Lung cancer remains the leading cause of cancer-related deaths globally, and the survival rate remains low despite advances in diagnosis and treatment. The progression of lung cancer is a multifaceted and dynamic phenomenon that encompasses interplays among cancerous cells and their microenvironment, which incorporates immune cells. Exosomes, which are small membrane-bound vesicles, are released by numerous cell types in normal and stressful situations to allow communication between cells. Tumor-derived exosomes (TEXs) possess diverse neo-antigens and cargoes such as proteins, RNA, and DNA and have a unique molecular makeup reflecting tumor genetic complexity. TEXs contain both immunosuppressive and immunostimulatory factors and may play a role in immunomodulation by influencing innate and adaptive immune components. Moreover, they transmit signals that contribute to the progression of lung cancer by promoting metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunosuppression. This makes them a valuable resource for investigating the immune environment of tumors, which could pave the way for the development of non-invasive biomarkers that could aid in the prognosis, diagnosis, and immunotherapy of lung cancer. While immune checkpoint inhibitor (ICI) immunotherapy has shown promising results in treating initial-stage cancers, most patients eventually develop adaptive resistance over time. Emerging evidence demonstrates that TEXs could serve as a prognostic biomarker for immunotherapeutic response and have a significant impact on both systemic immune suppression and tumor advancement. Therefore, understanding TEXs and their role in lung cancer tumorigenesis and their response to immunotherapies is an exciting research area and needs further investigation. This review highlights the role of TEXs as key contributors to the advancement of lung cancer and their clinical significance in lung immune-oncology, including their possible use as biomarkers for monitoring disease progression and prognosis, as well as emerging shreds of evidence regarding the possibility of using exosomes as targets to improve lung cancer therapy.

Background: The Trauma Quality Improvement Program (American College of Surgery (ACS-TQIP)) uses the existing infrastructure of the Committee on Trauma programs and provides feedback to participating hospitals on risk-adjusted outcomes. This study aimed to analyze and compare the performance of the Level I Hamad Trauma Centre (HTC) with other TQIP participating centers by comparing TQIP aggregate database reports. The primary goal was to pinpoint the variations in adult trauma outcomes and quality measures, identify areas that need improvement, and leverage existing resources to facilitate quality improvement. Methods: A retrospective analysis was performed for the TQIP data from April 2019–March 2020 to April 2020–March 2021. We used the TQIP methodology, inclusion and exclusion criteria, and outcomes. Results: There were 915 patients from Fall 2020 and 884 patients from Fall 2021 that qualified for the TQIP database. The HTC patients’ demographics differed from the TQIP’s aggregate data; they were younger, more predominantly male, and had significantly different mechanisms of injury (MOI) with more traffic-related blunt trauma. Penetrating injuries were more severe in the other centers. During the TQIP Fall 2020 report, the HTC was a low outlier (good performer) in one cohort (all patients) and an average performer in the remaining cohorts. However, during Fall 2021, the HTC showed an improvement and was a low outlier in two cohorts (all patients and severe TBI patients). Overall, the HTC remained an average performer during the report cycles. Conclusions: There was an improvement over time in the risk-adjusted mortality, which reflects the continuous and demanding effort put together by the trauma team. The ACS-TQIP for the external benchmarking of quality improvement could be a contributor to better monitored patient care. Evaluating the TQIP data with emphases on appropriate methodologies, quality measurements, corrective measures, and accurate reporting is warranted.

Objectives: On-admission phosphate imbalance (OAPI) in traumatic brain injury (TBI) is scarce in the literature, either alone or with concomitant spinal injuries (CSI). We aimed to explore the OAPI in TBI and hypothesized that OAPI has unfavorable outcomes in TBI as well as spinal injury. Methods: In this retrospective study, all hospitalized patients with TBI were reviewed, and their serum phosphate levels were measured upon admission. Outcomes included in-hospital mortality and neurological deficit. Results: Among 912 TBI patients, 13% had hyperphosphatemia (n = 118/912) and 30% had associated CSI (n = 272/912). Hypophosphatemia was found in two-thirds of TBI patients (n = 607/912). Thirteen patients of CSI group developed neurological deficits (4.8%) with hypophosphatemia. Serum phosphate levels were significantly correlated with serum potassium, magnesium, and lactate levels, as well as Injury Severity Score (ISS). The serum glucose-phosphate ratio was higher in patients with severe Glasgow Coma Scale (GCS). The overall mortality was 21.3% (47% had hyperphosphatemia, 17% had hypophosphatemia, and 18% had normophosphatemia). Multivariable analysis showed that hyperphosphatemia, high serum lactate, sodium, and potassium levels, high head Abbreviated Injury Scale (AIS), and low GCS were significantly associated with increased mortality. Conclusions: Hypophosphatemia was common in TBI patients regardless of the presence of spinal injuries and was observed in all patients with neurological deficits. Routine phosphate monitoring may help in early risk stratification and targeted management of TBI.

Trauma is a serious public health issue, and remains a major cause of mortality and disability worldwide. The notion that genetic factors contribute to an individual's response to traumatic injury has advanced significantly. Genetic variations in severely injured patients have been linked to mortality, morbidity, and psychological outcomes. We conducted a comprehensive review of beta-adrenergic receptor polymorphisms and their impact on the pathogenetics of traumatic injuries, which could pave the way for a transformational frontier of personalized medicine in neurotrauma. It remains unclear why some individuals are vulnerable to worse outcomes, whereas others are resilient. Although genetic factors may be significant, the intricate interplay between environmental and genetic factors may be responsible for variations in the presentation and outcome after injury. Recent advancements in genetic analysis and molecular physiology have helped to shed light on the causes of such variability. Although exposure to trauma can initiate a cascade of stress-related responses, these responses alone are insufficient to explain etiopathogenesis. Therefore, gaining insights into how trauma and genetic predispositions to adrenergic variations interact at the molecular level to affect an individual's susceptibility and recuperation could provide an essential understanding of the molecular pathogenesis of traumatic injuries. Therefore, it is imperative to identify potential genetic and physiological markers to guide early management and prognosis of trauma. Such knowledge could pave the way for the discovery of novel biomarkers that can identify a transdiagnostic subgroup that is at high risk and requires early intervention. This could lead to the adoption of personalized medical approaches in neurotrauma care.

Introduction: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a critical complication in trauma patients, contributing to considerable morbidity and mortality. Multiple factors in trauma pose a challenge to the early initiation of VTE chemoprophylaxis, thereby underscoring the benefit of early detection strategies for DVT. This study evaluated the feasibility of intensivist-performed Compression Ultrasound (IPCUS) for screening of proximal lower limbs for DVT in the trauma intensive care unit (TICU). Methods: We conducted a prospective study at a level 1 trauma center from November 2021 to May 2023 to assess the utility of IPCUS at the TICU. The study cohort included 800 multi-trauma patients aged 14 years and older admitted to trauma intensive care and step-down units. IPCUS was performed using a three-point compression technique at multiple post-injury time points. Positive or equivocal findings were validated by duplex ultrasonography (DUS). Patients were followed up for one month after discharge. Results: The cohort was predominantly male (94.2%), with a mean injury severity score of 20. The overall incidence of VTE within the cohort was 3%. VTE chemoprophylaxis was administered to 60% of patients within the first 48 h. IPCUS identified DVT in 10 patients, with a sensitivity of 89% and specificity of 100%. There was no clinical evidence of missed proximal lower limb DVTs. There was a moderate agreement (Cohen’s Kappa score of 0.46) between IPCUS and radiographer-performed DUS. Conclusion: IPCUS is a feasible and effective screening method for proximal lower limb DVT in trauma patients with high diagnostic accuracy. Enhanced ultrasonography training for intensivists could further improve screening outcomes, reducing the number of equivocal cases. Larger studies are warranted to confirm these findings and establish standardized training protocols for IPCUS in trauma care settings.

Background: Traumatic head injury (THI) includes a diverse range of hemorrhagic brain lesions (HBL), which are distinct phenotypes with characteristic pathophysiological mechanisms. Computed tomography (CT) is the cornerstone of the initial assessment and diagnosis; however, its sensitivity is limited, especially in mild head injury. Blood-derived biomarkers, including Neuron-Specific Enolase (NSE) and S-100B, have been extensively studied; however, their efficacy in distinguishing HBL subtypes remains unclear. We evaluated whether circulating serum levels of S-100B and NSE can discriminate between distinct intracranial HBLs and extracranial hemorrhagic lesions (ECH). Methods: This is an interim analysis of a prospective, randomized, double-blind clinical trial including 434 adult patients with blunt THI. HBL phenotypes identified by CT scan included subarachnoid hemorrhage (SAH), subdural hematoma (SDH), epidural hematoma (EDH), and brain contusion (BC). Unique lesions were considered while overlapping lesions were excluded. Subgaleal hematoma (SGH) was included as an example of ECH. Serum S-100B was assessed within 6 h post-injury, while serum NSE was evaluated at admission, 24 h, and 48 h thereafter. Serum NSE and inflammatory cytokines were quantified in duplicates using a Human Magnetic Luminex 5-plex assay, while serum S-100B concentrations were measured separately. Serum epinephrine concentrations were quantified using an ELISA. Biomarker profiles were analyzed based on lesion phenotype, lesion multiplicity, injury pattern, and clinical outcomes, including hospital length of stay (HLOS) and the Glasgow Outcome Scale—Extended (GOSE). Results: Admission median S-100B levels were higher in patients with SAH (495 pg/mL) and lower in those with SGH (191 pg/mL); however, they did not show statistically significant difference among HBL phenotypes. They were significantly higher in patients with polytrauma TBI (420 pg/mL) compared to isolated TBI (258 pg/mL). Baseline and 48 h NSE concentrations were significantly higher in SDH (25,089 and 28,438 pg/mL) than in other THI lesions (p = 0.04). There were no statistically significant changes in NSE values over time across all THI lesions except for SDH in which they raised more after 48 h (p = 0.02). They had a significant drop in polytrauma over the time (p = 0.001). Compared to intracranial lesions, S-100 B levels were significantly lower in SGH and in skull fractures without intracranial hematomas. Both S-100B and NSE levels were elevated in individuals with unfavorable GOSE scores. Conclusions: In this secondary exploratory analysis, elevated serum NSE and S-100B levels discriminate between extra- and intracranial lesions and appear to represent distinct but complementary aspects of THI, indicating neuronal damage and its temporal evolution, and predicting clinical and functional outcomes. The present findings reflect association and not causation. Future studies incorporating larger or multicenter cohorts, volumetric imaging, and long-term outcomes are required to validate and refine biomarker-guided algorithms for personalized THI care.