Background Postoperative delirium, a common complication in the elderly, can occur following any type of surgery and is associated with increased morbidity and mortality; it may also be associated with subsequent cognitive problems. Effective therapy for postoperative delirium remains elusive because the causative factors of delirium are likely multiple and varied. Methods Patients ≥ 65 years old undergoing elective knee arthroplasty were prospectively evaluated for postoperative Diagnostic and Statistical Manual of Mental Disorders-IV delirium. Exclusion criteria included dementia, mini-mental state exam score<24, delirium, clinically significant CNS/neurological disorder, current alcoholism, or any serious psychiatric disorder. Delirium was assessed on postoperative days 2 and 3 using standardized scales. Patients’ pre-existing medical conditions were obtained from medical charts. The occurrence of obstructive sleep apnea (OSA) was confirmed by contacting patients to check their polysomnography records. Data were analyzed using Pearson Chi-Square or Wilcoxon Rank Sum tests and multiple logistic regressions adjusted for effects of covariates. Results Of 106 enrolled patients, 27 (25%) developed postoperative delirium. Of the 15 patients with obstructive sleep apnea, 8 (53%) experienced postoperative delirium, compared to 19 (20%) of the patients without obstructive sleep apnea (p=0.0123, OR: 4.3). Obstructive sleep apnea was the only statistically significant predictor of postoperative delirium in multivariate analyses. Conclusions This is the first prospective study employing validated measures of delirium to identify an association between pre-existing obstructive sleep apnea and postoperative delirium.

Previous studies have shown that neurokinin 1 receptor (NK1R) occurs naturally in human glioblastomas and its stimulation causes cell proliferation. In the present study we show that stimulation of NK1R in human U373 glioblastoma cells by substance P increases Akt phosphorylation by 2.5‐fold, with an EC50 of 57 nM. Blockade of NK1R lowers basal phosphorylation of Akt, indicating the presence of a constitutively active form of NK1R; similar results are seen in U251 MG and DBTRG‐05 glioblastoma cells. Linkage of NK1R to Akt implicates NK1R in apoptosis of glioblastoma cells. Indeed, treatment of serum‐starved U373 cells with substance P reduces apoptosis by 53 ± 1% (p < 0.05), and treatment with NK1R antagonist L‐733,060 increases apoptosis by 64 ± 16% (p < 0.01). Further, the blockade of NK1R in human glioblastoma cells with L‐733,060 causes cleavage of Caspase‐3 and proteolysis of poly (ADP‐ribose) polymerase. Experiments designed to elucidate the mechanism of NK1R‐mediated Akt phosphorylation revealed total involvement of non‐receptor tyrosine kinase Src and phosphatidyl‐3‐kinase, a partial involvement of epidermal growth factor receptor, and no involvement of mitogen‐activated protein/extracellular signal‐related kinase. Taken together, the results of the present study indicate a key role for NK1R in glioblastoma apoptosis.

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