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La revista El Gráfico en sus inicios: una pedagogía deportiva para la ciudad moderna

Integration of III–V semiconductors on Si substrates allows for the realization of high-performance, low power III–V electronics on the Si-platform. In this work, we demonstrate the implementation of single balanced down-conversion mixer circuits, fabricated using vertically aligned InAs nanowire devices on Si. A thin, highly doped InAs buffer layer has been introduced to reduce the access resistance and serve as a bottom electrode. Low-frequency voltage conversion gain is measured up to 7 dB for a supply voltage of 1.5V. Operation of these mixers extends into the GHz regime with a cut-off frequency of 2 GHz, limited by the optical lithography system used. The circuit dc power consumption is measured at 3.9 mW. [ABSTRACT FROM AUTHOR]

The article outlines the history of artists’ exploration of Svalbard as a motif, and then proceeds to describe a number of more recent art practices by the artists relating to Svalbard in the new millennium. The article traces the artists’ development from being supporters of research by providing visual material, to becoming researchers in their own right.

Objective: There is strong evidence that medication adherence and lifestyle changes are essential in patients undergoing secondary cardiovascular disease prevention. Cardiac rehabilitation (CR) increases medication adherence and improves lifestyle changes. Patients with cardiac diseases and a low educational level and patients with little social support are less responsive to improve medication adherence and to adapt lifestyle changes. The aim of the present study was to investigate the long-term effects of a socially differentiated CR intervention on medication adherence as well as changes in biological and lifestyle risk factors at two- five- and ten-year follow-up. Design: A prospective cohort study. Setting: The cardiac ward at Aarhus University Hospital, Denmark. Intervention: A socially differentiated CR intervention in addition to the standard CR program. Subjects: Patients admitted with first-episode myocardial infarction between 2000 and 2004, N = 379. Patients were defined as socially vulnerable or non-socially vulnerable according to their educational level and extent of social network. Main outcome measures: Primary outcome was medication adherence to antithrombotics, beta-blockers, statins and angiotensin-converting enzyme inhibitors. Secondary outcomes were biological and lifestyle risk factors defined as; total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glycated hemoglobin, blood pressure and smoking status. Results: No significant long-term effect of the intervention was found. Conclusions: The results indicate a non-significant effect of the intervention. However, it was found that equality in health was improved in the study population except concerning smoking. General practitioners manage to support the long-term secondary cardiovascular disease prevention in all patients regardless of social status. The socially differentiated intervention did not significantly improve medication adherence or biological and lifestyle risk factors. Despite the non-significant effect of the intervention, equality in health was improved except concerning smoking. General practitioners managed to support the long-term secondary cardiovascular disease prevention in all patients regardless of social status. [ABSTRACT FROM AUTHOR]

Background: Enthesitis is a major feature of psoriatic arthritis. However, clinical assessment of enthesitis is known to lack accuracy and have poor interobserver reliability. Objective: To determine effect of training on clinical assessment of enthesitis and to compare ultrasonography with clinical examination for the detection of entheseal abnormalities. Methods: 20 rheumatologists performed repeated assessment of enthesitis in patients with established psoriatic arthritis before and after a 2-hour training session in standardised enthesitis count according to Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Moreover, 20 patients underwent clinical and ultrasonographic examination of entheses to evaluate consensusbased elementary lesions of enthesitis. Results: Training significantly increased Intraclass Correlation Coefficient for LEI from 0.18 to 0.82 and for SPARCC from 0.38 to 0.67. Ultrasound examination showed high associations between hypoechogenicity and increased thickness of the entheses and clinical examination. There was no correlation between erosions and enthesophytes found by ultrasound and clinical assessments. Conclusion: Training in standardised enthesitis scoring systems significantly improved clinical assessments of enthesitis and should be performed before use in daily clinical practice. Ultrasound revealed more advanced stages of enthesitis, such as enthesophytes and erosions, which were not detected with clinical examination. [ABSTRACT FROM AUTHOR]

Plasma membrane damage and rupture occurs frequently in cells, and holes must be sealed rapidly to ensure homeostasis and cell survival. The membrane repair machinery is known to involve recruitment of curvature-inducing annexin proteins, but the connection between membrane remodeling and hole closure is poorly described. The induction of curvature by repair proteins leads to the possible formation of a membrane neck around the hole as a key intermediate structure before sealing. We formulate a theoretical model of equilibrium neck shapes to examine the potential connection to a repair mechanism. Using variational calculus, the shape equations for the membrane near a hole are formulated and solved numerically. The system is described under a condition of fixed area, and a shooting approach is applied to fulfill the boundary conditions at the free membrane edge. A state diagram of neck shapes is produced describing the variation in neck morphology with respect to the membrane area. Two distinct types of necks are predicted, one with conformations curved beyond π existing at positive excess area, whereas flat neck conformations (curved below π) have negative excess area. The results indicate that in cells, the supply of additional membrane area and a change in edge tension is linked to the formation of narrow and curved necks. Such necks may be susceptible to passive or actively induced membrane fission as a possible mechanism for hole sealing during membrane repair in cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Peripheral myelin protein 2 (P2) is a fatty acid-binding protein expressed in vertebrate peripheral nervous system myelin, as well as in human astrocytes. Suggested functions of P2 include membrane stacking and lipid transport. Mutations in the PMP2 gene, encoding P2, are associated with Charcot-Marie-Tooth disease (CMT). Recent studies have revealed three novel PMP2 mutations in CMT patients. To shed light on the structure and function of these P2 variants, we used X-ray and neutron crystallography, small-angle X-ray scattering, circular dichroism spectroscopy, computer simulations and lipid binding assays. The crystal and solution structures of the I50del, M114T and V115A variants of P2 showed minor differences to the wild-type protein, whereas their thermal stability was reduced. Vesicle aggregation assays revealed no change in membrane stacking characteristics, while the variants showed altered fatty acid binding. Time-lapse imaging of lipid bilayers indicated formation of double-membrane structures induced by P2, which could be related to its function in stacking of two myelin membrane surfaces in vivo. In order to better understand the links between structure, dynamics and function, the crystal structure of perdeuterated P2 was refined from room temperature data using neutrons and X-rays, and the results were compared to simulations and cryocooled crystal structures. Our data indicate similar properties for all known human P2 CMT variants; while crystal structures are nearly identical, thermal stability and function of CMT variants are impaired. Our data provide new insights into the structure-function relationships and dynamics of P2 in health and disease., (© 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Repair of damaged plasma membrane in eukaryotic cells is largely dependent on the binding of annexin repair proteins to phospholipids. Changing the biophysical properties of the plasma membrane may provide means to compromise annexin-mediated repair and sensitize cells to injury. Since, cancer cells experience heightened membrane stress and are more dependent on efficient plasma membrane repair, inhibiting repair may provide approaches to sensitize cancer cells to plasma membrane damage and cell death. Here, we show that derivatives of phenothiazines, which have widespread use in the fields of psychiatry and allergy treatment, strongly sensitize cancer cells to mechanical-, chemical-, and heat-induced injury by inhibiting annexin-mediated plasma membrane repair. Using a combination of cell biology, biophysics, and computer simulations, we show that trifluoperazine acts by thinning the membrane bilayer, making it more fragile and prone to ruptures. Secondly, it decreases annexin binding by compromising the lateral diffusion of phosphatidylserine, inhibiting the ability of annexins to curve and shape membranes, which is essential for their function in plasma membrane repair. Our results reveal a novel avenue to target cancer cells by compromising plasma membrane repair in combination with noninvasive approaches that induce membrane injuries., Competing Interests: Conflict of interest The authors declare no competing financial interests or other conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Plasma membrane repair is essential for eukaryotic cell life and is triggered by the influx of calcium through membrane wounds. Repair consists of sequential steps, with closure of the membrane hole being the key event that allows the cell to recover, thus identifying the kinetics of hole closure as important for clarifying repair mechanisms and as a quantitative handle on repair efficiency. We implement calcium imaging in MCF7 breast carcinoma cells subject to laser damage, coupled with a model describing the spatio-temporal calcium distribution. The model identifies the time point of hole closure as the time of maximum calcium signal. Analysis of cell data estimates the closure time as: [Formula: see text] s and [Formula: see text] s using GCaMP6s-CAAX and GCaMP6s probes respectively. The timescale was confirmed by independent time-lapse imaging of a hole during sealing. Moreover, the analysis estimates the characteristic time scale of calcium removal, the penetration depth of the calcium wave and the diffusion coefficient. Probing of hole closure times emerges as a strong universal tool for quantification of plasma membrane repair.

Background and Purpose: Delayed recanalization increases the risk of infarct growth and poor clinical outcome in acute ischemic stroke. The vasoactive agent theophylline has shown neuroprotective effects in animal stroke models but inconclusive results in case series and randomized clinical trials. The primary objective of this study was to evaluate whether theophylline, as an add-on to thrombolytic therapy, is safe and effective in acute ischemic stroke patients., Methods: The TEA-Stroke trial (The Theophylline in Acute Ischemic Stroke) was an investigator-initiated 2-center, proof-of-concept, phase II clinical study with a randomized, double-blinded, placebo-controlled design. The main inclusion criteria were magnetic resonance imaging-verified acute ischemic stroke, moderate to severe neurological deficit (National Institutes of Health Stroke Scale score of ≥4), and treatment with thrombolysis within 4.5 hours of onset. Participants were randomly assigned in the ratio 1:1 to either 220 mg of intravenous theophylline or placebo. The co-primary outcomes were early clinical improvement on the National Institutes of Health Stroke Scale score and infarct growth on magnetic resonance imaging at 24-hour follow-up., Results: Theophylline as an add-on to thrombolytic therapy improved the National Institutes of Health Stroke Scale score at 24 hours by mean 4.7 points (SD, 5.6) compared with an improvement of 1.3 points (SD, 7.5) in the control group ( P =0.044). Mean infarct growth was 141.6% (SD, 126.5) and 104.1% (SD, 62.5) in the theophylline and control groups, respectively ( P =0.146). Functional independence at 90 days was 61% in the theophylline group and 58% in the control group ( P =0.802)., Conclusions: This proof-of-concept trial investigated theophylline administration as an add-on to thrombolytic therapy in acute ischemic stroke. The co-primary end points early clinical improvement and infarct growth at 24-hour follow-up were not significantly different after post hoc correction for multiplicity (Bonferroni technique). The small study size precludes a conclusion as to whether theophylline has a neuroprotective effect but provides a promising clinical signal that may support a future clinical trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: EudraCT number 2013-001989-42.

Objective: To evaluate the association between socioeconomic status (SES) and referral to cardiac rehabilitation (CR) after incident acute coronary syndrome (ACS) by dividing the referral process into three phases: (1) informed about CR, (2) willingness to participate in CR, (3) and assigned CR setting., Design: Cross-sectional study., Setting: Department of Cardiology at a Danish University Hospital from 1 January 2011 to 31 December 2014., Participants: A total of 1229 patients assessed for CR during hospitalisation with ACS were prospectively registered in the Rehab-North Register from 2011 to 2014. SES was assessed using data from national registers, concerning: personal income, occupational status, educational level and civil status. Patients were excluded if one of the following criteria was fulfilled: (1) missing data on SES, or (2) acceptable reason for not informing patients about CR (treatment with coronary artery bypass grafting, transfer to another hospital, still under treatment or death)., Main Outcome Measures: Outcomes were defined by dividing the referral process into three phases: (1) informed about CR, (2) willingness to participate, and (3) assigned CR setting (in-hospital/community centre) after ACS., Results: A total of 854 (69.5 %) patients were referred to CR. After adjustment for age, gender, ACS diagnosis (ST-elevated myocardial infarction, non-ST-elevated myocardial infarction, unstable angina pectoris) and comorbidity, high income had the strongest association of referral to CR in all three phases (informed about CR: OR 2.17, 95% CI 1.01 to 4.64; willingness to participate in CR: OR 1.55, 95% CI 1.02 to 2.35; assigned in-hospital CR: OR 1.47, 95% CI 0.91 to 2.36). Educational level showed similar tendencies, however not statistically significant. The results did not vary according to gender., Conclusion: This is the first study to investigate the referral process to CR using a three-phase structure. It suggests income and education to influence all phases in the referral process to CR after ACS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale & Objective: Patients with kidney failure treated with maintenance dialysis experience a high rate of mortality, in part due to sudden cardiac death caused by arrhythmias. The prevalence of arrhythmias, including the subset that are clinically significant, is not well known. This study sought to estimate the prevalence of arrhythmias, characterize the pattern of arrhythmic events in relation to dialysis treatments, and identify associated clinical characteristics., Study Design: Cross-sectional study., Setting & Participants: 152 patients with kidney failure treated with maintenance dialysis in Denmark., Exposures: Dialysis treatment; clinical characteristics; cardiac output and preload defined using echocardiography., Outcomes: Prevalence and pattern of arrhythmias on 48-hour Holter monitoring; odds ratios for arrhythmias., Analytical Approach: Descriptive analysis of the prevalence of arrhythmias. Pattern of arrhythmias described using a repeated-measures negative binomial regression model. Associations between clinical characteristics and echocardiographic findings with arrhythmias were assessed using logistic regression., Results: Among the 152 patients studied, 83.6% were treated with in-center dialysis; 10.5%, with home hemodialysis; and 5.9%, with peritoneal dialysis. Premature atrial and ventricular complexes were seen in nearly all patients and 41% had paroxysmal supraventricular tachycardia. Clinically significant arrhythmias included persistent atrial fibrillation observed among 8.6% of patients, paroxysmal atrial fibrillation among 3.9%, nonsustained ventricular tachycardia among 19.7%, bradycardia among 4.6%, advanced second-degree atrioventricular block among 1.3%, and third-degree atrioventricular block among 2.6%. Premature ventricular complexes were more common on dialysis days, while tachyarrhythmias were more often observed during dialysis and in the immediate postdialytic period. Older age (OR per 10 years older, 1.53; 95% CI, 1.15-2.03; P=0.003), elevated preload (OR, 4.02; 95% CI, 1.05-15.35; P=0.04), and lower cardiac output (OR per 1L/min greater, 0.66; 95% CI, 0.44-1.00; P=0.05) were independently associated with clinically significant arrhythmias., Limitations: Arrhythmia monitoring limited to 48 hours; small sample size; heterogeneous nature of the population, risk for residual confounding., Conclusions: Arrhythmias, including clinically significant abnormal rhythms, were common. Tachyarrhythmias were more frequent during dialysis and the immediate postdialytic period. The relevance of these findings to clinical outcomes requires additional study., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

It has been a challenge to verify the dose of exercise that will produce the maximum health benefits in hypertension. This study aimed to explore the association between level of daily physical activity, all-cause mortality and cardiovascular outcome at different blood pressure levels. A random sample of 18 974 white men and women aged 20 to 98 years were examined in a prospective cardiovascular population study. Self-reported activity level in leisure-time was drawn from the Physical Activity Questionnaire (level I: inactivity; II: light activity; and III: moderate/high-level activity). Blood pressure was defined as normal blood pressure: <120/<80 mm Hg; Prehypertension: 120-139/80-89 mm Hg; Stage I hypertension: 140-159/90-99 mm Hg; Stage II hypertension ≥160/≥100 mm Hg. The mean follow-up time was 23.4±11.7 years. At all levels of blood pressure, higher levels of physical activity were associated with lower all-cause mortality in a dose-response pattern. The pattern remained unchanged after adjustment for following confounders: sex, age, smoking status, education, diabetes mellitus, previous cardiovascular disease, body mass index, and calendar time. Compared with inactivity, following hazard ratios were found for stage I hypertension: light activity, hazard ratio 0.78 (0.72-0.84; P <0.001), moderate/high-level activity, hazard ratio 0.69 (0.63-0.75; P <0.001). At all levels of blood pressure, the risk of cardiovascular events was significantly reduced independent of the level of physical activity. In conclusion, the association between physical activity and all-cause mortality was present in an inverse dose-response pattern at all levels of blood pressure. Physical activity was associated with reduction in cardiovascular events independent of the level of physical activity.

Objective: To examine the long-term effect of a socially differentiated cardiac rehabilitation (CR) intervention tailored to reduce social inequalities in health regarding use of healthcare services in general practice and hospital among socially vulnerable patients admitted with first-episode myocardial infarction (MI)., Design: A prospective cohort study with 10 years' follow-up., Setting: Department of cardiology at a university hospital in Denmark between 2000 and 2004., Participants: Patients <70 years admitted with first-episode MI categorised as socially vulnerable (n=208) or non-socially vulnerable (n=171) based on educational level and social network., Intervention: A socially differentiated CR intervention. The intervention consisted of standard CR and expanded CR with focus on cross-sectional collaboration., Main Outcome Measures: Participation in annual chronic care consultations in general practice, contacts to general practice, all-cause hospitalisations and cardiovascular readmissions., Results: At 2-year and 5-year follow-up, socially vulnerable patients receiving expanded CR participated significantly more in annual chronic care consultations (p=0.02 and p<0.01) but at 10-year follow-up, there were no significant differences in annual chronic care consultations (p=0.13). At 10-year follow-up, socially vulnerable patients receiving standard CR had significantly more contacts to general practice (p=0.03). At 10-year follow-up, there were no significant differences in the proportion of socially vulnerable patients receiving expanded CR in the mean number of all-cause hospitalisations and cardiovascular readmissions (p>0.05)., Conclusions: The present study found no persistent association between the socially differentiated CR intervention and use of healthcare services in general practice and hospital in patients admitted with first-episode MI during a 10-year follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this study was to investigate if there was an association between infarct size (IS) measured by cardiac magnetic resonance (CMR) and echocardiographic global longitudinal strain (GLS) in the early stage of acute myocardial infarction in patients with preserved left ventricular ejection fraction (LVEF). Patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention were assessed with CMR and transthoracic echocardiogram within 1 week of hospital admission. Two-dimensional speckle tracking was performed using a semi-automatic algorithm (EchoPac, GE Healthcare). Longitudinal strain curves were generated in a 17-segment model covering the entire left ventricular myocardium. GLS was calculated automatically. LVEF was measured by auto-LVEF in EchoPac. IS was measured by late gadolinium enhancement CMR in short-axis views covering the left ventricle. The study population consisted of 49 patients (age 60.4 ± 9.7 years; 92% male). The study population had preserved echocardiographic LVEF with a mean of 45.8 ± 8.7%. For each percent increase of IS, we found an impairment in GLS by 1.59% (95% CI 0.57-2.61), P  = 0.02, after adjustment for sex, age and LVEF. No significant association between IS and echocardiographic LVEF was found: -0.25 (95% CI: -0.61 to 0.11), P  = 0.51. At the segmental level, the strongest association between IS and longitudinal strain was found in the apical part of the LV: impairment of 1.69% (95% CI: 1.14-2.23), P  < 0.001, for each percent increase in IS. In conclusion, GLS was significantly associated with IS in the early stage of acute myocardial infarction in patients with preserved LVEF, and this association was strongest in the apical part of the LV. No association between IS and LVEF was found.

Aims: To evaluate the association between education and living arrangements and the intake of fish, red meat and fruit and vegetables. Methods : The study design was cross-sectional and conducted in Denmark in 2013. Participants filled in questionnaires about their educational level and living arrangements (living alone or with others) and dietary intake including fish, red meat, fruit and vegetables. Regression analyses were performed to assess the associations within 85,456 randomly sampled healthy men and women who were at least 25 years old. Results : Length of education was statistically significant and positively associated with the intake of fruit and vegetables and negatively associated with the intake of red meat for both men and women. Men with a high level of education had a 187g/week (95% confidence interval: 199-175g/week) lower intake of red meat and a 109g/day (95% confidence interval: 102-117g/day) higher intake of fruit and vegetables than men with a low level of education. Women with a high level of education had a 175g/week (95% confidence interval: 186-164g/week) lower intake of red meat and a 106g/day (95% confidence interval: 97-114g/day) higher intake of fruit and vegetables than women with a low level of education. Living with others was statistically significant and positively associated with the intake of red meat, and fruit and vegetables. There were no clear associations between education, living arrangements and intake of fish. Conclusions : Men and women with a high educational level ate more fruit and vegetables but less red meat than men and women with a low educational level. Men and women living with others ate more red meat, fruit and vegetables than men and women living alone.

Introduction: Ischaemic heart disease (IHD) is the leading cause of mortality in the Western world. Therefore, to focus on those at risk of having IHD while at the same time avoiding unnecessary patient concern, it is important to have diagnostic tools capable of refuting an IHD diagnosis. Within the past 30 years, myocardial perfusion imaging (MPI) has been used increasingly to detect myocardial perfusion defects. MPI is a safe and non-invasive method with a sensitivity and specificity of > 90%. The aim of this study was to evaluate the long-term prognostic outcome after a normal MPI. 
Methods: The study population comprised patients referred for MPI from one single department of cardiology with invasive facilities, from 2008 to 2009. The patients' demographics and the results of the MPIs were collected from their medical records. Only patients without known IHD and with a normal MPI were included. After a follow-up period of 7.8 years (range: 6.8-8.8 years), a retrospective database search was performed. The major outcomes were all-cause mortality, cardiac events defined as nonfatal myocardial infarct or coronary revascularisation by percutaneous coron-ary intervention or coronary artery bypass grafting. 
Results: The risk of a cardiac event or death following a normal MPI was 9.6% during long-term follow-up, with an estimated annual death rate of 1.4% per year (95% confidence interval: 0.8-2.5%). This was not different from the background population. 
Conclusion: A normal MPI predicts a favourable long-term prognostic outcome. 
Funding: none.
 Trial registration: FSEID-00002257., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Correct staging of pancreatic cancer is paramount, as treatment is stage specific. However, minimally invasive tools to facilitate staging are lacking. DNA promoter hypermethylation is a hallmark of cancer. The aim of this study is to evaluate promoter hypermethylation in cell-free DNA as a prognostic marker for stage classification of pancreatic adenocarcinoma. Consecutive patients with pancreatic adenocarcinoma were prospectively included. Plasma samples were obtained before diagnostic work-up and treatment. Patients were staged according to the TNM classification. Methylation-specific PCR of 28 genes was performed. Prognostic prediction models for staging of pancreatic adenocarcinoma were developed by multivariable logistic regression analysis using stepwise backwards elimination. Ninety-five patients with pancreatic adenocarcinoma were included. The mean number of hypermethylated genes was identical for stage I, II and III disease (7.09 (95% CI; 5.51-8.66), 7.00 (95% CI; 5.93-8.07) and 6.77 (95% CI; 5.08-8.46)), respectively, and highly significantly different from stage IV disease (10.24 (95% CI; 8.88-11.60)). The prediction model (SEPT9v2, SST, ALX4, CDKN2B, HIC1, MLH1, NEUROG1, and BNC1) enabled the differentiation of stage IV from stage I-III disease (AUC of 0.87 (cut point 0.55; sensitivity 74%, specificity 87%)). Model (MLH1, SEPT9v2, BNC1, ALX4, CDKN2B, NEUROG1, WNT5A, and TFPI2) enabled the differentiation of stage I-II from stage III-IV disease (AUC of 0.82 (cut point 0.66; sensitivity 73%, specificity 80%)). Cell-free DNA promoter hypermethylation has the potential to be blood-based prognostic markers for pancreatic adenocarcinoma, as panels of hypermethylated genes enables the differentiation according to cancer stage. However, further validation is required., (© 2017 UICC.)

Purpose: It is unknown whether irradiation of the internal mammary lymph nodes improves survival in patients with early-stage breast cancer. A possible survival benefit might be offset by radiation-induced heart disease. We assessed the effect of internal mammary node irradiation (IMNI) in patients with early-stage node-positive breast cancer., Patients and Methods: In this nationwide, prospective population-based cohort study, we included patients who underwent operation for unilateral early-stage node-positive breast cancer. Patients with right-sided disease were allocated to IMNI, whereas patients with left-sided disease were allocated to no IMNI because of the risk of radiation-induced heart disease. The primary end point was overall survival. Secondary end points were breast cancer mortality and distant recurrence. Analyses were by intention to treat., Results: A total of 3,089 patients were included. Of these, 1,492 patients were allocated to IMNI, whereas 1,597 patients were allocated to no IMNI. With a median of 8.9 years of follow-up time, the 8-year overall survival rates were 75.9% with IMNI versus 72.2% without IMNI. The adjusted hazard ratio (HR) for death was 0.82 (95% CI, 0.72 to 0.94; P = .005). Breast cancer mortality was 20.9% with IMNI versus 23.4% without IMNI (adjusted HR, 0.85; 95% CI, 0.73 to 0.98; P = .03). The risk of distant recurrence at 8 years was 27.4% with IMNI versus 29.7% without IMNI (adjusted HR, 0.89; 95% CI, 0.78 to 1.01; P = .07). The effect of IMNI was more pronounced in patients at high risk of internal mammary node metastasis. Equal numbers in each group died of ischemic heart disease., Conclusion: In this naturally allocated, population-based cohort study, IMNI increased overall survival in patients with early-stage node-positive breast cancer., (© 2015 by American Society of Clinical Oncology.)

Introduction: The objective of this study was to evaluate the incidence of death, cardiovascular events and the use of later non-scheduled imaging for coronary artery disease (CAD) in patients suspected for CAD and discharged without a need for further examination or treatment from an outpatient clinic following coronary computed tomography angiography (CCTA)., Material and Methods: This was a retrospective cohort study among patients discharged from an outpatient clinic after CCTA at our institution during 2009 and 2010. Follow-up was performed using nationwide Danish registers., Results: A total of 683 (68.2%) out of 1001 patients were discharged from the outpatient clinic after CCTA with no need for further examination. These patients were included in our study. After a median follow-up of 37 months, a low all-cause mortality of 3.7 per 1,000 person-years was found. There was only one case of acute myocardial infarction and no cases of death related to cardiovascular disease. A total of 5.0% of the patients later underwent non-scheduled imaging, predominantly invasive coronary angiography. No patients had revascularisation performed during the study period., Conclusion: Patients with suspected CAD discharged after CCTA with no need for further examination have a favourable cardiovascular prognosis., Funding: Not relevant., Trial Registration: Not relevant.

Introduction: Beta-blockers have cardioprotective, metabolic and immunomodulating effects that may be beneficial to patients in intensive care. We examined the association between preadmission beta-blocker use and 30-day mortality following intensive care., Methods: We identified 8,087 patients over age 45 admitted to one of three multidisciplinary intensive care units (ICUs) between 1999 and 2005. Data on the use of beta-blockers and medications, diagnosis, comorbidities, surgery, markers of socioeconomic status, laboratory tests upon ICU admission, and complete follow-up for mortality were obtained from medical databases. We computed probability of death within 30 days following ICU admission for beta-blocker users and non-users, and the odds ratio (OR) of death as a measure of relative risk using conditional logistic regression and also did a propensity score-matched analysis., Results: Inclusion of all 8,087 ICU patients in a logistic regression analysis yielded an adjusted OR of 0.82 (95% confidence interval (CI): 0.71 to 0.94) for beta-blocker users compared with non-users. In the propensity score-matched analysis we matched all 1,556 beta-blocker users (19.2% of the entire cohort) with 1,556 non-users; the 30-day mortality was 25.7% among beta-blocker users and 31.4% among non-users (OR 0.74 (95% CI: 0.63 to 0.87)]. The OR was 0.69 (95% CI: 0.54 to 0.88) for surgical ICU patients and 0.71 (95% CI: 0.51 to 0.98) for medical ICU patients. The OR was 0.99 (95% CI: 0.67 to 1.47) among users of non-selective beta-blockers, and 0.70 (95% CI: 0.58 to 0.83) among users of cardioselective beta-blockers., Conclusions: Preadmission beta-blocker use is associated with reduced mortality following ICU admission.

Background: Physiology-based severity of illness scores are often used for risk adjustment in observational studies of intensive care unit (ICU) outcome. However, the complexity and time constraints of these scoring systems may limit their use in administrative databases. Comorbidity is a main determinant of ICU outcome, and comorbidity scores can be computed based on data from most administrative databases. However, limited data exist on the performance of comorbidity scores in predicting mortality of ICU patients., Objectives: To examine the performance of the Charlson comorbidity index (CCI) alone and in combination with other readily available administrative data and three physiology-based scores (acute physiology and chronic health evaluations [APACHE] II, simplified acute physiology score [SAPS] II, and SAPS III) in predicting short- and long-term mortality following intensive care., Methods: For all adult patients (n = 469) admitted to a tertiary university-affiliated ICU in 2007, we computed APACHE II, SAPS II, and SAPS III scores based on data from medical records. Data on CCI score age and gender, surgical/medical status, social factors, mechanical ventilation and renal replacement therapy, primary diagnosis, and complete follow-up for 1-year mortality was obtained from administrative databases. We computed goodness-of-fit statistics and c-statistics (area under ROC [receiver operating characteristic] curve) as measures of model calibration (ability to predict mortality proportions over classes of risk) and discrimination (ability to discriminate among the patients who will die or survive), respectively., Results: Goodness-of-fit statistics supported model fit for in-hospital, 30-day, and 1-year mortality of all combinations of the CCI score. Combining the CCI score with other administrative data revealed c-statistics of 0.75 (95% confidence interval [CI] 0.69-0.81) for in-hospital mortality, 0.75 (95% CI 0.70-0.80) for 30-day mortality, and 0.72 (95% CI 0.68-0.77) for 1-year mortality. There were no major differences in c-statistics between physiology-based systems and the CCI combined with other administrative data., Conclusion: The CCI combined with administrative data predict short- and long-term mortality for ICU patients as well as physiology-based scores.