Sequential treatment with teriparatide and strontium ranelate in a postmenopausal woman with atypical femoral fractures after long-term bisphosphonate administration

AbstrAct ObJEctIVE: Despite the existence of numerous case series, no evidenced-based medical management for atypical fractures associated with bisphosphonate (bP) treatment has been established. DEsIGN: We report the outcome of teriparatide (trP) administration followed by strontium ranelate (sr) in a woman with a complete and an incomplete contralateral atypical fracture of the femoral diaphysis (AFF) associated with bP treatment. the spontaneous complete AFF was managed with intramedullary nailing, discontinuation of bP and initiation trP. rEsULts: Eleven months later, she suffered a contralateral incomplete AFF. At the completion of the trP treatment, she had only slight discomfort in the femur with the incomplete AFF. bMD testing revealed increase of 7.61% at the lumbar spine (Ls) and 0.8% at the hip. Following trP, 1-year sr treatment resulted in further bMD increase of 9.2% at the Ls and 1.4% in the hip, while she does not report any pain. bone markers remain within the normal range. cONcLUsION: Our case indicates that sequential therapy with trP and sr in cases of AFF might be a rational treatment option. However, there is a need for additional information concerning the effect of trP and sr, given alone or sequentially, in these patients in order to incorporate these drugs into the management of AFF

Impact of minimal residual disease detection by next-generation flow cytometry in multiple myeloma patients with sustained complete remission after frontline therapy

Minimal residual disease (MRD) was monitored in 52 patients with sustained CR (≥2 years) after frontline therapy using next-generation flow (NGF) cytometry. 25% of patients initially MRD- reversed to MRD+. 56% of patients in sustained CR were MRD+; 45% at the level of 10−5; 17% at 10−6. All patients who relapsed during follow-up were MRD+ at the latest MRD assessment, including those with ultra-low tumor burden. MRD persistence was associated with specific phenotypic profiles: higher erythroblasts’ and tumor-associated monocytes/macrophages’ predominance in the bone marrow niche. NGF emerges as a suitable method for periodic, reproducible, highly-sensitive MRD-detection at the level of 10−6

Static and dynamic mechanics of the murine lung after intratracheal bleomycin

<p>Abstract</p> <p>Background</p> <p>Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure.</p> <p>Methods</p> <p>Single intratracheal injections of saline (50 μL) or bleomycin (2 mg/Kg in 50 μL saline) were administered to C57BL/6 (<it>n </it>= 40) and Balb/c (<it>n </it>= 32) mice. Injury/fibrosis score, tissue volume density (TVD), collagen content, airway resistance (<it>R_N</it>), tissue damping (<it>G</it>) and elastance coefficient (<it>H</it>), hysteresivity (<it>η</it>), and area of pressure-volume curve (PV-A) were determined after 7 and 21 days (inflammation and fibrosis stage, respectively). Statistical hypothesis testing was performed using one-way ANOVA with LSD <it>post hoc </it>tests.</p> <p>Results</p> <p>Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and <it>G </it>and <it>H </it>non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. <it>G </it>and <it>H</it>, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, <it>H </it>and <it>G </it>was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls.</p> <p>Conclusions</p> <p>Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.</p

Mutant KRAS promotes malignant pleural effusion formation

Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity. However, the mechanisms responsible for the development of MPE are still obscure. Here we show that mutant KRAS is important for MPE induction in mice. Pleural disseminated, mutant KRAS bearing tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into the bloodstream to mobilize myeloid cells from the host bone marrow to the pleural space via the spleen. These cells promote MPE formation, as indicated by splenectomy and splenocyte restoration experiments. In addition, KRAS mutations are frequently detected in human MPE and cell lines isolated thereof, but are often lost during automated analyses, as indicated by manual versus automated examination of Sanger sequencing traces. Finally, the novel KRAS inhibitor deltarasin and a monoclonal antibody directed against CCL2 are equally effective against an experimental mouse model of MPE, a result that holds promise for future efficient therapies against the human condition

Optical Modelling of Planar and Fibre Perovskite Solar Cells

We present the optical modelling of a mesoporous fibre perovskite solar cell (PSC). It was conducted by means of the transmission line method (TLM), which was used to calculate the efficiency and short-circuit photo-current density of the cell. The TLM was first applied for a planar mesoporous PSC and verified with the experimental results from the literature. Numerical calculations for both planar and fibre PSC were conducted and analysed regarding their efficiency in terms of optical simulation. The importance of choosing the thin-film layers’ materials and thickness was demonstrated, and a potential improvement using anti-reflection coatings was also examined

Evaluation of an Erbium-Doped Fiber Ring Laser as an Edge Filtering Device for Fiber Bragg Grating Sensor Interrogation

An easy-to-implement and cost-effective Fiber Bragg Grating (FBG) sensor interrogation technique based on a ring Erbium-Doped Fiber Laser (EDFL) topology is proposed and experimentally assessed. The FBG sensor is part of the EDFL cavity and must have a central wavelength located within the linear region of the EDF’s amplified spontaneous emission (ASE) spectrum, which occurs at between 1530 and 1540 nm. In this manner, the wavelength-encoded response of the FBG under strain is converted to a linear variation in the laser output power, removing the need for spectrum analysis as well as any limitations from the use of external edge-filtering components. In addition, the laser linewidth is significantly reduced with respect to the FBG bandwidth, thus improving the resolution of the system, whereas its sensitivity can be controlled through pumping power. The performance of the system has been characterized by modeling and experiments for EDFs with different lengths, doping concentrations, and pumping power levels. The influence of mode-hopping in the laser cavity on the resolution and accuracy of the system has also been investigated