97 research outputs found

    Burst strength of BIOLOX\uaedelta femoral heads and its dependence on low-temperature environmental degradation

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    Zirconia-toughened alumina (ZTA) currently represents the bioceramic gold standard for load-bearing components in artificial hip joints. ZTA is long known for its high flexural strength and fracture toughness, both properties arising from a microscopic crack-tip shielding mechanism due to the stress-induced tetragonal-to-monoclinic (t\u2192m) polymorphic transformation of zirconia. However, there have been concerns over the years regarding the long-term structural performance of ZTA since the t\u2192m transformation also spontaneously occurs at the material's surface under low-temperature environmental conditions with a concomitant degradation of mechanical properties. Spontaneous surface degradation has been extensively studied in vitro, but predictive algorithms have underestimated the extent of in vivo degradation observed in retrievals. The present research focused on burst-strength assessments of 828 mm ZTA femoral before and after long-term in vitro hydrothermal ageing according to ISO 7206-10. An average burst strength of 52 kN was measured for pristine femoral heads. This value was 3c36% lower than results obtained under the same standard conditions by other authors. A further loss of burst strength 3c13% in ultimate load) was observed after hydrothermal ageing, with increased surface monoclinic content ranging from 3c6% to >50%. Nevertheless, the repetitively stressed and hydrothermally treated ZTA heads exceeded the minimum burst strength stipulated by the US Food and Drug Administration (FDA) despite severe test conditions. Lastly, Raman spectroscopic assessments of phase transformation and residual stresses on the fracture surface of the femoral heads were used to clarify burst-strength fluctuations and the effect of hydrothermal ageing on the material's overall strength degradation

    Isolation and characterization of two newly established thymoma PDXs from two relapses of the same patient: a new tool to investigate thymic malignancies

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    BackgroundThymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies.Main bodyStarting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin.Short conclusionThe newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer

    The influence of simulator input conditions on the wear of total knee replacements: an experimental and computational study

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    Advancements in knee replacement design, material and sterilisation processes have provided improved clinical results. However, surface wear of the polyethylene leading to osteolysis is still considered the longer-term risk factor. Experimental wear simulation is an established method for evaluating the wear performance of total joint replacements. The aim of this study was to investigate the influence of simulation input conditions, specifically input kinematic magnitudes, waveforms and directions of motion and position of the femoral centre of rotation, on the wear performance of a fixed-bearing total knee replacement through a combined experimental and computational approach. Studies were completed using conventional and moderately cross-linked polyethylene to determine whether the influence of these simulation input conditions varied with material. The position of the femoral centre of rotation and the input kinematics were shown to have a significant influence on the wear rates. Similar trends were shown for both the conventional and moderately cross-linked polyethylene materials, although lower wear rates were found for the moderately cross-linked polyethylene due to the higher level of cross-linking. The most important factor influencing the wear was the position of the relative contact point at the femoral component and tibial insert interface. This was dependent on the combination of input displacement magnitudes, waveforms, direction of motion and femoral centre of rotation. This study provides further evidence that in order to study variables such as design and material in total knee replacement, it is important to carefully control knee simulation conditions. This can be more effectively achieved through the use of displacement control simulation

    Intravitreal Brolucizumab for Pachychoroid Neovasculopathy Associated With Chronic Central Serous Chorioretinopathy

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    Purpose: To evaluate the anatomical and functional outcomes of intravitreal brolucizumab in eyes with chronic central serous chorioretinopathy complicated by pachychoroid neovasculopathy. Methods: Retrospective analysis of 34 eyes treated with intravitreal brolucizumab. Twenty-five eyes (73.5%) had been treated with other anti-vascular endothelial growth factor agents before switching to brolucizumab, whereas nine eyes were naïve. Outcome measures included the change of central foveal thickness and subfoveal choroidal thickness, evaluation of sub/intraretinal fluid on optical coherence tomography, and change in best-corrected visual acuity. Results: Before starting brolucizumab, 23 eyes showed subretinal fluid, 8 both subretinal and intraretinal fluid, and 3 intraretinal fluid only. At the last visit, 22 eyes (64.7%) showed complete reabsorption of both intraretinal and subretinal fluid, whereas subretinal fluid was still present in 8 eyes (23.5%), and both intraretinal and subretinal fluid in 4 eyes (11.8%). The mean number of brolucizumab injections required to achieve complete fluid reabsorption was 2.8 ± 1.8. central foveal thickness decreased from 317.8 ± 109.3 μm to 239.8 ± 74.8 μm (P = 0.0005) and subfoveal choroidal thickness decreased from 399.3 ± 86.2 μm to 355.5 ± 92.7 μm at the end of the follow-up period (P = 0.0008). The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.4 ± 0.2 to 0.3 ± 0.2 at 1 month after the first injection and remained stable at the same values at the end of the follow-up period (P = 0.04). Conclusions: Intravitreal brolucizumab is effective for the treatment of naïve and recalcitrant pachychoroid neovasculopathy. Translational relevance: Intravitreal brolucizumab may represent an option in patients with pachychoroid neovasculopathy complicating chronic central serous chorioretinopathy

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    UN'INCHIESTA A PIù VOCI PROVA A RIATTRAVERSARE LE MOLTEPLICI IMPLICAZIONI DI VALORE CULTURALE E DI POTERE COMUNICATIVO AFFIORANTI DALLA GENESI E DAI TANTI RIUSI DEL MITO DI NARCISO, ALLA RICERCA DELLE FORME E DELLE RAGINI CHE LO HANNO PORTATO A MARCARE PROFONDAMENTE I LINGUAGGI E LE VISIONI DELLA MODERNIT

    Overcoming platinum-acquired resistance in ovarian cancer patient-derived xenografts

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    Background: Epithelial ovarian cancer is the most lethal gynecological cancer and the high mortality is due to the frequent presentation at advanced stage, and to primary or acquired resistance to platinum-based therapy. Methods: We developed three new models of ovarian cancer patient-derived xenografts (ovarian PDXs) resistant to cisplatin (cDDP) after multiple in vivo drug treatments. By different and complementary approaches based on integrated metabolomics (both targeted and untargeted mass spectrometry-based techniques), gene expression, and functional assays (Seahorse technology) we analyzed and compared the tumor metabolic profile in each sensitive and their corresponding cDDP-resistant PDXs. Results: We found that cDDP-sensitive and -resistant PDXs have a different metabolic asset. In particular, we found, through metabolomic and gene expression approaches, that glycolysis, tricarboxylic acid cycle and urea cycle pathways were deregulated in resistant versus sensitive PDXs. In addition, we observed that oxygen consumption rate and mitochondrial respiration were higher in resistant PDXs than in sensitive PDXs under acute stress conditions. An increased oxidative phosphorylation in cDDP-resistant sublines led us to hypothesize that its interference could be of therapeutic value. Indeed, in vivo treatment of metformin and cDDP was able to partially reverse platinum resistance. Conclusions: Our data strongly reinforce the idea that the development of acquired cDDP resistance in ovarian cancer can bring about a rewiring of tumor metabolism, and that this might be exploited therapeutically
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