Nidogen 1 regulates proliferation and migration/invasion in murine claudin-low mammary tumor cells

Nidogen 1 (NID1) is a glycoprotein found in basement membranes involved in cross-linking collagen IV and laminin. The role of NID in breast cancer has only been evaluated in a small number of studies and the findings of these studies have been inconsistent. Our previous work revealed that highly tumorigenic murine mammary tumor cells express high levels of Nid1 while weakly tumorigenic mammary tumor cells express low levels of Nid1. To investigate Nid1, two stable knockdown lines were created, and Nid1 knockdown was confirmed at both the mRNA and protein level. Nid1 knockdown significantly reduced cell proliferation and migration/invasion and these reductions in proliferation and migration/invasion could be rescued by conditioned media containing NID1 protein. The reduced migration/invasion observed in the Nid1 knockdown cells was not associated with significant alterations in the epithelial gene Cdh1 or the mesenchymal genes Snai1, Snai2, Twist1, Twist2, Zeb1 and Zeb2. Therefore, suppression of Nid1 expression reduces proliferation and migration/invasion in claudin-low murine mammary tumor cells.     

Patients Requiring Conversion to General Anesthesia during Endovascular Therapy Have Worse Outcomes: A Post Hoc Analysis of Data from the SAGA Collaboration

BACKGROUND AND PURPOSE:Endovascular therapy for acute ischemic stroke is often performed with the patient under conscious sedation. Emergent conversion from conscious sedation to general anesthesia is sometimes necessary. The aim of this study was to assess the functional outcome in converted patients compared with patients who remained in conscious sedation and to identify predictors associated with the risk of conversion.MATERIALS AND METHODS:Data from 368 patients, included in 3 trials randomizing between conscious sedation and general anesthesia before endovascular therapy (SIESTA, ANSTROKE, and GOLIATH) constituted the study cohort. Twenty-one (11%) of 185 patients randomized to conscious sedation were emergently converted to general anesthesia.RESULTS:Absence of hyperlipidemia seemed to be the strongest predictor of conversion to general anesthesia, albeit a weak predictor (area under curve = 0.62). Sex, hypertension, diabetes, smoking status, atrial fibrillation, blood pressure, size of the infarct, and level and side of the occlusion were not significantly associated with conversion to general anesthesia. Neither age (mean age, 71.3   ± 13.8 years for conscious sedation versus 71.6  ± 12.3 years for converters, P = .58) nor severity of stroke (mean NIHSS score, 17 ± 4 versus 18 ± 4, respectively, P = .27) were significantly different between converters and those who tolerated conscious sedation. The converters had significantly worse outcome with a common odds ratio of 2.67 (P = .015) for a shift toward a higher mRS score compared with the patients remaining in the conscious sedation group.CONCLUSIONS:Patients undergoing conversion had significantly worse outcome compared with patients remaining in conscious sedation. No factor was identified that predicted conversion from conscious sedation to general anesthesia.

Five studies published in 2015 proved the efficacy of endovascular therapy (EVT) for acute ischemic stroke caused by a large-vessel occlusion.¹ However, numerous questions remain regarding how to best deliver this treatment, including evaluation of the optimal thrombectomy technique,² the most effective method of patient triage,³ or whether EVT should be performed with the patient under either general anesthesia (GA) or conscious sedation (CS).Observational studies have suggested that EVT with the patient under CS is associated with better neurologic outcome and lower mortality compared with GA.⁴ However, 3 randomized trials reported similar outcomes between CS and GA.^5-7 Proposed benefits of CS include stable hemodynamics, clinical monitoring, and a potentially shorter procedure. The disadvantages are an unprotected airway and patient movement, which sometimes may require emergent conversion to GA. Patients who need conversion might be sicker (larger strokes, more medical complications), but the conversion procedure itself may also have a potentially deleterious influence on outcome due to the emergent anesthetic induction, associated hypotension, and added time delay before reperfusion.Although most patients can be treated under the less complex CS, it is of interest to identify factors that can predict the risk of conversion and hence the requirement for GA. We undertook a detailed analysis of the patients who were converted from CS to GA in our individual patient data base from the 3 randomized trials to examine the outcome of the converted patients compared with patients who remained in CS. We also aimed to identify possible predictors associated with a need for GA with EVT.     

A Tool to Assess Patient and Surrogate Knowledge About the POLST (Physician Orders for Life-Sustaining Treatment) Program

ContextIt is especially important that patients are well informed when making high-stakes, preference-sensitive decisions like those on the Physician Orders for Life-Sustaining Treatment (POLST) form. However, there is currently no way to easily evaluate whether patients understand key concepts when making these important decisions.ObjectivesTo develop a POLST knowledge survey.MethodsExpert (n = 62) ratings of key POLST facts were used to select items for a POLST knowledge survey. The survey was administered to nursing facility residents (n = 97) and surrogate decision-makers (n = 112). A subset (n = 135) were re-administered the survey after a standardized advance care planning discussion to assess the scale's responsiveness to change.ResultsThe 19-item survey demonstrated adequate reliability (α = 0.72.). Residents' scores (x = 11.4, standard deviation 3.3) were significantly lower than surrogate scores (x = 14.7, standard deviation 2.5) (P < 0.001). Scores for both groups increased significantly after administration of a standardized advance care planning discussion (P < 0.001). Although being a surrogate, age, race, education, cognitive functioning, and health literacy were significantly associated with higher POLST Knowledge Survey scores in univariate analyses, only being a surrogate (P < 0.001) and being white (P = 0.028) remained significantly associated with higher scores in multivariate analyses.ConclusionThe 19-item POLST Knowledge Survey demonstrated adequate reliability and responsiveness to change. Findings suggest the survey could be used to identify knowledge deficits and provide targeted education to ensure adequate understanding of key clinical decisions when completing POLST.