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Magnetostriction is a phenomenon occurring in transformer core in normal operation mode. Yet in time, it can cause the delamination of magnetic core resulting in higher level of vibrations that are measured on the surface of transformer tank during diagnostic tests. The aim of this paper is to create a model for evaluating elastic deformations in magnetic core that can be used for power transformers with intensive vibrations in order to eliminate magnetostriction as a their cause. Description of the developed model in Matlab and COMSOL software is provided including restrictions concerning geometry and properties of materials, and the results of performed research on magnetic core anisotropy are provided. As a case study modelling of magnetostriction for 5-legged 200 MVA power transformer with the rated voltage of 13.8/137kV is conducted, based on which comparative analysis of vibration levels and elastic deformations is performed.

Abstract Background Discovery of tumor-selective antibodies or antibody fragments is a promising approach for delivering therapeutic agents to antigen over-expressing cancers. Therefore it is important to develop methods for the identification of target- and function specific antibodies for effective drug delivery. Here we describe a highly selective and sensitive method for characterizing the internalizing potential of multivalently displayed antibodies or ligands conjugated to liposomes into tumor cells. The assay requires minute amounts of histidine-tagged ligand and relies on the non-covalent coupling of these antibodies to fluorescent liposomes containing a metal ion-chelating lipid. Following incubation of cells with antibody-conjugated liposomes, surface bound liposomes are gently removed and the remaining internalized liposomes are quantitated based on fluorescence in a high throughput manner. We have termed this methodology "Chelated Ligand Internalization Assay", or CLIA. Results The specificity of the assay was demonstrated with different antibodies to the ErbB-2 and EGF receptors. Antibody-uptake correlated with receptor expression levels in tumor cell lines with a range of receptor expression. Furthermore, Ni-NTA liposomes containing doxorubicin were used to screen for the ability of antibodies to confer target-specific cytotoxicity. Using an anti-ErbB2 single chain Fv (scFv) (F5) antibody, cytotoxicity could be conferred to ErbB2-overexpressing cells; however, a poly(ethylene glycol)-linked lipid (DSPE-PEG-NTA-Ni) was necessary to allow for efficient loading of the drug and to reduce nonspecific drug leakage during the course of the assay. Conclusion The CLIA method we describe here represents a rapid, sensitive and robust assay for the identification and characterization of tumor-specific antibodies capable of high drug-delivery efficiency when conjugated to liposomal nanocarriers.

Smoking is a leading cause of preventable morbidity and mortality. Smoking is heritable, and genome-wide association studies (GWASs) of smoking behaviors have identified hundreds of significant loci. Most GWAS-identified variants are noncoding with unknown neurobiological effects. We used genome-wide genotype, DNA methylation, and RNA sequencing data in postmortem human nucleus accumbens (NAc) to identify cis-methylation/expression quantitative trait loci (meQTLs/eQTLs), investigate variant-by-cigarette smoking interactions across the genome, and overlay QTL evidence at smoking GWAS-identified loci to evaluate their regulatory potential. Active smokers (N = 52) and nonsmokers (N = 171) were defined based on cotinine biomarker levels and next-of-kin reporting. We simultaneously tested variant and variant-by-smoking interaction effects on methylation and expression, separately, adjusting for biological and technical covariates and correcting for multiple testing using a two-stage procedure. We found >2 million significant meQTL variants (p adj  < 0.05) corresponding to 41,695 unique CpGs. Results were largely driven by main effects, and five meQTLs, mapping to NUDT12, FAM53B, RNF39, and ADRA1B, showed a significant interaction with smoking. We found 57,683 significant eQTL variants for 958 unique eGenes (p adj  < 0.05) and no smoking interactions. Colocalization analyses identified loci with smoking-associated GWAS variants that overlapped meQTLs/eQTLs, suggesting that these heritable factors may influence smoking behaviors through functional effects on methylation/expression. One locus containing MUSTN1 and ITIH4 colocalized across all data types (GWAS, meQTL, and eQTL). In this first genome-wide meQTL map in the human NAc, the enriched overlap with smoking GWAS-identified genetic loci provides evidence that gene regulation in the brain helps explain the neurobiology of smoking behaviors., (© 2024. The Author(s).)

Background: One third of organ donors suffer catastrophic brain injury (CBI). There are no standard guidelines for the management of traumatic CBI prior to brain death, and not all trauma centers have institutional CBI guidelines. In addition, there is high variability in management between institutions with guidelines. Catastrophic brain injury guidelines vary and may include various combinations of hormone therapy, vasopressors, fluid resuscitation, and other practices. We hypothesized that centers with CBI guidelines have higher organ donation rates than those without., Methods: This prospective, observational EAST-sponsored multicenter trial included adult (18+ years old) traumatic-mechanism CBI patients at 33 level I and II trauma centers from January 2022 to May 2023. Catastrophic brain injury was defined as a brain injury causing loss of function above the brain stem and subsequent death. Cluster analysis with linear mixed-effects model including UNOS regions and hospital size by bed count was used to determine whether CBI guidelines are associated with organ donation., Results: A total of 790 CBI patients were included in this analysis. In unadjusted comparison, CBI guideline centers had higher rates of organ donation and use of steroids, whole blood, and hormone therapy. In a linear mixed-effects model, CBI guidelines were not associated with organ donation. Registered organ donor status, steroid hormones, and vasopressin were associated with increased relative risk of donation., Conclusion: There is high variability in management of CBI, even at centers with CBI guidelines in place. While the use of institutional CBI guidelines was not associated with increased organ donation, guidelines in this study were not identical. Hormone replacement with steroids and vasopressin was associated with increased donation. Hormone resuscitation is a common feature of CBI guidelines. Further analysis of individual practices that increase organ donation after CBI may allow for more effective guidelines and an overall increase in donation to decrease the long waiting periods for organ transplant recipients., Level of Evidence: Prognostic; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: MET exon 14 skipping alterations (METex14+) represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) with distinct biological and genomic features. We characterized this heterogeneity in a large cohort, integrating genomic and transcriptomic profiling with clinical outcomes, to elucidate the histologic and molecular traits and survival patterns of METex14+ NSCLC., Materials and Methods: NSCLC tissue samples (n = 28,739) underwent DNA-based next-generation sequencing (592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-sequencing including whole transcriptome sequencing (WTS, NovaSeq), and PD-L1 IHC (Dako 22C3) at Caris Life Sciences. Immune cell fractions were estimated from bulk RNA sequencing (quanTIseq). Real-world survival data (mOS) was calculated from insurance claims. Statistical analyses employed Chi-square, Fisher's exact, or Mann-Whitney U and log-rank tests and were corrected for hypothesis testing where applicable., Results: A total of 711 METex14+ cases were detected. Of 575 cases of defined histology, 77 (13.6 %) were squamous (Sq), 474 (82.3 %) were nSq (non-squamous), and 24 (4.1 %) were adenosquamous. Mutations in POT1 and BRCA2 were enriched, and amplifications in MDM2, HMGA2, CDK4, and MET were common in METex14+ tumors. TMB-high and TP53 mutated tumors were reduced in METex14+ independent of histology. KEAP1 (2.1 vs 14.7 %) and STK11 mutations (0.8 vs 17.1 %) were reduced only in METex14+ nSq (vs METex14+ Sq, q < 0.05). While the prevalence of PD-L1 high tumors was enriched in METex14+ independent of histology, T-cell inflamed tumors were enriched only in nSq METex14+. B-cells and CD8+ T-cells (1.07-1.43-fold) were enriched in nSq METex14+, and dendritic cells (0.32 fold) were reduced only in METex14+ Sq. METex14+ tumors had a modest improvement in mOS compared to METex14- tumors (mOS = 22.9 m vs 18.6 m, HR = 0.914, p = 0.04). Moreover, METex14+ tumors who received immunotherapy (IO) had a modest improvement in survival (mOS = 27.5 m vs 21.8 m; HR = 0.803, p = 0.03) compared to those who did not receive IO. METex14+ nSq tumors were associated with improved mOS compared to METex14+ Sq tumors (mOS = 27.7 vs 8.9 m, HR = 0.493, p < 0.0001)., Conclusion: METex14+ alterations are a heterogeneous subgroup of NSCLC. Our analysis reveals that METex14+ nSq exhibit improved survival compared to METex14+ Sq. The distinct genomic and transcriptomic variations across histologies warrant clinical consideration., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jennifer Marks holds R&D authorship with Janssen Scientific Affairs. Nishant Gandhi, Joanne Xiu, Phillip Walker, and Matthew J. Oberley are employed by Caris Life Sciences. So Yeon Kim receives institutional grant funding from Boehringer Ingelheim, Astra Zeneca, Genentech, BMS, Loxo-Lilly, Genmab, and Dynamicure. Additionally, she has consulted for Amgen.Balazs Halmos receives institutional grant funding from Boehringer Ingelheim, Astra Zeneca, Merck, BMS, Advaxis, Amgen, AbbVie, Daiichi, Pfizer, GSK, Beigene, Janssen, Black Diamond Therapeutics, Forward Pharma, Numab, and Arrivent. He also serves on the Data Safety Monitoring Board/Advisory board for BMS, TPT, Apollomics, eFECTOR, and City of Hope. Melina E. Marmarelis reports research funding from Eli Lilly (Inst), AstraZeneca (Inst), Merck (Inst), Genentech (Inst), and holds a consulting role with Astra Zeneca, Novocure, Boehringer Ingelheim, Janssen, Takeda, Blueprint Pharmaceuticals, Bayer, Bristol Myers Squibb, Ikena, Regeneron. She also receives honorarium from Thermo Fisher and holds stock in Merck and Johnson & Johnson. Lyudmila Bazhenova reports a professional medical writing service funded by Mirati Therapeutics Inc, along with consulting roles with Pfizer, Genentech, Janssen, Novocure, Daiichi Sankyo, Anheart, BMS, Sanofi, Gilead, Teligene, Boehringer Ingelheim, Neuvogen, Bayer, BioAtla, Summit Therapeutics, Merck, Abbvie, Regeneron, Intervenn, Elevation Oncology, and Mirati. Additionally, she has institutional consulting with Takeda and Astra Zeneca, serves on the Data Safety Monitoring for ORIC Pharmaceuticals and Neuvogen, and holds stock in Epic Sciences. Stephen V. Liu holds a consulting role with AstraZeneca, Bristol-Myers Squibb, Catalyst, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech/Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Merck, Merus, Novartis, Regeneron, Sanofi, and Takeda. He also receives research institutional grant funding from Alkermes, Bristol-Myers Squibb, Elevation Oncology, Genentech, Gilead, Merck, Merus, Nuvalent, Pfizer, RAPT, and Turning Point Therapeutics, and serves on the Data Safety Monitoring Board for Candel Therapeutics. The remaining authors have no relevant financial disclosures to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Amorphous solid dispersion (ASD) in a polymer matrix is a powerful method for enhancing the solubility and bioavailability of otherwise crystalline, poorly water-soluble drugs. 6-Carboxycellulose acetate butyrate (CCAB) is a relatively new commercial cellulose derivative that was introduced for use in waterborne coating applications. As CCAB is an amphiphilic, carboxyl-containing, high glass transition temperature ( T g ) polymer, characteristics essential to excellent ASD polymer performance, we chose to explore its ASD potential. Structurally diverse drugs quercetin, ibuprofen, ritonavir, loratadine, and clarithromycin were dispersed in CCAB matrices. We evaluated the ability of CCAB to create ASDs with these drugs and its ability to provide solubility enhancement and effective drug release. CCAB/drug dispersions prepared by spray drying were amorphous up to 25 wt % drug, with loratadine remaining amorphous up to 50% drug. CCAB formulations with 10% drug proved effective at providing in vitro solubility enhancement for the crystalline flavonoid drug quercetin as well as ritonavir, but not for the more soluble APIs ibuprofen and clarithromycin and the more hydrophobic loratadine. CCAB did provide slow and controlled release of ibuprofen, offering a simple and promising Long-duration ibuprofen formulation. Formulation with clarithromycin showed the ability of the polymer to protect against degradation of the drug at stomach pH. Furthermore, CCAB ASDs with both loratadine and ibuprofen could be improved by the addition of the water-soluble polymer poly(vinylpyrrolidone) (PVP), with which CCAB shows good miscibility. CCAB provided solubility enhancement in some cases, and the slower drug release exhibited by CCAB, especially in the stomach, could be especially beneficial, for example, in formulations containing known stomach irritants like ibuprofen.

Increasing palliative care presence in the intensive care unit (ICU) improves symptom management, increases goals-of-care discussion, and reduces unnecessary procedures in ICU patients. An interdisciplinary study team developed a palliative care trigger program in a 17-bed surgical ICU (SICU). Surgical ICU patients who met 3 triggers (ICU length of stay > 10 days, repeat ICU admission, and metastatic cancer) automatically received a palliative care consult. The purpose of the current study was to survey SICU health care professionals before and after the institution of the palliative care trigger program. Overall, the palliative care trigger program was viewed positively by interdisciplinary team members with increased team communication and decreased resistance for the inclusion of palliative care in the SICU plan of care. The palliative care trigger program was successfully developed and implemented in a SICU and was accepted by the interdisciplinary team members caring for SICU patients. Team member feedback is being used to expand the palliative care trigger program to improve care for SICU patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 by The Hospice and Palliative Nurses Association. All rights reserved.)

The management of elderly patients diagnosed with acute myelogenous leukemia (AML) is complicated by high relapse risk and comorbidities that often preclude access to allogeneic hematopoietic cellular transplantation (allo-HCT). In recent years, fast-paced FDA drug approval has reshaped the therapeutic landscape, with modest, albeit promising improvement in survival. Still, AML outcomes in elderly patients remain unacceptably unfavorable highlighting the need for better understanding of disease biology and tailored strategies. In this review, we discuss recent modifications suggested by European Leukemia Network 2022 (ELN-2022) risk stratification and review recent aging cell biology advances with the discussion of four AML cases. While an older age, >60 years, does not constitute an absolute contraindication for allo-HCT, the careful patient selection based on a detailed and multidisciplinary risk stratification cannot be overemphasized.

Objective: The objective of this study was to identify out-of-hospital cardiac arrest characteristics for patients treated by collegiate-based emergency medical services (CBEMS) organizations., Participants: CBEMS organizations provided data via the National Collegiate EMS Foundation Cardiac Arrest Data Registry., Methods: CBEMS organization details, patient demographics, cardiac arrest characteristics and treatments, and prehospital outcomes for cases spanning October 2007 to May 2020 were analyzed with descriptive statistics., Results: There were 65 OHCA entries. The majority were for male patients (82%) and a notable number of cases occurred in patients 45 years of age or younger (41%). Cases were frequently witnessed (71%) with high rates of bystander cardiopulmonary resuscitation (57%) and defibrillation (29%) prior to EMS arrival. Almost half of the patients (48%) had achieved return of spontaneous circulation until care was transferred to a provider of equal/higher level., Conclusions: CBEMS organizations may be well situated to respond rapidly to on-campus OHCAs.

Objective: To determine the relationship between race/ethnicity and case volume among graduating surgical residents., Background: Racial/ethnic minority individuals face barriers to entry and advancement in surgery; however, no large-scale investigations of the operative experience of racial/ethnic minority residents have been performed., Methods: A multi-institutional retrospective analysis of the Accreditation Council for Graduate Medical Education case logs of categorical general surgery residents at 20 programs in the US Resident OPerative Experience Consortium database was performed. All residents graduating between 2010 and 2020 were included. The total, surgeon chief, surgeon junior, and teaching assistant case volumes were compared between racial/ethnic groups., Results: The cohort included 1343 residents. There were 211 (15.7%) Asian, 65 (4.8%) Black, 73 (5.4%) Hispanic, 71 (5.3%) "Other" (Native American or Multiple Race), and 923 (68.7%) White residents. On adjusted analysis, Black residents performed 76 fewer total cases (95% CI, -109 to -43, P <0.001) and 69 fewer surgeon junior cases (-98 to -40, P <0.001) than White residents. Comparing adjusted total case volume by graduation year, both Black residents and White residents performed more cases over time; however, there was no difference in the rates of annual increase (10 versus 12 cases per year increase, respectively, P =0.769). Thus, differences in total case volume persisted over the study period., Conclusions: In this multi-institutional study, Black residents graduated with lower case volume than non-minority residents throughout the previous decade. Reduced operative learning opportunities may negatively impact professional advancement. Systemic interventions are needed to promote equitable operative experience and positive culture change., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Prior analyses of general surgery resident case logs have indicated a decline in the number of endocrine procedures performed during residency. This study aimed to identify factors contributing to the endocrine operative experience of general surgery residents and compare those who matched in endocrine surgery fellowship with those who did not., Methods: We analyzed the case log data of graduates from 18 general surgery residency programs in the US Resident Operative Experience Consortium over an 11-year period., Results: Of the 1,240 residents we included, 17 (1%) matched into endocrine surgery fellowships. Those who matched treated more total endocrine cases, including more thyroid, parathyroid, and adrenal cases, than those who did not (81 vs 37, respectively, P < .01). Program-level factors associated with increased endocrine volume included endocrine-specific rotations (+10, confidence interval 8-12, P < .01), endocrine-trained faculty (+8, confidence interval 7-10, P < .01), and program co-location with otolaryngology residency (+5, confidence interval 2 -8, P < .01) or endocrine surgery fellowship (+4, confidence interval 2-6, P < .01). Factors associated with decreased endocrine volume included bottom 50th percentile in National Institute of Health funding (-10, confidence interval -12 to -8, P < .01) and endocrine-focused otolaryngologists (-3, confidence interval -4 to -1, P < .01)., Conclusion: Several characteristics are associated with a robust endocrine experience and pursuit of an endocrine surgery fellowship. Modifiable factors include optimizing the recruitment of dedicated endocrine surgeons and the inclusion of endocrine surgery rotations in general surgery residency., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cannabis is widely used worldwide, yet its links to health outcomes are not fully understood. DNA methylation can serve as a mediator to link environmental exposures to health outcomes. We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and lifetime cannabis use (ever vs. never) in a meta-analysis including 9436 participants (7795 European and 1641 African ancestry) from seven cohorts. Accounting for effects of cigarette smoking, our trans-ancestry EWAS meta-analysis revealed four CpG sites significantly associated with lifetime cannabis use at a false discovery rate of 0.05 ( p < 5.85 × 10 - 7 ) : cg22572071 near gene ADGRF1, cg15280358 in ADAM12, cg00813162 in ACTN1, and cg01101459 near LINC01132. Additionally, our EWAS analysis in participants who never smoked cigarettes identified another epigenome-wide significant CpG site, cg14237301 annotated to APOBR. We used a leave-one-out approach to evaluate methylation scores constructed as a weighted sum of the significant CpGs. The best model can explain 3.79% of the variance in lifetime cannabis use. These findings unravel the DNA methylation changes associated with lifetime cannabis use that are independent of cigarette smoking and may serve as a starting point for further research on the mechanisms through which cannabis exposure impacts health outcomes., (© 2023. The Author(s).)

Where sufficiently large genome-wide association study (GWAS) samples are not currently available or feasible, methods that leverage increasing knowledge of the biological function of variants may illuminate discoveries without increasing sample size. We comprehensively evaluated 17 functional weighting methods for identifying novel associations. We assessed the performance of these methods using published results from multiple GWAS waves across each of five complex traits. Although no method achieved both high sensitivity and positive predictive value (PPV) for any trait, a subset of methods utilizing pleiotropy and expression quantitative trait loci nominated variants with high PPV (>75%) for multiple traits. Application of functionally weighting methods to enhance GWAS power for locus discovery is unlikely to circumvent the need for larger sample sizes in truly underpowered GWAS, but these results suggest that applying functional weighting to GWAS can accurately nominate additional novel loci from available samples for follow-up studies., (© 2023. The Author(s).)

Although palliative care focuses on supporting patients and families through serious illness, it is underutilized in the surgical intensive care unit (SICU). In 2020, patients in the SICU represented only 2.75% of our palliative team's consults. We hypothesize that utilization of palliative care triggers in the SICU will increase collaboration between SICU and palliative care teams and improve patient/family experiences. After reviewing our team's consultation records and the published literature, a consult trigger program was implemented for patients with a SICU length of stay >10 days, unplanned SICU readmission, or new diagnosis of metastatic cancer. A pre-intervention survey assessed SICU providers' perceptions of palliative care. Retrospective analysis evaluated qualitative and quantitative measures. 97% of SICU providers felt increased palliative care would be helpful. During the 6-month project, January 1, 2021 - June 30, 2021, our palliative team performed 27 triggered consults, representing 3.3% of the total 818 consults performed during this period and thus a 20% increase in SICU palliative consults. Triggered consults represented many primary surgical services and the most common consult reason was length-of-stay. All consults included discussions about goals of care and 16 of the 27 patients/families expressed restorative goals. Numerous notes documented family appreciation.

MDS and AML are clonal hematopoietic stem cell disorders of increasing incidence, having a variable prognosis based, among others, on co-occurring molecular abnormalities. TP53 mutations are frequently detected in these myeloid neoplasms and portend a poor prognosis with known therapeutic resistance. This article provides a timely review of the complexity of TP53 alterations, providing updates in diagnosis and prognosis based on new 2022 International Consensus Classification (ICC) and World Health Organization (WHO) guidelines. The article addresses optimal testing strategies and reviews current and arising therapeutic approaches. While the treatment landscape for this molecular subgroup is under active development, further exploration is needed to optimize the care of this group of patients with unmet needs., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To examine differences in resident operative experience between male and female general surgery residents., Background: Despite increasing female representation in surgery, sex and gender disparities in residency experience continue to exist. The operative volume of male and female general surgery residents has not been compared on a multi-institutional level., Methods: Demographic characteristics and case logs were obtained for categorical general surgery graduates between 2010 and 2020 from the US Resident OPerative Experience Consortium database. Univariable, multivariable, and linear regression analyses were performed to compare differences in operative experience between male and female residents., Results: There were 1343 graduates from 20 Accreditation Council for Graduate Medical Education-accredited programs, and 476 (35%) were females. There were no differences in age, race/ethnicity, or proportion pursuing fellowship between groups. Female graduates were less likely to be high-volume residents (27% vs 36%, P < 0.01). On univariable analysis, female graduates performed fewer total cases than male graduates (1140 vs 1177, P < 0.01), largely due to a diminished surgeon junior experience (829 vs 863, P < 0.01). On adjusted multivariable analysis, female sex was negatively associated with being a high-volume resident (OR = 0.74, 95% CI: 0.56 to 0.98, P = 0.03). Over the 11-year study period, the annual total number of cases increased significantly for both groups, but female graduates (+16 cases/year) outpaced male graduates (+13 cases/year, P = 0.02)., Conclusions: Female general surgery graduates performed significantly fewer cases than male graduates. Reassuringly, this gap in operative experience may be narrowing. Further interventions are warranted to promote equitable training opportunities that support and engage female residents., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Antibody-drug conjugates (ADCs) are a class of therapeutics that combine target-specific monoclonal antibodies with cytotoxic chemotherapy. Here, we describe the components of ADCs and review their promising activity, safety, and applicability in non-small cell lung cancer (NSCLC)., Recent Findings: Technological advancements have reinvigorated ADCs as a viable treatment strategy in advanced solid tumors. Several target-specific ADCs have shown promise in treatment-refractory NSCLC, including agents targeting HER2, HER3, TROP2, CEACAM5, and MET, among others, with multiple confirmatory phase 3 trials ongoing. Critically, ADCs have demonstrated efficacy signals in both driver mutation-positive and mutation-negative advanced NSCLC, reinforcing their potential as an efficacious treatment strategy that transcends diverse tumor biology in advanced NSCLC. ADCs are a promising class of anti-cancer therapeutics that have significant potential in advanced NSCLC. Beyond confirmatory phase 3 trials, several questions remain including optimal agent sequencing, combinatorial methods, and unique toxicity management., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: The authors report no financial relationships with commercial interests.

Background: There is concern regarding the competency of today's general surgery graduates as a large proportion defer independent practice in favor of additional fellowship training. Little is known about the graduates who directly enter general surgery practice and if their operative experiences during residency differ from graduates who pursue fellowship., Methods: Nineteen Accreditation Council for Graduate Medical Education-accredited general surgery programs from the US Resident OPerative Experience Consortium were included. Demographics, career choice, and case logs from graduates between 2010 to 2020 were analyzed., Results: There were 1,264 general surgery residents who graduated over the 11-year period. A total of 248 (19.6%) went directly into practice and 1,016 (80.4%) pursued fellowship. Graduates directly entering practice were more likely to be a high-volume resident (43.1% vs 30.5%, P < .01) and graduate from a high-volume program (49.2% vs 33.0%, P < .01). Direct-to-practice graduates performed 53 more cases compared with fellowship-bound graduates (1,203 vs 1,150, P < .01). On multivariable analysis, entering directly into practice was positively associated with total surgeon chief case volume (odds ratio = 1.47, 95% confidence interval 1.18-1.84, P < .01) and graduating from a US medical school (odds ratio = 2.54, 95% confidence interval 1.45-4.44, P < .01) while negatively associated with completing a dedicated research experience (odds ratio = 0.31, 95% confidence interval 0.22-0.45, P < .01)., Conclusion: This is the first multi-institutional study exploring resident operative experience and career choice. These data suggest residents who desire immediate practice can tailor their experience with less research time and increased operative volume. These data may be helpful for programs when designing their experience for residents with different career goals., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cigarette smoking and alcohol use are among the most prevalent substances used worldwide and account for a substantial proportion of preventable morbidity and mortality, underscoring the public health significance of understanding their etiology. Genome-wide association studies (GWAS) have successfully identified genetic variants associated with cigarette smoking and alcohol use traits. However, the vast majority of risk variants reside in non-coding regions of the genome, and their target genes and neurobiological mechanisms are unknown. Chromosomal conformation mappings can address this knowledge gap by charting the interaction profiles of risk-associated regulatory variants with target genes. To investigate the functional impact of common variants associated with cigarette smoking and alcohol use traits, we applied Hi-C coupled MAGMA (H-MAGMA) built upon cortical and newly generated midbrain dopaminergic neuronal Hi-C datasets to GWAS summary statistics of nicotine dependence, cigarettes per day, problematic alcohol use, and drinks per week. The identified risk genes mapped to key pathways associated with cigarette smoking and alcohol use traits, including drug metabolic processes and neuronal apoptosis. Risk genes were highly expressed in cortical glutamatergic, midbrain dopaminergic, GABAergic, and serotonergic neurons, suggesting them as relevant cell types in understanding the mechanisms by which genetic risk factors influence cigarette smoking and alcohol use. Lastly, we identified pleiotropic genes between cigarette smoking and alcohol use traits under the assumption that they may reveal substance-agnostic, shared neurobiological mechanisms of addiction. The number of pleiotropic genes was ~26-fold higher in dopaminergic neurons than in cortical neurons, emphasizing the critical role of ascending dopaminergic pathways in mediating general addiction phenotypes. Collectively, brain region- and neuronal subtype-specific 3D genome architecture helps refine neurobiological hypotheses for smoking, alcohol, and general addiction phenotypes by linking genetic risk factors to their target genes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Direct to operating room resuscitation (DOR) is used by some trauma centers for severely injured trauma patients as an approach to minimize time to hemorrhage control. It is unknown whether this strategy results in favorable outcomes. We hypothesized that utilization of an emergency department operating room (EDOR) for resuscitation of patients with abdominal trauma at an urban Level I trauma center would be associated with decreased time to laparotomy and improved outcomes., Methods: We included patients 15 years or older with abdominal trauma who underwent emergent laparotomy within 120 minutes of arrival both at our institution and within a National Trauma Data Bank sample between 2007 to 2019 and 2013 to 2016, respectively. Our institutional sample was matched 1:1 to an American College of Surgeons National Trauma Databank sample using propensity score matching based on age, sex, mechanism of injury, and abdominal Abbreviated Injury Scale score. The primary outcome was time to laparotomy incision. Secondary outcomes included blood transfusion requirement, intensive care unit (ICU) length of stay (LOS), ventilator days, hospital LOS, and in-hospital mortality., Results: Two hundred forty patients were included (120 institutional, 120 national). Both samples were well balanced, and 83.3% sustained penetrating trauma. There were 84.2% young adults between the ages of 15 and 47, 91.7% were male, 47.5% Black/African American, with a median Injury Severity Score of 14 (interquartile range [IQR], 8-29), Glasgow Coma Scale score of 15 (IQR, 13-15), 71.7% had an systolic blood pressure of >90 mm Hg, and had a shock index of 0.9 (IQR, 0.7-1.1) which did not differ between groups (p > 0.05). Treatment in the EDOR was associated with decreased time to incision (25.5 minutes vs. 40 minutes; p ≤ 0.001), ICU LOS (1 vs. 3.1 days; p < 0.001), transfusion requirement within 24 hours (3 units vs. 5.8 units packed red blood cells; p = 0.025), hospital LOS (5 days vs. 8.5 days, p = 0.014), and ventilator days (1 day vs. 2 days; p ≤ 0.001). There were no significant differences in in-hospital mortality (22.5% vs. 15.0%; p = 0.14) or outcome-free days (4.9 days vs. 4.5 days, p = 0.55)., Conclusion: The use of an EDOR is associated with decreased time to hemorrhage control as evidenced by the decreased time to incision, blood transfusion requirement, ICU LOS, hospital LOS, and ventilator days. These findings support DOR for patients sustaining operative abdominal trauma., Level of Evidence: Therapeutic/Care Management, Level III., (Copyright © 2022 American Association for the Surgery of Trauma.)

Introduction: Utilizing a physician-reported survey, we assessed general surgeons (GS) comfort level in the management of bladder trauma, from a GS and urologist's perspective., Materials and Methods: Online questionnaires were distributed electronically to physicians of the American College of Surgeons and American Urological Association. This survey queried demographic data, clinical factors that may influence urology consultations, and bladder injury scenarios of varying severities. Two questions were presented for each scenario, the first querying GS comfort level in bladder trauma management, the second assessing the likelihood of obtaining urology consultations in such scenarios. Responses were graded on a Likert scale., Results: Overall, 108 (51%) GS and 104 (49%) urologists responded. When compared to managing Grade I injuries, the comfort level of GS decreased as the severity of bladder trauma increased, while the likelihood of obtaining a urology consultation increased. While the perceived comfort of GS by urologists decreased from 84% to 5% for Grade I to Grade V injuries, GS reported a significantly higher comfort level (Grade I: 92%, p = 0.09; Grade V: 31%, p < 0.001). Majority of GS indicated that preoperative diagnosis on imaging (56%), intraoperative diagnosis (62%), and timing of patient presentation (76%), did not affect their decision to consult urology for assistance in bladder trauma (p < 0.001)., Conclusions: GS-reported comfort levels for bladder trauma management remains higher than urology-perceived comfort levels. Contrary to urologists' perception, most peri-injury factors did not affect GS decision to consult urology for bladder trauma. We hope this study can foster discussion and improve interdisciplinary collaboration in bladder trauma management.

Background: The Surgeon General oversees the Commissioned Corps of the U.S. Public Health Service (USPHS) and is viewed as the "Nation's Doctor," responsible for providing the public with information on living healthier and safer lives. The Surgeon General's influence is seen through public health initiatives such as warning labels on tobacco and alcohol products. The objectives of this paper are to describe the tradition of the Office of the Surgeon General as created by Dr John M. Woodworth and to describe the careers of Dr C. Everett Koop and Dr Richard H. Carmona-the only 2 surgeons by training to hold the role., Methods: This is a historical literature review using a combination of primary and secondary sources., Results: Dr Woodworth set the priorities and responsibilities of the Surgeon General's Office: education, public service, sanitation, and public health. Dr Koop is widely regarded as the most influential Surgeon General of all time. He was both a pioneer in pediatric surgery and a highly influential public figure, issuing landmark reports on smoking, violence, and AIDS. Dr Carmona is a trauma surgeon by training and focused on the dangers of second-hand smoke as Surgeon General. Dr Carmona served in a more political role as Surgeon General, eventually running for Senate at the end of his term., Conclusion: This brief review of the history of the Surgeon General's Office highlights the contributions of the first Surgeon General and the only 2 surgeons who have held the position., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: The authors report no financial relationships with commercial interests.

Importance: The evidence provided supports routine and systematic capture of long-term outcomes after trauma, lengthening the follow-up for patients at risk for incisional hernia (IH) after trauma laparotomy (TL), counseling on the risk of IH during the postdischarge period, and consideration of preventive strategies before future abdominal operations to lessen IH prevalence as well as the patient and health care burden., Objective: To determine burden of and factors associated with IH formation following TL at a population-based level across health care settings., Design, Setting, and Participants: This population-based cohort study included adult patients who were admitted with traumatic injuries and underwent laparotomy with follow-up of 2 or more years. The study used 18 statewide databases containing data collected from January 2006 through December 2016 and corresponding to 6 states in diverse regions of the US. Longitudinal outcomes were identified within the Statewide Inpatient, Ambulatory, and Emergency Department Databases. Patients admitted with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for traumatic injuries with 1 or more concurrent open abdominal operations were included. Data analysis was conducted from March 2020 through June 2020., Main Outcomes and Measures: The primary outcome was IH after TL. Risk-adjusted Cox regression allowed identification of patient-level, operative, and postoperative factors associated with IH., Results: Of 35 666 patients undergoing TL, 3127 (8.8%) developed IH (median [interquartile range] follow-up, 5.6 [3.4-8.6] years). Patients had a median age of 49 (interquartile range, 31-67) years, and most were male (21 014 [58.9%]), White (21 584 [60.5%]), and admitted for nonpenetrating trauma (28 909 [81.1%]). The 10-year IH rate and annual incidence were 11.1% (95% CI, 10.7%-11.5%) and 15.6 (95% CI, 15.1-16.2) cases per 1000 people, respectively. Within risk-adjusted analyses, reoperation (adjusted hazard ratio [aHR], 1.28 [95% CI, 1.2-1.37]) and subsequent abdominal surgeries (aHR, 1.71 [95% CI, 1.56-1.88]), as well as obesity (aHR, 1.88 [95% CI, 1.69-2.10]), intestinal procedures (aHR, 1.47 [95% CI, 1.36-1.59]), and public insurance (aHRs: Medicare, 1.38 [95% CI, 1.20-1.57]; Medicaid, 1.35 [95% CI, 1.21-1.51]) were among the variables most strongly associated with IH. Every additional reoperation at the index admission and subsequently resulted in a 28% (95% CI, 20%-37%) and 71% (95% CI, 56%-88%) increased risk for IH, respectively. Repair of IH represented an additional $36.1 million in aggregate costs (39.9%) relative to all index TL admissions., Conclusions and Relevance: Incisional hernia after TL mirrors the epidemiology and patient profile characteristics seen in the elective setting. We identified patient-level, perioperative, and novel postoperative factors associated with IH, with obesity, intestinal procedures, and repeated disruption of the abdominal wall among the factors most strongly associated with this outcome. These data support preemptive strategies at the time of reoperation to lessen IH incidence. Longer follow-up may be considered after TL for patients at high risk for IH.

Importance: The prognostic significance of clonal T-cell receptor (TCR) rearrangement or low-level blood involvement as assessed by flow cytometry for patients with early-stage cutaneous T-cell lymphoma (CTCL) is not clear., Objective: To assess the association of low-level blood involvement by TCR clonality and flow cytometry with outcomes for patients with early-stage CTCL., Design, Setting, and Participants: A retrospective cohort analysis was conducted from September 1, 2019, to February 29, 2020, of 322 patients with early-stage (I-IIA) CTCL seen at the Winship Cancer Institute of Emory University and Grady Memorial Hospital. T-cell receptor gene rearrangement and flow cytometry records from the peripheral blood were documented at initial assessment., Exposures: T-cell receptor clonality and peripheral blood flow cytometry., Main Outcomes and Measures: Univariate and multivariable models and Kaplan-Meier assessments were analyzed for overall survival (OS) and time to next treatment. The primary outcome was OS from diagnosis and time to next treatment, and the hypotheses were formulated prior to data collection., Results: A total of 322 patients (166 female patients [51.6%]; median age at diagnosis, 53.8 years [range, 8.6-87.4 years]) with early-stage CTCL diagnosed from 1990 to 2018 were identified; of these, 258 had data available for both flow cytometry and TCR. Positive results for both TCR clonality and flow cytometry were associated with inferior OS in early-stage CTCL compared with both having negative results (hazard ratio [HR], 2.86; 95% CI, 1.02-8.06; P = .046). Positive results for only TCR clonality or only flow cytometry were not associated with OS (TCR clonality: HR, 1.31; 95% CI, 0.70-2.47; P = .40; flow cytometry: HR, 1.21; 95% CI, 0.58-2.52; P = .61) or time to next treatment (TCR clonality: HR, 1.05; 95% CI, 0.77-1.43; P = .76; flow cytometry: HR, 0.74; 95% CI, 0.47-1.16; P = .12). However, positive flow cytometry results were associated with reduced OS in the stage IIA subgroup (n = 94; HR, 1.17; 95% CI, 1.18-8.74; P = .02). Covariates associated with reduced survival included advanced age at diagnosis, male sex, and higher disease stage., Conclusions and Relevance: This cohort study of patients with early-stage CTCL suggests that low-level blood involvement as indicated by positive results for both TCR gene rearrangement and flow cytometry was associated with inferior OS, whereas positive results for either flow cytometry or TCR clonality was not. More precise measurements of blood involvement in CTCL and larger multi-institutional cohorts are needed to validate the prognostic significance of low-level blood involvement in early-stage CTCL.

Competing Interests: The authors report no financial relationships with commercial interests.

Purpose: Human papilloma virus (HPV) association remains one of the most important predictors of clinical outcome in oropharyngeal squamous cell carcinoma (OPSCC). We aimed to determine whether the relationship between HPV status and overall survival was influenced by socioeconomic factors., Materials and Methods: Using the National Cancer Database, we examined the relationship between socioeconomic status and overall survival, controlling for demographics and socioeconomic variables (age at diagnosis, race, sex, clinical stage, facility type, facility location, insurance status, median-income quartiles, percent of no high-school education quartiles, rural-urban dwelling, Charlson-Deyo score, primary site, and treatment type)., Results: HPV-positive patients with private insurance have improved overall survival compared with HPV-positive patients who are uninsured (hazard ratio [HR], 0.51, 95% CI, 0.41 to 0.63, P < .001). HPV-negative patients with private insurance have improved overall survival compared with HPV-negative patients who were uninsured (HR, 0.62, 95% CI, 0.53 to 0.73, P < .001). HPV-positive patients living in the south had improved overall survival compared with HPV-positive patients living in the west (HR, 0.83, 95% CI, 0.72 to 0.96, P = .013). As assessed through interaction, relationships between survival and insurance ( P = .004), rural-urban status ( P = .009), and facility location ( P = .021) statistically differed between HPV-positive and HPV-negative patients., Conclusion: HPV status impact on overall survival for patients with OPSCC is influenced by socioeconomic factors including insurance status and treatment facility. A deeper understanding of these interactions is needed to improve equity of care for patients with OPSCC.

Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, and cessation. We present a Fagerström Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. We observe five genome-wide significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416), and extend loci reported for other smoking traits to nicotine dependence. Using the heaviness of smoking index from UK Biobank (N = 33,791), rs2714700 is consistently associated; rs1862416 is not associated, likely reflecting nicotine dependence features not captured by the heaviness of smoking index. Both variants influence nearby gene expression (rs2714700/MAGI2-AS3 in hippocampus; rs1862416/TENM2 in lung), and expression of genes spanning nicotine dependence-associated variants is enriched in cerebellum. Nicotine dependence (SNP-based heritability = 8.6%) is genetically correlated with 18 other smoking traits (r g  = 0.40-1.09) and co-morbidities. Our results highlight nicotine dependence-specific loci, emphasizing the FTND as a composite phenotype that expands genetic knowledge of smoking.

Deep vein thrombosis (DVT) is linked to reimbursements and publicly reported metrics. Some hospitals discourage venous duplex ultrasound (VDUS) screening in asymptomatic trauma patients because they often find higher rates of DVT. We aim to evaluate the association between lower extremity (LE) VDUS screening and pulmonary embolism (PE) in trauma patients. Trauma patients admitted to an urban Level-1 trauma center between 2010 and 2015 were retrospectively analyzed. We characterized the association of asymptomatic LE VDUSs with PE, upper extremity DVT, proximal LE DVT, and distal LE DVT by univariate and multivariable logistic regression controlling for confounders. Of the 3959 trauma patients included in our study-after adjusting for covariates related to patient demographics, injury, and procedures-there was a significantly lower likelihood of PE in screened patients (odds ratio (OR) = 0.02, P < 0.001) and a higher rate of distal LE DVT (OR 11.1, P = 0.004). Screening was not associated with higher rates of proximal LE DVT after adjustment for covariates (OR = 1.8, P = 0.193). PE was associated with patient transfer status, pelvis fracture, and spinal procedures in unscreened patients. After adjusting for covariates, we have shown that LE VDUS asymptomatic screening is associated with lower rates of PE in trauma patients and not associated with higher rates of proximal LE DVT. Our detailed institutional review of a large cohort of trauma patients over five years provides support for ongoing asymptomatic screening and better characterizes venous thromboembolism outcomes than similarly sized purely administrative data reviews. As a retrospective cohort study with a large sample size, no loss to follow-up, and a population with low heterogeneity, this study should be considered as level III evidence for care management.

Background: Our institution amended its trauma activation criteria to require a Level II activation for patients ≥65 years old on antithrombotic medication presenting with suspected head trauma., Methods: Our institutional trauma registry was queried for geriatric patients on antithrombotic medication in the year before and after this criteria change. Demographics, presentation metrics, level of activation, and outcomes were compared between groups., Results: After policy change, a greater proportion of patients received a trauma activation (19.9 vs. 74.9%, P < 0.001) and a greater proportion of these patients were discharged directly home without injury (4.3 vs. 44%, P < 0.001). However, a smaller proportion of patients with a critical Emergency Department disposition or traumatic intracranial hemorrhage failed to receive a trauma activation (65.1 vs. 23.5%, P < 0.001; 70.7% vs. 27.3%, P < 0.001). There was no change in mortality (4.3 vs. 2.0%, P = 0.21)., Conclusions: Implementing new criteria increased overtriage, decreased undertriage, and had little effect on mortality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Cervical spine injuries (CSIs) can have major effects on the respiratory system and carry a high incidence of pulmonary complications. Respiratory failure can be due to spinal cord injuries, concomitant facial fractures or chest injury, airway obstruction, or cognitive impairments. Early tracheostomy (ET) is often indicated in patients with CSI. However, in patients with anterior cervical fusion (ACF), concerns about cross-contamination often delay tracheostomy placement. This study aimed to demonstrate the safety of ET within 4 days of ACF., Methods: Retrospective chart review was performed for all trauma patients admitted to our institution between 2001 and 2015 with diagnosis of CSI who required both ACF and tracheostomy, with or without posterior cervical fusion, during the same hospitalization. Thirty-nine study patients with ET (within 4 days of ACF) were compared with 59 control patients with late tracheostomy (5-21 days after ACF). Univariate and logistic regression analyses were performed to compare risk of wound infection, length of intensive care unit and hospital stay, and mortality between both groups during initial hospitalization., Results: There was no difference in age, sex, preexisting pulmonary or cardiac conditions, Glasgow Coma Scale score, Injury Severity Score, Chest Abbreviated Injury Scale score, American Spinal Injury Association score, cervical spinal cord injury levels, and tracheostomy technique between both groups. There was no statistically significant difference in surgical site infection between both groups. There were no cases of cervical fusion wound infection in the ET group (0%), but there were five cases (8.47%) in the late tracheostomy group (p = 0.15). Four involved the posterior cervical fusion wound, and one involved the ACF wound. There was no statistically significant difference in intensive care unit stay (p = 0.09), hospital stay (p = 0.09), or mortality (p = 0.06) between groups., Conclusion: Early tracheostomy within 4 days of ACF is safe without increased risk of infection compared with late tracheostomy., Level of Evidence: Evidence, level III.

The human microbiome encodes vast numbers of uncharacterized enzymes, limiting our functional understanding of this community and its effects on host health and disease. By incorporating information about enzymatic chemistry into quantitative metagenomics, we determined the abundance and distribution of individual members of the glycyl radical enzyme superfamily among the microbiomes of healthy humans. We identified many uncharacterized family members, including a universally distributed enzyme that enables commensal gut microbes and human pathogens to dehydrate trans -4-hydroxy-l-proline, the product of the most abundant human posttranslational modification. This "chemically guided functional profiling" workflow can therefore use ecological context to facilitate the discovery of enzymes in microbial communities., (Copyright © 2017, American Association for the Advancement of Science.)

Background: The indications and outcomes associated with temporary intravascular shunting (TIVS) for vascular trauma in the civilian sector are poorly understood. The objective of this study was to perform a contemporary multicenter review of TIVS use and outcomes., Methods: Patients sustaining vascular trauma, requiring TIVS insertion (January 2005 to December 2013), were retrospectively identified at seven Level I trauma centers. Clinical demographics, operative details, and outcomes were abstracted., Results: A total of 213 injuries (2.7%; 94.8% arterial) requiring TIVS were identified in 7,385 patients with vascular injuries. Median age was 27.0 years (range, 4-89 years), 91.0% were male, Glasgow Coma Scale (GCS) score was 15.0 (interquartile range, 4.0), Injury Severity Score (ISS) was 16.0 (interquartile range, 15.0), 26.0% had an ISS of 25 or greater, and 71.1% had penetrating injuries. The most common mechanism was gunshot wound (62.7%), followed by auto versus pedestrian (11.4%) and motor vehicle collision (6.5%). Shunts were placed for damage control in 63.4%, staged repair for combined orthopedic and vascular injuries in 36.1%, and for insufficient surgeon skill set in 0.5%. The most common vessel shunted was the superficial femoral artery (23.9%), followed by popliteal artery (18.8%) and brachial artery (13.2%). An argyle shunt (81.2%) was the most common conduit, followed by Pruitt-Inahara (9.4%). Dwell time was less than 6 hours in 61.4%, 24 hours in 86.5%, 48 hours in 95.9%, with only 4.1% remaining in place for more than 48 hours. Of the patients, 81.6% survived to definitive repair, and 79.6% survived overall. Complications included shunt thrombosis (5.6%) and dislodgment (1.4%). There was no association between dwell time and shunt thrombosis. The use of a noncommercial shunt (chest tube/feeding tube) did not impact shunt thrombosis but was an independent risk factor for subsequent graft failure. The limb salvage rate was 96.3%. No deaths could be attributed to a shunt complication., Conclusion: In the largest civilian TIVS experience insertion to date, both damage control and staged orthopedic vascular injuries were common indications for shunting. With an acceptable complication burden and no associated mortality attributed to this technique, shunting should be considered a viable treatment option., Level of Evidence: Therapeutic study, level V.

We present images showing surgical clips from a remotely repaired cerebral arteriovenous malformation in a patient treated safely with electroconvulsive therapy.

Background: Traumatic brain injury (TBI) confers a high risk of venous thrombosis, but early prevention with heparinoids is often withheld, fearing cerebral hematoma expansion. Yet, studies have shown heparinoids not only to be safe but also to limit brain edema and contusion size after TBI. Human TBI data also suggest faster radiologic and clinical neurologic recovery with earlier heparinoid administration. We hypothesized that enoxaparin (ENX) after TBI blunts in vivo leukocyte (LEU) mobilization to injured brain and cerebral edema, while improving neurologic recovery without increasing the size of the cerebral hemorrhagic contusion., Methods: CD1 male mice underwent either TBI by controlled cortical impact (CCI, 1-mm depth, 6 m/s) or sham craniotomy. ENX (1 mg/kg) or vehicle (VEH, 0.9% saline, 1 mL/kg) was administered at 2, 8, 14, 23, and 32 hours after TBI. At 48 hours, intravital microscopy was used to visualize live LEUs interacting with endothelium and microvascular leakage of fluorescein isothiocyanate-albumin. Neurologic function (Neurological Severity Score, NSS), activated clotting time, hemorrhagic contusion size, as well as brain and lung wet-to-dry ratios were evaluated post mortem. Analysis of variance with Bonferroni correction was used for statistical comparisons between groups., Results: Compared with VEH, ENX significantly reduced in vivo LEU rolling on endothelium (72.7 ± 28.3 LEU/100 μm/min vs. 30.6 ± 18.3 LEU/100 μm/min, p = 0.02) and cerebrovascular albumin leakage (34.5% ± 8.1% vs. 23.8% ± 5.5%, p = 0.047). CCI significantly increased ipsilateral cerebral hemisphere edema, but ENX treatment reduced post-CCI edema to near control levels (81.5% ± 1.5% vs. 77.6% ± 0.6%, p < 0.01). Compared with VEH, ENX reduced body weight loss at 24 hours (8.7% ± 1.2% vs. 5.8% ± 1.1%, p < 0.01) and improved NSS at 24 hours (14.5 ± 0.5 vs. 16.2 ± 0.4, p < 0.01) and 48 hours (15.1 ± 0.4 vs. 16.7 ± 0.5, p < 0.01) after injury. There were no significant differences in activated clotting time, hemorrhagic contusion size, and lung water content between the groups., Conclusion: ENX reduces LEU recruitment to injured brain, diminishing visible microvascular permeability and edema. ENX may also accelerate neurologic recovery without increasing cerebral contusion size. Further study in humans is necessary to determine safety, appropriate dosage, and timing of ENX administration early after TBI.