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.

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.

Tranexamic acid (TXA), a fibrinolytic agent, effectively inhibits plasminogen activation, thereby reducing fibrinolysis and hemorrhage. This study focused on its application in trauma patients undergoing emergency surgery, a critical area due to trauma's significant role in mortality. Our investigation involved a meticulous screening of randomized controlled trials from databases including Scopus, PubMed, Web of Science, and Cochrane. The findings indicate that TXA intervention is promising in enhancing outcomes for trauma patients. However, the drug's effectiveness may vary based on the specific nature of the medical condition. In summary, robust evidence suggests that TXA can diminish blood loss, lower transfusion rates, reduce complications, and improve hemoglobin and hematocrit levels in surgical patients. Consequently, TXA should be considered a crucial medication, readily available to mitigate morbidity and mortality in surgical settings. Future research should explore factors influencing TXA's effectiveness in traumatic brain injury cases and across a broad spectrum of surgical scenarios in diverse patient populations. This would further guide clinicians in refining and optimizing the use of TXA.

Introduction: Burn injuries in elderly patients result in higher morbidity and mortality compared to younger individuals. This study investigates age-related differences in inflammatory hepatic responses to burn injuries. Method: Young (8–10 weeks) and aged (20-21 months) female C57BL/6 mice were subjected to a 15% total body surface area burn or sham injury. Serum and liver samples collected at 3, 6-, 9-, 12-, and 24-hours post-injury were analyzed for serum amyloid A (SAA) levels, SAA1 and SAA2 hepatic gene expression, serum cytokines (IL-6, IL-1β, TNF-α, and IL-10), and hepatic STAT3 activation. Results: Aged mice showed a delayed and dysregulated response. In young mice, SAA levels rose significantly at 6 hours postburn (5.09 ± 0.2-fold), while in aged mice, SAA increased at 12 hours (39.1 ± 2.06-fold), p < 0.01. Hepatic expression of SAA1 and SAA2 also peaked early in young mice (8.357 ± 1.257-fold and 5.91 ± 0.664-fold at 3 hours) but was delayed until 12 hours in aged mice. Young mice demonstrated early IL-6 peaks at 3 hours (990 ± 83.2 pg/ml), while aged mice reached a delayed, higher IL-6 peak at 24 hours (3804 ± 1408 pg/ml, p < 0.05). Similar age-related delays occurred for IL-1β and TNF-α. Aged mice had significantly elevated IL-10 at 6 hours (993.9 ± 99.41 pg/ml vs. 67.69 ± 6.635 pg/ml in young, p < 0.001). STAT3 activation peaked at 3 hours in young mice (2.686 ± 0.226-fold) but was delayed until 24 hours in aged mice (0.5958 ± 0.0368-fold, p < 0.05). Conclusions: This study identifies age-related variations in inflammatory markers and acute hepatic responses to burn injuries, with aged mice showing delayed and reduced inflammatory responses compared to younger counterparts. These findings underscore the importance of age-specific strategies in burn injury management to enhance outcomes for elderly burn patients.

BACKGROUND Burn injuries trigger a systemic hyperinflammatory response, leading to multiple organ dysfunction, including significant hepatic damage. The liver plays a crucial role in regulating immune responses and metabolism after burn injuries, making it critical to develop strategies to mitigate hepatic impairment. This study investigates the role of methylation-controlled J protein (MCJ), an inner mitochondrial protein that represses complex I in burn-induced oxidative stress and mitochondrial dysfunction, using an in vitro Alpha Mouse Liver 12 cell model. METHODS Alpha Mouse Liver 12 cells were treated with serum from burn-injured mice (SBIM) to simulate burn injury in vitro. Methylation-controlled J protein was silenced using shRNA. Cell viability, apoptosis markers, reactive oxygen species levels, antioxidant response elements, electron transport chain components, and mitochondrial respiration were assessed using various techniques, including Cell Counting Kit-8 assay, Western blotting, MitoSOX Red staining, and Seahorse XF analysis. RESULTS Serum from burn-injured mice treatment (10%) for 8 hours reduced Alpha Mouse Liver 12 cell viability to 50% of control levels and increased MCJ expression fivefold. It also significantly upregulated apoptosis markers: cleaved caspase-3 (4-fold), Bax (3.8-fold), and cytosolic cytochrome c (3.5-fold). Methylation-controlled J protein silencing improved cell viability to 85% of control levels and reduced apoptosis markers by 75% to 78%. Serum from burn-injured mice increased reactive oxygen species levels by 3-fold, while MCJ silencing reduced this by 2.5-fold. Antioxidant proteins (NRF2, HO-1, NQO-1, GCLC, catalase) were suppressed by SBIM but upregulated 3.2- to 3.8-fold with MCJ silencing. Serum from burn-injured mice reduced electron transport chain components (NDUFS1, SDHB, MTCO2) by 45% to 65%, which MCJ silencing restored 2.5- to 3-fold. Mitochondrial respiration improved significantly with MCJ silencing: basal respiration (+26%), maximal respiration (+66%), adenosine triphosphate production (+25%), and spare respiratory capacity (+63%). CONCLUSION Methylation-controlled J protein plays a critical role in burn-induced hepatocyte damage. Its silencing alleviates SBIM-induced cytotoxicity, oxidative stress, and mitochondrial dysfunction. These findings highlight MCJ as a potential therapeutic target for preserving liver function in burn patients, warranting further in vivo studies to explore its clinical potential. Export

Background Burn injuries can lead to substantial liver damage, and this response appears to worsen with age. Although clinical patterns suggest that older individuals are more susceptible to poor outcomes, the biological mechanisms contributing to this increased vulnerability are poorly understood. Sirtuins, a family of nicotinamide adenine dinucleotide (NAD+)-dependent enzymes involved in cellular stress regulation, metabolism, and aging, may play a key role in modulating the hepatic response to burn injury. This study explores the potential mechanistic involvement of sirtuins in age-related liver damage following thermal injury. Methods Female C57BL/6 mice (young: four months; aged: 20-22 months) underwent sham or 15% total body surface area scald burn. Liver tissue was collected at 24- and 48-hours post-injury for quantitative polymerase chain reaction (qPCR) analysis of all seven sirtuin family members. Results Burn injury significantly altered hepatic sirtuin expression in an age- and time-dependent manner. Inflammatory regulators, Sirt1 and Sirt2, showed immediate downregulation in young mice with partial recovery at 48 hours, while aged mice exhibited delayed, more profound, and persistent suppression. In contrast, mitochondrial sirtuins (Sirt3-5) were downregulated in both age groups, and only young burned mice showed recovery of Sirt3 and Sirt4 expression at 48 hours. The most pronounced age-dependent difference occurred with Sirt4. At this time point, the expression of Sirt4 was 71% higher in young burned mice compared to aged injured counterparts (p < 0.05). Genome stability regulating Sirt6 and Sirt7 exhibited age-specific responses, with Sirt6 remaining stable in young injured mice, while Sirt7 was lower in aged mice at 48 hours (p < 0.05). Conclusion This study reveals for the first time that burn injury triggers age-dependent alterations in the pattern of hepatic sirtuin expression, with delayed and/or more severe and persistent suppression across all sirtuin family members. These findings provide new mechanistic insights into the dysregulation of critical cellular homeostatic mechanisms in aged livers following burn injury and identify sirtuins as potential therapeutic targets for mitigating age-associated hepatic damage in elderly burn patients.