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1.
Fabrice Barlesi Edward B. Garon Dong-Wan Kim Enriqueta Felip Ji-Youn Han Joo-Hang Kim Myung-Ju Ahn Mary Jo Fidler Matthew A. Gubens Gilberto de Castro Veerle Surmont Qiao Li Anne C. Deitz Gregory M. Lubiniecki Roy S. Herbst 《Journal of thoracic oncology》2019,14(5):793-801
Introduction
In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.Methods
Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ–Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain.Results
Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had “deteriorated” status and more had “improved” status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose.Conclusions
These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. 相似文献2.
Talita da Silva Mendes de Farias Ariclécio Cunha de Oliveira Sandra Andreotti Fernanda Gaspar do Amaral Patrícia Chimin André Ricardo Alves de Proença Francisco Leonardo Torres Leal Rogério Antonio Laurato Sertié Amanda Baron Campana Andressa Bolsoni Lopes Arnaldo Henrique de Souza José Cipolla‐Neto Fabio Bessa Lima 《Journal of pineal research》2015,58(3):251-261
Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24‐hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev‐erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP‐citrate lyase, malic enzyme, fatty acid synthase, and glucose‐6‐phosphate dehydrogenase) was abolished in pinealectomized animals. 相似文献
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5.
Rubens Souza de OLIVEIRA Lanna Jamile Corrêa da COSTA Fernanda Atanaena Gon?alves de ANDRADE Wilson UIEDA Luzia Fátima Alves MARTORELLI Ana Paula de Arruda Geraldes KATAOKA Elizabeth Salbé Travassos da ROSA Pedro Fernando da Costa VASCONCELOS Armando de Souza PEREIRA Ant?nio Ismael Barros do CARMO Marcus Emanuel Barroncas FERNANDES 《Revista do Instituto de Medicina Tropical de S?o Paulo》2015,57(6):497-503
The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and 2005,
in the northeast of the Brazilian State of Para, eastern Amazon basin, made this a
priority area for studies on this zoonosis. Given this, the present study provides
data on this phenomenon in an urban context, in order to assess the possible
circulation of the classic rabies virus (RABV) among bat species in Capanema, a town
in the Amazon basin. Bats were collected, in 2011, with mist nets during the wet and
dry seasons. Samples of brain tissue and blood were collected for virological and
serological survey, respectively. None of the 153 brain tissue samples analyzed
tested positive for RABV infection, but 50.34% (95% CI: 45.67-55.01%) of the serum
samples analyzed were seropositive. Artibeus planirostris was the most common
species, with a high percentage of seropositive individuals (52.46%, 95% CI: 52.31
52.60%). Statistically, equal proportions of seropositive results were obtained in
the rainy and dry seasons (c2 = 0.057, d.f. = 1, p = 0.88). Significantly
higher proportions of males (55.96%, 95% CI: 48.96-62.96%) and adults (52.37%, 95%
CI: 47.35-57.39%) were seropositive. While none of the brain tissue samples tested
positive for infection, the high proportion of seropositive specimens indicates that
RABV may be widespread in this urban area. 相似文献
6.
Gabriela Perdomo Coral Angelo Alves de Mattos 《Journal canadien de gastroenterologie》2003,17(3):187-190
BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) is an important complication in cirrhotic patients. The aim of the present study was to assess the incidence, predictive factors and prognosis for renal impairment (RI) after SBP in cirrhotic patients from southern Brazil. METHODS: Of the 1030 hospitalizations evaluated, 114 episodes of SBP were diagnosed in 94 patients (mean age 49 years; 76.59% men). SBP diagnosis was established when the ascitic fluid polymorphonuclear cell count was equal to or greater than 250 cells/mm3. Five cases were excluded. The variables assessed as possible predictors of steady or progressive RI were blood urea nitrogen and creatinine levels before the diagnosis of SBP; type of infection, antibiotic prophylaxis, first episode or recurrent SBP, presence of gastrointestinal bleeding and hepatic encephalopathy during hospitalization, SBP resolution, Child-Pugh classification, levels of blood pressure, ascitic fluid and blood polymorphonuclear cell count, bacteriological data (positive and negative ascitic fluid culture), albumin, bilirubin, sodium and prothrombin time at the moment of diagnosis. RESULTS: The incidence of SBP was 11.07%. In 61 (55.96%) episodes, SBP was associated with RI (transient in 57.37%; steady in 19.67%; and progressive in 22.95%). The mortality rate associated with progressive RI was 100%; 58.33% with steady RI; and 2.85% with transient RI. The mortality rate in patients with or without RI was 36.07% and 6.25%, respectively (P<0.001). The level of creatinine (greater than or equal to 1.3mg/dL) before the diagnosis of SBP and the rate of infection resolution were the only predictors of RI in the multivariate analysis. CONCLUSIONS: RI after SBP is a common complication, and indicates a poor prognosis for this infection. High levels of creatinine before infection and the rate of infection resolution are independent predictors of RI. 相似文献
7.
Mariela Dutra Gontijo Moura Soraya de Mattos Camargo Grossmann Linaena Méricy da Silva Fonseca Maria Inês Barreiros Senna Ricardo Alves Mesquita 《Journal of oral pathology & medicine》2006,35(6):321-326
BACKGROUND: Oral hairy leukoplakia (OHL) may be an indicator of the progression of Human Immunodeficiency Virus (HIV)-induced immuno-depression, and the evaluation of risk factors leading to OHL is important in the management of these HIV-infected patients. However, there are few studies that analyze risk factors leading to OHL in the Brazilian population. The aim of this case-control study is to present data about prevalence rates and risk factors leading to OHL in a sample of HIV-infected adults in Brazil. METHODS: This case-control study included 111 HIV-infected patients treated at a clinic for sexually transmitted diseases and HIV. In the initial examinations with dentists, variables were collected from all patients. Diagnosis of OHL was performed in accordance with the International Classification System and cytological features. The Fisher and the chi-squared tests were used for statistical analysis. The proportional prevalence and odds ratio were estimated. RESULTS: Outcome presented a positive, statistically significant association among the presence of OHL and viral load of 3000 copies/mul or greater (P = 0.0001; odds ratio (OR) = 5.8), presence of oral candidiasis (P = 0.0000; OR = 11.1), previous use of fluconazole (P = 0.0000; OR = 24.6), and use of systemic acyclovir (P = 0.032; OR = 4.3). Antiretroviral medication presented a negative, statistically significant association with the presence of OHL (P = 0.002; OR = 8.4). CONCLUSIONS: Prevalence of OHL was 28.8%. Viral load, oral candidiasis, previous use of fluconazole, and systemic acyclovir were determined to be risk factors for OHL. Antiretroviral medication proved to be protective against the development of OHL. 相似文献
8.
Lázaro Alessandro S Nunes Paulo Guimar?es Gandra Armindo Antonio Alves Lauro T Kubota Denise Vaz de Macedo 《Clinical journal of sport medicine》2006,16(5):418-421
OBJECTIVE: The authors tested the effect of blood sampling (skin versus venous puncture) on some biochemical and hematological blood parameters in athletes to answer whether skin puncture could be used as a substitute for venous puncture. DESIGN: Comparative study of 2 methods of blood samples collection. SETTING: The blood was collected in the same athletes at 3 different moments of the preparatory training phase. PARTICIPANTS: Fourteen male indoor soccer players (22 +/- 1 years old) and 7 female handball players (18 +/- 1 years old) participated. MAIN OUTCOME MEASUREMENT: Blood was collected in heparin and K3EDTA by Vacutainer BD or Microvette Sarstedt system for biochemical and hematological analyses, respectively. RESULTS: There were no significant statistical differences between the 2 methods for the values of creatine kinase, urea, creatinine, lymphocytes, and platelets. The other hematological analyzes and uric acid exhibited significant higher values in skin blood, although they were all within the normal expected range. A high degree of correlation was observed between the 2 techniques for all parameters. CONCLUSIONS: Skin puncture is a reliable, easy, accurate, and less invasive sampling method for assessing hematological and some biochemical parameters in athletes, respecting that blood samples should always be obtained from the same site, especially in follow-up studies. 相似文献
9.
C Pereira Alves 《Phlébologie》1989,42(4):585-589
Varitest plethysmography is a non-invasive diagnostic method of venous insufficiency based on the study of the emptying of leg veins by flexion movements and their subsequent filling. The Varitest records the curves and measurements of these two stages. The physiological bases of the test and its technique are presented. Our experience, following the first few cases, enabled us to identify three main groups of patients:--Patients presenting chronic symptoms, in whom the clinical examination was negative or not obvious;--Patients presenting a problem of differential diagnosis with a deep/superficial or mixed chronic venous insufficiency. It also enabled us to specify the results of the treatments. According to our results, Varitest is a simple, easy to reproduce method, presenting a sensitivity and specificity with regard to the clinical symptoms and the Doppler, of approximately 80%. Its negative aspects are the poor collaboration of the patients or their inability to be available in order to study acute venous thromboses. 相似文献
10.
A Todo-Bom A Mota Pinto V Alves S Vale Pereira M Santos Rosa 《Journal of investigational allergology & clinical immunology》2007,17(2):107-112
BACKGROUND: Asthma is a chronic inflammatory disorder of the airways. The persistence of airway inflammation depends on a decrease in apoptosis of T lymphocytes and eosinophils and survival of these activated cells. T lymphocytes expressing gamma delta receptors can be identified in human lungs and play an important role in immune defence against pathogens and in the regulation of chronic inflammation. Aging is associated with evidence of some immune dysregulation. OBJECTIVE: The aim of this study was to analyze the apoptosis receptors of T lymphocytes in long-lasting asthma, to establish their correlation with activation markers such as CD25+ and human leukocyte antigen (HLA)-DR+, and to analyze the gama delta T cell expression in this disease. METHODS: A group of 64 individuals (group A) who had had asthma for more than 30 years (mean age [+/-SD] 72 +/- 5 years) and 61 healthy individuals acting as controls--group B with 41 individuals (mean age 79 +/- 7 years) and group C with 20 individuals (mean age 38 +/- 12 years) were included in the study. All subjects underwent clinical evaluation and spirometric testing. Peripheral blood cells were stained with monoclonal antibodies anti-CD3, anti-CD4, anti-CD8, anti-CD25, anti-TCR gamma delta, anti-HLA-DR and anti-CD95. Statistical comparisons were performed between the asthmatics and the elderly control group and between the elderly control group and the adult control group. RESULTS: The average percentage of predicted forced expiratory volume in the first second was 73.6 gamma delta 25.3. The mean values of T cell receptors for asthma group A vs elderly control group B vs adult control group C respectively, were the following: CD3, 74.9+/-7 vs. 74.8 +/- 8.8 (P=ns) vs. 76.7 +/- 4.2 (P=ns); CD4, 48.8 +/- 8.7 vs. 43.5 +/- 10.2 (P=ns) vs. 44.8 +/- 3.8 (P=ns); CD8, 23.3 +/- 7.9 vs. 25.7 +/- 10.2 (P=ns) vs. 25.6 +/- 4.5 (P=ns); CD25, 14.3 +/- 5.9 vs. 22.4 +/- 7.8 (P = .0001) vs. 5.5 +/- 2.4 (P = .0001); TCR gamma delta, 2.8 +/- 2.1 vs. 4.1 +/- 3.3 (P < .05) vs. 4.6 +/- 2.1 (P=ns); HLA-DR, 18.4 +/- 9.2 vs. 17.8 +/- 5.9 (P=ns) vs. 15.4 +/- 5.1 (P=ns) and CD95, 49.3 +/- 13.7 vs. 52.6 +/- 12.1 (P=ns) vs. 13.8 +/- 10.8 (P = .0001). CONCLUSIONS: The immunological and inflammatory changes related to ageing may cause an increase in CD95 and CD25 T cell expression. In asthma, blood cells may express increased activation and apoptosis markers but in elderly patients taking steroids, these receptors remain within normal ranges. The number of gamma delta T cells may be lower in long-lasting asthma, and have a limited modulatory effect on allergic inflammatory reactions. The evaluation of patients with long-lasting asthma should take into account the immunological and inflammatory changes present in the elderly in order to avoid results being misinterpreted. 相似文献