Rapid Alteplase Administration Improves Functional Outcomes in Patients With Stroke due to Large Vessel Occlusions.

Background and Purpose- We report the relation of onset-to-treatment time and door-to-needle time with functional outcomes and mortality among patients with ischemic stroke with imaging-proven large vessel occlusion treated with intravenous alteplase. Methods- Individual patient-level data from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration were pooled from 7 trials that randomized patients to mechanical thrombectomy added to best medical therapy versus best medical therapy alone. Analysis was restricted to patients who received alteplase directly at the endovascular hospital.

Response-guided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell transplantation in first complete remission: Results from protocol DB AML-01.

Background: Children with acute myeloid leukemia (AML) have a 70% survival rate with treatment regimens containing high doses of cytarabine and anthracyclines and, in some, hematopoietic stem cell transplantation (allo-HSCT).

Procedure: In this multicenter Dutch-Belgian protocol (DB AML-01), 112 children with de novo AML were included. Treatment was stratified according to day 15 bone marrow response after the first induction course.

Gender-related vitamin D deficiency in a Dutch 19th century farming community.

The most common cause of vitamin D deficiency is inadequate dermal exposure to sunlight. Residual rickets is nonadult vitamin D deficiency still evident in an adult individual, whereas osteomalacia occurs in adulthood. Previous research on the Beemster population, a 19th century rural community in the Netherlands, identified rickets in 30.

Obeticholic Acid Modulates Serum Metabolites and Gene Signatures Characteristic of Human NASH and Attenuates Inflammation and Fibrosis Progression in Ldlr-/-.Leiden Mice.

Concerns have been raised about whether preclinical models sufficiently mimic molecular disease processes observed in nonalcoholic steatohepatitis (NASH) patients, bringing into question their translational value in studies of therapeutic interventions in the process of NASH/fibrosis. We investigated the representation of molecular disease patterns characteristic for human NASH in high-fat diet (HFD)-fed Ldlr-/-.Leiden mice and studied the effects of obeticholic acid (OCA) on these disease profiles.

Sacral chordoma: a clinical review of 101 cases with 30-year experience in a single institution.

Background: Local recurrence rates are high in sacral chordoma patients. Adjuvant radiotherapy may play a role in increasing local control. Patients with locally recurrent tumors continue to comprise a significant proportion of the sacral chordoma population and appear to have worse prognosis than those with primary tumors.

Predilection of Low Protein C-induced Spontaneous Atherothrombosis for the Right Coronary Sinus in Apolipoprotein E deficient mice.

Silencing of anticoagulant protein C using RNA interference (siProc) evokes low incident but spontaneous atherothrombosis in the aortic root of apolipoprotein E-deficient (Apoe) mice. The aims of the current study were (1) to analyze if plaque characteristics or circulating factors could be linked to atherothrombosis susceptibility, (2) to increase the incidence of atherothrombosis by transiently increasing blood pressure, and (3) to direct atherothrombosis to an additional predefined vascular site by applying a semi-constrictive collar around the carotid artery. siProc-driven spontaneous atherothrombosis in the aortic root of Apoe mice was reproduced and occurred at an incidence of 23% (9 out of 39 mice), while the incidence of collar-induced atherothrombosis in the carotid artery was 2.

Risk of diabetes after para-aortic radiation for testicular cancer.

Background: While the risk of diabetes is increased following radiation exposure to the pancreas among childhood cancer survivors, its association among testicular cancer (TC) survivors has not been investigated.

Methods: Diabetes risk was studied in 2998 1-year TC survivors treated before 50 years of age with orchidectomy with/without radiotherapy between 1976 and 2007. Diabetes incidence was compared with general population rates.

The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity.

Sepsis involves simultaneous hyperactivation of the immune system and immune paralysis, leading to both organ dysfunction and increased susceptibility to secondary infections. Acute activation of myeloid cells induced itaconate synthesis, which subsequently mediated innate immune tolerance in human monocytes. In contrast, induction of trained immunity by β-glucan counteracted tolerance induced in a model of human endotoxemia by inhibiting the expression of immune-responsive gene 1 (IRG1), the enzyme that controls itaconate synthesis.

Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci.

Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors.

Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus.

Evidence for a shared genetic basis of association between coronary artery disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis, we performed a GWAS meta-analysis. In the discovery stage, we used a German aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls).

Meta-analysis on the effect of hyperbaric oxygen as adjunctive therapy in the outcome of anastomotic healing of experimental colorectal resections in rats.

Background: Colorectal cancer is the third most common form of cancer and colorectal surgery is the treatment of choice in local disease. Anastomotic leakage following colorectal surgery is a major complication with a high incidence and mortality. Adjuvant hyperbaric oxygen treatment (HBOT) may be associated with reduction of anastomotic leakage.

Gamma knife radiosurgery for recurrent gliomas.

Objective: In recent years, gamma knife radiosurgery (GKRS) has become increasingly more popular as a salvage treatment modality for patients diagnosed with recurrent gliomas. The goal of GKRS for recurrent glioma patients is to improve survival rates with minimal burden for these patients. The emphasis of this report is on local tumor control (TC), clinical outcome and survival analysis.

From design to the clinic: practical guidelines for translating cardiovascular nanomedicine.

Cardiovascular diseases (CVD) account for nearly half of all deaths in Europe and almost 30% of global deaths. Despite the improved clinical management, cardiovascular mortality is predicted to rise in the next decades due to the increasing impact of aging, obesity, and diabetes. The goal of emerging cardiovascular nanomedicine is to reduce the burden of CVD using nanoscale medical products and devices.

Integrated proteomic analysis of tumor necrosis factor α and interleukin 1β-induced endothelial inflammation.

The vascular endothelium provides a unique interaction plane for plasma proteins and leukocytes in inflammation. The pro-inflammatory cytokines Tumor Necrosis Factor α (TNFα) and interleukin 1β (IL-1β) have a profound effect on endothelial cells, which includes increased levels of adhesion molecules and a disrupted barrier function. To assess the endothelial response to these cytokines at the protein level, we evaluated changes in the whole proteome, cell surface proteome and phosphoproteome after 24 h of cytokine treatment.

A Mobile App (WhiteTeeth) to Promote Good Oral Health Behavior Among Dutch Adolescents with Fixed Orthodontic Appliances: Intervention Mapping Approach.

Background: The insertion of fixed orthodontic appliances increases the risk of dental caries, particularly in adolescents. Caries can be prevented through good oral health behavior. To support adolescents with fixed orthodontic appliances and for promoting oral health behavior, we developed a theory- and evidence-based mHealth program, the WhiteTeeth app.

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids.

Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner.

An Overview of Clinical Outcomes in Transvenous and Subcutaneous ICD Patients.

Purpose Of Review: Clear guidelines on when to select a subcutaneous ICD (S-ICD) over a transvenous ICD (TV-ICD) are lacking. This review will provide an overview of the most recent clinical data on S-ICD and TV-ICD therapy by pooling comparison studies in order to aid clinical decision making.

Recent Findings: Pooling of observational-matched studies demonstrated an incidence rate ratio (IRR) for device-related complication of 0.

Long-Term Air Pollution Exposure and Amyotrophic Lateral Sclerosis in Netherlands: A Population-based Case-control Study.

Background: Recently, there has been increasing evidence that exposure to air pollution is linked to neurodegenerative diseases, but little is known about the association with amyotrophic lateral sclerosis (ALS).

Objectives: We investigated the association between long-term exposure to air pollution and risk of developing ALS.

Methods: A population-based case-control study was conducted in Netherlands from 1 January 2006 to 1 January 2013.

Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia.

Background: Children with acute lymphoblastic leukemia (ALL) often suffer from toxicity of chemotherapeutic drugs such as Methotrexate (MTX). Previously, we reported that 20% of patients receiving high-dose MTX developed oral mucositis. MTX inhibits folate metabolism, which is essential for DNA methylation.

Frequency of Impaired Spinal Mobility in Patients with Chronic Back Pain Compared to Patients with Early Axial Spondyloarthritis.

Objective: To examine the frequency of impaired spinal mobility in patients with chronic back pain of short duration and to compare it with the frequency of impaired spinal mobility in patients with axial spondyloarthritis (axSpA), possible SpA, and no SpA.

Methods: The SpondyloArthritis Caught Early (SPACE) cohort includes patients with chronic back pain (≥ 3 mos, ≤ 2 yrs, onset < 45 yrs). Spinal mobility was assessed with lateral spinal flexion, chest expansion, cervical rotation, occiput-to-wall distance, and lumbar flexion.