Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study.

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

Impact of different sequential triple oral combination therapies based selexipag on outcomes in pulmonary arterial hypertension.

BACKGROUND: While the GRIPHON study and others have confirmed the efficacy and safety of selexipag with single, dual, and initial triple combination therapy for patients with pulmonary arterial hypertension (PAH), multicenters studies concerning diverse triple oral combination therapies based on selexipag are limited. HYPOTHESIS: This study was conducted to evaluate the effects of various sequential triple oral combination therapies on PAH outcomes. METHODS: A retrospective study was carried out involving 192 patients from 10 centers, who were receiving sequential triple oral combination therapy consisting of an endothelin receptor antagonist (ERA), a phosphodiesterase 5 inhibitor (PDE5i)/riociguat and selexipag. Clinical parameters, event-free survival, and all-cause survival were assessed and analyzed at baseline and posttreatment. RESULTS: Among the 192 patients, 37 were treated with ERA + riociguat + selexipag, and 155 patients received ERA + PDE5i + selexipag. Both sequential triple oral combination therapies improved the World Health Organization functional class and raised the count of low-risk parameters. As a result of the larger patients' population in the ERA + PDE5i + selexipag group, these individuals exhibited significant increases in 6-minute walking distance (6MWD), pulmonary arterial systolic pressure, pulmonary arterial pressure, right ventricle, and eccentricity index, and significant decreases in N-terminal probrain natriuretic peptide after 6 months of treatment. Nevertheless, both sequential triple oral combination therapy groups demonstrated similar shifts in these clinical parameters between baseline and 6 months. Baseline 6MWD and mean pulmonary arterial pressure were independent predictors of survival in patients undergoing ERA + PDE5i + selexipag therapy. Importantly, no significant differences were found in 6-month event-free survival and all-cause survival between two groups. CONCLUSIONS: Different oral sequential triple combination therapies based on selexipag could comparably improve outcomes in patients with PAH.

Prognostic role of neutrophil-to-lymphocyte ratio to laryngeal squamous cell carcinoma: a meta-analysis / Papel prognóstico da relação neutrófilo-linfócito no carcinoma espinocelular da laringe: uma metanálise

Abstract Introduction New evidence suggests that the ratio of neutrophils to lymphocytes is associated with the prognosis of other carcinoma, but the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma remains controversial. Objective The objective of this meta-analysis was to clarify the prognostic effectiveness of the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma. Methods According to the meta-analysis of the free guide, we searched EMBASE, Pubmed, the Cochrane Library databases. The ratio of neutrophils to lymphocytes of laryngeal squamous cell carcinoma patients was evaluated using mean standard vehicle and confidence interval. The overall survival, disease-free survival and progression free survival of patients with laryngeal squamous cell carcinoma were expressed by standard mean carrier method and confidence interval. The risk ratio of 95% confidence interval was used as an evaluation index for patients with laryngeal squamous cell carcinoma. Results Eight studies, including 1780 patients, used a variety of different end values to classify the ratio of neutrophils to lymphocytes (range 1.78-4.0). Among the eight studies that reported risk ratio of the overall survival, the higher median value was 2.72, and 2 of 4 studies reported disease-free survival results. The critical value of ratio of neutrophils to lymphocytes and overall survival deterioration (risk ratio = 1.68, 95% confidence interval 1.43-1.99, p< 0.001), disease-free survival (risk ratio = 2.09, 95% confidence interval 1.62-2.6, p< 0.001) and progression free survival (risk ratio = 1.92, 95% confidence interval 1.75-2.10, p< 0.001) was associated with with laryngeal aquamous cell carcinoma. The ratio of neutrophils to lymphocytes had prognostic value for laryngeal squamous cell carcinoma. Conclusion The results of this meta-analysis showed that the increase of neutrophils to lymphocytes ratio was related to poor prognosis of laryngeal squamous cell carcinoma. The neutrophils to lymphocytes ratio may serve as a cost-effective prognostic biomarker of poor prognosis of laryngeal squamous cell carcinoma. More high-quality prospective trials are needed to assess the practicability of evaluating the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma.

Resumo Introdução Novas evidências sugerem que a relação neutrófilo-linfócito está associada ao prognóstico de vários carcinomas, mas a relação neutrófilo-linfócito no carcinoma espinocelular da laringe ainda permanece controversa. Objetivo Esclarecer a eficácia prognóstica da relação neutrófilo-linfócito no carcinoma espinocelular de laringe. Método De acordo com as diretrizes de metanálise, conduzimos uma busca nas bases de dados Embase, PubMed, e Cochrane Library. A relação neutrófilo-linfócito de pacientes com carcinoma espinocelular de laringe foi avaliado com a diferença de médias padronizadas e intervalo de confiança. A sobrevida global, sobrevida livre de doença e sobrevida livre de progressão de pacientes com carcinomaespinocelular de laringe foram expressas pelo método da diferença de médias padronizadas e intervalo de confiança. A razão de risco do intervalo de confiança 95% foi usada como um índice de avaliação para pacientes com carcinoma espinocelular de laringe. Resultados Oito estudos, que incluíram 1.780 pacientes, usaram uma variedade de valores finais diferentes para classificar a relação neutrófilo-linfócito (intervalo de 1,78-4,0). Entre os oito estudos que relataram a razão de risco de sobrevida global, o maior valor médio foi de 2,72 e 2 de 4 estudos relataram resultados com sobrevida livre de doença. O valor crítico de relação neutrófilo-linfócito e deterioração da sobrevida global (razão de risco = 1,68, intervalo de confiança 95% 1,43-1,99, p ˂ 0,001), sobrevida livre de doença (razão de risco = 2,09, intervalo de confiança 95% 1,62-2,6, p ˂ 0,001) e sobrevida livre de progressão (razão de risco = 1,92, intervalo de confiança 95% 1,75-2,10, p ˂ 0,001) foi associado com carcinoma espinocelular de laringe. A relação neutrófilo-linfócito tem valor prognóstico para carcinoma espinocelular de laringe. Conclusão Os resultados da metanálise mostraram que o aumento da relação neutrófilo-linfócito estava relacionado ao mau prognóstico do carcinoma espinocelular de laringe. A relação neutrófilo-linfócito pode servir como um biomarcador custo-efetivo de prognóstico do carcinoma espinocelular de laringe. Entretanto, mais estudos prospectivos de alta qualidade são necessários para avaliar a sua praticabilidade.

Prognostic role of neutrophil-to-lymphocyte ratio to laryngeal squamous cell carcinoma: a meta-analysis.

INTRODUCTION: New evidence suggests that the ratio of neutrophils to lymphocytes is associated with the prognosis of other carcinoma, but the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma remains controversial. OBJECTIVE: The objective of this meta-analysis was to clarify the prognostic effectiveness of the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma. METHODS: According to the meta-analysis of the free guide, we searched EMBASE, Pubmed, the Cochrane Library databases. The ratio of neutrophils to lymphocytes of laryngeal squamous cell carcinoma patients was evaluated using mean standard vehicle and confidence interval. The overall survival, disease-free survival and progression free survival of patients with laryngeal squamous cell carcinoma were expressed by standard mean carrier method and confidence interval. The risk ratio of 95% confidence interval was used as an evaluation index for patients with laryngeal squamous cell carcinoma. RESULTS: Eight studies, including 1780 patients, used a variety of different end values to classify the ratio of neutrophils to lymphocytes (range 1.78-4.0). Among the eight studies that reported risk ratio of the overall survival, the higher median value was 2.72, and 2 of 4 studies reported disease-free survival results. The critical value of ratio of neutrophils to lymphocytes and overall survival deterioration (risk ratio = 1.68, 95% confidence interval 1.43-1.99, p < 0.001), disease-free survival (risk ratio = 2.09, 95% confidence interval 1.62-2.6, p < 0.001) and progression free survival (risk ratio = 1.92, 95% confidence interval 1.75-2.10, p < 0.001) was associated with with laryngeal aquamous cell carcinoma. The ratio of neutrophils to lymphocytes had prognostic value for laryngeal squamous cell carcinoma. CONCLUSION: The results of this meta-analysis showed that the increase of neutrophils to lymphocytes ratio was related to poor prognosis of laryngeal squamous cell carcinoma. The neutrophils to lymphocytes ratio may serve as a cost-effective prognostic biomarker of poor prognosis of laryngeal squamous cell carcinoma. More high-quality prospective trials are needed to assess the practicability of evaluating the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma.