Preoperative heart rate and myocardial injury after non-cardiac surgery: results of a predefined secondary analysis of the VISION study

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Funding for this study comes from more than 50 grants for VISION and its sub-studies: Canadian Institutes of Health Research (six grants); Heart and Stroke Foundation of Ontario (two grants); Academic Health Science Centres Alternative Funding Plan Innovation Fund Grant; Population Health Research Institute Grant; Clarity Research Group Grant; McMaster University, Department of Surgery, Surgical Associates Research Grant; Hamilton Health Science New Investigator Fund Grant; Hamilton Health Sciences Grant; Ontario Ministry of Resource and Innovation Grant; Stryker Canada, McMaster University, Department of Anesthesiology (two grants); Saint Joseph′s Healthcare, Department of Medicine (two grants); Father Sean O′Sullivan Research Centre (two grants); McMaster University, Department of Medicine (two grants); Hamilton Health Sciences Summer Studentships (six grants); McMaster University, Department of Clinical Epidemiology and Biostatistics Grant; McMaster University, Division of Cardiology Grant, and Canadian Network and Centre for Trials International Grant; Winnipeg Health Sciences Foundation Operating Grant; Diagnostic Services of Manitoba Research Grant; University of Manitoba, Faculty of Dentistry Operational Fund; Projeto Hospitais de Excelencia a Serviço do SUS grant from the Brazilian Ministry of Health in Partnership with Hcor (Cardiac Hospital Sao Paulo-SP); School of Nursing, Universidad Industrial de Santander; Grupo de Cardiología Preventiva, Universidad Autónoma de Bucaramanga; Fundación Cardioinfantil Instituto de Cardiología; Alianza Diagnóstica SA; University of Malaya Research Grant; and University of Malaya, Penyelidikan Jangka Pendek Grant. Roche Diagnostics provided the troponin T assays and some financial support for the VISION Study. Medical Research Council and British Journal of Anaesthesia clinical research training fellowship (grant reference MR/M017974/1 to T.E.F.A.); National Institute for Health Research professorship (to R.P.); British Journal of Anaesthesia and Royal College of Anaesthetists basic science fellowship (to G.A.); National Research Foundation of South Africa (to R.N.R.); Heart and Stroke Foundation of Ontario Career Investigator Award (to P.J.D.); Yusuf Chair in Cardiology (P.J.D.).Funding for this study comes from more than 50 grants for VISION and its sub-studies: Canadian Institutes of Health Research (six grants); Heart and Stroke Foundation of Ontario (two grants); Academic Health Science Centres Alternative Funding Plan Innovation Fund Grant; Population Health Research Institute Grant; Clarity Research Group Grant; McMaster University, Department of Surgery, Surgical Associates Research Grant; Hamilton Health Science New Investigator Fund Grant; Hamilton Health Sciences Grant; Ontario Ministry of Resource and Innovation Grant; Stryker Canada, McMaster University, Department of Anesthesiology (two grants); Saint Joseph′s Healthcare, Department of Medicine (two grants); Father Sean O′Sullivan Research Centre (two grants); McMaster University, Department of Medicine (two grants); Hamilton Health Sciences Summer Studentships (six grants); McMaster University, Department of Clinical Epidemiology and Biostatistics Grant; McMaster University, Division of Cardiology Grant, and Canadian Network and Centre for Trials International Grant;Winnipeg Health Sciences Foundation Operating Grant; Diagnostic Services of Manitoba Research Grant; University of Manitoba, Faculty of Dentistry Operational Fund; Projeto Hospitais de Excelencia a Serviço do SUS grant from the Brazilian Ministry of Health in Partnership with Hcor (Cardiac Hospital Sao Paulo-SP); School of Nursing, Universidad Industrial de Santander; Grupo de Cardiología Preventiva, Universidad Autónoma de Bucaramanga; Fundación Cardioinfantil Instituto de Cardiología; Alianza Diagnóstica SA; University of Malaya Research Grant; and University of Malaya, Penyelidikan Jangka Pendek Grant. Roche Diagnostics provided the troponin T assays and some financial support for the VISION Study. Medical Research Council and British Journal of Anaesthesia clinical research training fellowship (grant reference MR/M017974/1 to T.E.F.A.); National Institute for Health Research professorship (to R.P.); British Journal of Anaesthesia and Royal College of Anaesthetists basic science fellowship (to G.A.); National Research Foundation of South Africa (to R.N.R.); Heart and Stroke Foundation of Ontario Career Investigator Award (to P.J.D.); Yusuf Chair in Cardiology (P.J.D.)

Association between preoperative pulse pressure and perioperative myocardial injury: an international observational cohort study of patients undergoing noncardiac surgery

Background. The management of elevated blood pressure before non-cardiac surgery remains controversial. Pulse pressure is a stronger predictor of cardiovascular morbidity in the general population than systolic blood pressure alone. We hypothesized that preoperative pulse pressure was associated with perioperative myocardial injury. Methods. This is a secondary analysis of the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) international cohort study. Participants were aged ≥45 yr and undergoing non-cardiac surgery at 12 hospitals in eight countries. The primary outcome was myocardial injury, defined using serum troponin concentration, within 30 days after surgery. The sample was stratified into quintiles by preoperative pulse pressure. Multivariable logistic regression analysis explored associations between pulse pressure and myocardial injury. We accounted for potential confounding by systolic blood pressure and other co-morbidities known to be associated with postoperative cardiovascular complications. Results. One thousand one hundred and ninety-one of 15 057 (7.9%) patients sustained myocardial injury, which was more frequent amongst patients in the highest two preoperative pulse pressure quintiles {63–75 mm Hg, risk ratio (RR) 1.14 [95% confidence interval (CI): 1.01–1.28], P=0.03; >75 mm Hg, RR 1.15 [95% CI: 1.03–1.29], P=0.02}. After adjustment for systolic blood pressure, preoperative pulse pressure remained the dominant predictor of myocardial injury (63–75 mm Hg, RR 1.20 [95% CI: 1.05–1.37], P75 mm Hg, RR 1.25 [95% CI: 1.06–1.48], P160 mm Hg was not associated with myocardial injury in the absence of pulse pressure >62 mm Hg (RR 0.67 [95% CI: 0.30–1.44], P=0.31). Conclusions. Preoperative pulse pressure >62 mm Hg was associated with myocardial injury, independent of systolic blood pressure. Elevated pulse pressure may be a useful clinical sign to guide strategies to reduce perioperative myocardial injur

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types

Gauging the Student Learning Experience of a Mobile Application Using iBeacon Technology

Innovative technology has been revolutionizing the educational experience in tertiary institutions over the past decades. Using novel iBeacon Technology, a mobile application called “iClassPolyU” was developed for collecting and disseminating information to and from students. The application was employed in four medium to large classrooms and the user experience was evaluated through a survey. Usage of the application was examined through quiz completion and usage rates. Results showed that each class had a quiz completion rate of over 80%. Moreover, students believed that their physical participation could be enhanced by the application and that it was effective, easy to use, and flexible. Students proposed the inclusion of mixed reality, virtual reality, and augmented reality in the future. This type of technology provides another pathway for student learning, an opportunity to give students more control over their learning, and educators with more information regarding their students

Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery

Medical Research Council and British Journal of Anaesthesia clinical research training fellowship (grant reference MR/M017974/1) to T.E.F.A.; UK National Institute for Health Research Professorship to R.P.; British Journal ofAnaesthesia/Royal College of Anaesthetists basic science Career Development award, British Oxygen Company research chair grant in anaesthesia from the Royal College of Anaesthetists, and British Heart Foundation Programme Grant (RG/14/4/30736) to G.L.A

Current treatment options for recurrent nasopharyngeal cancer

Loco-regional control rate of nasopharyngeal carcinoma (NPC) has improved significantly in the past decade. However, local recurrence still represents a major cause of mortality and morbidity in advanced stages, and management of local failure remains a challenging issue in NPC. The best salvage treatment for local recurrent NPC remains to be determined. The options include brachytherapy, external radiotherapy, stereotactic radiosurgery, and nasopharyngectomy, either alone or in different combinations. In this article we will discuss the different options for salvage of locally recurrent NPC. Retreatment of locally recurrent NPC using radiotherapy, alone or in combination with other treatment modalities, as well as surgery, can result in long-term local control and survival in a substantial proportion of patients. For small-volume recurrent tumors (T1–T2) treated with external radiotherapy, brachytherapy or stereotactic radiosurgery, comparable results to those obtained with surgery have been reported. In contrast, treatment results of advanced-stage locally recurrent NPC are generally more satisfactory with surgery (with or without postoperative radiotherapy) than with reirradiation

State-of-the-art management of nasopharyngeal carcinoma: current and future directions

Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer. Approximately 70% of patients with newly diagnosed NPC present with locally advanced disease. Phase III clinical trials support the addition of chemotherapy to radiotherapy for the initial treatment of these patients. Once metastatic disease develops, practices become varied. Further experience needs to be gained with both targeted therapies and immunotherapy to gauge whether they will improve treatment outcomes in NPC

Neogenin May Functionally Substitute for Dcc in Chicken

Dcc is the key receptor that mediates attractive responses of axonal growth cones to netrins, a family of axon guidance cues used throughout evolution. However, a Dcc homolog has not yet been identified in the chicken genome, raising the possibility that Dcc is not present in avians. Here we show that the closely related family member neogenin may functionally substitute for Dcc in the developing chicken spinal cord. The expression pattern of chicken neogenin in the developing spinal cord is a composite of the distribution patterns of both rodent Dcc and neogenin. Moreover, whereas the loss of mouse neogenin has no effect on the trajectory of commissural axons, removing chicken neogenin by RNA interference results in a phenotype similar to the functional inactivation of Dcc in mouse. Taken together, these data suggest that the chick neogenin is functionally equivalent to rodent Dcc

Effects of Deletion of Macrophage ABCA7 on Lipid Metabolism and the Development of Atherosclerosis in the Presence and Absence of ABCA1

ABCA7, a close relative of ABCA1 which facilitates cholesterol efflux to lipid-poor apoproteins, has been implicated in macrophage lipid efflux and clearance of apoptotic cells in in vitro studies. In the current study, we investigated the in vivo effects of macrophage ABCA7 deficiency on lipid metabolism and atherosclerosis. Chimeras with dysfunctional ABCA7 in macrophages and other blood cells were generated by transplantation of bone marrow from ABCA7 knockout (KO) mice into irradiated low-density lipoprotein receptor (LDLr) KO mice. Unexpectedly, macrophage ABCA7 deficiency did not significantly affect atherosclerosis susceptibility of LDLr KO mice after 10 weeks Western-type diet feeding. However, ABCA7 deficiency was associated with 2-fold (p<0.05) higher macrophage ABCA1 mRNA expression levels. Combined disruption of ABCA1 and ABCA7 in bone-marrow-derived cells increased atherosclerotic lesion development (1.5-fold (p>0.05) as compared to wild type transplanted mice. However, single deletion of ABCA1 had a similar effect (1.8-fold, p<0.05). Macrophage foam cell accumulation in the peritoneal cavity was reduced in ABCA1/ABCA7 dKO transplanted animals as compared to single ABCA1 KO transplanted mice, which was associated with increased ABCG1 expression. Interestingly, spleens of ABCA1/ABCA7 double KO transplanted mice were significantly larger as compared to the other 3 groups and showed massive macrophage lipid accumulation, a reduction in CD3+ T-cells, and increased expression of key regulators of erythropoiesis. In conclusion, deletion of ABCA7 in bone marrow-derived cells does not affect atherogenesis in the arterial wall neither in the absence or presence of ABCA1. Interestingly, combined deletion of bone marrow ABCA1 and ABCA7 causes severe splenomegaly associated with cellular lipid accumulation, a reduction in splenic CD3+ T cells, and induced markers of erythropoeisis. Our data indicate that ABCA7 may play a role in T cell proliferation and erythropoeisis in spleen

Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid A beta 42 Levels in Cognitively Normal Elderly

Study Objectives: Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (Aβ). We thus aimed to examine relationships between concentrations of Aβ42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. Methods: Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF Aβ42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into “high” and “low” Aβ42 groups to compare SWS bout length using survival analyses. Results: A significant inverse correlation was found between CSF Aβ42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF Aβ42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF Aβ42. Conclusions: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF Aβ42, suggesting that disturbed sleep might drive an increase in soluble brain Aβ levels prior to amyloid deposition