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.

Original Article Glypican 1 promotes proliferation and migration in esophagogastric adenocarcinoma via activating AKT/GSK/β-catenin pathway Akshay Pratap, Anqi Li, Lindsey Westbrook, Anna K. Gergen, Sanchayita Mitra, Argudit Chauhan, Linling Cheng, Michael J. Weyant, Martin McCarter, Sachin Wani, Robert Alexander Meguid, John D. Mitchell, Mitchell Cohen, David Fullerton, Xianzhong Meng

Introduction: Data is limited on hybrid transoral incisionless fundoplication (TIF) and hiatal hernia repair in giant paraoesophageal hernia (GPEH). We aimed to assess the safety, patient satisfaction, and symptom resolution following a hybrid paraoesophageal hernia (PEH) repair and TIF in patients with GPEH. Patients and Methods: All single-session hybrid TIF combined with minimally invasive PEH repair performed between February 2020 and June 2021 were evaluated. Procedures were performed in the operating room under general anesthesia with robotic or laparoscopic PEH repair followed by TIF. Results: Twelve patients underwent combined surgical hiatal hernia repair and TIF. Primary presenting symptoms included heartburn (75.0%), dysphagia (41.7%), and chronic anemia from Cameron’s ulcers (16.7%). The mean hernia defect size was 5.0 cm (range 3.0 to 6.0 cm). Hiatal hernia repairs were performed robotically in 7 patients and laparoscopically in 5 patients. The total mean operative time was 254 minutes (range: 180 to 390 min). One patient reported postoperative dysphagia requiring endoscopic dilation postdischarge with a resolution of symptoms. No gas-bloat symptoms were reported. All patients reported complete resolution of presenting symptoms at the time of follow-up. Postoperative mean follow-up for 4 patients at 6 months with upper endoscopy and pH testing showed an intact valve with no evidence of esophagitis or acid reflux. Conclusions: In our experience, hybrid hiatal hernia repair and TIF is a safe and effective therapeutic option for patients with GPEH. This hybrid procedure allows for more expeditious completion of the repair and results in lower rates of postfundoplication dysphagia and gas-bloat. Furthermore, this approach requires a less extensive surgical dissection on the greater curvature of the stomach, thereby minimizing the risk of vagal nerve injury and bleeding from the short gastric vessels.