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1.
Healthcare (Basel) ; 12(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38610181

RESUMO

BACKGROUND: Dating violence has become a problem of social relevance with short- and long-term health consequences. Nurses are in a privileged position to detect and address this problem in health facilities and as school nurses in schools, providing health education and detecting this violence correctly. AIM: The aim of this study was to evaluate the cross-cultural validation of the Portuguese version of the Multidimensional Scale of Dating Violence-Short (MSDV 2.0). METHODS: A validation investigation was carried out in two phases: (1) cross-cultural adaptation of the items and content validation of the Portuguese version of MSDV 2.0 and (2) psychometric validation. RESULTS: Phase (1): The items of the original version include a cross-cultural translation from Spanish to Portuguese and analysed by a group of experts in gender violence and by the authors of the original scale, then a back translation was made and again reviewed by the experts. Young university students also participated for face validity, and a pilot test was carried out. Phase (2): Confirmatory factor analysis was performed using the robust maximum-likelihood estimation method, which confirmed the five-dimensional structure, obtaining good fit rates (chi-square significance (χ2) = 187.860 (p < 0.0001); root mean square error of approximation (RMSEA) = 0.049; comparative fit index (CFI) = 0.937; Tucker-Lewis index (TLI) = 0.923). Reliability analysis indicated adequate internal consistency (Cronbach's alpha (α) = 0.88 to 0.70). Finally, scores of the Portuguese versions MSDV 2.0 were correlated, as expected, positively with the Depression, Anxiety, and Stress Scale (DASS-21) (r = 0.36 to 0.16) and negatively with the Medical Outcomes Study Questionnaire Short Form 36, Health Survey (SF-36) (r = -0.30 to -0.14). CONCLUSIONS: To date, it is the only instrument that measures dating violence in a multidimensional way validated in the Portuguese university context.

2.
Healthcare (Basel) ; 12(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38338285

RESUMO

BACKGROUND: Resilience is an important aspect of mental health in young people, which has become more relevant after the COVID-19 pandemic. It is therefore of paramount importance to have valid and reliable instruments that measure the globality of this aspect. One of the instruments that has been shown to have good psychometric properties and which has been widely adapted in several languages is the Connor-Davidson resilience scale, composed of 10 elements (10-item CD-RISC). AIM: The aim of this study was to evaluate the validity and reliability of the Portuguese version of the 10-item CD-RISC among young university students. METHODS: a cross-sectional observational study of psychometric validation was conducted with a sample of 206 university students. RESULTS: Good and adequate fit indices were obtained for the confirmatory factor analysis (CFA): Standardized Root-Mean-Square Residual [SRMR] = 0. 056; comparative fit index [CFI] = 0.958; and the Tucker-Lewis index [TLI] = 0.946. It also showed an average degree of convergent validity with the Depression, Anxiety and Stress Scale (DASS-21) and the General Health Scale (SF-36), and its internal consistency was good (Cronbach's alpha = 0.842) with a range of factor loadings between 0.42 and 0.77. CONCLUSIONS: the results show that the 10-item CD-RISC is a valid, reliable scale to measure resilience among young Portuguese university students.

3.
J Antimicrob Chemother ; 78(9): 2354-2360, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37545387

RESUMO

BACKGROUND: This was a substudy of a Phase IV, randomized clinical trial (ClinicalTrials.gov identifier: NCT04295460) aiming to compare the activity of dolutegravir/lamivudine versus dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) in the male genital tract. METHODS: Participants were asymptomatic adults without sexually transmitted diseases, treatment-naive people living with HIV (PLWH), with CD4+ T cell counts >200 cells/mm3 and plasma HIV-1-RNA levels >5000 and <500 000 copies/mL, randomized (1:1) to DTG + TAF/FTC or dolutegravir/lamivudine. Blood plasma (BP) and seminal plasma (SP) were collected at baseline and Weeks 4, 8, 12 and 24. HIV-1-RNA was measured in BP and SP using the Cobas 6800 system (Roche Diagnostics) with a lower detection limit of 20 copies/mL. The primary efficacy endpoint was the proportion of subjects with undetectable SP HIV-1-RNA at Week 12 by intention-to-treat analysis. RESULTS: Fifteen participants in the DTG + TAF/FTC and 16 in the dolutegravir/lamivudine arms were analysed, with basal SP viral load of 4.81 (4.30-5.43) and 4.76 (4.09-5.23), P = 0.469, respectively. At Week 12, only one participant in each treatment arm had a detectable SP HIV-1-RNA (DTG + TAF/FTC, 141 copies/mL; dolutegravir/lamivudine, 61 copies/mL). Based on the estimated means, there was no significant difference in the decay of HIV-1-RNA in both BP and SP over time between the two arms of treatment (F = 0.452, P = 0.662, and F = 1.147, P = 0.185, respectively). CONCLUSIONS: After 12 weeks of treatment, there were no differences in the percentage of undetectable SP HIV-1-RNA in naive PLWH who started dolutegravir/lamivudine compared with DTG + TAF/FTC.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Adulto , Humanos , Masculino , Lamivudina/uso terapêutico , HIV-1/genética , Infecções por HIV/tratamento farmacológico , Sêmen , Cinética , Quimioterapia Combinada , Emtricitabina/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Piridonas/uso terapêutico , Oxazinas/uso terapêutico , RNA Viral , Fármacos Anti-HIV/uso terapêutico
4.
Gut ; 73(1): 166-174, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36963815

RESUMO

OBJECTIVE: We aimed to compare the response rates between two different hepatitis B virus vaccination schedules for cirrhotic subjects who were non-responders to the first three 40 µg doses (month 0-1-2), and identify factors associated with the final response. DESIGN: A total of 120 cirrhotic patients (72.5% decompensated) were randomised at a 1:1 ratio to receive a single 40 µg booster vaccination at month 6 (classical arm) versus an additional round of three new 40 µg doses administered at monthly intervals (experimental arm). The main outcome was the rate of postvaccinal anti-hepatitis B surface antibodies levels ≥10 mIU/mL. RESULTS: Efficacy by ITT analysis was higher in the experimental arm (46.7%) than in the classical one (25%); OR 2.63, p=0.013. The experimental arm increased response rates compared with the classical one from 31% to 68% (OR 4.72; p=0.007), from 24.4% to 50% (OR 3.09; p=0.012) and from 24.4% to 53.8% (OR 3.62; p=0.007), in Child A, Model for End-Stage Liver Disease (MELD) <15 and MELD-Na<15 patients, respectively. Patients with more advanced liver disease did not benefit from the reinforced scheme. Both regimens showed similar safety profiles. Multivariable analysis showed that the experimental treatment was independently response associated when adjusted across three logistic regression models indicating equivalent cirrhosis severity. CONCLUSION: For cirrhotic patients, the revaccination of non-responders to the first three dose cycle, with three additional 40 µg doses, achieved significantly better response rates to those obtained with an isolated 40 µg booster dose. TRIAL REGISTRATION NUMBER: NCT01884415.


Assuntos
Doença Hepática Terminal , Hepatite B , Criança , Humanos , Imunização Secundária , Anticorpos Anti-Hepatite B , Índice de Gravidade de Doença , Hepatite B/prevenção & controle , Cirrose Hepática/complicações , Vacinas contra Hepatite B
5.
PLoS One ; 17(7): e0269875, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35834501

RESUMO

BACKGROUND: The SARS-CoV-2 pandemic has overwhelmed hospital services due to the rapid transmission of the virus and its severity in a high percentage of cases. Having tools to predict which patients can be safely early discharged would help to improve this situation. METHODS: Patients confirmed as SARS-CoV-2 infection from four Spanish hospitals. Clinical, demographic, laboratory data and plasma samples were collected at admission. The patients were classified into mild and severe/critical groups according to 4-point ordinal categories based on oxygen therapy requirements. Logistic regression models were performed in mild patients with only clinical and routine laboratory parameters and adding plasma pro-inflammatory cytokine levels to predict both early discharge and worsening. RESULTS: 333 patients were included. At admission, 307 patients were classified as mild patients. Age, oxygen saturation, Lactate Dehydrogenase, D-dimers, neutrophil-lymphocyte ratio (NLR), and oral corticosteroids treatment were predictors of early discharge (area under curve (AUC), 0.786; sensitivity (SE) 68.5%; specificity (S), 74.5%; positive predictive value (PPV), 74.4%; and negative predictive value (NPV), 68.9%). When cytokines were included, lower interferon-γ-inducible protein 10 and higher Interleukin 1 beta levels were associated with early discharge (AUC, 0.819; SE, 91.7%; S, 56.6%; PPV, 69.3%; and NPV, 86.5%). The model to predict worsening included male sex, oxygen saturation, no corticosteroids treatment, C-reactive protein and Nod-like receptor as independent factors (AUC, 0.903; SE, 97.1%; S, 68.8%; PPV, 30.4%; and NPV, 99.4%). The model was slightly improved by including the determinations of interleukine-8, Macrophage inflammatory protein-1 beta and soluble IL-2Rα (CD25) (AUC, 0.952; SE, 97.1%; S, 98.1%; PPV, 82.7%; and NPV, 99.6%). CONCLUSIONS: Clinical and routine laboratory data at admission strongly predict non-worsening during the first two weeks; therefore, these variables could help identify those patients who do not need a long hospitalization and improve hospital overcrowding. Determination of pro-inflammatory cytokines moderately improves these predictive capacities.


Assuntos
COVID-19 , SARS-CoV-2 , Biomarcadores , Citocinas , Humanos , Masculino , Alta do Paciente
6.
Front Immunol ; 13: 891456, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35634332

RESUMO

IL-6 is one of the major mediators of the hyper-inflammatory responses with complex biological functions as it can signal via different modes of action. IL-6 by classical signalling has anti-inflammatory and antibacterial activities, while trans-signalling mediates pro-inflammatory effects. The net biological effect of IL-6 is established by multiple factors beyond its absolute concentration. Here, we assess the relationship between IL-6 signalling variables [IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)] and outcomes in a cohort of 366 COVID-19 patients. The potential trans-signalling was evaluated by a ratio between the pro-inflammatory binary IL-6:sIL-6R complex and the inactive ternary IL-6:sIL-6R:sgp130 complex (binary/ternary complex) and the fold molar excess of sgp130 over sIL-6R (FME). Our data provide new evidence that high levels of IL-6, sIL-6R, sgp130, binary/ternary complex ratio, and low FME are independent predictors of COVID-19 severity in survivor patients (without death), and the combination of IL-6 + sIL-6R + sgp130 exhibited the most robust classification capacity. Conversely, in a subgroup of patients with a very poor prognosis, we found that high levels of IL-6 and low levels of sIL-6R, sgp130, and binary/ternary complex ratio were predictors of death. In this context, the highest predictive capacity corresponded to the combined analysis of IL-6 + FME + lymphopenia + creatinine. Herein, we present IL-6 signalling variables as a helpful tool for the early identification and stratification of patients with clear implications for treatment and clinical decision-making.


Assuntos
COVID-19 , Interleucina-6 , Receptores de Interleucina-6 , Transdução de Sinais , COVID-19/diagnóstico , COVID-19/imunologia , Receptor gp130 de Citocina/metabolismo , Humanos , Interleucina-6/metabolismo , Receptores de Interleucina-6/metabolismo , Índice de Gravidade de Doença
7.
Clin Microbiol Infect ; 28(8): 1151.e9-1151.e16, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35289296

RESUMO

OBJECTIVES: To evaluate whether simplification of antiretroviral treatment to dual therapy (DT) negatively impacts immune recovery (IR), immune activation and inflammation (IA/I), and HIV reservoir. METHODS: An open-label, single-centre, randomized controlled trial conducted in adult virologically suppressed HIV-infected patients on triple therapy (TT) with elvitegravir-cobicistat, emtricitabine and tenofovir alafenamide or dolutegravir (DTG), abacavir, and lamivudine (3TC). Participants were randomized to continue TT or switch to DTG, or darunavir/cobicistat (DRVc) plus 3TC. IR was assessed by CD4+/CD8+ ratio at 48 and 96 weeks. Changes in immune activation, proliferation, exhaustion, senescence, and apoptosis in CD4+ and CD8+ T cells, plasma sCD14, hsCRP, D-dimers, ß2-microglobulin, IL-6, TNF-α and IP-10 levels, cell-associated HIV-DNA (CA-DNA), and unspliced HIV-RNA (usRNA) were also analysed. RESULTS: One hundred and fifty-one participants were enrolled. Fourteen patients did not complete the follow up. In the ITT and PP analysis, the IR was similar between the treatment arms. In the ITT analysis, the median increase in CD4+/CD8+ ratio was 0.10, 0.04, and 0.07 at week 48, and 0.09, 0.05, and 0.08 at week 96 for TT, DTG/3TC, and DRVc/3TC, respectively. After adjusting for confounding factors, the slopes of changes in CD4+/CD8+ ratio over time were independent of treatment (F = 1.699; p = 0.436) and related only to baseline values (F = 756.871; p = 0.000). There were no differences in IA/I, CA-DNA, or usRNA between treatment arms. DISCUSSION: Both IR and IA/I, CA-DNA, and usRNA were similar in the three treatment groups, regardless of maintaining TT or simplifying to DTG/3TC or DRVc/3TC in virologically suppressed HIV-infected patients.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Linfócitos T CD8-Positivos , Cobicistat/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis , Humanos , Lamivudina/uso terapêutico , Carga Viral
8.
J Clin Med ; 11(2)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35054112

RESUMO

The emergency contraception pill (ECP) is a non-prescribed medication in Spain. However, there is not enough evidence of its use among young people to define sex education contents. The aims of this research were to describe the experiences of the use of the ECP in university students and analyze their knowledge, attitude, and awareness regarding the ECP. The cross-sectional, analytic study was conducted with nursing degree students at the University of Seville. A total of 478 students answered the questionnaire. All of the students (100%) had heard about the ECP and had a positive attitude towards this contraceptive. A total of 25.7% had used the ECP, mainly because a condom had failed or because they did not use any contraceptive at all. Deficiencies in knowledge are related with the ECPs' mechanism of action, efficacy after repeated use, and the type of ECP available. Female students who used no method at all or withdrawal, and who were over 20 years old, used ECP to a greater extent (p < 0.005). Further education initiatives focused on the use of the ECP, its efficacy, and typology are needed, particularly among future health professionals who will later educate other young people.

9.
Rep Pract Oncol Radiother ; 26(6): 839-848, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34992855

RESUMO

BACKGROUND: A clinical decision support system (CDSS ) has been designed to predict the outcome (overall survival) by extracting and analyzing information from routine clinical activity as a complement to clinical guidelines in lung cancer patients. MATERIALS AND METHODS: Prospective multicenter data from 543 consecutive (2013-2017) lung cancer patients with 1167 variables were used for development of the CDSS. Data Mining analyses were based on the XGBoost and Generalized Linear Models algorithms. The predictions from guidelines and the CDSS proposed were compared. RESULTS: Overall, the highest (> 0.90) areas under the receiver-operating characteristics curve AUCs for predicting survival were obtained for small cell lung cancer patients. The AUCs for predicting survival using basic items included in the guidelines were mostly below 0.70 while those obtained using the CDSS were mostly above 0.70. The vast majority of comparisons between the guideline and CDSS AUCs were statistically significant (p < 0.05). For instance, using the guidelines, the AUC for predicting survival was 0.60 while the predictive power of the CDSS enhanced the AUC up to 0.84 (p = 0.0009). In terms of histology, there was only a statistically significant difference when comparing the AUCs of small cell lung cancer patients (0.96) and all lung cancer patients with longer (≥ 18 months) follow up (0.80; p < 0.001). CONCLUSIONS: The CDSS successfully showed potential for enhancing prediction of survival. The CDSS could assist physicians in formulating evidence-based management advice in patients with lung cancer, guiding an individualized discussion according to prognosis.

10.
Tumori ; 107(3): 209-215, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32779517

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein ß1 (HSPB1) and transforming growth factor ß1 (TGFß1) and survival have been investigated. METHODS: A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFß1 gene and 5 of HSPB1 gene) variables were analyzed. RESULTS: The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFß1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19-8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37-10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98-3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p < 0.001) and DFS (p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. CONCLUSIONS: Genetic analysis showed the CA genotype of TGFß1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.


Assuntos
Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Carcinoma de Pequenas Células do Pulmão/genética , Fator de Crescimento Transformador beta1/genética , Adulto , Idoso , Antineoplásicos/uso terapêutico , Irradiação Craniana/métodos , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/radioterapia
11.
Thromb Res ; 192: 134-140, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32480167

RESUMO

BACKGROUND: The aim was to analyze the temporal relationship between short-term air pollution exposure and acute symptomatic unprovoked pulmonary embolism (PE). PATIENTS/METHODS: We performed a prospective, multicenter study in consecutive patients diagnosed with acute symptomatic unprovoked PE from February 2012 to January 2013. We analyzed demographic and clinical data, patients' addresses, meteorological and air pollutants data (PM10, SO2, CO, NO2, ozone emission data). We considered the number of days the patient had symptoms, and the study period constituted the previous 30 days. Likewise, the mean annual data of the reference season were calculated as well as the data of the 30-day study period corresponding to the same dates in the previous 3 years in order to obtain the monthly mean of the different pollutants for each period. RESULTS: A total of 162 patients with acute symptomatic PE were recruited (43.2% unprovoked PE). The air pollutants could be determined in 50% of the patients with unprovoked PE, and a final analysis was performed in 35 patients. In the multiple comparison analysis to verify a possible correlation between the study period and the annual median, only NO2 showed a statistically significant association (p = 0.009). When comparing the study period with the previous 3 years, only NO2 maintained a statistically significant association for the 3 study periods. CONCLUSIONS: We found a relationship between short-term exposure to NO2 and the presence of unprovoked PE.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Embolia Pulmonar , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Pulmão , Material Particulado/efeitos adversos , Material Particulado/análise , Estudos Prospectivos , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Pirazinas
12.
Cancers (Basel) ; 12(4)2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32344577

RESUMO

Canonical prefoldin is a protein cochaperone composed of six different subunits (PFDN1 to 6). PFDN1 overexpression promotes epithelial-mesenchymal transition (EMT) and increases the growth of xenograft lung cancer (LC) cell lines. We investigated whether this putative involvement of canonical PFDN in LC translates into the clinic. First, the mRNA expression of 518 non-small cell LC (NSCLC) cases from The Cancer Genome Atlas (TCGA) database was evaluated. Patients with PFDN1 overexpression had lower overall survival (OS; 45 vs. 86 months; p = 0.034). We then assessed the impact of PFDN expression on outcome in 58 NSCLC patients with available tumor tissue samples. PFDN1, 3, and 5 overexpression were found in 38% (n = 22), 53% (n = 31), and 41% (n = 24) of tumor samples. PFDN1, 3, and 5 overexpression were significantly associated with lower OS, lower disease-free survival (DFS), and lower distant metastasis-free survival (DMFS) for PFDN1 and 3 with a trend for PFDN5. In multivariate analysis, PFDN5 retained significance for OS (hazard ratio (HR) 2.56; p = 0.007) and PFDN1 for DFS (HR 2.53; p = 0.010) and marginally for DMFS (HR 2.32; p = 0.053). Our results indicate that protein response markers, such as PFDN1, 3, and 5, may complement mRNA signatures and be useful for determining the most appropriate therapy for NSCLC patients.

13.
Rep Pract Oncol Radiother ; 24(3): 298-305, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192999

RESUMO

AIM: The purpose of this study is to evaluate the long term tolerability of hypofractionated helical tomotherapy (HT) in localized prostate cancer patients. BACKGROUND: Previous hypofractionated schedules with conventional RT were associated with excessive toxicity, likely due to inadequate sophistication of treatment delivery. There are few data about late toxicity after HT. MATERIALS AND METHODS: We evaluated 38 patients with primary adenocarcinoma of the prostate. There were 9 (24%), 15 (39%), and 14 (37%) patients with high, intermediate, and low risk, respectively. Patients were treated with hypofractionated HT from May 2008 to February 2011. Hypofractionation regimens included: 68.04 Gy at 2.52 Gy/fraction (N = 25; 66%), 70 Gy at 2.5 Gy/fraction (N = 4; 11%) and 70.2 Gy at 2.6 Gy/fraction (N = 9; 23%). Late genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system. RESULTS: Median age at diagnosis was 70 years (range 49-80) and median follow-up, 5.8 years. Late grade 1, 2 and 3 GI toxicity were 13%, 24%, and 2.6%, respectively. Late grade 1, 2, 3 GU toxicity were 29%, 21%, and 8%, respectively. Sexual toxicity was evaluated in 19 patients to be grade 1, 2 in 11% and grade 3 in 16%. Multivariate analysis showed that patients with higher values of rectum V50 associated with late GI toxicity (P = 0.025). Patients with PSA ≤8 (P = 0.048) or comorbidities (P = 0.013) at diagnosis were associated with higher late GU toxicity. Additionally, PSA ≤8 also associated with moderate (grade ≥2) late GU toxicity in the multivariate analysis (P = 0.028). CONCLUSIONS: Hypofractionated HT can be delivered safely with limited rates of moderate and severe late toxicity. The proportion of the rectum that receives a moderate and high dose, having comorbidities, and PSA at diagnosis seem to associate with long term toxicity.

14.
Radiother Oncol ; 136: 29-36, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31015126

RESUMO

BACKGROUND AND PURPOSE: Definitive radiation therapy (RT) with or without chemotherapy has become the standard treatment for non-metastatic unresectable non-small cell lung cancer (NSCLC). However, treatment outcomes can differ substantially and patients' genetic background could play a crucial role. Potential associations between single-nucleotide polymorphisms (SNP) in Heat shock protein beta-1 (HSPB1) and survival have been reported in prior single-institution retrospective reports. MATERIALS AND METHODS: The current assay aims to validate such connection in a prospective multicenter study in a European cohort including 181 NSCLC patients. Median follow-up time for all patients was 13 months (range, 3-57 months). RESULTS: The results obtained show an association between the rs2868371 GG genotype and better overall survival (HR: 0.35; 95%CI: 0.13-0.96; p = 0.042) in multivariate analysis. Two-year overall survival rate was 72% for patients carrying the rs2868371 GG genotype versus 36% for those patients harboring the rs2868371 CC/CG genotypes (p = 0.013). Additionally, the rs2868371 GG genotype was found to be associated with better disease-free survival in the multivariate analysis (HR: 0.36; 95%CI: 0.13-0.99; p = 0.048). In silico analysis of the potential functional SNP suggested significant difference in the affinity of the Glucocorticoid Receptor binding site between alternative allelic variants, confirmed by chromatin immunoprecipitation analysis displaying stronger affinity for the risk allele (C). Furthermore, our findings indicate that the rs2868371 influences (mRNA) HSPB1 expression, offering insight into the regulation of HSPB1 transcription. CONCLUSION: The functional HSPB1 rs2868371 promoter variant may affect lung cancer survival by regulation of HSPB1 expression levels through glucocorticoid receptor interaction.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Choque Térmico/genética , Neoplasias Pulmonares/genética , Chaperonas Moleculares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptores de Glucocorticoides/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida
15.
Radiother Oncol ; 135: 161-169, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31015163

RESUMO

BACKGROUND AND PURPOSE: Radiochemotherapy (RCT) success in lung cancer (LC) can be limited due to the onset of adverse effects in the adjacent normal tissue such as radiation-induced esophageal toxicity (RIET). Therefore, specific biomarkers to customize the RCT dose administration and esophageal toxicity prediction are necessary to improve treatment effectiveness. MATERIALS AND METHODS: 247 LC patients prospectively recruited between 2012 and 2016 from 3 institutions were genotyped for 7 SNPs along TGFB1 and HSPB1 genes seeking an association with RIET risk development. Kaplan-Meier cumulative probability and Cox proportional hazards analyses were used to evaluate the effect of TGFB1 and HSPB1 genotypes on such risk. RESULTS: Multivariate analyses showed that patients carrying the HSPB1 rs7459185 CC genotype were associated with a significantly higher risk of acute grade 3 RIET than those carrying the GG/GC genotypes (HR = 17.73; 95% CI = 2.896-108.49; p = 0.002). LC patients who received higher (>median) volume of esophagus exposed to 30 Gy and harboring the rs7459185 GG/GC genotypes showed a significantly lower RIET incidence (p < 0.001). Additionally, LC patients carrying the TGFB1 rs11466353 GG genotype were found to be associated with a lower risk of late grade 2 RIET compared with those with the TT/TG genotypes (HR = 0.29; 95% CI = 0.103-0.830; p = 0.021). Patients receiving a high (>60 Gy) radiation dose who presented the rs11466353 GG genotype had a significantly lower RIET incidence (p = 0.025). CONCLUSION: The presence of different rs7459185/rs11466353 genotypes in LC patients associated with RIET risk and may be useful biomarkers along with other risk factors for guiding therapy intensity in an individualized therapy.


Assuntos
Esofagite/etiologia , Proteínas de Choque Térmico/genética , Neoplasias Pulmonares/radioterapia , Chaperonas Moleculares/genética , Polimorfismo de Nucleotídeo Único , Lesões por Radiação/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esofagite/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões por Radiação/etnologia , Fator de Crescimento Transformador beta1/genética
16.
Br J Cancer ; 119(8): 915-921, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30318508

RESUMO

BACKGROUND: Optimal duration of anticoagulation for cancer-associated thrombosis (CAT) remains unclear. This study assessed D-dimer (DD) and high-sensitivity C-reactive protein (hs-CRP) levels after the withdrawal of anticoagulation treatment to predict the risk of venous thromboembolism (VTE) recurrence among patients with CAT. METHODS: Prospective, multicentre study to evaluate CAT with ≥3 months of anticoagulation that was subsequently discontinued. Blood samples were taken when patients stopped the anticoagulation and 21 days later to determine the DD and hs-CRP levels. All patients were followed up for 6 months to detect VTE recurrence. RESULTS: Between 2013 and 2015, 325 patients were evaluated and 114 patients were ultimately enrolled in the study. The mean age was 62 ± 14 years and nearly 40% had metastasis. Ten patients developed VTE recurrence within 6 months (8.8%, 95% confidence interval [CI]: 4.3-15.5%). The DD and hs-CRP levels after 21 days were associated with VTE recurrence. The subdistribution hazard ratios were 9.82 for hs-CRP (95% CI: 19-52) and 5.81 for DD (95% CI: 1.1-31.7). CONCLUSIONS: This study identified that hs-CRP and DD were potential biomarkers of VTE recurrence after discontinuation of anticoagulation in CAT. A risk-adapted strategy could identify low-risk patients who may benefit from discontinuation of anticoagulation.


Assuntos
Anticoagulantes/administração & dosagem , Proteína C-Reativa/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Neoplasias/patologia , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/prevenção & controle , Suspensão de Tratamento/estatística & dados numéricos , Anticoagulantes/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/irrigação sanguínea , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Prevenção Secundária/métodos , Tromboembolia Venosa/tratamento farmacológico , Trombose Venosa/tratamento farmacológico
17.
Cir. Esp. (Ed. impr.) ; 96(8): 501-507, oct. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-176653

RESUMO

INTRODUCCIÓN: La mayor supervivencia del paciente trasplantado viene acompañada del aumento en la tasa de tumores de novo (TN) que representan la complicación tardía más frecuente. Podemos distinguir entre tumores de piel no melanoma (TPNM), síndrome linfoproliferativo postrasplante (SLPT) y tumores de órgano sólido (TOS). Nuestro objetivo es determinar la incidencia de los distintos TN, el tiempo trascurrido hasta su diagnóstico y su supervivencia en nuestro medio. MATERIAL Y MÉTODO: Realizamos un estudio retrospectivo de 1.071 trasplantados hepáticos desde 1990 hasta 2015 en nuestro centro. Analizamos las variables demográficas, la incidencia de TN y la supervivencia. RESULTADOS: Se desarrollaron 184 TN en 1.071 pacientes trasplantados (17%), en el 19% de los varones y en el 13% de las mujeres (p = 0,004). Los TN más frecuentes fueron los TPNM (29%), pulmón (18%), cabeza y cuello (16%), SLPT (10%) y gastrointestinales (8%). La mediana del tiempo de diagnóstico fue de 7,9 años en los TPNM, 3,9 años en SLPT y de 9,8 años en TOS. Los pacientes con TPNM tuvieron significativamente mejor supervivencia que aquellos con SLPT o TOS. La incidencia de los tumores de novo (excluidos TPNM) fue 1.889/100.000 trasplantados/año. Por género, el cáncer de pulmón fue el TOS más común en varones y el cáncer de mama en mujeres. CONCLUSIÓN: En nuestro medio, excluidos los TPNM, la incidencia es 8,8 veces la estimada para la población general, con una alta tasa de cáncer de pulmón por lo que deberíamos implementar estrategias preventivas y diagnósticas


INTRODUCTION: The greater survival of transplanted patients is accompanied by an increase in the rate of de novo malignancies (NM), which are the most frequent late-onset complication. We can distinguish between non-melanoma skin cancers (NMSC), post-transplant lymphoproliferative disorders (PTLD) and solid organ cancers (SOC). Our objective is to determine the incidence of the different types of NM, the time elapsed until diagnosis and survival rates in our setting. METHODS: We conducted a retrospective study of 1071 liver transplant patients from 1990 to 2015 at our center. We analyzed the demographic variables, incidence of NM and survival. RESULTS: 184 NM developed in 1071 transplant patients (17%), specifically 19% of the males and 13% of the females (P=.004). The most frequent NM were NMSC (29%), lung (18%), head and neck (16%), PTLD (10%) and gastrointestinal (8%). The median time of diagnosis was 7.9 years in NMSC, 3.9 years in PTLD and 9.8 years in SOC. Patients with NMSC had significantly better survival than those with PTLD or SOC. The incidence of de novo tumors (excluding NMSC) was 1889/100,000 transplants/year. By gender, lung cancer was the most common TOS in men and breast cancer in women. CONCLUSION: In our setting, excluding NMSC, the incidence is 8.8 times greater than estimations for the general population, with a high rate of lung cancer, so we should implement preventive and diagnostic strategies


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Transplante de Fígado , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Sobrevivência , Neoplasias Hepáticas/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Estudos Retrospectivos , Imunossupressores/uso terapêutico
18.
Cir Esp (Engl Ed) ; 96(8): 501-507, 2018 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30017062

RESUMO

INTRODUCTION: The greater survival of transplanted patients is accompanied by an increase in the rate of de novo malignancies (NM), which are the most frequent late-onset complication. We can distinguish between non-melanoma skin cancers (NMSC), post-transplant lymphoproliferative disorders (PTLD) and solid organ cancers (SOC). Our objective is to determine the incidence of the different types of NM, the time elapsed until diagnosis and survival rates in our setting. METHODS: We conducted a retrospective study of 1071 liver transplant patients from 1990 to 2015 at our center. We analyzed the demographic variables, incidence of NM and survival. RESULTS: 184 NM developed in 1071 transplant patients (17%), specifically 19% of the males and 13% of the females (P=.004). The most frequent NM were NMSC (29%), lung (18%), head and neck (16%), PTLD (10%) and gastrointestinal (8%). The median time of diagnosis was 7.9 years in NMSC, 3.9 years in PTLD and 9.8 years in SOC. Patients with NMSC had significantly better survival than those with PTLD or SOC. The incidence of de novo tumors (excluding NMSC) was 1889/100,000 transplants/year. By gender, lung cancer was the most common TOS in men and breast cancer in women. CONCLUSION: In our setting, excluding NMSC, the incidence is 8.8 times greater than estimations for the general population, with a high rate of lung cancer, so we should implement preventive and diagnostic strategies.


Assuntos
Transplante de Fígado , Neoplasias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
19.
Tumori ; 104(4): 300-306, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29714667

RESUMO

AIMS AND BACKGROUND: The treatment of glomus jugulare tumors (GJT) remains controversial due to high morbidity. Historically, these tumors have primarily been managed surgically. The purpose of this retrospective review was to assess the tumor and clinical control rates as well as long-term toxicity of GJT treated with radiosurgery. METHODS: Between 1993 and 2014, 30 patients with GJT (31 tumors) were managed with radiosurgery. Twenty-one patients were female and the median age was 59 years. Twenty-eight patients (93%) were treated with radiosurgery, typically at 14 Gy ( n = 26), and 2 patients (7%) with stereotactic radiosurgery. Sixteen cases (52%) had undergone prior surgery. RESULTS: The mean follow-up was 4.6 years (range 1.5-12). Crude overall survival, tumor control, clinical control, and long-term grade 1 toxicity rates were 97%, 97%, 97%, and 13% (4/30), respectively. No statistically significant risk factor was associated with lower tumor control in our series. Univariate analysis showed a statistically significant association between patients having 1 cranial nerve (CN) involvement before radiosurgery and a higher risk of lack of improvement of symptoms (odds ratio 5.24, 95% confidence interval 1.06-25.97, p = .043). CONCLUSIONS: Radiosurgery is an effective and safe treatment modality for GJT. Patients having 1 CN involvement before radiosurgery show a higher risk of lack of improvement of symptoms.


Assuntos
Tumor do Glomo Jugular/radioterapia , Tumor do Glomo Jugular/cirurgia , Radiocirurgia , Adolescente , Adulto , Idoso , Feminino , Tumor do Glomo Jugular/diagnóstico por imagem , Tumor do Glomo Jugular/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Radiother Oncol ; 127(2): 219-224, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29625808

RESUMO

BACKGROUND AND PURPOSE: High dose-rate (HDR) brachytherapy (BT) provides a highly conformal method of dose delivery to the prostate. The purpose of this study is to prospectively determine the toxicity of the treatment protocol of 13.5 Gy × 2 fractions. MATERIALS AND METHODS: From 2010 through 2017, 119 patients with low (71%) or intermediate-risk prostate cancer were prospectively treated in a single institute with HDR-BT at 13.5 Gy × 2 fractions within one day. Median follow-up time was 4.4 years. RESULTS: Actuarial rates of no biochemical evidence of disease, overall survival and metastasis-free survival for all patients were 96%,98% and 98%, respectively. The cumulative incidence of acute grade 2 and 3 genitourinary (GU) toxicity was 9% and 2%, respectively. The corresponding incidences of late GU toxicity were 18% and 1%. No grade ≥4 of either type of toxicity was detected. Multivariate analysis showed that having higher international prostate symptom score (IPSS; P = 0.041) or higher V200 (P = 0.013) was associated with a higher risk of experiencing any grade of acute GU toxicity. In addition, patients having a higher IPSS (P = 0.019) or a higher V150 (P = 0.033) were associated with a higher grade >1 acute GU toxicity. CONCLUSIONS: The findings of this study show that HDR-BT 13.5 Gy × 2 as monotherapy was safe and effective for prostate cancer patients with low-intermediate risk.


Assuntos
Braquiterapia/efeitos adversos , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Intervalo Livre de Doença , Humanos , Masculino , Doenças Urogenitais Masculinas/etiologia , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Neoplasias da Próstata/patologia , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Fatores de Risco
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