ABSTRACT
PURPOSE: To evaluate the prognostic value of C-reactive protein (CRP), albumin, CRP/albumin ratio (CAR), and modified Glasgow Prognostic Score (mGPS) at different thresholds in patients with advanced cancer in palliative care. METHODS: Prospective cohort study with patients evaluated at a palliative care unit in Brazil between July 2016 and March 2020. We included patients ≥ 20 years old, both sexes, able to provide the necessary information or accompanied by someone able to do so, and Karnofsky Performance Status ≥ 30 %. The exclusion criteria were the absence of laboratory data and previous diagnosis of autoimmune and infectious diseases. The thresholds analyzed were: CRP < 5 vs. 5-10 vs. > 10 mg/L, albumin < 2.4 vs. 2.4-2.9 vs. 3.0-3.5 vs. > 3.5 g/dL; CAR <1.2 vs. 1.2-2.0 vs. > 2.0, and mGPS equal to 0 vs. 1 vs. 2. Kaplan-Meier curves and Cox regression models (with hazard ratios [HR] and 95% confidence interval [CI]) were used to evaluate prognostic value, and the concordance statistic (C-statistic) was used to evaluate the predictive accuracy of these thresholds to predict death within 90 days. RESULTS: A total of 1,877 patients were included. Median overall survival was 51 (19;124) days and decreased in line with the deterioration of the inflammatory biomarkers. According to the Cox regression models, HR increased as the thresholds worsened (CRP: 1.74 [95% CI, 1.50-2.02] to 2.30 [95% CI, 2.00-2.64]; albumin: 1.77 [95% CI, 1.52-2.07] to 2.60 [95% CI, 2.15-3.14]; CAR: 1.47 [95% CI, 1.21-1.77] to 2.35 [95% CI, 2.05-2.69]; mGPS: 1.78 [95% CI, 1.40-2.23] to 1.89 [95% CI, 1.65-2.15]). All the inflammatory biomarkers evaluated showed discriminatory accuracy for predicting death (C-statistic >0.70), with CAR as the best parameter (C-statistic: 0.80). CONCLUSION: Our results suggest that CRP, albumin, CAR, and mGPS can be used as clinically meaningful biomarkers to stratify patients with advanced cancer in palliative care according to the severity of these indicators.
ABSTRACT
BACKGROUND & AIMS: It is a challenge in clinical practice to identify and classify cancer cachexia. Currently, it has been extensively discussed if the presence of alterations in inflammatory biomarkers implies the presence of cachexia. This study aimed to evaluate the clinical relevance of cachexia classification through modified Glasgow Prognostic Score (mGPS) in advanced cancer patients in palliative care. METHODS: Observational prospective cohort study conducted at a Palliative Care Unit in Brazil. Cachexia classification was performed according to mGPS (based on albumin and C-reactive protein) in four different stages: no cachexia (NCa), undernourished (Un), pre cachexia (PCa), and refractory cachexia (RCa). Logistic regression models were used to test the association between cachexia stages and clinical, nutritional and functional domains. Kaplan-Meier curve and Cox multivariate model were used to analyze overall survival (OS). RESULTS: A total of 1166 patients were included in the study. According to the cachexia framework 37.5% were NCa, 32.3% Un, 3.9% PCa and 26.4% RCa. Significant differences were observed among cachexia stages for most of the outcome measures. This classification was able to predict mortality in 90 days [Un (HR, 1.55; 95% CI, 1.25; 1.93); PCa (HR, 2.00; 95% CI, 1.34; 2.98); RCa (HR, 2.45; 95% CI, 1.34; 2.98)]. CONCLUSION: Cachexia stages were associated with significant differences in poor clinical outcomes and were also capable of predicting OS. This framework based on simple and objective criteria can be used as part of the routine to characterize the presence and stages of cachexia in advanced cancer patients.
Subject(s)
Cachexia/etiology , Neoplasms/complications , Neoplasms/pathology , Palliative Care , Aged , Biomarkers , Female , Humans , Male , Middle AgedABSTRACT
Introdução e objetivo: A identificação e caracterização dos estágios da caquexia no câncer é um desafio na prática clínica. Atualmente, discute-se que alterações nos marcadores inflamatórios seriam capazes de indicar a presença de caquexia. Esse estudo teve por objetivo avaliar a relevância clínica da classificação de caquexia por meio do Escore Prognóstico de Glasgow modificado (EPGm) em pacientes com câncer avançado em cuidados paliativos. Métodos: Estudo observacional de coorte prospectivo realizado em uma Unidade de Cuidados Paliativos no Brasil. A caquexia foi classificada de acordo com o EPGm (composto por albumina e proteína C reativa) em quatro estágios: não caquético (NCa), desnutrido (Un), pré-caquético (PCa) e caquético refratário (RCa). Modelos de regressão logística foram utilizados para avaliar a associação entre os estágios de caquexia e domínios clínicos, nutricionais e funcionais. Curvas de Kaplan-Meier e o modelo multivariado de Cox foram usados para analisar a sobrevida. Resultados: Foram incluídos 1.166 pacientes. De acordo com o critério baseado no EPGm 37,5% dos pacientes foram considerados NCa, 32,3% Un, 3,9% PCa e 26,4% RCa. Foram observadas diferenças significativas na maioria dos desfechos estudados de acordo com os estágios de caquexia. Houve diferença significativa na sobrevida global entre os grupos estudados (77 versus 37 versus 31 versus 17 dias, respectivamente; p-valor <0,001). Além disso, a classificação utilizada foi capaz de predizer a mortalidade em 90 dias [Un (HR, 1,55; IC 95%, 1,25-1,93); PCa (HR, 2,00; IC 95%, 1,34-2,98); RCa (HR, 2,45; IC 95%, 1,34-2,98)]. Conclusão: Os estágios de caquexia foram associados à piores desfechos clínicos e capazes de predizer a sobrevida. Este método, baseado em um critério simples e objetivo, pode ser usado na rotina para caracterizar a presença e os estágios de caquexia em pacientes com câncer avançado.
Background & Aims: It is a challenge in clinical practice to identify and classify cancer cachexia. Currently, it has been extensively discussed if the presence of alterations in inflammatory biomarkers implies the presence of cachexia. This study aimed to evaluate the clinical relevance of cachexia classification through modified Glasgow Prognostic Score (mGPS) in advanced cancer patients in palliative care. Methods: Observational prospective cohort study conducted at a Palliative Care Unit in Brazil. Cachexia classification was performed according to mGPS (based on albumin and C-reactive protein) in four different stages: no cachexia (NCa), undernourished (Un), pre cachexia (PCa), and refractory cachexia (RCa). Logistic regression models were used to test the association between cachexia stages and clinical, nutritional and functional domains. Kaplan-Meier curve and Cox multivariate model were used to analyze overall survival (OS). Results: A total of 1,166 patients were included in the study. According to the cachexia framework 37.5% were NCa, 32.3% Un, 23.9% PCa and 26.4% RCa. Significant differences were observed among cachexia stages for most of the outcome measures. There was also a significant difference of OS between cachexia groups (77 versus 37 versus. 31 versus 17 days, respectively; p-value <0.001). In addition, this classification was able to predict mortality in 90 days [Un (HR, 1.55; 95% CI, 1.25;1.93); PCa (HR, 2.00; 95% CI, 1.34;2.98); RCa (HR, 2.45; 95% CI, 1.34;2.98)]. Conclusion: Cachexia stages were associated with significant differences in poor clinical outcomes and were also capable of predicting OS. This framework based on simple and objective criteria can be used as part of the routine to characterize the presence and stages of cachexia in advanced cancer patients.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Palliative Care , Cachexia , Nutrition Assessment , Prognosis , NeoplasmsABSTRACT
Background Snakebite is considered a neglected tropical disease by the World Health Organization. In Brazil, about 70% of the envenomation cases are caused by Bothrops snakes. Its venom may provoke hemorrhage, pain, necrosis, hemolysis, renal or cardiac failure and even death in victims. Since commercial antivenom does not efficiently neutralize the local toxic effects of venoms, natural products have been tested in order to provide alternative or complementary treatment to serum therapy. Therefore, the present study aimed to evaluate the ability of the seaweed Plocamium brasiliense and its active derivatives to neutralize hemorrhagic, edematogenic, hemolytic, coagulant and proteolytic activities of B. jararaca venom. Methods Specimens of P. brasiliense were collected in Rio de Janeiro state, Brazil, dried and submitted to oil extraction using four solvents of increasing polarities, n-hexane (HEX), dichloromethane (DCM), ethyl acetate (ETA) and hydroalcoholic solution (HYD). The solvents were evaporated, yielding HEX, DCM, ETA and HYD extracts. Further, all extracts were dissolved in dimethylsulfoxide. In addition, two monoterpenes (8-bromo-3,4,7-trichloro-3,7-dimethyl-1E, 5E-octadiene and 1,8-dibromo-3,4,7-trichloro-3,7-dimethyl-1E, 5E-octadiene) and a cholesterol fraction were isolated from the extract of P. brasiliense prepared in hexane. Algal samples were incubated for 30 minutes with B. jararaca venom, and then tested for lethality; hemorrhagic, edematogenic, hemolytic, coagulant and proteolytic effects. Results Most of the algal extracts inhibited the toxic effects with different potencies. The DCM extract was the most effective, since it inhibited all types of toxic activity. On the other hand, the HYD extract failed to inhibit any effect. Moreover, the isolated products inhibited proteolysis and protected mice from hemorrhage in 30% of the cases, whereas 8-bromo-3,4,7-trichloro-3,7-dimethyl-1E, 5E-octadiene inhibited 100% and ...
