RESUMO
Background: Boiling histotripsy (BH), a mechanical focused ultrasound ablation strategy, can elicit intriguing signatures of anti-tumor immunity. However, the influence of BH on dendritic cell function is unknown, compromising our ability to optimally combine BH with immunotherapies to control metastatic disease. Methods: BH was applied using a sparse scan (1 mm spacing between sonications) protocol to B16F10-ZsGreen melanoma in bilateral and unilateral settings. Ipsilateral and contralateral tumor growth was measured. Flow cytometry was used to track ZsGreen antigen and assess how BH drives dendritic cell behavior. Results: BH monotherapy elicited ipsilateral and abscopal tumor control in this highly aggressive model. Tumor antigen presence in immune cells in the tumor-draining lymph nodes (TDLNs) was ~3-fold greater at 24h after BH, but this abated by 96h. B cells, macrophages, monocytes, granulocytes, and both conventional dendritic cell subsets (i.e. cDC1s and cDC2s) acquired markedly more antigen with BH. BH drove activation of both cDC subsets, with activation being dependent upon tumor antigen acquisition. Our data also suggest that BH-liberated tumor antigen is complexed with damage-associated molecular patterns (DAMPs) and that cDCs do not traffic to the TDLN with antigen. Rather, they acquire antigen as it flows through afferent lymph vessels into the TDLN. Conclusion: When applied with a sparse scan protocol, BH monotherapy elicits abscopal melanoma control and shapes dendritic cell function through several previously unappreciated mechanisms. These results offer new insight into how to best combine BH with immunotherapies for the treatment of metastatic melanoma.
Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Melanoma , Humanos , Melanoma/terapia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Antígenos de Neoplasias , Células DendríticasRESUMO
BACKGROUND: A recent real-world study observed that 24% of patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADOs) initiated nontargeted therapies before biomarker test results became available. This study assessed the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in aNSCLC. MATERIALS AND METHODS: This retrospective analysis of a nationwide electronic health record-derived deidentified database included patients agedâ ≥18 years diagnosed with aNSCLC with ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, and NTRK) from January 1, 2015, to October 18, 2022, by biomarker testing within 90 days after advanced diagnosis and received 1L treatment. Cohorts were defined by treatment patterns ≤42 days after test results: "Upfront TT" received 1L TT ≤42 days; "Switchers" initiated 1L non-TT before or after testing but switched to TT ≤42 days; and "Non-switchers" initiated non-TT before or after testing and did not switch at any time. Adjusted multivariate Cox regression evaluated real-world progression-free survival, real-world time to next treatment or death, and real-world overall survival. RESULTS: A total of 3540 patients met the study criteria; 78% were treated in a community setting, and 50% underwent next-generation sequencing (NGS). There was no significant difference in outcomes between Switchers and Upfront TT; inferior outcomes were observed in Non-switchers versus Upfront TT. CONCLUSION: Our findings demonstrated improved outcomes with upfront 1L TT versus non-TT in patients with aNSCLC with ADOs and observed timely switching to TT after biomarker test result had similar outcomes to Upfront TT. Opportunities remain to improve the use of NGS for early ADO identification and determination of 1L TT.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia de Alvo Molecular , Oncogenes , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Alvo Molecular/métodos , Idoso , Adulto , Biomarcadores Tumorais/genética , Idoso de 80 Anos ou maisRESUMO
Abstract The thickness and shade of a restoration will affect the transmission of light from the light-curing unit (LCU). This study determined the power (mW), spectral radiant power (mW/nm), and beam profile of different LCUs through various thicknesses and shades of a CAD-CAM resin composite (BRAVA Block, FGM). Five thicknesses: 0.5; 0.75; 1.0; 1.5, and 2.0 mm, in three shades: Bleach; A2 and A3.5 of a CAD-CAM resin (n = 5). Two single-peak LCUs: EL, Elipar DeepCure-S (3M Oral Care); and OP, Optilight Max (Gnatus), and one multiple-peak LCU: VL, VALO Grand (Ultradent), were used. The LCUs were positioned touching the surface of the BRAVA Block. The power and emission spectrum were measured using a fiberoptic spectrometer attached to an integrating sphere, and the beam profiles using a laser beam profiler. The effect of the material thickness on the light attenuation coefficients was determined. VL and EL delivered more homogeneous beam profiles than OP. The type of the BRAVA Block had a significant effect on the transmitted power, and wavelengths of transmitted light (p < 0.001). There was an exponential reduction in the power and emission spectrum as the thickness of the BRAVA Block increased (p < 0.001). The light transmission through the A2 shade was least affected by the thickness (p < 0.001). The attenuation coefficient was higher for the violet light and higher for A3.5 than the A2 or Bleach shades. No violet light from the VL could be detected at the bottom of 2.0 mm of the BRAVA Block.
RESUMO
Abstract The combination of the restoration location, the hand preference of the operator using the light-curing unit (LCU), and the design of the LCU all can have an impact on the amount of the light delivered to the restoration. To evaluate the effect of left-handed or right-handed users, the position of the operator (dentist or assistant), and the LCU design on the irradiance, radiant exposure and emission spectrum delivered to the same posterior tooth. Two light emitting diode (LED) LCUs were tested: an angulated monowave LCU Radii-Cal (SDI, Victoria, Australia) and a straight aligned multi-peak LCU Valo Cordless (Ultradent, South Jordan, UT, USA). The irradiance values (mW/cm2), radiant exposure (J/cm2) and emission spectrum were measured using a sensor in maxillary left second molar tooth. The irradiance and radiant exposure were analyzed using three-way ANOVA followed by Tukey test (a=0.05). The emission spectra (nm) were analyzed descriptively. The interaction between LCU design, operator position, and hand preference significantly influenced the irradiance and radiant exposure (P<0.001). In all cases, Valo delivered significantly higher irradiance than Radii-Cal. The handedness and the operator position affected the irradiance and radiant exposure delivered from Valo. Operator position and access affect the irradiance and radiant exposure delivered to the maxillary left second molar. The irradiance and radiant exposure can be greater when a right-hand operator is positioned on the right side of the chair and a left-hand operator is positioned on the left side of the chair. This may result in better resin composite polymerization.
Resumo A combinação da localização da restauração, a preferência de mão do operador ao utilizar aparelhos fotopolimerizadores (AFP) com luz emitida por diodo (LED) e o formato do AFP podem afetar a quantidade de luz fornecida à restauração. O objetivo foi avaliar o efeito de operadores canhotos e destros, a posição do operador (dentista ou auxiliar), e o formato do AFP na irradiância, energia radiante e espectro de luz entregue ao mesmo dente posterior. Dois AFP foram testados: um com formato angulado, onda única Radii-Cal (SDI, Victoria, Australia) e um formato reto multi-pico Valo Cordless (Ultradent, South Jordan, UT, USA). Os valores de irradiância (mW/cm²), energia radiante (J/cm²) e espectro de luz foram medidos utilizando um sensor no segundo molar superior esquerdo. A irradiância e energia radiante foram analisados utilizando ANOVA 3 fatores seguido por teste de Tukey (a=0.05). O espectro de luz (nm) foi analisado de forma descritiva. A interação entre o formato do AFP, posição do operador e preferência de mão foram significativamente influentes na irradiância e energia radiante (P<0.001). Em todos os casos, Valo teve irradiância significativamente maior que Radii-Cal. A mão dominante e a posição do operador afetaram a irradiância e energia radiante com o Valo. Posição do operador e acesso afetou a irradiância e exposição radiante entregue ao segundo molar superior esquerdo. A irradiância e exposição radiante teve melhores resultados quando AFP foi utilizado com a mão direita pelo operador posicionado na cadeira do lado direito e mão esquerda do operador posicionado do lado esquerdo da cadeira. Estes resultados podem levar a uma melhor polimerização da resina composta.
Assuntos
Humanos , Exposição à Radiação , Assistentes de Odontologia , Lâmpadas de Polimerização Dentária , Lateralidade Funcional , Luz , Desenho de EquipamentoRESUMO
Abstract: The effects of tooth brushing could affect the long-term esthetic outcome of composite restorations. This study evaluated the effect of two different emission spectrum light-curing units on the surface roughness, roughness profile, topography and microhardness of bulk-fill composites after in vitro toothbrushing. Valo (multiple-peak) and Demi Ultra (single-peak) curing lights were each used for 10s to polymerize three bulk-fill resin composites: Filtek Bulk Fill Posterior Restorative (FBF), Tetric EvoCeram Bulk Fill (TET) and Surefil SDR Flow (SDR). After 30,000 reciprocal strokes in a toothbrushing machine, the roughness profile, surface roughness, surface morphology, and microhardness were examined. Representative SEM images were also obtained. When light-cured with the Demi Ultra, SDR showed the most loss in volume compared to the other composites and higher volume loss compared to when was light-cured with Valo. The highest surface roughness and roughness profile values were found in SDR after toothbrushing, for both light-curing units tested. FBF always had the greatest microhardness values. Light-curing TET with Valo resulted in higher microhardness compared to when using the Demi Ultra. Confocal and SEM images show that toothbrushing resulted in smoother surfaces for FBF and TET. All composites exhibited surface volume loss after toothbrushing. The loss in volume of SDR depended on the light-curing unit used. Toothbrushing can alter the surface roughness and superficial aspect of some bulk-fill composites. The choice of light-curing unit did not affect the roughness profile, but, depending on the composite, it affected the microhardness.
Assuntos
Escovação Dentária/efeitos adversos , Resinas Compostas/efeitos da radiação , Lâmpadas de Polimerização Dentária , Propriedades de Superfície/efeitos dos fármacos , Propriedades de Superfície/efeitos da radiação , Fatores de Tempo , Teste de Materiais , Microscopia Eletrônica de Varredura , Reprodutibilidade dos Testes , Análise de Variância , Microscopia Confocal , Resinas Compostas/química , Cura Luminosa de Adesivos Dentários/métodos , Polimerização , Dureza/efeitos dos fármacos , Dureza/efeitos da radiaçãoRESUMO
Abstract Contemporary dentistry literally cannot be performed without use of resin-based restorative materials. With the success of bonding resin materials to tooth structures, an even wider scope of clinical applications has arisen for these lines of products. Understanding of the basic events occurring in any dental polymerization mechanism, regardless of the mode of activating the process, will allow clinicians to both better appreciate the tremendous improvements that have been made over the years, and will also provide valuable information on differences among strategies manufacturers use to optimize product performance, as well as factors under the control of the clinician, whereby they can influence the long-term outcome of their restorative procedures.
Assuntos
Lâmpadas de Polimerização Dentária , Cimentos Dentários/química , Cura Luminosa de Adesivos Dentários/instrumentação , Cura Luminosa de Adesivos Dentários/métodos , Fotoiniciadores Dentários/química , Polimerização , Absorção de Radiação , Cimentos Dentários/efeitos da radiação , Restauração Dentária Permanente/instrumentação , Restauração Dentária Permanente/métodos , Polimerização/efeitos da radiação , Doses de Radiação , Temperatura , Fatores de TempoRESUMO
Abstract This study measured the radiant power (mW), irradiance (mW/cm2) and emission spectra (mW/cm2/nm) of 22 new, or almost new, light curing units (LCUs): - Alt Lux II, BioLux Standard, Bluephase G2, Curing Light XL 3000, Demetron LC, DX Turbo LED 1200, EC450, EC500, Emitter C, Emitter D, KON-LUX, LED 3M ESPE, Led Lux II, Optilight Color, Optilight Max, Optilux 501, Poly Wireless, Radii cal, Radii plus, TL-01, VALO Cordless. These LCUs were either monowave or multiple peak light emitting diode (LED) units or quartz-tungsten-halogen LCUs used in anterior and posterior teeth. The radiant power emitted by the LCUs was measured by a laboratory grade laser power meter. The tip area (cm²) of the LCUs was measured and used to calculate the irradiance from the measured radiant power source. The MARC-Patient Simulator (MARC-PS) with a laboratory grade spectrometer (USB4000, Ocean Optics) was used to measure the irradiance and emission spectrum from each LCU three times at the sensor located on the facial of the maxillary central incisors and then separately at the occlusal of a maxillary second molar. The minimum acceptable irradiance level was set as 500 mW/cm2. Irradiance data was analyzed using two-way ANOVA and the radiant power data was analyzed by one-way ANOVA followed by Tukey test (a=0.05). In general, the irradiance was reduced at the molar tooth for most LCUs. Only the Valo, Bluephase G2 and Radii Plus delivered an irradiance similar to the anterior and posterior sensors greater than 500 mW/cm2. KON-LUX, Altlux II, Biolux Standard, TL-01, Optilux 501, DX Turbo LED 1200 LCUs delivered lower irradiance values than the recommended one used in molar region, KON-LUX and Altlux II LCUs used at the maxillary incisors. Bluephase G2 and Optilight Max delivered the highest radiant power and KON-LUX, Altlux II and Biolux Standard delivered the lowest power. The emission spectrum from the various monowave LED LCUs varied greatly. The multi-peak LCUs delivered similar emission spectra to both sensors.
Resumo Este estudo mediu a potência (mW), irradiância (mW/cm2) e espectro da luz (mW/cm2/nm) emitida por 22 fontes de luz (Alt Lux II, BioLux Standard, Bluephase G2, Curing Light XL 3000, Demetron LC, DX Turbo LED 1200, EC450, EC500, Emitter C, Emitter D, KON-LUX, LED 3M ESPE, Led Lux II, Optilight Color, Optilight Max, Optilux 501, Poly Wireless, Radii cal, Radii plus, TL-01, VALO Cordless) disponíveis comercialmente. A potência emitida pelas fontes de luz foi medida usando um medidor laboratorial de potencia com grade a laser. A área (cm²) da ponta ativa efetiva das fontes de luz foi medida com paquímetro digital e utilizada para calcular a irradiância emitida. O simulador de paciente-MARC (MARC - PS) com espectrómetro (USB4000, Ocean Optics) foi usado para medir a irradiância e o espectro de luz emitida por cada fonte de luz na região anterior e posterior. Esta medição foi repetida por três vezes em dois sensores localizados na região anterior e posterior da arcada dentária. Os dados de irradiância foram analisados utilizando análise de variância em dois fatores, e os dados de potência foram analisados com análise de variância em fator único seguido pelo teste de Tukey (a=0,05). As fontes de luz Valo, Bluephase G2, Radii Plus emitiram irradiância semelhante tanto na região anterior como posterior com valores superiores ao mínimo de 500 mW/cm2. Seis fontes de luz emitiram irradiância menor que o recomendado (500 mW/cm2) quando usadas na região posterior: Kon-lux, Altlux II, Biolux Standard TL-01, Optilux 501, DX Turbo LED 1200 e duas quando usadas na região anterior: Kon-lux e Altlux II LCUs. As fontes Bluephase G2, Optilight Max emitiram os maiores valores de potência e as fontes de luz Altlux II e Biolux Standard emitiram os menores valores de potência. O espectro de luz das fontes LED de espectro único variou de forma evidente entre as fontes. As fontes LED multi pico de espectro emitiram espectros de luz similar para ambos os sensores. A fotoativação na região posterior tende a reduzir substancialmente a irradiância da maioria das fontes de luzes testadas.
Assuntos
Humanos , Lâmpadas de Polimerização Dentária , Restauração Dentária Permanente , Lasers , Simulação de Paciente , Análise Espectral/instrumentação , Dente/efeitos da radiaçãoRESUMO
Abstract The high irradiance and the different emission spectra from contemporary light curing units (LCU) may cause ocular damage. This study evaluated the ability of 15 eye protection filters: 2 glasses, 1 paddle design, and 12 dedicated filters to block out harmful light from a monowave (HP-3M ESPE) and a broad-spectrum (Valo, Ultradent) LED LCU. Using the anterior sensor in the MARC-Patient Simulator (BlueLight Analytics) the irradiance that was delivered through different eye protection filters was measured three times. The LCUs delivered a similar irradiance to the top of the filter. The mean values of the light that passed through the filters as percent of the original irradiance were analyzed using two-way ANOVA followed by Tukey test (a= 0.05). The emission spectra from the LCUs and through the filters were also obtained. Two-way ANOVA showed that the interaction between protective filters and LCUs significantly influenced the amount of light transmitted (p< 0.001). Tukey test showed that the amount of light transmitted through the protective filters when using the HP-3M-ESPE was significantly greater compared to when using the Valo, irrespective of the protective filter tested. When using the HP-3M-ESPE, the Glasses filter allowed significantly more light through, followed by XL 3000, ORTUS, Google Professional, Gnatus filters. The Valo filter was the most effective at blocking out the harmful light. Some protective filters were less effective at blocking the lower wavelengths of light (<420 nm). However, even in the worst scenario, the filters were able to block at least 97% of the irradiance.
Resumo A alta irradiância e diferentes espectros de luz emitidos por aparelhos fotopolimerizadores (Fp) podem causar danos oculares. Este estudo avaliou a capacidade de 15 filtros de proteção ocular em bloquear a luz prejudicial de um Fp convencional (HP-3M ESPE) e outro de largo espectro (Valo, Ultradent). Utilizando sensor anterior do equioamento MARC-Patient Simulator (BlueLight Analytics inc.) a irradiância que passou através dos diferentes filtros protetores foi mensuradas três vezes. Os valores médios da irradiância que passaram pelos filtros foram analisados usando Análise de variância fatorial e pelo teste de Tukey (a= 0.05). O espetro emitido dos Fps através dos filtros também foi obtido. A análise de variância mostrou que a interação entre os filtros protetores e Fps influenciou significantemente a quantidade de luz transmitida (p<0,001). O teste de Tukey mostrou que a quantidade que luz transmitida através dos protetores oculares quando usado o HP-3M ESPE foi significantemente maior quando comparado aos valores para o Valo, independentemente do filtro testado. Quando foi utilizado a fonte de luz HP-3M ESPE, o filtro de proteção ocular permitiu significativamente maior passagem de luz, seguido por XL 3000, ORTUS, Google Professional, e pelo filtro Gnatus. O filtro do Valo foi o mais eficiente ao bloquear a luz prejudicial. Alguns filtros foram menos eficazes ao bloquear menores comprimentos de onde (<420 nm). No entanto, mesmo no pior cenário dos resultados deste estudo, os filtros foram capazes de bloquear ao menos 97% da irradiância emitida pelas fontes de luz testadas.