Hemorrhagic shock remains a leading cause of preventable death worldwide, with mortality patterns varying significantly based on injury mechanisms and severity. This comprehensive review examines the complex pathophysiology of hemorrhagic shock, focusing on the temporal evolution of inflammatory responses, biomarker utility, and evidence-based therapeutic interventions. The inflammatory cascade progresses through distinct phases, beginning with tissue injury and endothelial activation, followed by a systemic inflammatory response that can transition to devastating immunosuppression. Recent advances have revealed pattern-specific responses between penetrating and blunt trauma, necessitating tailored therapeutic approaches. While damage control resuscitation principles and balanced blood product administration have improved outcomes, many molecular targeted therapies remain investigational. Current evidence supports early hemorrhage control, appropriate blood product ratios, and time-sensitive interventions like tranexamic acid administration. However, challenges persist in biomarker validation, therapeutic timing, and implementation of personalized treatment strategies. Future directions include developing precision medicine approaches, real-time monitoring systems, and novel therapeutic modalities while addressing practical implementation barriers across different healthcare settings. Success in hemorrhagic shock management increasingly depends on integrating multiple interventions across different time points while maintaining focus on patient-centered outcomes.

BACKGROUND: Burn injury still has a high attributable mortality. The elevated mortality rate of severe burns is still concerning. Hepatic inflammation and injury are common after burns and are associated with poor outcomes. Necroptosis is a programmed cell death linked with inflammation. Thus, assessing necroptotic pathways in the liver can lead to new therapeutic modalities to improve mortality after severe burns.METHODS: Mice underwent 15% total body surface area burn or sham injury. Three hours after burn, the mice were euthanized to collect blood and livers. Histology, injury markers, genes expression, and tissue protein levels were compared between groups.RESULTS: Compared with sham, burned mice had heightened liver inflammatory cell infiltration and edema. Serum aspartate aminotransferase and alanine aminotransferase were increased by 4.9- and 3.4-fold, respectively, in burned mice relative to sham (p< 0.05). Expression of tumor necrosis factor α, interleukin-6, interleukin-1β, and CXCL1 (KC) genes were elevated in livers of burned mice by 10-, 86-, 10-, and 828-fold, respectively, compared with sham (p< 0.05). Expression of necroptotic genes, namely, receptor-interacting protein kinases 1 and 3, and mixed lineage kinase domain-like in livers of burned mice were increased by 10-, 13-, and 4.5-fold, respectively, relative to sham (p< 0.05). Receptor-interacting protein kinase 1 and phosphorylated mixed lineage kinase domain-like protein levels measured by Western-blot in livers after burn injury were elevated by 22- and 17-fold, respectively, compared with sham (p< 0.05).CONCLUSION: Liver damage occurs early after burns in mice and is associated with elevation of proinflammatory cytokines, chemokine, and proteins involved in the necroptotic pathway. This study suggests that necroptosis plays a role in the pathogenesis of liver failure secondary to burn injury.

Burn induces a systemic response affecting multiple organs, including the liver. Since the liver plays a critical role in metabolic, inflammatory, and immune events, a patient with impaired liver often exhibits poor outcomes. The mortality rate after burns in the elderly population is higher than in any other age group, and studies show that the liver of aged animals is more susceptible to injury after burns. Understanding the aged-specific liver response to burns is fundamental to improving health care. Furthermore, no liver-specific therapy exists to treat burn-induced liver damage highlighting a critical gap in burn injury therapeutics. In this study, we analyzed transcriptomics and metabolomics data from the liver of young and aged mice to identify mechanistic pathways and in-silico predict therapeutic targets to prevent or reverse burn-induced liver damage. Our study highlights pathway interactions and master regulators that underlie the differential liver response to burn injury in young and aged animals.

Postoperative delirium is a frequent and serious neurocognitive complication in older surgical patients, characterized by acute impairments in attention, awareness, and cognition. It is associated with increased morbidity, prolonged hospitalization, and persistent cognitive decline. In this narrative review, we synthesize translational research on biological mechanisms underlying delirium and emerging targeted interventions. We conducted a comprehensive search of major biomedical databases, with no date restrictions but prioritizing publications from 2018 to 2025. The multifactorial pathophysiology involves dysregulated cholinergic and dopaminergic signaling, systemic and neuroinflammation, oxidative stress, and metabolic disturbances. Pre-existing cognitive impairment and frailty emerge as key clinical risk factors linked to these mechanisms. Aged rodent models replicate delirium-like cognitive deficits and validate mechanistic pathways, while human neuroimaging studies demonstrate disrupted functional connectivity in attentional and consciousness networks. Genomic and proteomic analyses have identified candidate biomarkers for early detection and risk stratification, and genetic variants associated with inflammation and neurodegeneration contribute to individual vulnerability. Emerging therapies targeting inflammation, microglial activation, mitochondrial function, and neurotransmitter balance show promise in preclinical studies, although clinical trials report mixed results. We advocate integrating basic science with clinical care through thorough preoperative assessment, multicomponent non-pharmacological strategies, and mechanism-based preventive measures to reduce the burden of postoperative delirium.

Background Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, published tracheostomy guidelines have generally recommended deferral of the procedure beyond the initial weeks of intubation given high mortality as well as concerns about transmission of the infection to providers. It is unclear whether tracheostomy in patients with COVID-19 infection facilitates ventilator weaning, and long-term outcomes are not yet reported in the literature. Methods This is a retrospective study of tracheostomy outcomes in patients with COVID-19 infection at a single-center academic tertiary referral intensive care unit. Patients underwent percutaneous tracheostomy at the bedside; the procedure was performed with limited staffing to reduce risk of disease transmission. Results Between March 1 and June 30, 2020, a total of 206 patients with COVID-19 infection required mechanical ventilation and 26 underwent tracheostomy at a mean of 25±5 days after initial intubation. Overall, 81% of tracheostomy patients were liberated from the ventilator at a mean of 9±6 days postprocedure, and 54% were decannulated prior to hospital discharge at a mean of 21±10 days postprocedure. Sedation and pain medication requirements decreased significantly in the week after the procedure. In-hospital mortality was 15%. Among tracheostomy survivors, 68% were discharged to a facility. Discussion The management of patients with COVID-19 related respiratory failure can be challenging due to prolonged ventilator dependency. In our initial experience, outcomes post-tracheostomy in this population are encouraging, with short time to liberation from the ventilator, a high rate of decannulation prior to hospital discharge, and similar mortality to tracheostomy performed for other indications. Barriers to weaning ventilation in this cohort may be high sedation needs and ventilator dyssynchrony. Level of evidence Level V—Therapeutic/care management.