Predictive factors for postoperative delirium in thoracic surgery.

OBJECTIVE: We examined cases in which delirium developed after thoracic surgery under general anesthesia at our hospital to determine the predictive factors for postoperative delirium, as well as the perioperative findings in cases showing postoperative delirium. METHODS: This retrospective study included 1674 patients who underwent surgery under general anesthesia at our hospital between 2012 and 2022, A psychiatrist diagnosed postoperative delirium using the Confusion Assessment Method. RESULTS: There were 99 (5.9%) patients with postoperative delirium in our study, including 85 (86%) men, of whom 31 (31%) had a history of cerebrovascular disease. The incidence of postoperative delirium in patients aged > 80 years was 20% (36/182). The postoperative delirium group showed significantly longer hospital stays and more frequent postoperative complications than the group without postoperative delirium. In univariate analysis, age ≥ 80 years, male sex, history of cerebrovascular disease, hypertension, history of atrial fibrillation, and history of smoking were identified as significant factors, while multivariate analysis identified age ≥ 80 years, male sex, history of cerebrovascular disease, hypertension, and history of smoking as significant factors (odds ratios = 5.15, 2.04, 3.10, 1.67, and 2.36, respectively). In the 169 cases with none of these five factors, the postoperative delirium risk was 0% (0/169). CONCLUSIONS: In patients undergoing thoracic surgery, predictive factors for postoperative delirium include age ≥ 80 years, male sex, history of cerebrovascular disease, hypertension, and smoking history. The findings also indicate that patients with these risk factors may require psychiatric consultation before surgery.

Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1α and tumor progression of clear cell ovarian cancer.

Ovarian clear cell carcinoma (OCCC) is a gynecological cancer with a dismal prognosis; however, the mechanism underlying OCCC chemoresistance is not well understood. To explore the intracellular networks associated with the chemoresistance, we analyze surgical specimens by performing integrative analyses that combine single-cell analyses and spatial transcriptomics. We find that a chemoresistant OCCC subpopulation with elevated HIF activity localizes mainly in areas populated by cancer-associated fibroblasts (CAFs) with a myofibroblastic phenotype, which is corroborated by quantitative immunostaining. CAF-enhanced chemoresistance and HIF-1α induction are recapitulated in co-culture assays, which show that cancer-derived platelet-derived growth factor (PDGF) contributes to the chemoresistance and HIF-1α induction via PDGF receptor signaling in CAFs. Ripretinib is identified as an effective receptor tyrosine kinase inhibitor against CAF survival. In the co-culture system and xenograft tumors, ripretinib prevents CAF survival and suppresses OCCC proliferation in the presence of carboplatin, indicating that combination of conventional chemotherapy and CAF-targeted agents is effective against OCCC.