Role of calcium in hormone-independent and -resistant breast cancer.

Approximately one-third of estrogen receptor (ER) positive breast tumors fail to respond to or become resistant to hormonal therapy. Although the mechanisms responsible for hormone resistance are not completely understood, resistance is associated with alterations in ERα; overexpression of proteins that interact with the receptor; and hormone-independent activation of the receptor by growth factor signal transduction pathways. Our previous studies show that in estrogen dependent breast cancer cells, activation of the epidermal growth factor signaling pathway increases intracellular calcium which binds to and activates ERα through sites in the ligand-binding domain of the receptor and that treatment with extracellular calcium increases the concentration of intracellular calcium which activates ERα and induces hormone-independent cell growth. The present study asked whether overexpression of calcium channels contributes to the hormone-independent and -resistant phenotype of breast cancer cells and whether clinically used calcium channel blockers reverse hormone independence and resistance. The results show that hormone-independent and -resistant cells overexpress calcium channels, have high concentrations of intracellular calcium, overexpress estrogen responsive genes and, as expected, grow in the absence of estradiol and that treatment with calcium channel blockers decreased the concentration of intracellular calcium, the expression of estrogen responsive genes and cell growth. More importantly, in hormone-resistant cells, treatment that combined a calcium channel blocker with an antiestrogen reversed resistance to the antiestrogen.

Two- or 3-Dimensional Echocardiography-Derived Cardiac Output Cannot Replace the Pulmonary Artery Catheter in Cardiac Surgery.

OBJECTIVES: Three-dimensional (3D) transesophageal echocardiography (TEE) has been shown to be more accurate than 2D TEE for the evaluation of the left ventricular outflow tract area. The aim of the present study was to compare the agreement of 3D echocardiography-derived cardiac output (CO) with thermodilution-derived CO (TDCO) before and after cardiopulmonary bypass (CPB). DESIGN: This was a prospective observational study of patients who underwent cardiac surgery between 2016 and 2018. SETTING: Weill Cornell Medicine, a single large academic medical center. PARTICIPANTS: The study comprised 78 patients undergoing elective cardiac surgery. INTERVENTIONS: CPB, TEE, pulmonary artery catheter, and elective cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Two-dimensional CO, 3D CO-diameter, and 3D CO-area values pre-CPB were strongly correlated with one another both pre-CPB and post-CPB. The 3D CO-diameter and the 3D CO-area were mildly correlated, with TDCO measurements pre-CPB (r = 0.46 and 0.39, respectively) and post-CBP (r = 0.43 and 0.47, respectively). Pre-CPB 3D CO-diameter had the most agreement with TDCO in terms of bias (-0.13 L/min); however, the limits of agreement (LOA) were wide (-2.2- to- 2.45 L/min). Post-CPB, 3D CO-diameter had the most agreement with TDCO in terms of bias (0.41) but with wide LOA (-3.29 to 2.47). All pre-CPB echocardiography-derived CO (2D CO, 3D CO-diameter, 3D CO-area) had more agreement with TDCO than did post-CPB measurements. CONCLUSIONS: Three-dimensional CO measurements were only modestly correlated with pulmonary artery catheter-derived CO pre-bypass and post-bypass. Despite low bias, the wide LOA from 2D CO, 3D CO-diameter, and 3D-area compared with TDCO suggested that the 2 methods are not interchangeable.

Patient Demographics and Extracorporeal Membranous Oxygenation (ECMO)-Related Complications Associated With Survival to Discharge or 30-Day Survival in Adult Patients Receiving Venoarterial (VA) and Venovenous (VV) ECMO in a Quaternary Care Urban Center.

OBJECTIVE: Investigate how a multitude of patient demographics and extracorporeal membranous oxygenation (ECMO)-related complications affect 30-day survival or survival to discharge. DESIGN: Retrospective observational study. SETTING: Urban university hospital, quaternary care center. PARTICIPANTS: Patients who underwent ECMO circulatory support from January 2012 to May 2016. INTERVENTIONS: Date-based data extraction, univariate and multivariate regression analysis. MEASUREMENTS AND MAIN RESULTS: The hospital database contained complete data for 235 adult patients who received venoarterial ECMO (74.04 %) and venovenous ECMO (25.96 %); 106 patients (45.11%) survived. The independent predictors significant in the odds of in-hospital mortality in a multiregression model were age (odds ratio [OR] = 1.028, p = 0.008), extracorporeal cardiopulmonary resuscitation (ECPR) after unsuccessful high-quality CPR (OR = 7.93, p =0.002), cardiogenic shock as the primary indication for circulatory support (OR = 2.58, p = 0.02), acute kidney injury (AKI) before ECMO initiation (OR = 7.53, p < 0.001), time spent on ECMO in days (OR = 1.08, p = 0.03), and limb ischemia (OR = 3.18, p = 0.047). CONCLUSION: The most significant findings of advancing age, time spent on ECMO, AKI, ECMO use in the setting of cardiogenic shock, ECPR, and limb ischemia as a complication of ECMO all independently increase the odds of in-hospital and 30-day mortality. To the best of the authors' knowledge, this study is the first to demonstrate a significant relationship between limb ischemia and mortality.

Anticoagulation and Neuraxial/Peripheral Anesthesia.

Novel anticoagulants (NAGs) have emerged as the preferred alternatives to vitamin K antagonists. In patients being considered for regional anesthesia, these drugs present a layer of complexity in the preprocedure evaluation. There are no established tests to monitor anticoagulant activity and our experience is short with these drugs. These authors believe it is important to review the relevant hematology, orthopedics, and anesthesiology literature to provide a valuable reference for the clinician who is met with these challenges. In addition to discussing NAGs, we also review the existing American Society of Regional Anesthesia guidelines for heparin, low-molecular-weight heparin, and antiplatelet agents.