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/Objectives. Lymph Node Ratio (LNR) is increasingly recognized as an important prognostic factor in various cancer types, with the potential to enhance patient stratification for intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma. The study aimed to assess the impact of LNR on survival in surgically resected patients with ICC and ECC. Methods. This was a retrospective analysis of National Cancer Database (2004–2020) included ICC and ECC (excluding distal bile duct) patients who underwent primary site resection with adequate lymphadenectomy (≥4 LNs excised). Exclusions comprised age < 18 years, distant metastasis, or incomplete key data. LNR was calculated as the ratio of positive LNs to total examined LNs. Survival probabilities were estimated using Kaplan–Meier analysis and Cox regression. Results. The inclusion criteria were met by 954 patients with ICC and 1607 patients with ECC. In patients with ICC, the median OS time was 62.7 months in LNR0 group, 40.8 months in LNR < 30%, and 25.2 months in LNR ≥ 30% (p < 0.001). In ICC, 3-year OS was 69.3%, 54.6%, and 34% for LNR 0, LNR < 30%, and LNR ≥ 30%, respectively (p < 0.05). When adjusted for age, sex, Charlson–Deyo score, histology, surgical margins, chemo- and radiotherapy using Cox regression, LNR < 30% and LNR ≥ 30% were associated with worse OS in patients with ICC (HR 2.1 (95% CI 1.6–2.7) and HR 2.94 (95% CI 2.3–3.8)) and ECC (HR 2.1 (95% CI 1.8–2.5) and HR 3 (95% CI 2.4–3.7)). Conclusions. It is well-known that LN-negative patients have significantly better survival than LN-positive patients with ICC and ECC. This study strongly demonstrates that survival prognosis can be further stratified based on LNR for ICC and ECC patients and that it is not simply a binary factor.