Programmed Death Receptor Ligand One Expression May Independently Predict Survival in Patients With Non-Small Cell Lung Carcinoma Brain Metastases Receiving Immunotherapy.

PURPOSE: Programmed death receptor ligand 1 (PD-L1) expression is known to predict response to PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC). However, the predictive role of this biomarker in brain metastases (BMs) is unknown. The aim of this study was to assess whether PD-L1 expression predicts survival in patients with NSCLC BMs treated with PD-1/PD-L1 inhibitors, after adjusting for established prognostic models. METHODS AND MATERIALS: In this multi-institutional retrospective cohort study, we identified patients with NSCLC-BM treated with PD-1/PD-L1 inhibitors after local BM treatment (radiation therapy or neurosurgery) but before intracranial progression. Cox proportional hazards models were used to assess the predictive value of PD-L1 expression for overall survival (OS) and intracranial progression-free survival (IC-PFS). RESULTS: Forty-eight patients with BM with available PD-L1 expression were identified. PD-L1 expression was positive in 33 patients (69%). Median survival was 26 months. In univariable analysis, PD-L1 predicted favorable OS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.19-1.02; P = .055). This effect persisted after correcting for lung-graded prognostic assessment and other identified potential confounders (HR, 0.24; 95% CI, 0.10-0.61; P = .002). Moreover, when modeled as a continuous variable, there appeared to be a proportional relationship between percentage of PD-L1 expression and survival (HR, 0.86 per 10% expression; 95% CI, 0.77-0.98; P = .02). In contrast, PD-L1 expression did not predict IC-PFS in uni- or multivariable analysis (adjusted HR, 0.54; 95% CI, 0.26-1.14; P = .11). CONCLUSIONS: In patients with NSCLC-BMs treated with PD-1/PD-L1 checkpoint inhibitors and local treatment, PD-L1 expression may predict OS independent of lung-graded prognostic assessment. IC-PFS did not show association with PD-L1 expression, although the present analysis may lack power to assess this. Larger studies are required to validate these findings.

Impact of operative length on post-operative complications in meningioma surgery: a NSQIP analysis.

Many studies have implicated operative length as a predictor of post-operative complications, including venous thromboembolism [deep vein thrombosis (DVT) and pulmonary embolism (PE)]. We analyzed the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database from 2006 to 2014, to evaluate whether length of operation had a statistically significant effect on post-operative complications in patients undergoing surgical resection of meningioma. Patients were included for this study if they had a post-operative diagnosis of meningioma. Patient demographics, pre-operative comorbidities, and post-operative 30-day complications were analyzed. Of 3743 patients undergoing craniotomy for meningioma, 13.6 % experienced any complication. The most common complications and their median time to occurrence were urinary tract infection (2.6 %) at 10 days postoperatively (IQR 7-15), unplanned intubation (2.5 %) at 3 days (IQR 1-7), failure to wean from ventilator (2.4 %) at 2.0 days (IQR 2-4), and DVT (2.4 %) at 6 days (IQR 11-19). Postoperatively, 3.6 % developed VTE; 2.4 % developed DVT and 1.7 % developed PE. Multivariable analysis identified older age (third and upper quartile), obesity, preoperative ventilator dependence, preoperative steroid use, anemia, and longer operative time as significant risk factors for VTE. Separate multivariable logistic regression models demonstrated longer operative time as a significant risk factor for VTE, all complications, major complications, and minor complications. Meningioma resection is associated with various post-operative complications that increase patient morbidity and mortality risk. this large, multi-institutional patient sample, longer operative length was associated with increased risk for postoperative venous thromboembolisms, as well as major and minor complications.

Angiotensin II increases the expression of the transcription factor ETS-1 in mesangial cells.

Maladaptive activation of the renin-angiotensin system (RAS) has been shown to play a critical role in the pathogenesis of chronic kidney disease. Reactive oxygen species (ROS) are critical signals for many of the nonhemodynamic effects of angiotensin II (ANG II). We have demonstrated that ANG II increases mesangial and cortical cyclooxygenase-2 (COX-2) expression and activity via NADPH oxidase-derived ROS. The transcription factor ETS-1 (E26 transformation-specific sequence) has been identified as a critical regulator of growth-related responses and inflammation. The present studies were designed to determine: 1) whether ANG II induces ETS-1 expression in vitro in cultured rat mesangial cells and in vivo in rats infused with ANG II; and 2) whether ROS and COX-2 are mediators of ETS-1 induction in response to ANG II. Mesangial cells stimulated with ANG II (10(-7) M) exhibited a significant increase in ETS-1 expression that was prevented by the angiotensin type 1 receptor blocker candesartan. NADPH oxidase inhibition with dyphenilene iodinium or apocynin also prevented ETS-1 induction, establishing the role of ROS as mediators of ETS-1 expression in response to ANG II. COX-2 inhibition prevented ETS-1 expression in response to ANG II, suggesting that COX-2 is required for ETS-1 induction. By utilizing short interfering RNAs against ETS-1, we have also determined that ETS-1 is required to induce the production of fibronectin in response to ANG II. Furthermore, rats infused with ANG II manifested increased glomerular expression of ETS-1. These studies unveil novel pathways that may play an important role in the pathogenesis of renal injury when RAS is activated.