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SUMMARY OBJECTIVE: This study aimed to evaluate postoperative pain and quality of life in patients undergoing median sternotomy. METHODS: A cohort study was carried out on a sample of 30 patients who underwent elective cardiac surgery by longitudinal median sternotomy. Patients were interviewed at Intensive Care Unit discharge and hospital discharge, when the Visual Numeric Scale and the Brief Pain Inventory were applied, and 2 weeks after hospital discharge, when the World Health Organization Quality of Life-Bref questionnaire was administered. The normality of the results was analyzed by the Shapiro-Wilk test, and Wilcoxon Rank Sum and McNemar tests were utilized for the analysis of numerical and categorical variables. For correlation between numerical variables, Spearman's linear correlation test was applied. To compare numerical variables, Mann-Whitney U and Kruskal-Wallis tests were applied. Differences between groups were considered significant when the p-value was <0.05. RESULTS: Between Intensive Care Unit and hospital discharge, there was a reduction in median pain intensity assessed by the Visual Numeric Scale from 5.0 to 2.0 (p<0.001), as well as in eight Brief Pain Inventory parameters: worst pain intensity in the last 24 h (p=0.001), analgesic relief (p=0.035), and pain felt right now (p=0.009); and in interference in daily activities (p<0.001), mood (p=0.017), ability to walk (p<0.001), relationship with other people (p=0.005), and sleep (p=0.006). Higher pain intensity at Intensive Care Unit discharge was associated with worse performance in the psychological domain of quality of life at out-of-hospital follow-up. CONCLUSION: Proper management of post-sternotomy pain in the Intensive Care Unit may imply better quality of life at out-of-hospital follow-up.
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OBJECTIVE: This study aimed to evaluate postoperative pain and quality of life in patients undergoing median sternotomy. METHODS: A cohort study was carried out on a sample of 30 patients who underwent elective cardiac surgery by longitudinal median sternotomy. Patients were interviewed at Intensive Care Unit discharge and hospital discharge, when the Visual Numeric Scale and the Brief Pain Inventory were applied, and 2 weeks after hospital discharge, when the World Health Organization Quality of Life-Bref questionnaire was administered. The normality of the results was analyzed by the Shapiro-Wilk test, and Wilcoxon Rank Sum and McNemar tests were utilized for the analysis of numerical and categorical variables. For correlation between numerical variables, Spearman's linear correlation test was applied. To compare numerical variables, Mann-Whitney U and Kruskal-Wallis tests were applied. Differences between groups were considered significant when the p-value was <0.05. RESULTS: Between Intensive Care Unit and hospital discharge, there was a reduction in median pain intensity assessed by the Visual Numeric Scale from 5.0 to 2.0 (p<0.001), as well as in eight Brief Pain Inventory parameters: worst pain intensity in the last 24 h (p=0.001), analgesic relief (p=0.035), and pain felt right now (p=0.009); and in interference in daily activities (p<0.001), mood (p=0.017), ability to walk (p<0.001), relationship with other people (p=0.005), and sleep (p=0.006). Higher pain intensity at Intensive Care Unit discharge was associated with worse performance in the psychological domain of quality of life at out-of-hospital follow-up. CONCLUSION: Proper management of post-sternotomy pain in the Intensive Care Unit may imply better quality of life at out-of-hospital follow-up.
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Procedimentos Cirúrgicos Cardíacos , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Estudos de Coortes , Medição da Dor/métodos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Dor Pós-Operatória/etiologiaRESUMO
Abstract Introduction Pain is one of the main symptoms prevalent in most pathologies. Transcutaneous Electrical Nerve Stimulation (TENS) represents not only a therapeutic measure, but also a mean to quantify the neurosensory and pain perception in patients with chronic pain. Objective To evaluate the relationship between sex and age with neurosensory thresholds (sensory threshold and tolerance threshold) in the application of therapeutic current in patients with chronic pain. Methods Forty-five patients with chronic pain (30 women and 15 men) aged between 24 and 87 years were selected. Each patient answered the Individual Questionnaire, McGill Pain Questionnaire (MPQ) and Beck Depression Inventory (BDI). Subsequently, the electric current was applied, through which the sensory and pain thresholds were analyzed, as well as the perception of activation of the neurosensory pathways for each individual. Data were analyzed using the SPSS 24.0 for Windows. Results There was no significant correlation (p > 0.05) between a possible depressive diagnosis and the perception of current by the sensory and pain thresholds. Regarding sex, there was a significant difference in sensory thresholds (p = 0.003) between men and women, while no statistical differences were observed between sexes for pain complaint and pain threshold (p > 0.05). For the correlational analysis, a significant correlation (p = 0.05) was identified between the variables BMI and pain tolerance threshold (r = 0.68) for females and age and sensory threshold (r = 0.65) for males. Conclusion The sex and age variables are important in the measurement of TENS parameters because they lead to significant differences in sensory and pain thresholds.
Resumo Introdução A dor é um dos principais sintomas preva-lentes na maioria das patologias. A estimulação elétrica ervosa transcutânea (TENS) se apresenta não apenas como medida terapêutica, como também um meio de quantificar a percepção neurossensitiva e dolorosa em pacientes com dores crônicas. Objetivo Avaliar a relação entre sexo e idade com os limiares neurossensitivos (limiar sensitivo e limiar de tolerância) na aplicação da corrente terapêutica TENS, em pacientes com dores crônicas. Métodos Foram selecionados 45 pacientes com dores crônicas (30 mulheres), com idade entre 24 e 87 anos. Cada paciente respondeu ao Questionário Individual, ao Questionário McGill de Dor (MPQ) e ao Inventário de Depressão de Beck (BDI). Posteriormente, aplicou-se a corrente elétrica TENS, pela qual foram analisados o limiar sensitivo e doloroso, bem como a percepção de acionamento das vias neurossensitivas para cada indivíduo. Os dados foram analisados pelo pacote SPSS 24.0 for Windows. Resultados Não houve correlação significativa (p > 0,05) entre possível diagnós-tico depressivo e a percepção da corrente pelos limiares de sensibilidade e dor. Em relação ao sexo, houve diferença significativa nos limiares sensitivos (p = 0,003) entre homens e mulheres. Já para a queixa de dor e limiar de dor, não foram observadas diferenças estatísticas entre os sexos (p > 0,05). Para as análises correlacionais, identificou-se correlação significativa (p = 0,05) entre as variáveis de índice de massa corporal e limiar de tolerância à dor (r = 0,68) para o sexo feminino e idade e limiar sensitivo (r = 0,65) paro o sexo masculino. Conclusão As diferenças identificadas entre os limiares de sensibilidade entre os sexos, onde as mulheres identificaram o estímulo elétrico significativamente primeiro que os homens, podem auxiliar nas doses de intensidade ou tipo de corrente terapêutica dos pacientes.
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Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estimulação Elétrica Nervosa Transcutânea , Limiar da Dor , Dor Aguda , Dor Crônica , Limiar SensorialRESUMO
Management of locally advanced head and neck squamous cell carcinoma (HNSCC) requires a multi-prong approach comprising surgery, radiation and/or chemotherapy, yet outcomes are limited. This is largely due to a paucity of biomarkers that can predict response to specific treatment modalities. Here, we evaluated TGFß3 protein levels in extracellular vesicles (EVs) released by HNSCC cells as a predictor for response to chemoradiation therapy (CRT). To this end, specific EV-fractions were isolated from cell lines or HNSCC patient plasma, and TGFß3 protein was quantified. In patients treated with CRT, TGFß3 levels were found to be significantly higher in plasma EV-fractions or non-responders compared with responders. High levels of TGFß3 levels in Annexin V-EVs were associated with the worst progression-free survival. In vitro experiments demonstrated that TGFß3 silencing sensitized HNSCC cells to cytotoxic therapies, and this phenotype could be rescued by treatment with exogenous. In addition, specific EV-fractions shed by cisplatin-resistant cells were sufficient to transfer the resistant phenotype to sensitive cells through activation of TGFß-signaling pathway. Therefore, our data show that TGFß3 transmitted through EV plays a significant role in response to cytotoxic therapy, which can be exploited as a potential biomarker for CRT response in HNSCC patients treated with curative intent.
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Biomarcadores Tumorais/sangue , Vesículas Extracelulares/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Fator de Crescimento Transformador beta3/sangue , Adulto , Idoso , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Tolerância a Radiação/fisiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangueRESUMO
BACKGROUND: There is a paucity of plasma-based biomarkers that prospectively segregate the outcome of patients with head and neck squamous-cell carcinoma (HNSCC) treated with chemoradiation therapy (CRT). Plasma extracellular vesicles (EVs) might be an alternative source for discovery of new specific markers present in patients with HNSCC, which could help to re-direct patients to appropriate curative therapies without delay. METHODS: In order to identify new markers in plasma compartments, Cholerae toxin B chain (CTB) and Annexin V (AV) were used to isolate EVs from pooled plasma samples from patients with locally advanced HNSCC who responded (CR, n = 6) or presented incomplete response (NR, n = 6) to CRT. The crude plasma and EVs cargo were screened by antibody array. RESULTS: Of the 370 polypeptides detected, 119 proteins were specific to NR patients while 38 were exclusive of the CR subjects. The Gene Set Enrichment Analysis (GSEA) and Search Tool for the Retrieval of Interacting Genes (STRING) database analysis indicated that the content of circulating plasma EVs might have a relevant function for the tumor intercellular communication in the HNSCC patients. CONCLUSION: This study provides a list of potential markers present in plasma compartments that might contribute to the development of tools for prediction and assessment of CRT response and potentially guide therapeutic decisions in this context.
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Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/métodos , Vesículas Extracelulares/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/terapia , Ensaios Clínicos Fase II como Assunto , Vesículas Extracelulares/patologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise Serial de Proteínas , Mapas de Interação de ProteínasRESUMO
Lung cancer is the deadliest cancer worldwide. The mutational frequency of EGFR and KRAS genes in lung adenocarcinoma varies worldwide per ethnicity and smoking. The impact of EGFR and KRAS mutations in Brazilian lung cancer remains poorly explored. Thus, we investigated the frequency of EGFR and KRAS mutations in a large Brazilian series of lung adenocarcinoma together with patients' genetic ancestry, clinicopathological and sociodemographic characteristics. The mutational frequency of EGFR was 22.7% and KRAS was 20.4%. The average ancestry proportions were 73.1% for EUR, 13.1% for AFR, 6.5% for AME and 7.3% for ASN. EGFR mutations were independently associated with never-smokers, high-Asian ancestry, and better performance status. KRAS mutations were independently associated with tobacco exposure and non-Asian ancestry. EGFR-exon 20 mutations were associated with worse outcome. The Cox regression model indicated a worse outcome for patients whose were older at diagnosis (>61 y), solid histological subtype, loss of weight (>10%), worse performance status (≥2), and presence of KRAS mutations and EGFR mutational status in TKi non-treated patients. In conclusion, we assessed the clinicopathological and ethnic impact of EGFR and KRAS mutations in the largest series reported of Brazilian lung adenocarcinomas. These findings can support future clinical strategies for Brazilian lung cancer patients.
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Adenocarcinoma de Pulmão/genética , Povo Asiático/genética , Neoplasias Pulmonares/genética , Mutação/genética , Filogenia , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Análise Mutacional de DNA , Receptores ErbB/genética , Éxons/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Adulto JovemRESUMO
Epidermal growth factor (EGF) and its receptor (EGFR) play an important role in lung carcinogenesis. A functional single nucleotide polymorphism (SNP) in EGF promoter region (EGF+61 A>G-rs4444903) has been associated with cancer susceptibility. Yet, in lung cancer, the EGF+61 A>G role is unclear. The aim of this study was to evaluate the risk of lung cancer associated with EGF+61 A>G SNP in the Brazilian population. For that, 669 lung cancer patients and 1104 controls were analyzed. EGF+61 A>G genotype was assessed by PCR-RFLP and TaqMan genotyping assay. Both patients and controls were in Hardy-Weinberg equilibrium. As expected, uni- and multivariate analyses showed that tobacco consumption and age were significant risk factors for lung cancer. The genotype frequencies in lung cancer patients were 27.3% of AA, 47.4% of AG and 25.3% of GG, and for controls were 25.3% of AA, 51.6% of AG and 23.1% of GG. The allele frequencies were 51.1% of A and 48.9% of G for both cases and controls. No significant differences for the three genotypes (AA, AG and GG-codominant model) were observed between cases and controls. We then grouped AG and GG (recessive model) genotypes, as well as AA and AG (dominant model), and again, no significant differences were also found. This is the largest study to explore EGF+61 A>G polymorphism association with lung cancer risk and suggests that this SNP is not a risk factor for lung cancer in the Brazilian population.
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Fator de Crescimento Epidérmico/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Brasil , Estudos de Casos e Controles , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genética Populacional/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Fatores de RiscoRESUMO
BACKGROUND: There is a paucity of plasma-based biomarkers that predict outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation therapy (CRT). Here, we evaluate the prognostic potential of plasma Melanoma-Antigen Recognized by T-cells 1 (MLANA) in this setting. METHODS: MLANA expression in HNSCC lines were evaluated by reverse transcription polymerase chain reaction, whereas plasma levels were quantified using ELISA in 48 patients with locally advanced HNSCC undergoing a phase 2 trial with CRT. RESULTS: MLANA is expressed at variable levels in a panel of HNSCC lines. In plasma, levels were elevated in patients with tumor relapse compared to those without (P < .004); 73.9% of the patients expressing high plasma MLANA levels progressed with recurrent disease (P = .020). Multivariate analysis showed that plasma MLANA levels and tumor resectability were independent prognostic factors for progression free survival. CONCLUSION: Plasma MLANA expression appears to be an effective noninvasive biomarker for outcomes in patients treated with CRT, and could potentially guide therapeutic decisions in this context.
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Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/sangue , Antígeno MART-1/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Linhagem Celular Tumoral , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
Abstract Background The World Health Organization defines suicide as the act of deliberately killing oneself. It is the second leading cause of death among 15-29 year olds globally. Objective To analyze the epidemiological profile and the spatial distribution of suicide deaths in the state of Sergipe. Methods We performed an ecological time-series study with data from the Brazilian Mortality Information System (Sistema de Informações sobre Mortalidade - SIM) about deaths by suicide occurring between 2000 and 2015. We considered as suicide deaths cases recorded as voluntary self-inflicted injuries. Suicide rates were estimated and age-adjusted in the population above 9 years. We analyzed temporal trends by sex and age groups using the simple linear regression model. For the spatial analysis, we performed Kernel density estimation with the software TerraView version 4.2.2. Results We identified 1,560 suicide cases in the state of Sergipe between 2000 and 2015, with a mean of 97.5 cases per year. We also observed that suicide rates in the state increased 102.3% (from 2.69/100,000 population in 2000 to 5.44 in 2015). Suicides occurred predominantly among males (1,160 cases; 74.35%), single people (1,010 cases; 64.7%), and brown-skinned people (1,039 cases; 66.6%). We observed significantly growing temporal trends in the general population, especially among male adults. Spatial analysis allowed us to draw a map that showed the regions with the highest occurrence of suicide. Conclusion We observed growing suicide trends in the state of Sergipe and the spatial analysis was an important tool that showed the areas with higher incidences of suicide.
Resumo Introduçao A Organização Mundial da Saúde define o suicídio como o ato de se matar deliberadamente. É a segunda principal causa de morte entre jovens de 15 a 29 anos no mundo. Objetivo Analisar o perfil epidemiológico e a distribuição espacial dos óbitos por suicídio no estado de Sergipe. Métodos Foi realizado estudo ecológico e de série temporal com dados do Sistema de Informações sobre Mortalidade (SIM) dos óbitos por suicídio ocorridos entre 2000 e 2015. Foram considerados suicídio os casos de mortes registrados como lesões voluntárias autoinfligidas. As taxas de suicídio foram estimadas e ajustadas por idade na população acima de 9 anos. Foram analisadas as tendências temporais por sexo e grupos etários usando o modelo de regressão linear simples. Para a análise espacial, foi realizada a estimativa de Kernel com o software TerraView 4.2.2. Resultados Foram identificados 1.560 casos de suicídio no estado de Sergipe entre 2000 e 2015, com média de 97,5 casos por ano. Observou-se um aumento de 102,3% das taxas de suicídio no estado (de 2,69/100.000 habitantes em 2000 para 5,44 em 2015). Os suicídios ocorreram predominantemente no sexo masculino (1.160 casos; 74,35%), em solteiros (1.010 casos; 64,7%) e pardos (1.039 casos; 66,6%). Foram observadas tendências temporais crescentes na população geral, especialmente entre adultos do sexo masculino. A análise espacial permitiu a construção de mapas exibindo as regiões com maiores concentrações de suicídio. Conclusão Observaram-se tendências crescentes de suicídio no estado de Sergipe e a análise espacial foi uma importante ferramenta ao mostrar áreas com maiores incidências de suicídio.
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Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Adulto Jovem , Suicídio/tendências , Mortalidade/tendências , Brasil , Análise Espacial , Geografia Médica , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The evolution of radiotherapy over recent decades has reintroduced the hypofractionation for many tumor sites with similar outcomes to those of conventional fractionated radiotherapy. The use of hypofractionation in locally advanced head and neck cancer (LAHNC) has been already used, however, its use has been restricted to only a few countries. The aim of this trial was to evaluate the safety and feasibility of moderate hypofractionated radiotherapy (HYP-RT) with concomitant cisplatin (CDDP). METHODS: This single-arm trial was designed to evaluate the safety and feasibility of HYP-RT with concomitant CDDP in LAHNC. Stage III and IV patients withnonmetastatic disease were enrolled. Patients were submitted to intensity modulatedradiation therapy, which comprised 55 Gy/20 fractions to the gross tumor and44-48 Gy/20 fractions to the areas of subclinical disease. Concomitant CDDPconsisted of 4 weekly cycles of 35 mg/m2. The primary endpoints were the treatment completion rate and acute toxicity. RESULTS: Twenty patients were enrolled from January 2015 to September 2016, and 12 (60%) were classified as unresectable. All patients completed the total dose of radiotherapy, and 19 patients (95%) received at least 3 of 4 cycles of chemotherapy. The median overall treatment time was 29 days (27-34). Grade 4 toxicity was reported twice (1 fatigue and 1 lymphopenia). The rates of grade 3 dermatitis and mucositis were 30% and 40%, respectively, with spontaneous resolution. Nasogastric tubes were offered to 15 patients (75%) during treatment; 4 patients (20%) needed feeding tubes after 2 months, and only 1 patient needed a feeding tube after 12 months. CONCLUSION: HYP-RT with concomitant CDDP was considered feasible for LAHNC, and the rate of acute toxicity was comparable to that of standard concomitant chemoradiation. A feeding tube was necessary for most patients during treatment. Further investigation of this strategy is warranted. TRIAL REGISTRATION: ClinicalTrials, NCT03194061 . Registered 21 Jun 2017 - Retrospectively registered.