This review explores the concept of futility timeouts and the use of traumatic brain injury (TBI) as an independent predictor of the futility of resuscitation efforts in severely bleeding trauma patients. The national blood supply shortage has been exacerbated by the lingering influence of the COVID-19 pandemic on the number of blood donors available, as well as by the adoption of balanced hemostatic resuscitation protocols (such as the increasing use of 1:1:1 packed red blood cells, plasma, and platelets) with and without early whole blood resuscitation. This has underscored the urgent need for reliable predictors of futile resuscitation (FR). As a result, clinical, radiologic, and laboratory bedside markers have emerged which can accurately predict FR in patients with severe trauma-induced hemorrhage, such as the Suspension of Transfusion and Other Procedures (STOP) criteria. However, the STOP criteria do not include markers for TBI severity or transfusion cut points despite these patients requiring large quantities of blood components in the STOP criteria validation cohort. Yet, guidelines for neuroprognosticating patients with TBI can require up to 72 h, which makes them less useful in the minutes and hours following initial presentation. We examine the impact of TBI on bleeding trauma patients, with a focus on those with coagulopathies associated with TBI. This review categorizes TBI into isolated TBI (iTBI), hemorrhagic isolated TBI (hiTBI), and polytraumatic TBI (ptTBI). Through an analysis of bedside parameters (such as the proposed STOP criteria), coagulation assays, markers for TBI severity, and transfusion cut points as markers of futilty, we suggest amendments to current guidelines and the development of more precise algorithms that incorporate prognostic indicators of severe TBI as an independent parameter for the early prediction of FR so as to optimize blood product allocation.

Background/Objectives: The timely evaluation of blood clot formation and breakdown is essential in the care of patients with severe bleeding or critical illness. Resonant acoustic rheometry is a novel, non-contact ultrasound method that measures changes in the viscoelastic properties of blood in a standard microplate format. Here, we present the first clinical description of whole blood coagulation and fibrinolysis assessed with resonant acoustic rheometry, with paired thromboelastography measurements for comparison. Methods: In this retrospective analysis, whole blood samples from three critically ill patients were divided and tested under four different conditions that included a control mixture, kaolin activation, tissue factor activation, and a tissue factor mixture supplemented with tissue plasminogen activator. The resonant acoustic rheometry system obtained real time measurements of resonant surface waves and displacements from the samples. Heat maps and spectrograms of the resonant surface waves were analyzed to determine the onset of clotting, the rate of viscoelastic stiffening, the time to maximum rigidity, and the onset as well as magnitude of fibrinolysis. These measurements were compared with thromboelastography reaction time, clot strength, fibrinogen contribution, and lysis values. Results: Resonant acoustic rheometry detected reproducible transitions from liquid to clot and from clot to lysis in all samples. Activator-dependent changes in clot initiation and propagation matched the expected hierarchy observed in thromboelastography. Significantly, samples exposed to tissue plasminogen activator demonstrated a clear fall in resonant frequency and a corresponding rise in surface displacement that reflected fibrinolysis. The technique also reproduced clinically meaningful patterns of hemostasis that aligned with each patient’s underlying disease. Conclusions: Whole blood clotting can be measured with resonant acoustic rheometry in a manner that aligns with established clinical assays. These results suggest strong potential for future use of resonant acoustic rheometry as a cost-effective, complementary platform for rapid, scalable, and clinically informative hemostatic assessment.

Background/Objective: Despite the known mutagenicity of cigarette smoke, only 10-15% of smokers will develop lung cancer in their lifetimes. What determines a smoker’s susceptibility to lung cancer is poorly understood. We identify the nucleotide excision repair (NER) protein Xeroderma pigmentosum Complementation Group C (XPC) as a tumor suppressor that may contribute to lungtumorigenesis when mutated and combined with cigarette smoke. Micronuclei, which are chromosome fragments and/or lagging chromosomes separated from the main nucleus, occur in many cancers, and indicate genomic instability. We hypothesize that cigarette smoke and XPC knockdown will cause genomic instability that will activate the DNA Damage Response (DDR) and increase the frequency of micronuclei and nuclear aberrancies. Methods: A human bronchial epithelial cell line (Beas-2B), and two lung adenocarcinoma cell lines (H1299 and A549) with stable XPC lentiviral knock-down (shXPC) or control shRNA (shCtrl) were treated with cigarette smoke extract (CSE) or air control (AC). DNA Damage Response (DDR) proteins were analyzed via immunoblot (Western). Micronuclei and nuclear aberrancies were quantified through cytokinesis-block micronucleus assay (CBMT) using immunofluorescence microscopy (DAPI). Results: Both CSE and XPC knockdown independently amplify expression of phospho-ATM (pATM), a DDR protein, in H1299 cells. Nuclear aberrancies increased significantly (p<0.05) with CSE in all three cell lines. Micronucleus frequency increased significantly with CSE in H1299 and Beas-2B cells (p<0.05) and with XPC knockdown in Beas-2B cells compared to shCtrl (p<0.001). Scientific Impact and Implications: We identified a previously uncharacterized role of XPC deficiency in augmenting cigarette smoke induced chromosomal breaks manifesting as micronuclei, particularly in non-cancerous Beas-2B cells. These findings offer insight into tumorigenesis in cigarette smoking and shed light on mechanisms of continued DNA damage in cancer cells. Future research should clarify the mechanisms of micronucleus formation in human translational specimens and pinpoint additional functions of XPC beyond NER, including in replication repair.

This case demonstrates that for large vessel occlusion strokes in the acute stage before surgical, pharmacologic, or radiologic intervention, supine positioning may be assumed because of the hemodynamic changes that can prevent and alleviate stroke, supporting the results of the ZerO Degree head positioning In Acute ischemiC stroke (ZODIAC) trial.

Background/Objectives: Acute leukemias in adolescents and young adults (AYAs) with Down Syndrome (DS) are understudied. Methods: This was a single-center, retrospective cohort study. Medical records for pediatric DS (n = 41) and AYA-DS (n = 7) treated with a pediatric chemotherapy regimen for acute leukemia were evaluated. Results: Two-year event-free survival (EFS) in AYA DS acute leukemia patients was lower than that in their pediatric DS counterparts (28.6% (Confidence Interval (CI) 4.1, 61.2) vs. 84.9% (CI 69.5, 92.9); p = 0.002). Conclusions: Additional research is needed to improve outcomes in AYA DS leukemia.