Epidermal growth factor receptor (EGFR)—tyrosine kinase inhibitors as a first-line treatment for postoperative recurrent and EGFR-mutated non-small-cell lung cancer

[OBJECTIVES] To clarify survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) as first-line treatment for postoperative recurrence. [METHODS] A retrospective chart review was performed to identify consecutive patients who received EGFR-TKIs as first-line treatment for postoperative recurrence of non-small-cell lung cancer (NSCLC) harbouring EGFR gene mutations at our institution between August 2002 and October 2020. Therapeutic response, adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using the Kaplan–Meier analysis. The Cox proportional hazards model was used for univariable and multivariable analyses. [RESULTS] Sixty-four patients were included in the study. The objective response and disease control rates were 53% and 92%, respectively. Grade 3 or greater adverse events were noted in 4 (6.3%) patients, including 1 patient (1.6%) of interstitial pneumonia. The median follow-up period was 28.5 months (range 3–202 months). The total number of events was 43 for PFS and 23 for OS, respectively. The median PFS was 18 months, and the median OS was 61 months after EGFR-TKI treatment. In multivariable analysis, osimertinib showed a tendency to prolong PFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.12–1.1; P = 0.071], whereas the micropapillary component was significantly associated with shorter OS (HR 2.1, 95% CI 1.02–6.9; P = 0.045). [CONCLUSIONS] EGFR-TKIs as first-line treatment appeared to be a reasonable treatment option in selected patients with postoperative recurrent EGFR-mutated NSCLC. Osimertinib and the micropapillary component may be prognostic factors

The Sloan Digital Sky Survey Quasar Lens Search. VI. Constraints on Dark Energy and the Evolution of Massive Galaxies

We present a statistical analysis of the final lens sample from the Sloan Digital Sky Survey Quasar Lens Search (SQLS). The number distribution of a complete subsample of 19 lensed quasars selected from 50,836 source quasars is compared with theoretical expectations, with particular attention to the selection function. Assuming that the velocity function of galaxies does not evolve with redshift, the SQLS sample constrains the cosmological constant to \Omega_\Lambda=0.79^{+0.06}_{-0.07}(stat.)^{+0.06}_{-0.06}(syst.) for a flat universe. The dark energy equation of state is found to be consistent with w=-1 when the SQLS is combined with constraints from baryon acoustic oscillation (BAO) measurements or results from the Wilkinson Microwave Anisotropy Probe (WMAP). We also obtain simultaneous constraints on cosmological parameters and redshift evolution of the galaxy velocity function, finding no evidence for redshift evolution at z<1 in any combinations of constraints. For instance, number density evolution quantified as \nu_n=d\ln\phi_*/d\ln(1+z) and the velocity dispersion evolution \nu_\sigma=d\ln\sigma_*/d\ln(1+z) are constrained to \nu_n=1.06^{+1.36}_{-1.39}(stat.)^{+0.33}_{-0.64}(syst.) and \nu_\sigma=-0.05^{+0.19}_{-0.16}(stat.)^{+0.03}_{-0.03}(syst.) respectively when the SQLS result is combined with BAO and WMAP for flat models with a cosmological constant. We find that a significant amount of dark energy is preferred even after fully marginalizing over the galaxy evolution parameters. Thus the statistics of lensed quasars robustly confirm the accelerated cosmic expansion.Comment: 44 pages, 12 figures, 4 tables, accepted for publication in A

SDSS J133401.39+331534.3: A New Subarcsecond Gravitationally Lensed Quasar

The quasar SDSS J133401.39+331534.3 at z = 2.426 is found to be a two-image gravitationally lensed quasar with the image separation of 0.833. The object is first identified as a lensed quasar candidate in the Sloan Digital Sky Survey Quasar Lens Search, and then confirmed as a lensed system from follow-up observations at the Subaru and University of Hawaii 2.2-meter telescopes. We estimate the redshift of the lensing galaxy to be 0.557 based on absorption lines in the quasar spectra as well as the color of the galaxy. In particular, we observe the system with the Subaru Telescope AO188 adaptive optics with laser guide star, in order to derive accurate astrometry, which well demonstrates the usefulness of the laser guide star adaptive optics imaging for studying strong lens systems. Our mass modeling with improved astrometry implies that a nearby bright galaxy $\sim 4"$ apart from the lensing galaxy is likely to affect the lens potential.Comment: 24 pages, 6 figures. ApJ, in pres

Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety

<p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) stimulates hepatocyte proliferation, and also acts as an anti-apoptotic factor. Therefore, HGF is a potential therapeutic agent for treatment of fatal liver diseases. We performed a translational medicine protocol with recombinant human HGF (rh-HGF), including a phase I/II study of patients with fulminant hepatitis (FH) or late-onset hepatic failure (LOHF), in order to examine the safety, pharmacokinetics, and clinical efficacy of this molecule.</p> <p>Methods</p> <p>Potential adverse effects identified through preclinical safety tests with rh-HGF include a decrease in blood pressure (BP) and an increase in urinary excretion of albumin. Therefore, we further investigated the effect of rh-HGF on circulatory status and renal toxicity in preclinical animal studies. In a clinical trial, 20 patients with FH or LOHF were evaluated for participation in this clinical trial, and four patients were enrolled. Subjects received rh-HGF (0.6 mg/m²/day) intravenously for 12 to 14 days.</p> <p>Results</p> <p>We established an infusion method to avoid rapid BP reduction in miniature swine, and confirmed reversibility of renal toxicity in rats. Although administration of rh-HGF moderately decreased BP in the participating subjects, this BP reduction did not require cessation of rh-HGF or any vasopressor therapy; BP returned to resting levels after the completion of rh-HGF infusion. Repeated doses of rh-HGF did not induce renal toxicity, and severe adverse events were not observed. Two patients survived, however, there was no evidence that rh-HGF was effective for the treatment of FH or LOHF.</p> <p>Conclusions</p> <p>Intravenous rh-HGF at a dose of 0.6 mg/m²was well tolerated in patients with FH or LOHF; therefore, it is desirable to conduct further investigations to determine the efficacy of rh-HGF at an increased dose.</p

BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed

The Burden and Etiology of Community-Onset Pneumonia in the Aging Japanese Population: A Multicenter Prospective Study

Background: The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world\u27s most aged society. Methods: A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ?15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics. Results: A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ?85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ?65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000)

Ureteral reimplantation during augmentation cystoplasty is not needed for vesicoureteral reflux in patients with neurogenic bladder : a long-term retrospective study

Background To investigate the need for ureteral reimplantation for vesicoureteral reflux (VUR) during augmentation cystoplasty (AC) in the long term. Methods A total of 19 patients with a median age at surgery of 14 years (3-38 years) who underwent AC for neurogenic bladder with VUR between 1983 and 2016 were included in this study. The changes in VUR grade and urodynamic findings were retrospectively evaluated. We evaluated the renal function by periodic inspection of serum creatinine level and estimated glomerular filtration rate; eGFR. Results The median follow-up period from AC was 14.8 years (5.7-30 years). VUR was detected in 19 patients, involving 27 ureters. Reflux grade was V in 6, IV in 9, III in 5, II in 6, and I in 1. Ureteral reimplantation was not performed in 18 patients (26 ureters), whereas it was done for 1 patient (1 ureter) in the early era of our experience. Postoperative videourodynamics showed that the reflux was radiologically not verifiable in 23 ureters (85%), was downgraded in 3 ureters (11%), and was unchanged in 1 ureter (3%). There were no cases of deterioration of VUR. Conclusions Ureteral reimplantation is not necessary for VUR during augmentation cystoplasty