ABSTRACT
INTRODUCTION: The long-term clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) and a complete response (CR) to the tyrosine kinase inhibitor (TKI) sunitinib are poorly known. The characteristics of these patients could reveal previously undetected associations with clinical variables. PATIENTS AND METHODS: This observational, retrospective study (ATILA) used data from a registry of patients with mRCC who had received first-line sunitinib and had achieved CR from 2007 to 2018 in Spain. RESULTS: Sixty-two patients with CR were included; 48 patients (77.4%) received sunitinib in monotherapy and 14 (22.6%) combined with or followed by local treatment. Median age was 58.5 years (range, 32-81). Most patients (79.0%) had clear cell histology and had undergone previous nephrectomy (90.3%). The majority (70.2%) had an intermediate IMDC prognosis, 23% favorable and 7.0% poor. The median time on treatment with sunitinib was 28.2 months (IQR, 16.7-41.0) and the median time to CR was 10.9 months (IQR, 7.2-19.3). After a median follow-up of 8 years (range, 3-13 years), the median PFS was not reached. The overall median duration of complete response was 64.1 months (IQR, 32.2-99.4). The tolerance and safety profile of sunitinib was consistent with previous reports. CONCLUSION: Durable CR to sunitinib was observed in patients regardless the prognosis group, metastasis site or histology type, with 75% of patients remaining in CR after 10 years. CLINICALTRIALS: gov: NCT03916458.
Subject(s)
Antineoplastic Agents , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Middle Aged , Sunitinib/therapeutic use , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/secondary , Antineoplastic Agents/therapeutic use , Retrospective Studies , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Indoles/therapeutic use , Pyrroles/therapeutic useABSTRACT
In this paper, we present a theoretical model based on the nonlinear Schrödinger equation to characterize GHz-range passively mode-locked fiber lasers. The modeled cavities of the lasers are configured by a highly doped and polarization-maintaining single fiber of a single type. For different pulse repetition rates, ranging from 1.0 to 10.0 GHz, gain parameters and pump threshold for a stable mode-locked laser emission are studied. Pulse time width, spectral width, and semiconductor saturable absorber mirror (SESAM) properties are defined to achieve stable emission. To experimentally validate our theoretical model, 1.0 and 2.2 GHz laser cavities have been built up and amplified. A stable and robust operation for both frequencies was obtained, and the experimental measurements have been found to match the theoretical predictions. Finally, enhanced environmental stability has been achieved using a cavity temperature control system and an antivibration enclosure.
ABSTRACT
Once metastatic bladder cancer has progressed to first-line treatment, the number of therapeutic options is scarce. Among chemotherapeutic agents showing activity in phase II trials, including taxanes, vinflunine (VFL) is the only one shown to increase overall survival in a phase III trial. In addition to its efficacy, VFL is safe in special population groups. Despite this, the prognosis for these patients remains poor, and more effective therapies need to be developed. Agents acting on new therapeutic targets as well as biomarkers to aid matching patients to specific treatments are currently under evaluation. In this regard, immunotherapy is showing promising results. In this article, a critical review of current treatments and future prospects is made, and therapy recommendations are made based on existing scientific evidence.
Subject(s)
Antineoplastic Agents/therapeutic use , Practice Guidelines as Topic/standards , Urinary Bladder Neoplasms/drug therapy , Clinical Trials as Topic , Humans , Molecular Targeted Therapy , Prognosis , Urinary Bladder Neoplasms/secondaryABSTRACT
After progression during first-line treatment in advanced non-small-cell lung cancer (NSCLC), a large percentage of patients are candidates for second-line treatment. The majority do not have epidermal growth factor receptor-activating mutations (EGFRwt). This article reviews the treatment options available for this subpopulation of patients, which includes essentially docetaxel, pemetrexed and erlotinib. These drugs all have similar efficacy, both in terms of objective response rates and overall survival, although with different toxicity profiles. In view of the similar efficacy of the three agents (docetaxel, pemetrexed and erlotinib) in the second-line treatment of NSCLC in the EGFRwt population, and although there are no prospective studies on predictive variables or new molecular markers available, selection of the treatment will depend on the histological type (pemetrexed); patient preference (oral as opposed to intravenous formulation); the presence of comorbid conditions; quality of life; previous or residual toxicities; the risk of neutropenia; response to and the duration of the first-line chemotherapy; and history of smoking.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/metabolism , Glutamates/therapeutic use , Guanine/analogs & derivatives , Lung Neoplasms/drug therapy , Quinazolines/therapeutic use , Taxoids/therapeutic use , Animals , Carcinoma, Non-Small-Cell Lung/secondary , Docetaxel , ErbB Receptors/genetics , Erlotinib Hydrochloride , Guanine/therapeutic use , Humans , Lung Neoplasms/pathology , PemetrexedABSTRACT
Docetaxel is the standard first-line chemotherapy for men with metastatic castration-resistant prostate cancer. Until recently, there was no standard therapy after failure of docetaxel treatment. Cabazitaxel has been shown to improve overall survival in this setting. As a result, the treatment paradigm for mCRPC is changing rapidly. The improved survival shown with cabazitaxel provides an important new opportunity to treat men with mCRPC after docetaxel treatment. Despite the toxicity recorded in the pivotal study, subsequent trials have shown that cabazitaxel is a safe drug. Patient selection and the optimal interval between prior docetaxel treatment and cabazitaxel remain the critical issues. According to a subanalysis of the various studies discussed in this review, there is a patient profile that will probably benefit from use of cabazitaxel after docetaxel failure. Cabazitaxel represents a new treatment option for patients with prostate cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Taxoids/therapeutic use , Antineoplastic Agents/administration & dosage , Docetaxel , Humans , Male , Neoplasm Metastasis , Prostatic Neoplasms, Castration-Resistant/mortality , Prostatic Neoplasms, Castration-Resistant/pathology , Survival Rate , Taxoids/administration & dosageABSTRACT
Fundamentos y objetivo: Los contaminantes del aire urbano están constituidos por una mezcla heterogénea de sustancias presentes en estado gaseoso y aerosoles. El objetivo del presente estudio fue comparar los efectos causados por la exposición a contaminantes en fase gas y partículas atmosféricas en aire ambiente en pacientes que ingresan por un síndrome coronario agudo (SCA), en relación con la presencia o no de lesiones obstructivas significativas (LOS) en arterias coronarias epicárdicas. Pacientes y método: Analizamos de forma prospectiva a un total de 2.110 pacientes con el diagnóstico de SCA. Se determinaron las concentraciones medias de contaminantes en fase gas y partículas atmosféricas desde el día anterior hasta 7 días previos al ingreso. Se dividió la población de estudio en aquellos con presencia o no de LOS. Resultados: De los 2.110 pacientes con SCA, 1.892 presentaban LOS y 218 no. Cuando se compararon las concentraciones de los contaminantes en fase gas, se observó que, en los pacientes con LOS, el dióxido de azufre tenía una tendencia a tener valores más altos (media [DE] de 10,93 [9,31] frente a 8,33 [6,77] ¿g/m; p=0,004). El análisis multivariable muestra que por cada 10¿g/m3 de aumento del dióxido de azufre, aumenta el riesgo de ingreso por SCA con LOS frente a sin LOS un 41% (odds ratio 1,41; intervalo de confianza del 95% 1,039-1,931; p=0,028). Conclusiones: En nuestra población de estudio, la exposición a concentraciones elevadas de dióxido de azufre constituyen un factor precipitante de ingreso para pacientes con SCA y LOS (AU)
Background and objectives: Urban air pollutants are composed of a heterogeneous mixture of substances in gas and aerosol states. The aim of this study was to compare the effects caused by exposure to contaminants in the gas phase and atmospheric particles in ambient air in patients hospitalized for acute coronary syndrome (ACS) regarding the presence or absence of significant obstructive lesions (SOL) in epicardial coronary arteries. Patients and methods: Prospectively analyzed a total of 2,110 patients with a diagnosis of ACS. We determined the mean concentrations of contaminants in the gas phase and atmospheric particles from the day before until 7 days prior to admission (1 to 7 days lag time). We divided the study population into those with presence or absence of SOL. Results: Of the 2,110 patients with ACS, 1,892 presented SOL and 218 without SOL. When comparing the concentrations of contaminants in the gas phase, we observed that the sulfur dioxide in patients with SOL had a trend toward higher values (10.93±8.33 versus 9.31±6.77¿g/m3; P=.004). Multivariate analysis shows that for every 10¿g/m3 increase of sulfur dioxide, there is an increase in the risk of hospitalization for ACS with SOL a 41% (odds ratio 1.41; 95% confidence interval 1.039-1.931; P=.028). Conclusions: In our study population, exposure to high concentrations of sulfur dioxide is a precipitating factor for admission of patients with ACS and SOL (AU)
Subject(s)
Humans , Sulfur Dioxide/adverse effects , Environmental Exposure/adverse effects , Acute Coronary Syndrome/complications , Coronary Occlusion/chemically induced , Myocardial Infarction/complications , Angina, Unstable/complications , Risk FactorsABSTRACT
AIM: To study whether the concentrations of particulate matter in ambient air are associated with hospital admission due to heart failure in patients with heart failure with preserved ejection fraction and reduced ejection fraction. METHODS: We studied 353 consecutive patients admitted into a tertiary care hospital with a diagnosis of heart failure. Patients with ejection fraction of ≥ 45% were classified as having heart failure with preserved ejection fraction and those with an ejection fraction of < 45% were classified as having heart failure with reduced ejection fraction. We determined the average concentrations of different sizes of particulate matter (< 10, < 2.5, and < 1 µm) and the concentrations of gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide and ozone) from 1 d up to 7 d prior to admission. RESULTS: The heart failure with preserved ejection fraction population was exposed to higher nitrogen dioxide concentrations compared to the heart failure with reduced ejection fraction population (12.95 ± 8.22 µg/m(3) vs 4.50 ± 2.34 µg/m(3), P < 0.0001). Multivariate analysis showed that nitrogen dioxide was a significant predictor of heart failure with preserved ejection fraction (odds ratio ranging from (1.403, 95%CI: 1.003-2.007, P = 0.04) to (1.669, 95%CI: 1.043-2.671, P = 0.03). CONCLUSION: This study demonstrates that short-term nitrogen dioxide exposure is independently associated with admission in the heart failure with preserved ejection fraction population.
ABSTRACT
BACKGROUND AND OBJECTIVES: Urban air pollutants are composed of a heterogeneous mixture of substances in gas and aerosol states. The aim of this study was to compare the effects caused by exposure to contaminants in the gas phase and atmospheric particles in ambient air in patients hospitalized for acute coronary syndrome (ACS) regarding the presence or absence of significant obstructive lesions (SOL) in epicardial coronary arteries. PATIENTS AND METHODS: Prospectively analyzed a total of 2,110 patients with a diagnosis of ACS. We determined the mean concentrations of contaminants in the gas phase and atmospheric particles from the day before until 7 days prior to admission (1 to 7 days lag time). We divided the study population into those with presence or absence of SOL. RESULTS: Of the 2,110 patients with ACS, 1,892 presented SOL and 218 without SOL. When comparing the concentrations of contaminants in the gas phase, we observed that the sulfur dioxide in patients with SOL had a trend toward higher values (10.93 ± 8.33 versus 9.31 ± 6.77 µg/m(3); P = .004). Multivariate analysis shows that for every 10 µg/m(3) increase of sulfur dioxide, there is an increase in the risk of hospitalization for ACS with SOL a 41% (odds ratio 1.41; 95% confidence interval 1.039-1.931; P = .028). CONCLUSIONS: In our study population, exposure to high concentrations of sulfur dioxide is a precipitating factor for admission of patients with ACS and SOL.
Subject(s)
Acute Coronary Syndrome/etiology , Air Pollutants/toxicity , Coronary Stenosis/etiology , Environmental Exposure , Particulate Matter/toxicity , Sulfur Dioxide/toxicity , Acute Coronary Syndrome/epidemiology , Acute Coronary Syndrome/pathology , Aged , Air Pollutants/analysis , Catchment Area, Health , Coronary Angiography , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/epidemiology , Dose-Response Relationship, Drug , Environmental Monitoring , Female , Gases/toxicity , Hospitalization , Hospitals, University/statistics & numerical data , Humans , Male , Meteorological Concepts , Middle Aged , Particulate Matter/analysis , Prospective Studies , Risk Factors , Spain/epidemiology , Sulfur Dioxide/analysis , Time Factors , Urban PopulationABSTRACT
An environmentally-stable low-repetition rate fiber oscillator is developed to produce narrow-bandwidth pulses with several tens of picoseconds duration. Based on this oscillator an alignment-free all-fiber laser for multi-photon microscopy is realized using in-fiber frequency conversion based on four-wave-mixing. Both pump and Stokes pulses for coherent anti-Stokes Raman scattering (CARS) microscopy are readily available from one fiber end, intrinsically overlapped in space and time, which drastically simplifies the experimental handling for the user. The complete laser setup is mounted on a home-built laser scanning microscope with small footprint. High-quality multimodal microscope images of biological tissue are presented probing the CH-stretching resonance of lipids at an anti-Stokes Raman-shift of 2845 cm(-1) and second-harmonic generation of collagen. Due to its simplicity, compactness, maintenance-free operation, and ease-of-use the presented low-cost laser is an ideal source for bio-medical applications outside laser laboratories and in particular inside clinics.
Subject(s)
Lasers , Microscopy/methods , Spectrum Analysis, Raman/methods , Arteries/pathology , Atherosclerosis/pathology , Crystallization , Humans , Lipids/analysis , PhotonsABSTRACT
Introducción y objetivos: Actualmente se considera la contaminación atmosférica como un factor de riesgo emergente de enfermedades cardiovasculares. Nuestro objetivo fue comparar las concentraciones de partículas atmosféricas en aire ambiente y analizar su relación con los factores de riesgo cardiovascular en pacientes que ingresan en un servicio de cardiología de un hospital terciario con el diagnóstico de insuficiencia cardiaca y síndrome coronario agudo (SCA). Métodos: Analizamos a un total de 3.950 pacientes ingresados de forma consecutiva con el diagnóstico de insuficiencia cardiaca y SCA. Se determinaron las concentraciones medias de material particulado con tamaño < 10, 2,5 y 1μm y partículas ultrafinas, desde el día anterior hasta los 7 días previos al ingreso (1 a 7 días de retardo). Resultados: No se observaron diferencias estadísticamente significativas en las concentraciones medias de material particulado con tamaño < 10, 2,5 y 1μm en ambos grupos de población. Cuando se compararon las concentraciones de partículas ultrafinas de los pacientes ingresados por insuficiencia cardiaca y SCA, se observó que los primeros tenían tendencia a valores más altos (19.845,35±8.806,49 frente a 16.854,97±8.005,54/cm−3; p<0 001 el análisis multivariable muestra que las partículas ultrafinas son un factor de riesgo para ingresar por insuficiencia cardiaca tras controlar los distintos factores cardiovascular odds ratio=1,4; intervalo de confianza del 95%, 1,15-1,66; p=0,02). Conclusiones: En nuestra población de estudio, comparada con pacientes con SCA, la exposición a partículas ultrafinas constituye un factor precipitante del ingreso por insuficiencia cardiaca (AU)
Introduction and objectives: Currently air pollution is considered as an emerging risk factor for cardiovascular disease. Our objective was to study the concentrations of particulate matter in ambient air and analyze their relationship with cardiovascular risk factors in patients admitted to a cardiology department of a tertiary hospital with the diagnosis of heart failure or acute coronary syndrome (ACS). Methods: We analyzed 3950 consecutive patients admitted with the diagnosis of heart failure or ACS. We determined the average concentrations of different sizes of particulate matter (<10 2 5 and <1 956 m and ultrafine particles from 1 day or up to 7 days prior admission lag time Results: There were no statistically significant differences in mean concentrations of particulate matter <10 2 5 and <1 956 m in size both populations when comparing the concentrations of ultrafine particles patients admitted due to heart failure and acute coronary syndrome it was observed that former had a tendency have higher values 19 845 35 8 806 49 vs 16 854 97 8005 54cm −3, P <.001). The multivariate analysis showed that ultrafine particles are a risk factor for admission for heart failure, after controlling for other cardiovascular risk factors (odds ratio=1.4; confidence interval 95%, from 1.15 to 1.66 P=.02). Conclusions: In our study population, compared with patients with ACS, exposure to ultrafine particles is a precipitating factor for admission for heart failure (AU)
Subject(s)
Humans , Male , Female , Heart Failure/complications , Heart Failure/diagnosis , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/diagnosis , Risk Factors , Myocardial Infarction/complications , Air Pollution/adverse effects , Angina, Unstable/complications , Angina, Unstable/diagnosis , Multivariate Analysis , Odds Ratio , Confidence Intervals , 28599 , Air Pollution/prevention & controlABSTRACT
INTRODUCTION AND OBJECTIVES: Currently air pollution is considered as an emerging risk factor for cardiovascular disease. Our objective was to study the concentrations of particulate matter in ambient air and analyze their relationship with cardiovascular risk factors in patients admitted to a cardiology department of a tertiary hospital with the diagnosis of heart failure or acute coronary syndrome (ACS). METHODS: We analyzed 3950 consecutive patients admitted with the diagnosis of heart failure or ACS. We determined the average concentrations of different sizes of particulate matter (<10, <2.5, and <1 µm and ultrafine particles) from 1 day or up to 7 days prior to admission (1 to 7 days lag time). RESULTS: There were no statistically significant differences in mean concentrations of particulate matter <10, <2.5 and <1 µm in size in both populations. When comparing the concentrations of ultrafine particles of patients admitted due to heart failure and acute coronary syndrome, it was observed that the former had a tendency to have higher values (19 845.35 ± 8 806.49 vs 16 854.97 ± 8005.54 cm⻳, P <.001). The multivariate analysis showed that ultrafine particles are a risk factor for admission for heart failure, after controlling for other cardiovascular risk factors (odds ratio=1.4; confidence interval 95%, from 1.15 to 1.66 P=.02). CONCLUSIONS: In our study population, compared with patients with ACS, exposure to ultrafine particles is a precipitating factor for admission for heart failure.