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BACKGROUND/AIMS: The safety profile of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors when associated with chemotherapy for the treatment of patients with extensive-stage small-cell lung cancer is still not fully unraveled. METHODS: We performed a comprehensive searrch of the PubMed, Embase, and Cochrane databases for randomized controlled trials that investigated the addition of PD-1 or PD-L1 inhibitors to standard investigator choice chemotherapy. We used risk -ratios (RRs) with 95% confidence intervals (CIs) for all endpoints. RESULTS: Six studies and 2,995 patients were included. At the baseline, the median age of the patients varied from 62 to 65 years, 311 (10.4%) had brain metastases, and 1,060 (35.4%) had liver metastases. PD-1/PD-L1 inhibitors were found to reduce fatal toxicities-related mortality (RR: 0.85; 95% CI: 0.80-0.91; p < 0.001; I2 = 49%). The intervention group had a higher incidence of decreased appetite (RR: 1.19; 95% CI: 1.02-1.40; p = 0.03; I2 = 0%), hyponatremia (RR: 1.51; 95% CI: 1.08-2.12; p = 0.02; I2 = 0%), and hypothyroidism (RR: 3.14; 95% CI: 1.10-8.95; p = 0.03; I2 = 81%) of any grade. Regarding adverse events of grade 3-4, there was no association of the addition of PD-1/PD-L1 inhibitors with an increased occurrence of any of the evaluated outcomes. CONCLUSION: In this systematic review and meta-analysis, the incorporation of PD-1/PD-L1 inhibitors to chemotherapy demonstrated an excellent safety profile and to be a promising prospect for reshaping the established treatment paradigms for patients with extensive-stage small cell lung cancer.
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INTRODUÇÃO: Em pacientes que foram submetidos a ablação por cateter devido a fibrilação atrial pode ocorrer a recorrência deste quadro. Não é estabelecido o efeito do S/V na prevenção da recorrência de fibrilação atrial (FA) comparado a Inibidores da Enzima Conversora da Angiotensina (IECA) ou Bloqueadores do Receptor da Angiotensina II (BRA). Essa metaanálise visa estabelecer qual a melhor escolha terapêutica para prevenção da recorrência de FA após ablação por catéter. MÉTODO: Foi realizada uma busca sistemática nas bases do PubMed, Embase e Cochrane para ensaios clínicos randomizados (ECR) e estudos observacionais comparando uso de S/V com IECA/BRA em pacientes que realizaram ablação por cateter. Os resultados foram apresentados em diferenças de médias (DM), com intervalo de confiança de 95% (IC). A heterogeneidade foi avaliada pelo I2 e desfechos expressos em riscos relativos (RR), utilizando o software R versão 4.2.3. RESULTADOS: Foram incluídos 3 ensaios clínicos randomizados e 1 estudo de coorte, composto por 642 pacientes, com 319 pacientes no grupo S/V e 323 no grupo controle. O seguimento dos estudos variou de 12 meses a 36 meses, a média de idade variou de 58.9 a 65.82 anos. Foi demonstrado a redução de ocorrência de FA persistente com uma diferença significativa favorecendo o grupo S/V (RR 0.43; 95% IC 0,25-0.76; P=0.003; I2=80%) comparado com o grupo IECA/BRA. Na análise houve uma redução significativa do Índice de Volume Atrial Esquerdo (IVAE) (MD -5.34ml/m2; 95% IC -8.77,-1.91; P=0.002; I2= 57%) no grupo S/V comparado com IECA/BRA. Não houve diferença significativa da fração de ejeção do ventrículo esquerdo com o uso de S/V (MD 1.24%; 95% IC -0.13, 2.61; P=0.076; I2= 0%) em comparação com IECA/BRA. CONCLUSÃO: Nesta metanálise, foi evidenciada a eficácia de S/V na diminuição da incidência de FA em pacientes submetidos à ablação por cateter, em comparação ao uso de IECA/ BRA. Contudo, ressalta-se a necessidade de realização de mais ensaios clínicos randomizados para uma avaliação mais abrangente de sua eficácia na redução da recorrência de FA em paciente pós ablação por cateter na prática clínica.
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Ablação por CateterRESUMO
INTRODUÇÃO: Diversos estudos foram publicados avaliando o uso da denervação renal por radiofrequência (DRR) no tratamento de pacientes com hipertensão arterial resistente (HAR). Essa técnica consiste em um procedimento minimamente invasivo que visa interromper a atividade dos nervosrenais via ablação. Entretanto,sua eficácia e segurança com cateter via radiofrequência ainda não foi elucidada. Essa meta-análise tem por objetivo investigar a eficácia da denervação renal por radiofrequência (DRR) comparado com sham ou anti hipertensivos. METODOLOGIA: Foi realizada uma busca nas bases de dados da PubMed, Embase e Cochrane, por ensaios clínicos randomizados que compararam a redução da pressão arterial entre a denervação renal por radiofrequência (DRR) e o sham ou tratamento padrão em pacientes com HAR. Os dados foram reunidos usando um modelo de efeito fixo, e os resultados foram dados em diferença de média (DM) e risco relativo (RR), com 95% de intervalo de confiança (IC). A heterogeneidade entre os estudos foi calculada pelo I2. Todas as estatísticas foram realizadas usando o R software(version 4.0.3). RESULTADOS: Ao todo foram incluídos 8 ensaios clínicos randomizados, composto por 934 pacientes (557 do grupo RDN e 377 do grupo controle). O seguimento dos estudos variou de 6 meses até 84 meses, a média de idade variou entre 53 a 64.5 anos e com 349 pacientes portadores de diabetes tipo 2. A DRR foi associada com redução significativa da pressão sistólica ambulatorial (DM: -6.25 mmHg, 95% IC: -8.83; -3.67, P< 0.001, I2= 52%), assim como na diastólica ambulatorial (DM: -2.67 mmHg, 95% IC: -4.38; -0.95, P=0.002, I2=50%) comparado com grupo controle. De maneira semelhante, houve redução significativa da pressão diastólica de consultório (DM: -5.11 mmHg, 95% IC: -9.19; -1.02, P=0.014, I2=72%). Não houve diferença estatística em relação à pressão sistólica de consultório (DM: -9.50 mmHg, 95% IC:-20.54; 1.54, P=0.092, I2=87%), aos efeitos adversos secundários (RR: 1.86, 95% IC: 0.66; 5.26, P=0.240, I2= 50%) e à crise hipertensiva (RR:1.10, 95% IC: 0.55; 2.22, P=0.780, I2=0%). CONCLUSÕES: Esta meta-análise demonstrou a eficácia do uso da DRR na redução da pressão arterial global ambulatorial e pressão diastólica de consultório, e não apresentou aumentos de efeitos adversos secundários e crise hipertensiva. Esses achados demonstram o potencial uso da DRR no tratamento de pacientes que possuem hipertensão arterial resistente.
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Ablação por Radiofrequência , HipertensãoRESUMO
The cowpea bean [Vigna unguiculata (L.) Walp.], a legume of great socioeconomic importance, it was previously cultivated exclusively for subsistence and commercial purposes, especially in the North and Northeast regions. This crop has a low production cost and high nutritional value, in addition to a high potential for productivity growth and expansion to other regions. The objective of this work was to evaluate parameters of growth and production in cowpea culture, as a function of potassium fertilization in soil of the cerrado of Amapá. The parameters of growth and production of the cowpea culture were evaluated, as a function of potassium fertilization in the soil of the cerrado of Amapá. The experiment was conducted in a greenhouse, using a completely randomized experimental design, with four replications, in a 5x2 factorial scheme, totaling 40 experimental units, which were composed of plastic pots containing 7 dm3 of soil collected from the arable layer (0-20 cm ) of a typical Hyperdystrophic Yellow Argisol, with a sandy clay loam texture, in a cerrado area in the municipality of Porto Grande-AP. The factors consisted of the control treatment (without K), four doses of K (45, 90, 135 and 180 kg ha-1) in the form of potassium chloride, and two cowpea cultivars (Pretinho and BRS Tumucumaque). The cultivar BRS Tumucumaque shows better growth and production of cowpea plants. Doses of 90 kg ha-1 provided greater height (98.75 cm) and stem diameter (10.0 mm). As for production, the dose of 135 kg ha-1 caused greater grain weight gain (5.25 g) and dry mass of pods (13.92 g), and the doses of 90 and 180 kg ha-1 induced greater number and length of pods (3.16 pods) respectively. These results show better responsiveness of the BRS Tumucumaque cultivar at doses of 90, 135 and 180 kg ha-1 in the type of soil where the study was conducted.
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Fabaceae , Vigna , Solo , Potássio , BrasilRESUMO
AIMS: Reports of stereotactic arrhythmia radioablation (STAR) in patients with refractory ventricular tachycardia after catheter ablation are limited to small series. Here, we carried out a systematic review and meta-analysis of studies to better determine the efficacy and toxicity of STAR for ventricular tachycardia. MATERIALS AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines, eligible studies were identified on Medline, Embase, Cochrane Library and the proceedings of annual meetings to 10 February 2023. Efficacy was defined as a ventricular tachycardia burden reduction >70% at 6 months; safety was defined as <10% of any grade ≥3 toxicity. RESULTS: Seven observational studies with a total of 61 patients treated were included. At 6 months, the ventricular tachycardia burden reduction was 92% (95% confidence interval 85-100%) and use of fewer than two anti-arrhythmic drugs was seen in 85% (95% confidence interval 50-100). Six months after STAR, an 86% reduction (95% confidence interval 80-93) in the number of implantable cardioverter-defibrillator shocks was observed. The rates for improved, unchanged and decreased cardiac ejection fraction were 10%, 84% and 6%, respectively. Overall survival at 6 and 12 months was 89% (95% confidence interval 81-97) and 82% (95% confidence interval 65-98). The cardiac-specific survival at 6 months was 87%. Late grade 3 toxicity occurred in 2% (95% confidence interval 0-5%) with no grade 4-5 toxicity. CONCLUSION: STAR demonstrated both satisfactory efficacy and safety for the management of refractory ventricular tachycardia and was also associated with a significant decline in anti-arrhythmic drugs consumption. These findings support the continued development of STAR as a treatment option.
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Ablação por Cateter , Desfibriladores Implantáveis , Taquicardia Ventricular , Humanos , Antiarrítmicos/uso terapêutico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/radioterapia , Taquicardia Ventricular/cirurgia , Coração , Ablação por Cateter/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The heterogeneity of ejaculate indicates that fertility is still variable among bulls and that more stringent evaluation methods are needed to identify the ejaculates suitable for AI. OBJECTIVE: To identify and characterize the sperm subpopulations (SP) in thawed semen doses of Nelore and Angus bulls and to evaluate the influence of these sperm subpopulations on pregnancy rate in cows submitted to fixed-time AI (FTAI). MATERIALS AND METHODS: A dose of post-thawed semen from each bull (n=18; consisting of Angus n = 9 and Nelore n = 9) was analyzed for: sperm kinetics; morphology and plasma membrane integrity; and the determination of the sperm subpopulations. Differences between the groups were estimated with the t-test considering a significance level of <5%. RESULTS: There was no influence between breeding bulls for sperm morphology, plasma membrane integrity, and pregnancy rate (P > 0.05). Regarding the kinetic parameters evaluated by the CASA system, Nelore had greater values, for cells with slow velocity (Angus: 16.4 %; Nelore: 21.7%; P = 0.028). In contrast, ANGUS bulls had more static cells (Angus: 27.2%; Nelore: 9.3%; P = 0.048). Based on CASA system data and clustering procedures, four sperm subpopulations were statistically established. In Angus bulls, a higher level of fast and nonlinear spermatozoa were found in SP3 (33.3%), followed by SP1 (32.7%%) with fast and progressive spermatozoa. Whereas, SP1 of Nelore bulls had 33.8% fast and progressive spermatozoa, followed by 32.2% of SP3 with fast and nonlinear spermatozoa. CONCLUSION: Both breeds of bulls presented similar proportions of sperm SP. Consequently, no influence on the pregnancy rates was shown in cows submitted to the IATF programs on a large scale. doi.org/10.54680/fr22310110312.
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Preservação do Sêmen , Sêmen , Gravidez , Feminino , Masculino , Animais , Bovinos , Taxa de Gravidez , Motilidade dos Espermatozoides , Criopreservação/veterinária , Criopreservação/métodos , Espermatozoides , Inseminação Artificial/veterinária , Inseminação Artificial/métodos , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , FertilidadeRESUMO
The innate immune response has a predominant role in Behçet's disease (BD) pathogenesis, but few studies have assessed monocytes in BD. This study aims to evaluate the profile of monocytes subsets in the peripheral blood of BD patients and healthy controls (HC). Monocytes subsets were identified as classical (CD14+CD16-), intermediate (CD14+CD16dim), and non-classical (CD14dimCD16high) subsets. Patients with BD presented a lower number of total monocytes (p = 0.020) and a lower number (p < 0.0001) of circulating classical monocytes than HC. In contrast, the number of intermediate monocytes was higher in BD patients than HC (p < 0.0001). In BD patients, no associations were observed with the severity of clinical manifestations or therapy. Colchicine was associated with a higher number of non-classical monocytes (p = 0.035). In conclusion, BD patients present an altered distribution of monocytes subsets with a reduction of classical and an increase of intermediate subsets.
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Síndrome de Behçet/imunologia , Colchicina/uso terapêutico , Monócitos/imunologia , Moduladores de Tubulina/uso terapêutico , Adulto , Síndrome de Behçet/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacosRESUMO
OBJECTIVES: Assess upfront Stereotactic radiosurgery (SRS) effectiveness for small cell lung cancer (SCLC) brain metastases (BM). Where possible, a comparison with whole-brain radiotherapy (WBRT) was performed. METHODS: Following PRISMA and MOOSE guidelines, eligible studies were identified on Medline, Embase, Cochrane Library, and proceedings of annual meetings between inception and July 01, 2020. RESULTS: Nine observational studies with 1638 patients were included. The median overall survival (OS) was 8.3 months (95% CI 7.1-9.5 months, I2 = 0%). OS rate at 12 months was 39% (95% CI 31-44%, I2 = 0%). The relative risk between SRS and WBRT for the OS at 12 months was 1.33 (95% CI 1.13-1.51, P = 0.0001). The projected OS for 6, 12, 18- and 24-months comparing SRS with WBRT was 67% vs. 57%, 39% vs. 29%, 22% vs. 15% and 15% vs 9%, favoring SRS (P < 0.001). The LC rate at 12 months was 93% (95% CI 91-94%, I2 = 0%). The distant brain failure rate (DBFR) at 12 months was 41% (95% CI 33-48%, I2 = 52%, P = 0.08). The SRS or WBRT as salvage treatment after upfront SRS was 32% and 19%, respectively. The freedom from neurologic death at 12 months was 87% (95% CI 84-89%). CONCLUSION: Based on the pooling of a large sample of retrospective studies our meta-analysis suggests that for high selected SCLC patients with limited BM upfront SRS produces favorable lesion control and survival outcomes. These findings support the design of randomized clinical trial to confirm the role of SRS in this clinical scenario.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão , Encéfalo , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Irradiação Craniana , Humanos , Neoplasias Pulmonares/radioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Carcinoma de Pequenas Células do Pulmão/cirurgiaRESUMO
AIM: To quantitatively and qualitatively compare the host proteomic profile in samples of symptomatic and asymptomatic apical periodontitis (AP) using nano-liquid chromatography-electron spray tandem mass spectrometry. METHODOLOGY: Samples were obtained from 18 patients with radiographically evident AP, divided into symptomatic and asymptomatic groups (nine per group) according to clinical characteristics. After sample collection, protein extraction, purification and quantification of the samples were performed, which were analysed by reverse-phase liquid chromatography coupled to mass spectrometry. Label-free quantitative proteomic analysis was performed by Protein Lynx Global Service software. Differences in expression of proteins between the groups were calculated using the Monte Carlo algorithm, considering P < 0.05 for down-regulated proteins and 1 - P > 0.95 for up-regulated proteins. Proteins were identified with the embedded ion accounting algorithm in the software and a search of the Homo sapiens UniProt database. RESULTS: A total of 853 individual human proteins were identified. In the quantitative analysis, common proteins to both groups accounted for 143 proteins. Differences in expression between groups resulted in 51 up-regulated proteins (1 - P > 0.95) in the symptomatic group, including alpha-1-antitrypsin, protein S100-A8, myeloperoxidase, peroxiredoxin and lactotransferrin. This group also had 43 down-regulated proteins (P < 0.05), comprising immunoglobulin, neutrophil defensin, pyruvate kinase and alpha-enolase. The qualitative analysis considered only the exclusive proteins of each group. For the symptomatic group, 318 complete proteins and 29 fragments were identified, such as dedicator of cytokinesis protein, intersectin, prostaglandin, phospholipase DDHD2 and superoxide dismutase. For the asymptomatic group, 326 complete proteins and 37 fragments were identified, including azurocidin, C-reactive protein, collagen alpha, cathepsin, heat shock and laminin. CONCLUSIONS: Quantitative differences in the expression of common proteins in cases of symptomatic and asymptomatic AP were found, which were mostly related to host immune response in both groups. Exclusive proteins in the symptomatic group were mainly related to the host response to the presence of viruses in endodontic infections, oxidative stress and proteolytic enzymes. The results provide a basis for a better understanding of cellular and molecular pathways involved in AP, establishing specific proteomic profiles for symptomatic and asymptomatic conditions.
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Periodontite Periapical , Proteômica , Humanos , FosfolipasesRESUMO
O tamanduá-bandeira (Myrmecophaga tridactyla) e o tamanduá-mirim (Tamandua tetradactyla) são mamíferos xenartros amplamente distribuídos no território nacional. Apesar disso, suas populações estão em constante ameaça, principalmente o primeiro, categorizado como vulnerável de acordo com classificação da União Internacional para Conservação da Natureza. Diante disso e da escassez de estudos com endoparasitas nesses animais, objetivou-se descrever a helmintofauna dessas duas espécies de tamanduá, utilizando espécimes atropelados nas rodovias BR-050 e BR-455, região do Triângulo Mineiro, Minas Gerais, Brasil. Os animais foram submetidos à necropsia, tendo seus órgãos e conteúdo intestinal e estomacal examinados para recuperação de helmintos. Os parasitos coletados foram identificados com base em suas características morfológicas e morfométricas. As espécies/os gêneros caracterizados para M. tridactyla e T. tetradactyla, suas respectivas prevalências, bem como órgãos de origem, foram: Gaphidiops dissimilis (33,33% e 0%) no estômago; Gigantorhynchus echinodiscus (25% e 66,66%) no intestino delgado; Physaloptera magnipapilla (50% e 66,6%) no estômago; e Mathevotaenia spp. (25% e 66,66%) no intestino delgado. Physaloptera magnipapilla foi a espécie com os maiores índices de infecção, e novo registro de localização foi registrado para o nematódeo Graphidiops dissimilis. Detectou-se uma provável sobreposição da área de vida dos tamanduás estudados, bem como uma helmintofauna característica da região.(AU)
Myrmecophaga tridactyla, giant anteater and Tamandua tetradactyla, collared anteater are nationally widespread mammals. Despite that, their populations are in danger, especially the first one, categorized as vulnerable according to the International Union for Conservation of Nature. This study reports the occurrence of helminths in these two anteater species using road killed specimens from BR-050 and BR-455 highways, Triângulo Mineiro region, Minas Gerais state, Brazil. The species were necropsied, and their gastrointestinal organs and contents were opened and examined for parasite recovery. The identification was based on morphological and morphometric features. The species/ genera found for M. tridactyla and T. tetradactyla, their prevalence, as well the organs, were: Gaphidiops dissimilis (33.33% and 0%) in stomach; Gigantorhynchus echinodiscus (25% and 66.66%) in small intestine; Physaloptera magnipapilla (50% and 66.6%) in stomach and Mathevotaenia spp. (25% and 66.66%) in small intestine. Physaloptera magnipapilla was the most common species and a new location was reported for Graphidiops dissimilis. There is a probable overlap in the home range of these animals and a local helminth diversity was described on the study site.(AU)
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Animais , Spirurina , Eutérios/parasitologia , Helmintos/isolamento & purificação , Nematoides/isolamento & purificação , Autopsia/veterinária , BrasilRESUMO
OBJECTIVES: This study aimed to evaluate the frequency of HLA-B*51 and its subtypes in Brazilian patients with Behçet's disease (BD) and healthy controls (HC) and to assess possible associations with disease manifestations. METHODS: A cross-sectional study with sequential BD patients and HC. HLAB*51 presence was determined by sequence-specific polymerase chain reaction (SSP-PCR) and HLA-B*51 subtypes by the Sanger sequencing method. RESULTS: Eighty-three BD patients and 258 HC were evaluated. HLA-B*51 was found in 30.1% of DB patients and in 15.5% of HC (p=0.003). The most prevalent subtypes in DB patients were HLA-B*51:01 (60.0%), HLA-B*51:08 (20.0%), HLA-B*51:22 (8.0%), HLAB* 51:29 (8.0%) and HLA-B*51:02 (4.0%), while HLA-B*51:01 (77.5%) and HLA-B*51:55 (7.5%) were the most prevalent in HC. HLA-B*51 was less frequently found in patients with neurologic involvement (8.0% vs. 29.3%; p=0.034) while HLAB*51:01 was more observed in patients with ocular involvement (93.3% vs. 60.3%; p=0.014). No BD patient with neurologic or vascular involvement presented HLA-B*51:01. HLAB*51:08 was more frequent in patients with vascular manifestations (60.0% vs. 15.4%; p=0.012). In multivariate analysis, HLA-B*51 was an independent risk factor for BD (OR=2.410; 95%CI: 1.332-4.361; p=0.004) and HLA-B*51:08 had an independent association with vascular manifestations of BD (OR = 14.843; 95%CI: 1.550 - 142.115; p=0.019). CONCLUSIONS: The prevalence of HLAB*51 is higher in Brazilian BD patients compared to HC, and it is a risk factor for BD. The HLA-B*51:08 subtype was independently associated with vascular manifestations of BD.
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Síndrome de Behçet , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/epidemiologia , Síndrome de Behçet/genética , Brasil , Estudos Transversais , Antígenos HLA-B/genética , Antígeno HLA-B51/genética , HumanosRESUMO
We report a previously undescribed pattern of brain metastases in patients with epidermal growth factor receptor-mutated non-small-cell lung cancer treated with tyrosine kinase inhibitors and radiation therapy. These highly distinct lesions appear to spread focally within the leptomeninges, with invasion along the perivascular spaces (FLIP). The survival of patients with FLIP was significantly better compared with patients with classic leptomeningeal disease (median survival, 21 versus 3 months; P = .003). It is unclear whether this pattern of growth is unique to epidermal growth factor receptor-mutated non-small-cell lung cancer.
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Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Carcinomatose Meníngea/secundário , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Carcinomatose Meníngea/genética , Carcinomatose Meníngea/mortalidade , Pessoa de Meia-Idade , MutaçãoRESUMO
BACKGROUND: The most common pattern of failure in major salivary gland carcinoma (SGC) is development of distant metastases (DMs). The objective of this study was to develop and validate a prediction score for DM in SGC. PATIENTS AND METHODS: Patients with SGC treated curatively at four tertiary cancer centers were divided into discovery (n = 619) and validation cohorts (n = 416). Multivariable analysis using competing risk regression was used to identify predictors of DM in the discovery cohort and create a prediction score of DM; the optimal score cut-off was determined using a minimal P value approach. The prediction score was subsequently evaluated in the validation cohort. The cumulative incidence and Kaplan-Meier methods were used to analyze DM and overall survival (OS), respectively. RESULTS: In the discovery cohort, DM predictors (risk coefficient) were: positive margin (0.6), pT3-4 (0.7), pN+ (0.7), lymphovascular invasion (0.8), and high-risk histology (1.2). High DM-risk SGC was defined by sum of coefficients greater than two. In the discovery cohort, the 5-year incidence of DM for high- versus low-risk SGC was 50% versus 8% (P < 0.01); this was similar in the validation cohort (44% versus 4%; P < 0.01). In the pooled cohorts, this model performed similarly in predicting distant-only failure (40% versus 6%, P < 0.01) and late (>2 years post surgery) DM (22% versus 4%; P < 0.01). Patients with high-risk SGC had an increased incidence of DM in the subgroup receiving postoperative radiation therapy (46% versus 8%; P < 0.01). The 5-year OS for high- versus low-risk SGC was 48% versus 92% (P < 0.01). CONCLUSION: This validated prediction-score model may be used to identify SGC patients at increased risk for DM and select those who may benefit from prospective evaluation of treatment intensification and/or surveillance strategies.
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Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Neoplasias das Glândulas Salivares/epidemiologia , Glândulas SalivaresRESUMO
AIMS: Among all malignancies, the use of radiotherapy incurs the highest survival benefit within cervical cancers. Radiotherapy, however, remains underutilised for cervical cancers within the Brazilian public health system (BPHS). The objective of this study was to estimate the potential health and monetary benefits for universal access to radiotherapy and chemoradiotherapy (CRT) for untreated cervical cancer patients in the BPHS. MATERIALS AND METHODS: Using 2016 data on Brazilian cervical cancer incidence and availability of radiotherapy/CRT in the BPHS, the number of cancer deaths due to radiotherapy/CRT underutilisation was estimated. The incremental effectiveness was calculated by life-year gain. The indirect costs from mortality-related productivity loss (MRPL) were estimated based on life expectancy, wage and labour force participation rate. MRPL was compared with direct medical costs after being adjusted to 2016 US dollars. This study was conducted from the payer's perspective; both costs and effectiveness were discounted at a rate of 3%. The incremental cost-effectiveness ratio (ICER) was calculated to determine the cost-effectiveness of radiotherapy for cervical cancer in Brazil. One-way sensitivity analyses were carried out to assess the robustness of the model. RESULTS: The total number of life-years lost due to lack of universal access to radiotherapy and CRT per year were 27 199 and 31 627, respectively. The annual cost to match the radiotherapy gap was $10.5 million, with an additional cost of $3 million to close the CRT gap. The mean years of potential life lost per death was 20.5. The cost per life saved was $7942 for radiotherapy alone (ICER $388/life-year) and $8774 for CRT (ICER $429/life-year). MRPL due to shortage of radiotherapy and CRT were $59 million and $69 million, respectively. CONCLUSION: Providing universal access to radiotherapy/CRT for cervical cancer patients in the BPHS is highly cost-effective and should be prioritised as an impactful public health initiative.
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Quimiorradioterapia/métodos , Análise Custo-Benefício/economia , Neoplasias do Colo do Útero/economia , Brasil , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/radioterapiaRESUMO
Time-resolved Kerr rotation measurements were performed in InGaAs/GaAs quantum wells nearby a doped Mn delta layer. Our magneto-optical results show a typical time evolution of the optically-oriented electron spin in the quantum well. Surprisingly, this is strongly affected by the Mn spins, resulting in an increase of the spin precession frequency in time. This increase is attributed to the variation in the effective magnetic field induced by the dynamical relaxation of the Mn spins. Two processes are observed during electron spin precession: a quasi-instantaneous alignment of the Mn spins with photo-excited holes, followed by a slow alignment of Mn spins with the external transverse magnetic field. The first process leads to an equilibrium state imprinted in the initial precession frequency, which depends on pump power, while the second process promotes a linear frequency increase, with acceleration depending on temperature and external magnetic field. This observation yields new information about exchange process dynamics and on the possibility of constructing spin memories, which can rapidly respond to light while retaining information for a longer period.
RESUMO
Effects of the pyrethroid lambda-cyhalothrin (LCH) were investigated in matrinxa Brycon amazonicus, a non-target freshwater teleost. The fish were submitted to a single-pulse exposure (10% of LC50; 96 h, 0.65 µg L-1), followed by 7 days of recovery in clean water. Hematologic parameters indicated impairments in oxygen transport, which were not recovered. Plasma [Na+], [Cl-], and protein were diminished, and only [Na+] remained low after recovery. Gill Na+/K+ATPase activity was increased and recovered to basal values. Brain acetylcholinesterase activity was not responsive to LCH. Liver ascorbic acid concentration was not altered, and reduced glutathione levels remained augmented even after recovery. LCH inhibited hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, while glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) activities were steady. After recovery, SOD remained low, and GPx was augmented. Liver depicted lipid peroxidation, which was not observed after recovery. Hepatic morphology was affected by LCH and was not completely recovered. These responses, combined with the persistence of changes even after recovery span, clearly show the feasibility of these biomarkers in evaluating LCH toxic potential to non-target organisms, highlighting the importance of pyrethroids' responsible use.
Assuntos
Caraciformes/metabolismo , Fungicidas Industriais/toxicidade , Nitrilas/toxicidade , Piretrinas/toxicidade , Animais , Antioxidantes/metabolismo , Biomarcadores , Fígado/efeitos dos fármacos , Fígado/metabolismoRESUMO
Clinical manifestations of Zika, dengue, and chikungunya virus infections are very similar, making it difficult to reach a diagnosis based only on clinical grounds. In addition, there is an intense cross-reactivity between antibodies directed to Zika virus and other flaviviruses, and an accurate Zika diagnosis is best achieved by real-time RT-PCR. However, some real-time RT-PCR show better performance than others. To reach the best possible Zika diagnosis, the analytic sensitivity of some probe-based real-time RT-PCR amplifying Zika virus RNA was evaluated in spiked and clinical samples. We evaluated primers and probes to detect Zika virus, which had been published before, and tested sensitivity using serum spiked and patient samples by real-time RT-PCR. When tested against spiked samples, the previously described primers showed different sensitivity, with very similar results when samples from patients (serum and urine) were analyzed. Real-time RT-PCR designed to amplify Zika virus NS1 showed the best analytical sensitivity for all samples.