Blunt Adrenal Injury is Not Associated With Worse Outcomes in Adult Trauma Patients.

INTRODUCTION: Blunt adrenal injury is rare. Given production of hormones including catecholamines, adrenal injury may lead to worse outcomes. However, there is a paucity of literature on this topic. As such, we compared blunt trauma patients (BTPs) with and without adrenal injuries, hypothesizing similar mortality and complications between cohorts. METHODS: The 2017-2019 Trauma Quality Improvement Program database was queried for adult (≥18-year-old) BTPs. Patients with penetrating trauma, traumatic brain injury, severe thoracic injury, or who were transferred from another hospital were excluded. Patients with adrenal injury were compared to those without using a 1:2 propensity score model. Matched variables included patient age, comorbidities, vitals on admission and concomitant injuries (i.e., liver, spleen, kidney, pancreas, and hollow viscus). Univariable logistic regression was then performed for associated risk of mortality. RESULTS: 2287 (0.2%) BTPs had an adrenal injury, with 1470 patients with adrenal injury matched to 2940 without adrenal injury. The rate of all complications including sepsis (0.1% versus 0.0%) was similar between cohorts (all P > 0.05). Patients with adrenal injury had a lower rate of mortality (0.1% versus 0.6%, P = 0.035) but increased length of stay (4 [3-6] versus 3 [2-5] days, P = 0.002). However, there was no difference in associated risk of mortality for patients with and without adrenal injury (odds ratio = 0.234; confidence interval = 0.54-1.015; P = 0.052). CONCLUSIONS: Blunt adrenal injury occurred in <1% of patients. After propensity matching, there was a similar associated rate of complications but longer hospital length of stay for patients with adrenal injury. Adrenal injury was not associated with an increased risk of mortality.

Firearm Violence Involving Adults 65 and Older During the Novel Coronavirus Disease Pandemic.

BACKGROUND: Rates of firearm violence (FV) surged during the COVID-19 pandemic. However, there is a paucity of data regarding older adults (OAs) (≥65 years old). This study aimed to evaluate patterns of FV against OAs before and after the COVID-19 pandemic, hypothesizing decreased firearm incidents, injuries, and deaths for OAs due to restricted social movement. METHODS: Retrospective (2016-2021) data for OAs were obtained from the Gun Violence Archive. The rate of FV was weighted per 10,000 OAs using annual population data from the United States Census Bureau. Mann-Whitney U tests were performed to compare annual firearm incidence rates, number of OAs killed, and number of OAs injured from 2016-2020 to 2021. RESULTS: From 944 OA-involved shootings, 842 died in 2021. The median total firearm incidents per month per 10,000 OAs decreased in 2021 vs 2016 (.65 vs .38, P < .001), 2017 (.63 vs .38, P < .001), 2018 (.61 vs .38, P < .001), 2019 (.39 vs .38, P = .003), and 2020 (.43 vs .38, P = .012). However, there was an increased median number of OAs killed in 2021 vs 2020 (.38 vs .38, P = .009), but no difference from 2016-2019 vs 2021 (all P > .05). The median number of firearm injuries decreased from 2017 to 2021 (.21 vs .19, P = .001) and 2020 to 2021 (.19 vs .19 P < .001). DISCUSSION: Firearm incidents involving OAs decreased in 2021 compared to pre-pandemic years; however, there was a slight increase in deaths compared to 2020. This may reflect increased social isolation; however, future research is needed to understand why this occurred.

Adolescent Trauma Patients With Isolated Head Trauma and Glasgow Coma Scale 6-8: Routine Intubation?

BACKGROUND: Recent evidence suggests that routine intubation upon arrival for adults with isolated head trauma and a depressed Glasgow Coma Scale (GCS) score is associated with increased risk of morbidity and mortality. Whether these outcomes are similar within an adolescent trauma population has not been previously investigated. We hypothesized intubation upon arrival for adolescent trauma patients with isolated head trauma to be associated with a higher risk of death and prolonged length of stay (LOS). METHODS: The 2017-2019 TQIP was queried for adolescents (age 12-16) presenting after isolated blunt head trauma (abbreviated injury scale [AIS] <1 spine/chest/abdomen/upper-extremity/lower-extremity) and GCS 6-8 on arrival. Transferred patients, dead-on-arrival, and those undergoing emergent operation from the emergency department were excluded. Patients intubated within one-hour were compared to patients not intubated within one-hour. A multivariable logistic regression analysis was performed adjusting for age, sex, GCS, and AIS-grade for the head. RESULTS: From 141 patients, 73 (51.8%) were intubated upon arrival. Intubated patients had a low complication rate (5.6%). Intubated and non-intubated patients had a similar rate and mortality risk (6.8% vs 1.5%, P = .11) (OR 1.84, CI .08-43.69, P = .71) and median length of stay (LOS) (2 days vs 2 days, P = .13). DISCUSSION: Unlike adult patients, adolescents with isolated head trauma and a depressed GCS have similar outcomes if they are intubated upon arrival. Utilizing initial GCS score to determine which adolescent trauma patients with isolated head trauma should be intubated appears to be a safe practice.

Clinical Outcome Comparison of Patients Requiring Extracorporeal Membrane Oxygenation With or Without COVID-19 Infection.

In severe COVID-19-related respiratory failure, extracorporeal membrane oxygenation (ECMO) is a useful modality that is used to provide effective oxygenation and ventilation to the patient. This descriptive study aimed to investigate and compare the outcomes between COVID-19-infected patients and patients who were not infected and required ECMO support. A retrospective study was undertaken on a cohort of 82 adult patients ([Formula: see text]18-year-old) who required venoarterial (VA-ECMO) and venovenous (VV-ECMO) ECMO between January 2019 and December 2022 in a single academic center. Patients who were cannulated for COVID-19-related respiratory failure (C-group) were compared to patients who were cannulated for non-COVID etiologies (non-group). Patients were excluded if data were missing regarding cannulation, decannulation, presenting diagnosis, and survival status. Categorical data were reported as counts and percentages, and continuous data were reported as means with 95% confidence intervals. Out of the 82 included ECMO patients, 33 (40.2%) were cannulated for COVID-related reasons, and 49 (59.8%) were cannulated for reasons other than COVID-19 infection. Compared to the non-group, the C-group had a higher in-hospital (75.8% vs. 55.1%) and overall mortality rate (78.8% vs. 61.2%). The C-group also had an average hospital length of stay (LOS) of 46.6 ± 13.2 days and an average intensive care unit (ICU) LOS of 44.1 ± 13.3 days. The non-group had an average hospital LOS of 24.8 ± 6.6 days and an average ICU LOS of 20.8 ± 5.9 days. Subgroup analysis of patients only treated with VV-ECMO yielded a greater in-hospital mortality rate for the C-group compared to the non-group (75.0% vs. 42.1%). COVID-19-infected patients may experience different morbidity and mortality rates as well as clinical presentations compared to non-COVID-infected patients when requiring ECMO support.

Perceptions of nonopioid treatment for pain in a homeless population.

CONTEXT: Opioid abuse has developed into a public health emergency within the last decade because opioid medications, while addictive, are effective and commonly used for pain management. In 2016, over 42,000 deaths were attributed to opioids. Chronic pain affects about 50% of people experiencing homelessness in the US, and they have a higher overall rate of chronic pain than the general population; opioids are among the methods they might use to manage that pain. Complementary and alternative therapies for pain management have largely gone unexplored in the homeless population. OBJECTIVES: To determine, among people experiencing homelessness, the willingness to use and current use of complementary and alternative treatments (physical and massage therapy, chiropractic treatments). A secondary objective was to investigate awareness and perception of osteopathic manipulative treatment (OMT) as a complementary treatment for chronic pain among the homeless population. METHODS: A 32 question survey was administered verbally to guests of True Worth Place Homeless Shelter in Fort Worth, Texas in three 4 hour sessions from February 2019 to April 2019. If participants gave verbal consent, a researcher read the questionnaire, one question at a time, and recorded the participant's responses. The survey included queries for opioid and nonopioid treatment modalities (physical and massage therapy, chiropractic, and OMT) to assess the perception of and current use of each among the population. Appropriate nonparametric statistical analysis was conducted to assess significance and correlations among the treatment groups. RESULTS: Of the 200 survey participants, 126 (91.3%) reported a history of opiate use for pain, but 136 (68.0%) believed that a nondrug pain intervention could better treat their pain. Additionally, 150 participants (75.0%) believed that regular manipulation, including OMT, would decrease their need for pain medications. Participants with a history of opioid use for pain were more likely to believe that the availability of regular manipulation, including OMT, at True Worth Place could decrease their need for pain medication (odds ratio=3.7143; 95% confidence interval=1.6122-8.5572; p=0.0009). Moreover, some participants (141; 70.5%) were already pursuing nondrug pain management modalities such as PT, massage therapy, and chiropractic care. The greatest barriers to receiving OMT were transportation and cost. CONCLUSIONS: This survey study was conducted to determine whether a homeless population would be willing to use nonopioid treatment, particularly OMT, for chronic pain management. Results revealed both a willingness to use and a previous use of nonopioid treatments for pain, along with a high prevalence of opiate use. Despite limited exposure to OMT, this population reported being potentially willing to pursue manipulation, including OMT, as a complementary treatment for pain relief alongside opioids if readily available.

Enhancing Antitumor Efficacy of Heavily Vascularized Tumors by RAMBO Virus through Decreased Tumor Endothelial Cell Activation.

Vascularization is a common pathology for many solid tumors, and therefore anti-angiogenic strategies are being investigated as a therapeutic target for treatment. Numerous studies are also being conducted regarding the effects of oncolytic viruses, including ImlygicTM, an FDA approved oncolytic herpes simplex virus-1 (oHSV) for the treatment of highly vascularized tumors such as Kaposi sarcoma (NCT04065152), and brain tumors. To our knowledge, the effects of combining oncolytic HSV with angiogenesis inhibition on endothelial cell activation has not been previously described. Here, we tested the effects of Rapid Antiangiogenesis Mediated By Oncolytic Virus (RAMBO), an oHSV which expresses a potent anti-angiogenic gene Vasculostatin on endothelial cell activation in heavily vascularized solid tumors. oHSV treatment induces endothelial cell activation, which inhibits virus propagation and oncolysis in adjacent tumor cells in vitro. Consistently, this was also observed in intravital imaging of intracranial tumor-bearing mice in vivo where infected tumor endothelial cells could efficiently clear the virus without cell lysis. Quantitative real-time PCR (Q-PCR), leukocyte adhesion assay, and fluorescent microscopy imaging data, however, revealed that RAMBO virus significantly decreased expression of endothelial cell activation markers and leukocyte adhesion, which in turn increased virus replication and cytotoxicity in endothelial cells. In vivo RAMBO treatment of subcutaneously implanted sarcoma tumors significantly reduced tumor growth in mice bearing sarcoma compared to rHSVQ. In addition, histological analysis of RAMBO-treated tumor tissues revealed large areas of necrosis and a statistically significant reduction in microvessel density (MVD). This study provides strong preclinical evidence of the therapeutic benefit for the use of RAMBO virus as a treatment option for highly vascularized tumors.

Responses of cerebral blood velocity and tissue oxygenation to low-frequency oscillations during simulated haemorrhagic stress in humans.

NEW FINDINGS: What is the central question of this study? Do low-frequency oscillations in arterial pressure and cerebral blood velocity protect cerebral blood velocity and oxygenation during central hypovolaemia? What is the main finding and its importance? Low-frequency oscillations in arterial pressure and cerebral blood velocity attenuate reductions in cerebral oxygen saturation but do not protect absolute cerebral blood velocity during central hypovolaemia. This finding indicates the potential importance of haemodynamic oscillations in maintaining cerebral oxygenation and therefore viability of tissues during challenges to cerebral blood flow and oxygen delivery. ABSTRACT: Tolerance to both real and simulated haemorrhage varies between individuals. Exaggerated low-frequency (∼0.1 Hz) oscillations in mean arterial pressure and brain blood flow [indexed via middle cerebral artery velocity (MCAv)] have been associated with improved tolerance to reduced central blood volume. The mechanism for this association has not been explored. We hypothesized that inducing low-frequency oscillations in arterial pressure and cerebral blood velocity would attenuate reductions in cerebral blood velocity and oxygenation during simulated haemorrhage. Fourteen subjects (11 men and three women) were exposed to oscillatory (0.1 and 0.05 Hz) and non-oscillatory (0 Hz) lower-body negative pressure profiles with an average chamber pressure of -60 mmHg (randomized and counterbalanced order). Measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and cerebral oxygenation of the frontal lobe via near-infrared spectroscopy. Tolerance was higher during the two oscillatory profiles compared with the 0 Hz profile (0.05 Hz, P = 0.04; 0.1 Hz, P = 0.09), accompanied by attenuated reductions in stroke volume (P < 0.001) and cerebral oxygenation of the frontal lobe (P ≤ 0.02). No differences were observed between profiles for reductions in mean arterial pressure (P = 0.17) and MCAv (P = 0.30). In partial support of our hypothesis, cerebral oxygenation, but not cerebral blood velocity, was protected during the oscillatory profiles. Interestingly, more subjects tolerated the oscillatory profiles compared with the static 0 Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of haemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissues during haemorrhagic stress.

Oncolytic HSV therapy increases trametinib access to brain tumors and sensitizes them in vivo.

BACKGROUND: Hyperactivation of the RAS-RAF-MEK-ERK signaling pathway is exploited by glioma cells to promote their growth and evade apoptosis. MEK activation in tumor cells can increase replication of ICP34.5-deleted herpes simplex virus type 1 (HSV-1), but paradoxically its activation in tumor-associated macrophages promotes a pro-inflammatory signaling that can inhibit virus replication and propagation. Here we investigated the effect of blocking MEK signaling in conjunction with oncolytic HSV-1 (oHSV) for brain tumors. METHODS: Infected glioma cells co-cultured with microglia or macrophages treated with or without trametinib were used to test trametinib effect on macrophages/microglia. Enzyme-linked immunosorbent assay, western blotting, and flow cytometry were utilized to evaluate the effect of the combination therapy. Pharmacokinetic (PK) analysis of mouse plasma and brain tissue was used to evaluate trametinib delivery to the CNS. Intracranial human and mouse glioma-bearing immune deficient and immune competent mice were used to evaluate the antitumor efficacy. RESULT: Oncolytic HSV treatment rescued trametinib-mediated feedback reactivation of the mitogen-activated protein kinase signaling pathway in glioma. In vivo, PK analysis revealed enhanced blood-brain barrier penetration of trametinib after oHSV treatment. Treatment by trametinib, a MEK kinase inhibitor, led to a significant reduction in microglia- and macrophage-derived tumor necrosis factor alpha (TNFα) secretion in response to oHSV treatment and increased survival of glioma-bearing mice. Despite the reduced TNFα production observed in vivo, the combination treatment activated CD8+ T-cell mediated immunity and increased survival in a glioma-bearing immune-competent mouse model. CONCLUSION: This study provides a rationale for combining oHSV with trametinib for the treatment of brain tumors.

Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults.

IMPACT STATEMENT: We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F2-isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.