RESUMO
BACKGROUND: Cyclin-dependent kinases (CDK) 4/6 inhibitors have significantly improved outcomes for patients with ER+/HER2- breast cancer. Nevertheless, they differ from each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing the prevalence of QTc prolongation as an adverse event in HR+ breast cancer patients treated with CDK4/6i vs those without CDK4/6i. We pooled relative risk (RR) and mean difference (MD) with 95% confidence interval (CI) for the binary endpoint of QT prolongation. RESULTS: We included 14 RCTs comprising 16â196 patients, of whom 8576 underwent therapy with CDK4/6i. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR = 2.35, 95% CI = 1.67 to 3.29, P < .001; I2 = 44%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a relative risk of 3.12 (95% CI = 2.09 to 4.65, P < .001; I2 = 12%), whereas the palbociclib subgroup had a relative risk of 1.51 (95% CI = 1.05 to 2.15, P = .025; I2 = 0%). CONCLUSION: Palbociclib was associated with QTc prolongation; however, the relative risk for any grade QTc was quantitively twice with ribociclib. Furthermore, grade 3 QTc prolongations were observed exclusively with ribociclib. These results are important for guiding clinical decision-making and provide reassurance regarding the overall safety profile of this drug class.
Assuntos
Aminopiridinas , Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Síndrome do QT Longo , Piperazinas , Inibidores de Proteínas Quinases , Purinas , Piridinas , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Purinas/efeitos adversos , Purinas/uso terapêutico , Purinas/administração & dosagem , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Síndrome do QT Longo/induzido quimicamente , Aminopiridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Aminopiridinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Feminino , Roscovitina/efeitos adversos , BenzimidazóisRESUMO
Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the best anthracycline-cyclophosphamide (AC) schedule remains to be determined. While the KEYNOTE-522 regimen employs AC every 3 weeks (q3w AC), previous studies have shown overall survival benefits of dose-dense regimens for early-stage breast cancer. The Neo-Real study (GBECAM-0123) is a real-world data effort evaluating patients with TNBC treated with neoadjuvant P + CT in ten cancer centers since July 2020. The objective of this analysis was to evaluate the effectiveness and safety of dose-dense AC (ddAC) versus q3w AC. Among 333 patients included until November 2023, 311 completed neoadjuvant therapy and 279 underwent surgery with pathology reports available; ddAC was used in 58.2% and q3w AC in 41.8% of the cases. Most patients (69.1%) had stage II TNBC. A pCR was observed in 65.4% with ddAC and 58.7% with q3w AC (P = 0.260), while RCB 0-1 occurred in 82.4% and 73.5%, respectively (P = 0.115). Patients with stage III disease had a numerically higher pCR with ddAC (59% vs 40%, P = 0.155), while pCR rates were similar regardless of AC regimen in stage II disease (66.6% vs 64.5%; P = 0.760). While no significant disparities in drug discontinuation was noted, ddAC showed a trend towards higher rates of grade ≥3 AE (40.5% vs. 30.7%, P = 0.092). The Neo-Real study could not rule out a difference between ddAC and q3w AC during neoadjuvant P + CT. The observation of a potentially higher pCR with ddAC in stage III disease warrants further investigation.
RESUMO
BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) is a well-established surgical technique in treating patients with early gastric cancer. However, the efficacy and safety of LAG versus open gastrectomy (OG) in patients with advanced gastric cancer (AGC) remains unclear. METHODS: We systematically searched PubMed, Embase, and Cochrane Library in June 2023 for RCTs comparing LAG versus OG in patients with AGC. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for binary and continuous endpoints, respectively. We performed all statistical analyses using R software version 4.3.1 and a random-effects model. RESULTS: Nine RCTs comprising 3827 patients were included. There were no differences in terms of intraoperative complications (RR 1.14; 95% CI 0.72 to 1.82), number of retrieved lymph nodes (MD -0.54 lymph nodes; 95% CI -1.18 to 0.09), or mortality (RR 0.91; 95% CI 0.30 to 2.83). LAG was associated with a longer operative time (MD 49.28 minutes; 95% CI 30.88 to 67.69), lower intraoperative blood loss (MD -51.24 milliliters; 95% CI -81.41 to -21.06), shorter length of stay (MD -0.83 days; 95% CI -1.60 to -0.06), and higher incidence of pancreatic fistula (RR 2.44; 95% CI 1.08 to 5.50). Postoperatively, LAG was also superior to OG in reducing bleeding rates (RR 0.44; 95% CI 0.22 to 0.86) and time to first flatus (MD -0.27 days; 95% CI -0.47 to -0.07), with comparable results in anastomotic leakage, wound healing issues, major complications, time to ambulation, or time to first liquid intake. In the long-term analyses at 3 and 5 years, there were no significant differences between LAG and OG in terms of overall survival (RR 0.99; 95% CI 0.96 to 1.03) or relapse-free survival (RR 0.99; 95% CI 0.94 to 1.04). CONCLUSION: This meta-analysis of RCTs suggests that LAG may be an effective and safe alternative to OG for treating AGC; albeit, it may be associated with an increased risk for pancreatic fistula.
Assuntos
Gastrectomia , Laparoscopia , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Gastrectomia/métodos , Gastrectomia/efeitos adversos , Laparoscopia/métodos , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tempo de Internação/estatística & dados numéricos , Resultado do Tratamento , Perda Sanguínea Cirúrgica/estatística & dados numéricosRESUMO
OBJETIVO: Analisar o perfil epidemiológico dos pacientes idosos internados na Unidade de Tratamento de Queimados (UTQ) do Hospital Padre Albino do município de Catanduva, SP. MÉTODO: Trata-se de um estudo transversal baseado na análise dos prontuários e do livro de registro da Unidade de Terapia de Queimados do Hospital Padre Albino. A coleta de dados ocorreu entre março de 2012 e março de 2013, sendo selecionados todos os idosos que passaram pela unidade. Foram coletados dados como: sexo, idade, local do acidente, período de internação, vícios apresentados pelos pacientes, comorbidades, agente agressor, profundidade da lesão, superfície da área queimada e evolução - que inclui enxertia, infecção e óbito. RESULTADOS: Houve predomínio de queimaduras em pacientes idosos do sexo masculino, tendo como local do acidente a própria casa. A maioria apresentava duas comorbidades associadas, sendo a principal a hipertensão arterial sistêmica. Chama direta foi o agente causal mais frequente, predominando queimaduras combinadas de 2o e 3o grau, sendo evidenciada elevada taxa de grandes queimados e necessidade de enxertia em alguns casos, seguida de alta possibilidade de infecção. CONCLUSÃO: O conhecimento do perfil epidemiológico é importante para medidas de prevenção, que devem ser tomadas por toda a comunidade. Além disso, com o conhecimento das principais comorbidades, características das queimaduras, condutas e evolução podem ser estabelecidas melhores estratégias de tratamento para o idoso.(AU)
OBJECTIVE: To analyze the epidemiological profile of the elderly patients hospitalized at the Burn Care Unit (BCU) of the Hospital Padre Albino in Catanduva-SP. METHOD: This is a retrospective study based on the analysis of the medical records from the Hospital Padre Albino's Burn Care Unit`s record book. For data collection it was used the period from March 2012 to March 2013, which were selected all elderly patients who passed through the unit. Data such as sex, age, the accident site, days of hospitalization comorbidities, agent, lesion depth, burn area and evolution, including grafting, infection and death were collected. RESULTS: There was a predominance of burns in elderly male patients, with the scene of the accident being the house itself. Most had two comorbidities, the main one was systemic hypertension; the direct flame is the most frequent causative agent, predominating combined burns of 2nd and 3rd degree, with evident high rate of major burns and the need for grafting in some cases, followed by high possibility of infection. CONCLUSION: The knowledge of the epidemiological profile is a matter of utmost importance to preventive measures that should be taken by the whole community. Also, with the knowledge of the main comorbidities, burn characteristics, behaviors and evolution, better treatment strategies can be established for the elderlies.
Objectivo: Analizar el perfil epidemiológico de los pacientes ancianos hospitalizados en la Unidad de Atención a Quemados del Hospital Padre Albino del municipio de Catanduva, Sao Paulo. Método: Se trata de un estudio retrospectivo basado en el análisis de la historia clínica y del libro de registros de la Unidad de Atención a Quemados del Hospital Padre Albino. La recolección de datos se hizo entre marzo de 2012 y marzo de 2013, periodo en que fueron seleccionadas todas las personas mayores que pasaron por la unidad. Los datos recolectados fueran: sexo, edad, lugar del accidente, días de internación adicciones que presentaban los pacientes, comorbilidades, agente agresor, profundidad de la lesión, superficie del área quemada y evolución, incluyéndose injerto, infección y muerte. Resultados: Se observó un predominio de quemaduras en los ancianos de sexo masculino, teniendo la propia casa como lugar del accidente. La mayoría tenía dos comorbilidades asociadas, principalmente hipertensión sistémica. La llama directa fue el causante más frecuente, ocasionando predominantemente quemaduras que combinan segundo y tercero grados, con evidente tasa de grandes quemados y necesidad de injerto en algunos casos, seguido de alta posibilidad de infección. Conclusión: El conocimiento del perfil epidemiológico es importante para las medidas preventivas que se deben tomar por toda la comunidad. Con el conocimiento de las principales comorbilidades, las características de las quemaduras, conductas y evolución, se pueden establecer mejores estrategias de tratamiento para las personas mayores.(AU)