-treated RM and 13 of 13 controls rebounded in <28 days with no difference in the time to rebound between treatment groups. Time to rebound and reactivation rate was associated with plasma viral loads (pVLs) at time of ART initiation, suggesting lymphocyte depletion had no durable impact on the RCVR. However, 3 alemtuzumab-treated RM that had lowest levels of pre-ART viremia, failed to rebound after ART withdrawal, in contrast to controls with similar levels of SIV replication. These observations suggest that alemtuzumab therapy has little to no ability to reduce well-established RCVRs but may facilitate RCVR destabilization when pre-ART virus levels are particularly low.

Andersen-Tawil syndrome.

Andersen-Tawil syndrome (ATS) is one of the periodic paralyses, a set of skeletal muscle disorders that cause transient weakness of the arms and legs lasting minutes to many hours. Distinguishing features of ATS include facial and limb dysmorphisms, cardiac arrhythmia, difficulties with executive function, and association with dominant mutations in the potassium channel, KCNJ2. In this review, we discuss the key features of ATS, diagnostic testing, pathophysiology and treatment of ATS, and compare them with other periodic paralyses.

Role of endovascular management on outcomes in patients with traumatic inferior vena cava injuries.

INTRODUCTION: The aim of this study was to examine the association between the injury mechanism and repair type with outcomes in patients with traumatic inferior vena cava injuries. METHODS: This is a retrospective analysis of the ACS-TQIP database (2017-2020), including patients with traumatic IVC injuries. Patients were stratified by injury mechanism and type of repair and compared. RESULTS: Out of 1334 patients, 5 â€‹% underwent endovascular repair while 95 â€‹% had an open procedure. Overall, 74.7 â€‹% sustained a penetrating injury. On multivariable regression analysis, the type of repair was not associated with mortality and morbidity for patients with penetrating injuries. However, among patients with blunt injuries, endovascular repair was associated with lower odds of in-hospital mortality (aOR:0.35, p â€‹= â€‹0.020) and non-venous thromboembolism (VTE) morbidity (aOR:0.41, p â€‹= â€‹0.015), and higher odds of VTE complications (aOR:6.74, p â€‹< â€‹0.001). CONCLUSIONS: Although the type of repair did not impact morbidity and mortality in patients with penetrating injuries, endovascular repair was identified as the only modifiable predictor of reduced non-VTE morbidity and mortality in patients with blunt injuries.

Early Vasopressor Requirement Among Hypotensive Trauma Patients: Does It Cause More Harm Than Good?

BACKGROUND: Optimal utilization of vasopressors during early post-injury resuscitation remains unclear. Our study aims to describe the relationship between the timing of vasopressor administration and outcomes among hypotensive trauma patients. METHODS: This was a retrospective analysis of the 2017-2018 ACS-TQIP database. We included adult (≥18 years) trauma patients presenting with hypotension (lowest SBP <90 mmHg) who received vasopressors within 6 hours of admission. We excluded patients who had a severe head injury (Head-AIS >3) and those with spinal cord injury (Spine-AIS >3). Patients were stratified based on the time to receive vasopressors. Multivariable regression analyses were performed to identify the independent association between timing of vasopressor initiation and outcomes. RESULTS: 1049 patients were identified. Mean age was 55 ± 20 years, and 70% of patients were male. The median ISS was 16 [9-24], 80% had a blunt injury, and the mean SBP was 61 ± 24 mmHg. The median time to first vasopressor administration was 319 [68-352] minutes. Overall, 24-hour and in-hospital mortality rates were 19% and 33%, respectively. Every one-hour delay in vasopressor administration beyond the first hour was independently associated with decreased odds of 24-hour mortality (aOR: 0.65, P < 0.001), in-hospital mortality (aOR: 0.65, P < 0.001), major complications (aOR: 0.77, P = 0.003), and increased odds of longer ICU LOS (ß + 2.53, P = 0.012). There were no associations between the timing of early vasopressor administration and 24-hour PRBC transfusion requirements (P > 0.05). CONCLUSION: Earlier vasopressor requirement among hypotensive trauma patients was independently associated with increased mortality and major complications. Further research on the utility and optimal timing of vasopressors during the post-injury resuscitative period is warranted. LEVEL OF EVIDENCE: III therapeutic/care management.

Survival loss linked to guideline-based indications for degenerative mitral regurgitation surgery.

AIMS: Operating on patients with severe degenerative mitral regurgitation (DMR) is based on ACC/AHA or ESC/EACTS-guidelines. Doubts persist on best surgical indications and their potential association with postoperative survival loss. We sought to investigate whether guideline-based indications lead to late postoperative survival loss in DMR-patients. METHODS AND RESULTS: : We analyzed outcome of 2833 patients from the MIDA-registry undergoing surgical correction of DMR. Patients were stratified by surgical indications: Class-I-trigger (symptoms, left ventricular end-systolic diameter≥40mm, or left ventricular ejection fraction<60%, n=1677), isolated-Class-IIa-trigger (atrial fibrillation [AF], pulmonary hypertension [PH], or left atrial diameter≥55mm, n=568), or no-trigger (n=588). Postoperative survival was compared after matching for clinical differences. Restricted-mean-survival time (RMST) was analyzed. During a median 8.5-year follow-up, 603 deaths occurred. Long-term postoperative survival was lower with Class-I-trigger than in Class-IIa-trigger and no-trigger (71.4±1.9%, 84.3±2.3%, 88.9±1.9% at 10 years, p<0.001). Having at least one Class-I-criterion led to excess mortality (p<0.001), while several Class-I-criteria conferred additional death-risk (HR:1.53, 95%CI:1.42-1.66). Isolated-Class-IIa-triggers conferred an excess mortality risk versus those without (HR:1.46, 95%CI:1.00-2.13, p=0.05). Among these patients, isolated-PH led to decreased postoperative-survival versus those without (83.7%±2.8% vs. 89.3%±1.6%, p=0.011), with the same pattern observed for AF (81.8%±5.0% vs. 88.3%±1.5%, p=0.023). According to RMST-analysis, compare to those operated on without triggers, operating on Class-I-trigger patients led to 9.4-month survival-loss (p<0.001) and operating on isolated-Class-IIa-trigger patients displayed 4.9-month survival loss (p=0.001) after 10-years. CONCLUSIONS: : Waiting for the onset of Class-I or isolated-Class-IIa-triggers before operating on DMR patients is associated with postoperative survival loss. These data encourage an early surgical-strategy.

Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge.

An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development.