Pathway-based approach reveals differential sensitivity to E2F1 inhibition in glioblastoma.

Analysis of tumor gene expression is an important approach for the classification and identification of therapeutic vulnerabilities. However, targeting glioblastoma (GBM) based on molecular subtyping has not yet translated into successful therapies. Here, we present an integrative approach based on molecular pathways to expose new potentially actionable targets.

Consensus on communication curriculum content in Danish undergraduate medical education: A Delphi study.

Background: The acquisition of skills in patient-centered communication is a critical aspect of medical education which demands both resource-intensive instruction and longitudinal opportunities for learning. Significant variation currently exists in the content and timing of communication education. The aim of this study was to establish consensus regarding communication curriculum content for undergraduate medical education (UME) within the country of Denmark.

Metformin and carotid intima-media thickness in never-smokers with type 1 diabetes: The REMOVAL trial.

Aim: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in type 1 diabetes differ according to smoking status.

Methods: Regression model effect estimates for the effect of metformin versus placebo (double-blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial.

Results: In 428 randomized participants (227 never-smokers, 201 ever-smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.

The match between need and use of health services among healthy under-fives in Denmark: A register-based national cohort study.

Objectives: To study a potential positive association (referred to as 'a match') between the need for health service (expressed by a mortality risk score) and observed health service utilisation among healthy Danish under-fives. Further, municipal differences in the match were examined to motivate focused comparisons between the organisation of regional health services.

Design: Register-based national cohort study.

Risk factors of post-discharge under-five mortality among Danish children 1997-2016: A register-based study.

Objectives: Estimating associations between somatic and socioeconomic risk factors and post-discharge under-five mortality.

Design: Register-based national cohort study using multiple Cox regression.

Participants: The population of 1,263,795 Danish children live-born 1997-2016 who survived until date of first discharge to the home after birth was followed from that date until death, emigration, 5 years of age or 31 December 2016.

Planar scan vs. SPECT/low-dose CT for estimating split renal function by Tc-DMSA scintigraphy in children.

In the present study, we compared estimates of split renal function (SRF) in paediatric patients of various diagnostic subgroups by Tc-dimercaptosuccinic acid (DMSA) scintigraphy using either geometric mean (GM) based on planar scans or a volume of interest (VOI)-based analysis on single photon emission tomography combined with low-dose CT (SPECT/ldCT). Two experienced physicians blinded to patient diagnosis retrospectively analysed all paediatric Tc-DMSA scintigraphies that were conducted in our department between 2011 and 2016 and which included both a planar scan and SPECT/ldCT. All scintigraphies were performed on either a Phillips Precedence 16 slice CT or a Siemens Symbia 16 slice CT.

Too much? Mortality and health service utilisation among Danish children 1999-2016: A register-based study.

Objectives: To describe the temporal development of mortality and health service utilisation defined as in- and outpatient hospital contacts, contacts with general practitioner and specialists, and prescribed dispensed medication among Danish children 0-5 years of age from 1999 to 2016.

Design: Register-based descriptive study.

Participants: All children born in Denmark in the period 1994-2016 followed until 5 years of age.

Biomarkers of Autoimmunity in Acute Psychiatric Disorders.

Objective: Previous studies have suggested that autoantibodies associated with systemic autoimmune disorders are more prevalent in patients with psychotic and affective disorders compared with healthy control subjects. However, most positive studies addressing this issue have been limited by small sample sizes and lack of correction for confounding factors. The authors aimed to assess the prevalence of several autoantibodies in patients admitted to acute psychiatric inpatient care and investigate whether patients with psychotic and affective disorders have an increased prevalence of autoantibodies compared with psychiatric patients admitted for other reasons.

Classification and Personalized Prognosis in Myeloproliferative Neoplasms.

Background: Myeloproliferative neoplasms, such as polycythemia vera, essential thrombocythemia, and myelofibrosis, are chronic hematologic cancers with varied progression rates. The genomic characterization of patients with myeloproliferative neoplasms offers the potential for personalized diagnosis, risk stratification, and treatment.

Methods: We sequenced coding exons from 69 myeloid cancer genes in patients with myeloproliferative neoplasms, comprehensively annotating driver mutations and copy-number changes.

Predictors of Left Ventricular Remodeling After Myocardial Infarction in Patients With a Patent Infarct Related Coronary Artery After Percutaneous Coronary Intervention (from the Post-Myocardial Infarction Remodeling Prevention Therapy [PRomPT] Trial).

Left ventricular (LV) remodeling after myocardial infarction (MI) is a strong predictor of heart failure and mortality. The predictors of long-term remodeling after MI have been incompletely studied. We therefore examined the correlates of LV remodeling in patients with large ST-segment elevation myocardial infarction and a patent infarct artery after percutaneous 2coronary intervention (PCI) from the randomized Post-Myocardial Infarction Remodeling Prevention Therapy trial.

Endothelial Damage Signals Refractory Acute Kidney Injury in Critically Ill Patients.

Unlabelled: Critically ill patients with acute kidney injury (AKI) are heterogeneous on pathophysiology and prognosis. The role of endothelial damage in the pathogenesis of refractory AKI has not been clarified. The aim was to determine if biomarkers of endothelial damage, independently of the inflammatory insult on the kidney, can predict recovery of acute kidney injury.

Comparative pharmacology of a new recombinant FSH expressed by a human cell line.

Recombinant FSH proteins are important therapeutic agents for the treatment of infertility, including follitropin alfa expressed in Chinese Hamster Ovary (CHO) cells and, more recently, follitropin delta expressed in the human cell line PER.C6. These recombinant FSH proteins have distinct glycosylation, and have distinct pharmacokinetic and pharmacodynamic profiles in women.

Metformin in adults with type 1 diabetes: Design and methods of REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL): An international multicentre trial.

Aims: Cardiovascular (CV) disease is a major cause of reduced life expectancy in type 1 diabetes (T1D). Intensive insulin therapy prevents CV complications but is constrained by hypoglycaemia and weight gain. Adjunct metformin reduces insulin dose requirement and stabilizes weight but there are no data on its cardiovascular effects.

Use of the nonavalent HPV vaccine in individuals previously fully or partially vaccinated with bivalent or quadrivalent HPV vaccines.

With the availability of the nonavalent human papillomavirus (HPV) vaccine, vaccinees, parents and healthcare providers need guidance on how to complete an immunization course started with the bi- or quadrivalent vaccine and whether to revaccinate individuals who have completed a full immunization course with the bi- or quadrivalent vaccine. To answer these questions three parameters should be considered: age at the start of vaccination (9 to 14 years of age versus 15 years and older, the cut-off for 2 or 3 doses schedule), the number of doses already received and the time interval between doses. Based on a number of scenarios, we propose that the 9-valent vaccine can be used to complete an incomplete vaccination regimen or might be added to a previous completed schedule to extend protection.

Peri-infarct zone pacing to prevent adverse left ventricular remodelling in patients with large myocardial infarction.

Aims: We sought to determine whether peri-infarct pacing prevents left ventricular (LV) remodelling and improves functional and clinical outcomes in patients with large first myocardial infarction (MI).

Methods And Results: A total of 126 patients at 27 international sites within 10 days of onset of anterior or non-anterior MI with creatine phosphokinase >3000 U/L and QRS duration ≤120 ms were randomized 1:1:1 to dual-site biventricular pacing vs. single-site LV only pacing vs.

Invasive Candida infections and the harm from antibacterial drugs in critically ill patients: data from a randomized, controlled trial to determine the role of ciprofloxacin, piperacillin-tazobactam, meropenem, and cefuroxime.

Objective: Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection.

Design: Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006-2010.

Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial.

Importance: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm.

Objective: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury.

In patients with neovascular age-related macular degeneration, physical activity may influence C-reactive protein levels.

Purpose: Association of neovascular age-related macular degeneration (AMD) with C-reactive protein (CRP) was previously reported, indicating a relation to systemic low-grade inflammation. However, visual impairment limits physical activity, and physical activity modulates CRP levels. Here, we investigated the impact of physical activity on CRP levels in patients with neovascular AMD and control individuals.

Cytokines and the risk of preterm delivery in twin pregnancies.

Objective: To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment.

Methods: This secondary analysis of a randomized placebo-controlled trial investigating the effect of progesterone treatment on preterm delivery in twin pregnancies included 523 women with available dried blood spot samples collected before treatment with progesterone (n=258) or placebo (n=265) and after 4-8 weeks of treatment. Samples were analyzed for cytokines using a sandwich immunoassay.

Lower motor neuron involvement examined by quantitative electromyography in amyotrophic lateral sclerosis.

Objective: The diagnosis of amyotrophic lateral sclerosis (ALS) includes demonstration of lower motor neuron (LMN) and upper motor neuron (UMN) involvement of bulbar and spinal muscles. Electromyography (EMG) is essential to confirm LMN affection in weak muscles, and to demonstrate changes in clinically non-involved muscles. The aim of the study was to determine the relative importance of ongoing (active) denervation, fasciculations, chronic partial denervation with reinnervation at weak effort and loss of motor units at maximal voluntary contraction (MVC) in ALS.

Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cells.

Objective: To examine if polymorphism 80G --> A in the Reduced Folate Carrier (RFC) affects uptake of MTX in B- and CD4+ T-cells.

Methods: Mononuclear cells were isolated from peripheral blood of healthy persons. Real-time PCR was used to detect the RFC80 variants.

Intensification of mercaptopurine/methotrexate maintenance chemotherapy may increase the risk of relapse for some children with acute lymphoblastic leukemia.

Purpose: Thioguanine nucleotides (TGNs) mediate the cytotoxicity of mercaptopurine (MP). Methylated MP metabolites (formed by thiopurine methyltransferase [TPMT]) and methotrexate (MTX) polyglutamates can inhibit de novo purine synthesis. We explored whether dose adjustment of MP and MTX by erythrocyte (E) levels of TGN and MTX (including polyglutamates) could improve outcome in childhood acute lymphoblastic leukemia (ALL).