Despite significant developments in the treatment of multiple myeloma (MM) over the past decade, many patients still experience relapse due to resistance to antimyeloma therapies. Particularly in the ...relapsed/refractory setting, recent treatment advances have resulted in significantly improved prognosis for MM patients. Among novel therapeutic modalities, B-cell maturation antigen (BCMA)-directed immunotherapies, including chimeric antigen receptor (CAR) T-cell therapy, antibody-drug conjugates (ADCs) and bispecific T cell engagers (BiTEs), have achieved remarkable clinical response in patients with relapsed/refractory MM (RRMM). This article discusses the recent progress in anti-BCMA targeted treatments for RRMM, with a focus on currently available agents.
Patients with recurrent or refractory Hodgkin’s lymphoma who are at increased risk of progression after high-dose chemotherapy and autologous stem-cell transplantation may benefit from consolidation ...therapy with brentuximab vedotin, according to the results of the AETHERA study.^1,2^ Based on clinical trial data, brentuximab vedotin in combination with adriblastina, vinblastine and dacarbazine (AVD) represents a good treatment option as the frontline therapy for Hodgkin’s lymphoma^3^ as well as in the sequential treatment of older patients.^4^ This report presents the case of a patient with relapsed/refractory cHL who received brentuximab vedotin maintenance after an inadequate response to first-line adriblastina, bleomycin, vinblastine and dacarbazine (ABVD) and reinduction chemotherapy with dexamethasone, high-dose cytarabine, platinum (cisplatin) (DHAP). Despite the high-risk features and multiple complications that occurred during the disease course, the patient is still in remission 3 years after the end of maintenance therapy.
This paper presents a method to predict dry sliding wear. It is developed for the wear simulation on a tilted shaft-bushing bearing of an automotive turbocharger wastegate system. Therefore the ...simulation of complex dynamic behavior with its respective contact situations is required and is performed by nonlinear, transient, three-dimensional finite element analysis (FEA). Simultaneous wear calculation on all contact surfaces is possible considering individual wear coefficients. In order to reduce computing time, the resulting ablation depth is extrapolated. Subsequently the mesh is adjusted by implementing nodal displacements. The progress of the calculated wear volume matches well with theoretical considerations for different mesh qualities. Mesh refinement only leads to a higher resolution of the results but good convergence is achieved.
•Simulation of dry sliding wear in a tilted shaft bushing bearing.•Simultaneous wear calculation on both 3D contact partners.•Prediction of wear evolution including change of wear shape.•Investigation of sensitivity to mesh refinement.•Good correlation between simulation and theoretical results.
A simulation model to determine dry sliding wear behavior of wastegate bearings is validated by comparison with experimental results. The wear results of a pin-on-plate tribometer running at 300∘C ...are used to define global wear coefficients. These serve as input information for a FEM simulation which is able to calculate local wear progress in the model. The simulation results show good correlation with the experiment for the general wear shape and the local wear depth. Volume gain is observed on one of the contact partners due to material transfer. This effect is not included in the simulation model and thus cannot be reproduced.
•Tribometer test at elevated temperature with austenitic steels.•Advanced wear simulation method for dry sliding based on finite elements.•Detailed comparison of test and simulation results.•High correlation between material removal in simulation and experiment.
Background The real-world experience of Swiss chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) is largely unknown, in particular with regard to achievement of ...response per European Leukemia Net (ELN) criteria and adherence to ELN recommendations. Methods This was a retrospective, non-interventional, multicenter chart review of patients with newly diagnosed CML who had received first-line TKI and were solely treated with TKIs between 2010 and 2015, with a minimum follow-up of 18 months, at six Swiss hospitals. Effectiveness was evaluated according to ELN 2013 milestone achievements at 3, 6, 12 and 18 months, and at last follow-up. Results Data from 63 patients (56% men; median age at diagnosis 55 years) were collected (first-line imatinib n = 27, nilotinib n = 27, dasatinib n = 8, or ponatinib n = 1). TKI switches (49 times) and dosing changes (165 times) due to intolerance or insufficient response were frequent. Compared with patients receiving first-line imatinib, a higher proportion of patients receiving first-line nilotinib or dasatinib achieved optimal response at all timepoints, irrespective of subsequent TKI therapy, and a higher proportion of patients treated with first-line nilotinib and dasatinib reached deep molecular response (BCR-ABL1.sup.IS less than or equai to 0.01%) at 18 months (42 and 38%, respectively, versus 27%). Patients who received nilotinib or dasatinib switched therapies less frequently than patients treated with imatinib, irrespective of subsequent TKI therapy. Conclusions Although patient numbers were small, this real-world evidence study with patients with CML confirms that ELN guidelines are generally implemented in Swiss clinical practice, with a large proportion of patients achieving ELN 2013 milestones. While TKI use involved all inhibitors approved at the time of the study, an unexpectedly high number of TKI therapy switches suggests a clear difference in TKI use between registration trials and clinical practice. Keywords: Chronic myeloid leukemia, Deep molecular response, Real-world evidence, Tyrosine kinase inhibitors
In this work, model approaches for the internal processes of large-format lithium-ion batteries are developed, experimentally parameterized, and validated. The electrochemical losses in the ...electrode’s microstructure are investigated as well as their interaction with the heterogeneous potential and temperature distribution of large-format cells. In addition, permissible operating conditions of the cells are identified as well as potentials with regard to increasing power and energy density.
Transthyretin amyloidosis (ATTR amyloidosis) is a disease caused by deposition of transthyretin fibrils in organs and tissues, which causes their dysfunction. The clinical heterogeneity of ATTR ...amyloidosis and the variable presentation of symptoms at early disease stages, historically meant treatment delays. Diagnostic tools and therapy options of ATTR amyloidosis have markedly improved in recent years. The first Swiss Amyloidosis Network (SAN) meeting (Zurich, Switzerland, January 2020) aimed to define a consensus statement regarding the diagnostic work-up and treatment for systemic amyloidosis, tailored to the Swiss healthcare system. A consortium of 45 clinicians and researchers from all Swiss regions and universities was selected by the SAN committee to represent all sub-specialty groups involved in care of patients with amyloidosis. A steering committee conducted the literature search and analysis, wrote the critical synthesis and elaborated a list of statements that were evaluated by all the participants. These recommendations will improve outcomes and quality of life for patients with ATTR amyloidosis. A global review of these guidelines is planned every 3 years with a formal meeting of all the involved experts.
Prothrombinase-induced clotting time (PiCT) is proposed as a rapid and inexpensive laboratory test to measure direct oral anticoagulant (DOAC) drug levels. In a prospective, multicenter ...cross-sectional study, including 851 patients, we aimed to study the accuracy of PiCT in determining rivaroxaban, apixaban, and edoxaban drug concentrations and assessed whether clinically relevant drug levels could be predicted correctly. Citrated plasma samples were collected, and the Pefakit® PiCT was utilized. Ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure drug concentrations. Cut-off levels were established using receiver-operating characteristics curves. We calculated sensitivities and specificities with respect to clinically relevant drug concentrations. Spearman’s correlation coefficient between PiCT and drug concentrations was 0.85 in the case of rivaroxaban (95% CI 0.82, 0.88), 0.66 for apixaban (95% CI 0.60, 0.71), and 0.78 for edoxaban (95% CI 0.65, 0.86). The sensitivity to detect clinically relevant drug concentrations was 85.1% in the case of 30 µg L−1 (95% CI 82.0, 87.7; specificity 77.9; 72.1, 82.7), 85.7% in the case of 50 µg L−1 (82.4, 88.4; specificity 77.3; 72.5, 81.5), and 85.1% in the case of 100 µg L−1 (80.9, 88.4; specificity 73.2%; 69.1, 76.9). In conclusion, the association of PiCT with DOAC concentrations was fair, and the majority of clinically relevant drug concentrations were correctly predicted.
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