Potassium Concentration on Admission Is an Independent Risk Factor for Target Lesion Revascularization in Acute Myocardial Infarction

Background. Acute myocardial infarction (AMI) is accompanied by excessive production of catecholamines, which is characterized by a hypokalemic dip. A polymorphism of the adrenergic receptor has also been reported to be associated with target lesion revascularization (TLR) after coronary intervention. Subjects and Methods. We enrolled 276 consecutive patients with AMI within 24 hours of symptom onset, who underwent emergency coronary intervention using bare metal stents and had examinations over a 5-10-month follow-up period. The patients were divided into tertiles based on their serum potassium level on admission (low K, <3.9; mid K, ≥3.9, <4.3; and high K, ≥4.3). Results. Sixty-four TLRs were observed in the study. Increased potassium concentration was associated significantly with TLR. Patients in the high K group were about two and a half times more likely to have a TLR after AMI compared to those in the low K group. Multiple logistic analysis showed that potassium level on admission was an independent risk factor for TLR (odds ratio 1.69; confidence interval 1.04 to 2.74; = 0.036). Conclusions. These findings indicated that increased potassium levels on admission might predict TLRs in AMI patients treated with bare metal stents

SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma

The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker, and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9+ cells were capable of self-renewal and differentiation into SOX9-cells, and displayed high proliferation capacity in vitro. Xenotransplantation experiments revealed that SOX9+ cells reproduced, differentiated into SOX9-cells, and generated tumors at a high frequency in vivo. Moreover, SOX9+ cells were found to be involved in epithelial-mesenchymal transition (EMT) and activation of TGFb/Smad signaling. Gain/loss of function experiments showed that SOX9 regulates Wnt/beta-catenin signaling, including cyclin D1 and OPN. Immunohistochemistry of 166 HCC surgical specimens and serum OPN measurements showed that compared to SOX9-patients, SOX9+ patients had significantly poorer recurrence-free survival, stronger venous invasion, and higher serum OPN levels. In conclusion, SOX9 is a novel HCCCSC marker regulating the Wnt/beta-catenin pathway and its downstream target, OPN. OPN is a useful surrogate marker of SOX9 in HCC

Potassium Concentration on Admission Is an Independent Risk Factor for Target Lesion Revascularization in Acute Myocardial Infarction

Background. Acute myocardial infarction (AMI) is accompanied by excessive production of catecholamines, which is characterized by a hypokalemic dip. A polymorphism of the adrenergic receptor has also been reported to be associated with target lesion revascularization (TLR) after coronary intervention. Subjects and Methods. We enrolled 276 consecutive patients with AMI within 24 hours of symptom onset, who underwent emergency coronary intervention using bare metal stents and had examinations over a 5–10-month follow-up period. The patients were divided into tertiles based on their serum potassium level on admission (low K, <3.9; mid K, ≥3.9, <4.3; and high K, ≥4.3). Results. Sixty-four TLRs were observed in the study. Increased potassium concentration was associated significantly with TLR. Patients in the high K group were about two and a half times more likely to have a TLR after AMI compared to those in the low K group. Multiple logistic analysis showed that potassium level on admission was an independent risk factor for TLR (odds ratio 1.69; confidence interval 1.04 to 2.74; P=0.036). Conclusions. These findings indicated that increased potassium levels on admission might predict TLRs in AMI patients treated with bare metal stents

2-year follow-up from JAVELIN Lung 200, an open-label, randomized, phase 3 study of avelumab vs docetaxel in patients with platinum-treated advanced non-small cell lung cancer (NSCLC)

MUSTAFA, OZGUROGLU/0000-0002-8417-8628WOS: 000496473200760[No abstract available]Merck KGaA, Darmstadt, Germany; Pfizer Inc., New York, NY, USAPfizerThis study was funded by Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer Inc., New York, NY, USA

Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial

Introduction: In the JAVELIN Lung 200 trial, avelumab (anti-programmed death-ligand 1 [PD-L1] antibody) did not significantly prolong overall survival (OS) versus docetaxel in patients with platinum-treated PD-L1+ NSCLC. We report greater than 2-year follow-up data. Methods: Patients with stage IIIB or IV or recurrent NSCLC with disease progression after platinum-doublet chemotherapy were randomized 1:1 to avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m(2) every 3 weeks. The primary end point was OS in patients with PD-L1+ tumors (greater than or equal to 1% tumor cell expression; IHC 73-10 pharmDx assay). Results: Of 792 patients, 529 had PD-L1+ tumors (264 versus 265 in the avelumab versus docetaxel arms, respectively). As of March 4, 2019, median duration of follow-up for OS in the PD L1+ population was 35.4 months in the avelumab arm and 34.7 months in the docetaxel arm; study treatment was ongoing in 25 (9.5%) versus 0 patients, respectively. In the PD-L1+ population, 2-year OS rates (95% confidence interval [CI]) with avelumab versus docetaxel were 29.9% (24.5%-35.5%) versus 20.5% (15.6%-25.8%); in greater than or equal to 50% PD L1+ subgroups, 2-year OS rates were 36.4% (29.1%-43.7%) versus 17.7% (11.8%-24.7%) and in the greater than or equal to 80% subgroup were 40.2% (31.3%-49.0%) versus 20.3% (12.9%-28.8%), respectively. Median duration of response (investigator assessed) was 19.1 months (95% CI: 10.8-34.8) versus 5.7 months (95% CI: 4.1-8.3). Safety profiles for both arms were consistent with the primary analysis. Conclusions: Although the JAVELIN Lung 200 primary analysis (reported previously) revealed that avelumab did not significantly prolong OS versus docetaxel in patients with platinum-treated PD-L1+ NSCLC, posthoc analyses at 2 years of follow-up revealed that 2-year OS rates were doubled with avelumab in subgroups with higher PD-L1 expression (greater than or equal to 50% and greater than or equal to 80%). (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc.EMD Serono Research & Development Institute, Inc., an affiliate of Merck KGaA, Darmstadt, Germany; Pfizer; Merck KGaALL This study was sponsored by EMD Serono Research & Development Institute, Inc., an affiliate of Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer. Employees of the sponsor are coauthors of this manuscript and contributed to the design, execution, and interpretation of the analyses being reported, writing the report, and the decision to submit the article for publication, along with the other coauthors. The authors thank the patients and their families; the investigators, coinvestigators, and study teams at each participating center and at Merck KGaA, Darmstadt, Germany, and EMD Serono Research & Development Institute, Inc., Billerica, MA, an affiliate of Merck KGaA, Darmstadt, Germany, and Quintiles (Durham, NC) . Medical writing support was provided by Abhijith Thippeswamy of ClinicalThinking and funded by Merck KGaA and Pfizer