Antiaromatic 15Diazasindacenes

At the final analysis (median follow-up 19.9 months), median centrally-assessed PFS was 4.1 months in the niraparib arm (n=141) versus 3.1 months in the PC arm (n=74; hazard ratio [HR] 0.96; 95% CI 0.65-1.44;
=0.86). HRs for OS and local-PFS were 0.95 (95% CI 0.63-1.42) and 0.65 (0.46-0.93), respectively. ORR was 35% (95% CI 26-45) with niraparib and 31% (19-46) in the PC arm.
Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.
Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.On December 18, 2020, the U.S. Food and Drug Administration (FDA) approved osimertinib as adjuvant therapy in patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations, as detected by an FDA-approved test. The approval was based on the ADAURA study in which 682 patients with NSCLC were randomized to receive osimertinib (n=339) or placebo (n=343). Disease free survival (DFS) in the overall population (Stage IB-IIIA) was improved for patients who received osimertinib, with a hazard ratio (HR) of 0.20; 95% CI 0.15, 0.27; p less then 0.0001. Median DFS was not reached for the osimertinib arm compared to 27.5 months (95% CI 22.0, 35.0) for patients receiving placebo. Overall survival (OS) data was not mature at the time of the approval. This application was reviewed under FDA's Project Orbis, in collaboration with Australia Therapeutic Goods Administration (TGA), Brazil ANVISA, Health Canada, Singapore Health Sciences Authority (HSA), Switzerland Swissmedic, and the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA). This is the first targeted therapy adjuvant approval for NSCLC and has practice changing implications.Liquid biopsy approaches for the detection of viral DNA can provide important information for the diagnosis and identification of virally-associated cancers. Here we discuss the next-generation sequencing (NGS)-based CaptHPV method for the detection and characterization of plasma human papillomavirus (HPV) DNA in HPV-associated cancers and its potential clinical utility.Highlighted Research Paper AMPA Receptors Exist in Tunable Mobile and Immobile Synaptic Fractions In Vivo, by Haiwen Chen, Richard H. Roth, Elena Lopez-Ortega, Han L. Tan, and Richard L. Huganir.
Dabigatran-induced oesophagitis has emerged in recent years. However, the incidence and clinical characteristics of patients with dabigatran-induced oesophagitis have not yet been clarified. The aim of this study was to examine the clinical characteristics of the disease.
A retrospective analysis was undertaken of the literature on dabigatran-induced oesophagitis in Chinese and English from 2008 onwards.
There were 20 men (74.07%) and seven women (25.93%) in the study; their median age was 75 years (range 37-90). The main clinical symptoms were dysphagia (42.31%), odynophagia (26.92%), retrosternal pain (23.08%) and heartburn (23.08%). Endoscopy mainly showed sloughing mucosal casts (14 cases, 56%), ulcers (8 cases, 32%) and erosion (6 cases, 24%). The main injury sites were the mid to lower oesophagus (32%) and the mid oesophagus (32%). Withdrawal of dabigatran or giving the correct medication regimen resulted in rapid recovery of clinical symptoms from 1 day in some patients and up to 4 weeks, and mucosal recovery (2-5 weeks) in a median time of 3 weeks (range 0.29-48) in all patients.
Oesophagitis is a rare complication of dabigatran with a good prognosis. Patients should be given proper medication instructions to prevent the occurrence of dabigatran-induced oesophagitis.
Oesophagitis is a rare complication of dabigatran with a good prognosis. Patients should be given proper medication instructions to prevent the occurrence of dabigatran-induced oesophagitis.
Ambient fine particulate matter with aerodynamic diameter less than 2.5 µm (PM
) has been associated with deteriorated respiratory health, but evidence on particles in smaller sizes and childhood respiratory health has been limited.
We collected time-series data on daily respiratory emergency room visits (ERVs) among children under 14 years old in Beijing, China, during 2015-2017. Concurrently, size-fractioned number concentrations of particles in size ranges of 5-560 nm (PNC
) and mass concentrations of PM
, black carbon (BC) and nitrogen dioxide (NO
) were measured from a fixed-location monitoring station in the urban area of Beijing. Confounder-adjusted Poisson regression models were used to estimate excessive risks (ERs) of particle size fractions on childhood respiratory ERVs, and positive matrix factorisation models were applied to apportion the sources of PNC
.
Among the 136 925 cases of all-respiratory ERVs, increased risks were associated with IQR increases in PNC
(ER=5.4%, 95% CI 2.4% ton control priority in urban areas.
Lung clearance index (LCI) is a valuable research tool in cystic fibrosis (CF) but clinical application has been limited by technical challenges and uncertainty about how to interpret longitudinal change. In order to help inform clinical practice, this study aimed to assess feasibility, repeatability and longitudinal LCI change in children and adults with CF with predominantly mild baseline disease.
Prospective, 3-year, multicentre, observational study of repeated LCI measurement at time of clinical review in patients with CF >5 years, delivered using a rapid wash-in system.
112 patients completed at least one LCI assessment and 98 (90%) were still under follow-up at study end. The median (IQR) age was 14.7 (8.6-22.2) years and the mean (SD) FEV
z-score was -1.2 (1.3). Of 81 subjects with normal FEV
(>-2 z-scores), 63% had raised LCI (indicating worse lung function). For repeat stable measurements within 6 months, the mean (limits of agreement) change in LCI was 0.9% (-18.8% to 20.7%). Linsitinib clinical trial A latent class growth model analysis identified four discrete clusters with high accuracy, differentiated by baseline LCI and FEV
.