Impact of switching oral bisphosphonates to denosumab or daily teriparatide on the progression of radiographic joint destruction in patients with biologic-naïve rheumatoid arthritis

Summary: In biologic-naïve female RA patients, switching oral BPs to DMAb significantly reduced radiographic joint destruction compared to continuing oral BPs or switching to TPTD at 12 months, which were significantly associated with a decrease of a bone resorption marker at 6 months. Introduction: The aim of this study was to clarify the effects of switching oral bisphosphonates (BPs) to denosumab (DMAb) or daily teriparatide (TPTD) on the progression of radiographic joint destruction in patients with biologic-naïve rheumatoid arthritis (RA). Methods: A retrospective, case-controlled study involving 90 female RA patients (mean age 68.2 years, 96.7% postmenopausal, disease activity score assessing 28 joints with CRP (DAS28-CRP) 2.4, methotrexate treatment 81.1%, prednisolone treatment 68.9%, and prior BP treatment 44.8 months), who were allocated depending on each patient’s and physician’s wishes, to (1) the BP-continue group (n = 30), (2) the switch-to-DMAb group (n = 30), or (3) the switch-to-TPTD group (n = 30), was conducted. Patients were retrospectively selected to minimize the difference of possible clinical backgrounds that may affect the joint destruction of RA. The primary endpoint was to clarify the change of the modified total Sharp score (mTSS) from baseline to 12 months. Results: After 12 months, the mean changes of the modified Sharp erosion score were significantly lower in the switch-to-DMAb group (0.2 ± 0.1; mean ± standard error) than in the switch-to-TPTD group (1.3 ± 0.5; P < 0.05), and mTSS was significantly lower in the switch-to-DMAb group (0.3 ± 0.2) than in the BP-continue group (1.0 ± 0.3; P < 0.05) and the switch-to-TPTD group (1.7 ± 0.6; P < 0.05). The logistic regression analysis showed that mTSS changes were significantly associated with the percent changes of TRACP-5b at 6 months (β = 0.30, 95% CI = 0.002–0.016; P < 0.01). Conclusions: Changes of systemic bone turnover induced by switching BPs to DMAb or TPTD may affect not only systemic bone mass, but also local joint destruction, and its clinical relevance should be considered comprehensively.This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00198-018-4492-yEbina K., Hirao M., Hashimoto J., et al. Impact of switching oral bisphosphonates to denosumab or daily teriparatide on the progression of radiographic joint destruction in patients with biologic-naïve rheumatoid arthritis. Osteoporosis International 29, 1627 (2018); https://doi.org/10.1007/s00198-018-4492-y

Developmental roadmap for antimicrobial susceptibility testing systems

Antimicrobial susceptibility testing (AST) technologies help to accelerate the initiation of targeted antimicrobial therapy for patients with infections and could potentially extend the lifespan of current narrow-spectrum antimicrobials. Although conceptually new and rapid AST technologies have been described, including new phenotyping methods, digital imaging and genomic approaches, there is no single major, or broadly accepted, technological breakthrough that leads the field of rapid AST platform development. This might be owing to several barriers that prevent the timely development and implementation of novel and rapid AST platforms in health-care settings. In this Consensus Statement, we explore such barriers, which include the utility of new methods, the complex process of validating new technology against reference methods beyond the proof-of-concept phase, the legal and regulatory landscapes, costs, the uptake of new tools, reagent stability, optimization of target product profiles, difficulties conducting clinical trials and issues relating to quality and quality control, and present possible solutions

Gemcitabine and docetaxel as second-line chemotherapy in elderly patients with metastatic urothelial carcinoma: a retrospective analysis

Taku Naiki,1 Keitaro Iida,1 Toshiki Etani,1 Takashi Nagai,2 Yutaro Tanaka,1 Yosuke Sugiyama,3 Ryosuke Ando,1 Shuzo Hamamoto,1 Rika Banno,4 Daisuke Nagata,4 Noriyasu Kawai,1 Takahiro Yasui1 1Department of Nephro-Urology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan; 2Department of Urology, Anjo Kosei Hospital, Anjo, Japan; 3Department of Pharmacy, Nagoya City University Hospital, Nagoya, Japan; 4Department of Urology, Konan Kosei Hospital, Konan, Japan Background: The objective of this study was to evaluate the efficacy of a combination of gemcitabine and docetaxel (GD) as a second-line treatment for elderly patients with metastatic urothelial carcinoma (mUC).Patients and methods: A total of 122 patients with mUC who were previously treated with platinum-based chemotherapy received second-line GD therapy from July 2010 to June 2016. This consisted of 800&nbsp;mg/m2 gemcitabine and 40&nbsp;mg/m2 docetaxel on days 1 and 8 in each 21-day cycle. Using pooled cumulative data, we divided patients into the following three groups based on age: &lt;65&nbsp;years (Group A), from 65 to 74&nbsp;years (Group B), and &ge;75&nbsp;years (Group C), and then the data were retrospectively analyzed. All patients were evaluated for treatment-related toxicities and assessed at every cycle by imaging studies. Kaplan&ndash;Meier curves were used for survival and recurrence analyses. Furthermore, potential prognostic factors for progression-free survival (PFS) and overall survival (OS) were assessed via univariate and multivariate Cox regression analyses.Results: The median follow-up period was 8.2&nbsp;months (range: 2.1&ndash;100). The median number of treatment cycles was three (range: 1&ndash;16) in Group A, three (1&ndash;15) in Group B, and two (1&ndash;11) in Group C. The objective response rate was not significantly different between the three groups. In addition, PFS and OS from the start of second-line GD therapy were also not significantly different. According to univariate and multivariate analyses of the second-line GD-treated cohort, a good performance status was the only prognostic factor for PFS and OS. In Group C, myelosuppression including predominant neutropenia and anemia, fatigue, and nausea were the main common adverse events. However, the incidence of neutropenia and a reduction in platelets were not significantly different between the three groups. Treatment-related deaths did not occur in this study.Conclusion: In this study, GD combination therapy as a second-line treatment for mUC resulted in favorable tumor responses and few treatment-related toxicities, even among elderly patients. Keywords: gemcitabine and docetaxel, elderly patients, second-line, metastatic urothelial carcinom

Charge-order melting in charge-disproportionated perovskite CeCu3Fe4O12

A novel quadruple perovskite oxide CeCu3Fe4O12 has been synthesized under high-pressure and high-temperature conditions of 15 GPa and 1473 K. (57)Fe Mössbauer spectroscopy displays a charge disproportionation transition of 4Fe(3.5+) → 3Fe(3+) + Fe(5+) below ∼270 K, whereas hard X-ray photoemission and soft X-ray absorption spectroscopy measurements confirm that the Ce and Cu valences are retained at approximately +4 and +2, respectively, over the entire temperature range measured. Electron and X-ray diffraction studies reveal that the body-centered cubic symmetry (space group Im3̅, No. 204) is retained at temperatures as low as 100 K, indicating the absence of any types of charge-ordering in the charge-disproportionated CeCu3Fe4O12 phase. The magnetic susceptibility and neutron powder diffraction data illustrate that the antiferromagnetic ordering of Fe ions is predominant in the charge-disproportionated CeCu3Fe4O12 phase. These findings suggest that CeCu3Fe4O12 undergoes a new type of electronic phase in the ACu3Fe4O12 series and that the melting of the charge-ordering in CeCu3Fe4O12 is caused by the substantial decrease in the Fe valence and the resulting large deviation from the ideal abundance ratio of Fe(3+):Fe(5+) = 1:1 for rock-salt-type charge-ordering. © 2014, American Chemical Society