The European Medicines Agency Review of Kymriah (Tisagenlecleucel) for the Treatment of Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma.

Chimeric antigen receptor (CAR)-engineered T-cell therapy is becoming one of the most promising approaches in the treatment of cancer. On June 28, 2018, the Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kymriah for pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse after transplant, or in second or later relapse and for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. Kymriah became one of the first European Union-approved CAR T therapies.

CETSA-based target engagement of taxanes as biomarkers for efficacy and resistance.

The use of taxanes has for decades been crucial for treatment of several cancers. A major limitation of these therapies is inherent or acquired drug resistance. A key to improved outcome of taxane-based therapies is to develop tools to predict and monitor drug efficacy and resistance in the clinical setting allowing for treatment and dose stratification for individual patients.

Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer: Results from the phase 3 PANTHER trial.

Background: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)-positive disease.

Methods: This was a protocol-predefined secondary analysis of the randomized phase 3 Pan-European Tailored Chemotherapy (PANTHER) trial.

The Association of Oral Bisphosphonate Use With Mortality Risk Following a Major Osteoporotic Fracture in the United Kingdom: Population-Based Cohort Study.

Objectives: Bisphosphonates (BPs) might have extra benefits in reducing mortality because of their anti-atherosclerotic effects, but studies reported conflicting results. We investigated the association between oral BP use and mortality risk following a major osteoporotic fracture (MOF) in the United Kingdom.

Design: This was a population-based cohort study.

Diabetes and fractures: new evidence of atypical femoral fractures?

Unlabelled: Patients with diabetes have an increased risk of fractures. In this study, subtrochanteric and femoral shaft fractures were increased in patients with type 1 diabetes compared with the general population. In the light of this, more evidence points towards an association between diabetes and atypical femoral fractures.

Association between vertebral fractures and coronary artery calcification in current and former smokers in the ECLIPSE cohort.

Unlabelled: In smokers and former smokers from the ECLIPSE cohort, there is an association between prevalent vertebral fractures (VFs) and coronary artery calcification (CAC). Chest CT scans provide the opportunity to evaluate VFs and CAC, which are potentially important comorbidities, each of which is amenable to effective interventions.

Introduction: Prevalence of VFs among smokers and patients with chronic obstructive pulmonary disease (COPD) is high, and an association between CAC and osteoporosis has been described.

The Implantation of Bioactive Glass Granules Can Contribute the Load-Bearing Capacity of Bones Weakened by Large Cortical Defects.

Bioactive glass (BAG) granules (S53P4) have shown good clinical results in one-stage treatment of osteomyelitis. During this treatment, a cortical window is created, and infected bone is debrided, which results in large defects that affect the mechanical properties of the bone. This study aimed to evaluate the role of BAG granules in load-bearing bone defect grafting.

Neutropenic complications in the PANTHER phase III study of adjuvant tailored dose-dense chemotherapy in early breast cancer.

Myelosuppresion is a common side effect of chemotherapy and granulocyte-colony stimulating factor (G-CSF) is often used to reduce the risk of neutropenic events. The purpose of this exploratory analysis was to investigate neutropenic complications in the phase III PANTHER trial of standard 3-weekly chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide plus docetaxel (FEC/D) versus bi-weekly tailored dose-dense EC/D adjuvant chemotherapy in breast cancer. Febrile neutropenia, neutropenic infection and infection grade 3-4 according to CTC AE 3.

STAT3 Activity Promotes Programmed-Death Ligand 1 Expression and Suppresses Immune Responses in Breast Cancer.

Signal transducer and activator of transcription 3 (STAT3) is an oncogene and multifaceted transcription factor involved in multiple cellular functions. Its role in modifying anti-tumor immunity has been recently recognized. In this study, the biologic effects of STAT3 on immune checkpoint expression and anti-tumor responses were investigated in breast cancer (BC).

European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

On 21 November 2016, the European Commission issued a marketing authorisation valid throughout the European Union for ixazomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Ixazomib was evaluated in one, randomised, double-blind, phase III study comparing ixazomib plus lenalidomide and dexamethasone (n=360; ixazomib arm) versus placebo plus lenalidomide and dexamethasone (n=362; placebo arm) in adult patients with relapsed and/or refractory multiple myeloma who had received at least one prior therapy. The median progression-free survival (PFS) in the intent-to-treat population was 20.

Fracture liaison programs.

In view of the high imminent risk of having subsequent fractures after a fracture, early evaluation and treatment decisions to prevent subsequent fractures are advocated. After a hip fracture, the fracture liaison service (FLS) and orthogeriatric care are considered the most appropriate organisational approaches for secondary fracture prevention following a recent fracture. Their introduction and implementation have been shown to increase evaluation and treatment of patients at high risk for subsequent fracture.

Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer.

Background: Gene expression analysis of breast cancer largely relies on homogenized tissue samples. Due to the high degree of cellular and molecular heterogeneity of tumor tissues, bulk tissue-based analytical approaches can only provide very limited system-level information about different signaling mechanisms and cellular interactions within the complex tissue context.

Methods: We describe an analytical approach using in situ sequencing (ISS), enabling highly multiplexed, spatially and morphologically resolved gene expression profiling.

Season-Long Monitoring of the Brown Marmorated Stink Bug (Hemiptera: Pentatomidae) Throughout the United States Using Commercially Available Traps and Lures.

Reliable monitoring of the invasive Halyomorpha halys abundance, phenology and geographic distribution is critical for its management. Halyomorpha halys adult and nymphal captures on clear sticky traps and in black pyramid traps were compared in 18 states across the Great Lakes, Mid-Atlantic, Southeast, Pacific Northwest and Western regions of the United States. Traps were baited with commercial lures containing the H.

The Feasibility of High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) in Patients with Suspected Scaphoid Fractures.

Introduction: Diagnosing scaphoid fractures remains challenging. High-resolution peripheral quantitative computed tomography (HR-pQCT) might be a potential imaging technique, but no data are available on its feasibility to scan the scaphoid bone in vivo.

Methodology: Patients (≥18 years) with a clinically suspected scaphoid fracture received an HR-pQCT scan of the scaphoid bone (three 10.

Secular trends in major osteoporotic fractures among 50+ adults in Denmark between 1995 and 2010.

Unlabelled: We investigated the incidence trend in all major osteoporotic fractures for the whole country of Denmark between 1995 and 2010. Hip and other osteoporotic fractures declined for the general population and especially among women. But, we observed some increasing trend among men which needs more attention.

Reduced Bone Loss Is Associated With Reduced Mortality Risk in Subjects Exposed to Nitrogen Bisphosphonates: A Mediation Analysis.

Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss.

Adjuvant Therapy and Mammographic Density Changes in Women With Breast Cancer.

Background: Tamoxifen decreases mammographic density. Whether compliance affects this relationship is unclear as is the relationship between other types of adjuvant treatment and changes in mammographic density.

Methods: This prospective cohort study included 2490 women diagnosed with breast cancer during 2001-2015 in Sweden.

Outcome and presentation of heart failure in breast cancer patients: findings from a Swedish register-based study.

Aims: Heart failure (HF) patients diagnosed with breast cancer (BC) may have a higher risk of death, and different HF presentation and treatment than patients without BC.

Methods And Results: A total of 14 998 women with incident HF (iHF) or prevalent HF (pHF) enrolled in the Swedish HF Registry within and after 1 month since HF diagnosis, respectively, between 2008 and 2013. Patients were linked with the National Patient-, Cancer-, and Cause-of-Death Registry.

Two-year persistence with teriparatide improved significantly after introduction of an educational and motivational support program.

Unlabelled: This study evaluated the 2-year persistence with teriparatide in the Netherlands. Analyses showed that the risk of non-persistence was 28% lower in patients who were followed according to an additional educational and motivational support program.

Introduction: Until recently, teriparatide (TPTD) was a third-line treatment option for severe osteoporosis in the Netherlands, which could only be prescribed by medical specialists based on a specific medical statement.

The association between prevalent vertebral fractures and bone quality of the distal radius and distal tibia as measured with HR-pQCT in postmenopausal women with a recent non-vertebral fracture at the Fracture Liaison Service.

Unlabelled: We evaluated the association between prevalent vertebral fractures and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women with a recent non-vertebral fracture visiting the Fracture Liaison Service. The presence and severity of prevalent vertebral fracture reflect generalized bone deterioration.

Introduction: We evaluated the association between prevalent vertebral fractures (VFs) and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women visiting the Fracture Liaison Service.

Retraction Note to: Secular trends in major osteoporotic fractures among 50+ adults in Denmark between 1995 and 2010.

The publisher has retracted this article [1] from Archives of Osteoporosis in order to publish in Osteoporosis International as originally intended by the authors and the Editors of Osteoporosis International. Springer Nature apologizes to readers and the authors.

Correction: Large cortical bone pores in the tibia are associated with proximal femur strength.

[This corrects the article DOI: 10.1371/journal.pone.

Prognostic Implications of PD-L1 Expression in Breast Cancer: Systematic Review and Meta-analysis of Immunohistochemistry and Pooled Analysis of Transcriptomic Data.

Purpose: Conflicting data have been reported on the prognostic value of PD-L1 protein and gene expression in breast cancer. Medline, Embase, Cochrane Library, and Web of Science Core Collection were searched, and data were extracted independently by two researchers. Outcomes included pooled PD-L1 protein positivity in tumor cells, immune cells, or both, per subtype and per antibody used, and its prognostic value for disease-free and overall survival.