RESUMO
Currently, wide arrays of fixed functional appliances are available for the correction of Class II malocclusion. The orthodontist must choose from these appliances depending on the mechanics, efficiency, and cost of the appliance. Fixed functional appliances may reduce the individual visits and hence the cost as compared to the removable appliances. Additionally, it may save the clinician's chair time. This report discussed the in-house laboratory fabrication and clinical procedure of customized fixed functional appliances by utilizing the readily available dental materials in the orthodontic clinical setting.
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BACKGROUND: Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood. METHODS: This study included all adult patients who received BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or combinations BRAF/MEK inhibitors (vemurafenib/cobimetinib; dabrafenib/trametinib; encorafenib/binimetinib). We utilized the cross-sectional FDA's Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics/IBM MarketScan database from 2011 to 2018. Various CVAEs, including arterial hypertension, heart failure (HF), and venous thromboembolism (VTE), were studied using adjusted regression techniques. RESULTS: In FAERS, 7752 AEs were reported (40% BRAF and 60% BRAF/MEK). Median age was 60 (IQR 49-69) years with 45% females and 97% with melanoma. Among these, 567 (7.4%) were cardiovascular adverse events (mortality rate 19%). Compared with monotherapy, combination therapy was associated with increased risk for HF (reporting odds ratio [ROR] = 1.62 (CI = 1.14-2.30); p = 0.007), arterial hypertension (ROR = 1.75 (CI = 1.12-2.89); p = 0.02) and VTE (ROR = 1.80 (CI = 1.12-2.89); p = 0.02). Marketscan had 657 patients with median age of 53 years (IQR 46-60), 39.3% female, and 88.7% with melanoma. There were 26.2% CVAEs (CI: 14.8%-36%) within 6 months of medication start in those receiving combination therapy versus 16.7% CVAEs (CI: 13.1%-20.2%) among those receiving monotherapy. Combination therapy was associated with CVAEs compared to monotherapy (adjusted HR: 1.56 (CI: 1.01-2.42); p = 0.045). CONCLUSIONS AND RELEVANCE: In two independent real-world cohorts, combination BRAF/MEK inhibitors were associated with increased CVAEs compared to monotherapy, especially HF, and hypertension.
Assuntos
Antineoplásicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azetidinas/efeitos adversos , Benzimidazóis/efeitos adversos , Carbamatos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cardiotoxicidade/etiologia , Neoplasias do Colo/tratamento farmacológico , Estudos Transversais , Feminino , Insuficiência Cardíaca/induzido quimicamente , Humanos , Hipertensão/induzido quimicamente , Imidazóis/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Oximas/efeitos adversos , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Sistema de Registros , Análise de Regressão , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/efeitos adversos , Vemurafenib/efeitos adversos , Tromboembolia Venosa/induzido quimicamente , Adulto JovemRESUMO
Immune checkpoint inhibitors, mainly drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways, represent a remarkable advance in lung cancer treatment. Immune checkpoint inhibitors targeting PD-1 and PD-L1 are approved for the treatment of patients with non-small-cell lung cancer, with impressive clinical activity and durable responses in some patients. This review will summarize the mechanism of action of these drugs, the clinical development of these agents and the current role of these agents in the management of patients with lung cancer. In addition, the review will discuss the role of predictive biomarkers for optimal patient selection for immunotherapy and management of autoimmune side effects of these agents.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Antineoplásicos Imunológicos/efeitos adversos , Autoimunidade/efeitos dos fármacos , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Tomada de Decisão Clínica , Humanos , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Seleção de Pacientes , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
We reveal the potential of step-index fibers consisting of a metaphosphate glass core and a silica cladding as an ultrafast octave-spanning supercontinuum source. The hybrid waveguide was fabricated by pressure-assisted melt filling and possesses a sophisticated dispersion behavior with two zero-dispersion points in the proximity of the Erbium laser bands. The fiber generates an octave-spanning supercontinuum from 0.7 to 2.4 µm if pumped at 1.56 µm with 30 fs pulses and energies as low as 300 pJ. Numerical simulations reveal soliton fission and double dispersive wave generation as the dominant broadening effect. This study highlights phosphate glasses as a promising new candidate for the next generation of broadband photonic devices, as they allow for high rare earth-doping levels and dispersion posttuning via plasmonic nanoparticle growth.
RESUMO
We show broadband azimuthal polarization state conversion using an entirely connectorized step-index fiber with a central gold nanowire. This device provides broadband polarization discrimination of the low-loss TE01 fiber mode with respect to all other modes, and converts light into the azimuthal polarization state, resulting in a high beam quality and an azimuthal conversion efficiency of 37%. The device is monolithically integrated into fiber circuitry, representing a new platform for plasmonics and fiber optics and enabling important applications in super-resolution microscopy, laser tweezing, and plasmonic superfocussing.
RESUMO
Phosphate glasses represent promising candidates for next-generation photonic devices due to their unique characteristics, such as vastly tunable optical properties, and high rare earth solubility. Here we show that silver metaphosphate wires with bulk optical properties and diameters as small as 2 µm can be integrated into silica fibers using pressure-assisted melt filling. By analyzing two types of hybrid metaphosphate-silica fibers, we show that the filled metaphosphate glass has only negligible higher attenuation and a refractive index that is identical to the bulk material. The presented results pave the way towards new fiber-type optical devices relying on metaphosphate glasses, which are promising materials for applications in nonlinear optics, sensing and spectral filtering.