RESUMO
Breast Cancer (BC) is one of the most common cancers diagnosed in population femmale and it has several subtypes, one of them being theexpressing human epidermal growth factor receptor 2 positive (HER2 +), one of the treatments for HER2+ breast cancer consists of chemotherapy plus trastuzumab deruxtecan. Several clinical trials have shown the effectiveness and safety of trastuzumabe deruxtecano in cancer patients, however, several Adverse Events (AEs) have been described and the decrease in left ventricular ejection has been singled out for more prominent analysis. Objective: We conducted a systematic review and meta-analysis to investigate the cardiovascular effects of Trastuzumab Deruxtecano and whether it can influence the appearance of reduced left ventricular ejection fraction.. METHODS: We performed a systematic search in Embase, PubMed and Cochrane databases for randomized controlled trials (RCTs) showed a decrease in left ventricular ejection fraction in patients using trastuzumab deruxtecan against Her-2-positive breast cancer compared to patients to used another's treatments against this disease. Mean difference (MD) with 95% confidence intervals (CI) were calculated using a random effects model. The heterogeneity was examined in the I2 statistic. P-values > 0.05 were considered statistically significant. The statistical analysis was carried out using R software version 4.2.3. RESULTS: A total of 3 RCTs were included, with a total of 1656 patients evaluated, 928 patients randomized to the use of Trastuzumab Deruxtecan and 728 patients to the use of other treatments according to medical choice, follow-up ranged from 10 to 38 months. There was a visible in the decrease in left ventricular ejection fraction, with a higher incidence in the group that used trastuzumab compared to the placebo group (RR: 5.73%; 95% CI 1.51 - 21.78; I2 33% ; P= 0.010466). Another important point is the discontinuation of treatment due to grade 2 adverse events, classified as reduced LVEF, where a higher incidence is seen in the group that used Trastuzumab Deruxtecan compared to the placebo group (RR 2.11%; 95% CI 1.54 - 2.89; P = 0.000003),7. CONCLUSION: In this meta-analysis, Trastuzumab Deruxtecan showed a relationship with a decrease in left ventricular ejection fraction, displaying the need for more studies to evaluate the cardiotoxicity of trastuzumab and its effects as a whole on the cardiovascular system.
Assuntos
Terapêutica , Neoplasias da Mama , Doenças Cardiovasculares , Tratamento Farmacológico , Cardiotoxicidade , Trastuzumab , Interpretação Estatística de Dados , Receptores ErbBRESUMO
BACKGROUND: Contemporary understanding characterizes cardiotoxicity as a reduction in left ventricular ejection fraction (LVEF) by at least 10%, resulting in a final value below 53% in successive assessments. Nevertheless, breast cancer therapy can impact the cardiovascular system through various avenues. Cardiotoxicity is a known side effect of anthracycline chemotherapy, and the effectiveness of concomitant statin use in mitigating this risk is still unclear. PURPOSE: We aimed to evaluate the potential cardioprotective effects of statin exposure during anthracycline treatment. Our hypothesis posited that patients receiving statins during their treatment would experience a lesser decline in left ventricular ejection fraction (LVEF), lower levels of cholesterol and a reduced occurrence of cardiotoxicity compared to those not exposed to statins. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing statin versus placebo in patients undergoing anthracycline therapy. We searched PubMed, Embase and Cochrane for eligible trials. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was examined with I2 statistics. P values of < 0.05 were considered statistically significant. Statistical analysis were performed using R software version 4.2.3. RESULTS: A total of 4 RCTs comprising 580 patients were included, of whom 281 were randomized to statins and 299 to placebo. The follow up period ranged from 2.5 to 24 months, with participant ages varying between 36 to 68.9 in the intervention group and 37.9 to 72 in the control group. Compared with placebo, statins were significantly associated with a higher left ventricular ejection fraction (MD 2.57%; 95% CI 1.05-4.08; p<0.001; I2=0%), reduction in left ventricular systolic end-volume (MD -4.5 mL; 95% CI -7.57 to -1.44; p<0.004; I2=0%) and diastolic end-volume (MD -6.08 mL; 95% CI -11.27 to -0.9; p<0.021; I2=0%), with a low heterogeneity value. Statins also showed important reduction of total cholesterol (MD -46.28 mg/dL; 95% CI -71.3 to -21.25; p<0.001; I2=89%) and LDL-C (MD -39.45 mg/dL; 95% CI -52.27 to -26.64; p<0.001; I2=84%). CONCLUSIONS: In this metaanalysis of RCTs, the use of statins showed a correlation with improved cardiovascular parameters, indicating their effectiveness in minimizing cardiotoxicity in breast cancer patients undergoing anthracycline chemotherapy
Assuntos
Neoplasias da Mama , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Interpretação Estatística de Dados , Tratamento Farmacológico , CardiotoxicidadeRESUMO
OBJECTIVE: Triple-negative breast cancer (TNBC) presents a clinical challenge as an aggressive tumor, correlated with unfavorable prognosis. Tumor-infiltrating lymphocytes (TILs) have garnered interest as a potential prognostic biomarker. However, the disparity in outcomes between varying TILs rates remains inadequately explored. METHODS: PubMed, Scopus, Web of Science, and Cochrane databases were searched for studies about the prognostic value of TILs in patients with TNBC receiving neoadjuvant chemotherapy. The hazard ratios (HRs) or odds ratios (ORs) were computed for binary endpoints, with 95% confidence intervals (CIs). RESULTS: Twenty-nine studies were included, involving a population of six thousand one hundred sixty-one (80.41%) with TNBC. The cut-off TILs value ranged from 10 to 60%, with 50% being the most related value. Compared with the low-TIL expression group, the disease-free survival (DFS) (HR 0.71; 95% CI 0.61-0.82; p < 0.00001) and overall survival (OS) (HR 0.76; 95% CI 0.63-0.90; p = 0.002) rates showed significant improvement with higher TIL infiltrations. In the subgroup analyses of the lymphocyte subtypes CD4 + and CD8 + , there was statistical significance favoring higher TILs rates in both subtypes, each associated with improved DFS (HR 0.48; 95% CI 0.33-0.71; p = 0.0002) and OS (HR 0.53; 95% CI 0.36-0.78; p = 0.001), regardless of which cell subtype was predominantly infiltrated. The complete pathological response analysis showed better rates for the higher TIL group than the control for both the TIL (OR 1.29; 95% CI 1.13-1.48; p = 0.0003) and Ki-67 (OR 2.74; 95% CI 2.01-3.73; p < 0.00001) analyses. CONCLUSION: Higher expressions of TILs in patients with TNBC were associated with improved significantly DFS, OS, and pCR outcomes.
RESUMO
BACKGROUND Atherosclerotic cardiovascular disease (ASCVD), affects approximately 18.6 million individuals worldwide and poses a significant healthcare related challenge. Despite the established efficacy of both high-intensity statin monotherapy (HIS) and moderate-intensity statin plus ezetimibe (MIS+EZT) in ASCVD management, the optimal treatment strategy remains unclear. METHODS A thorough literature study was conducted across PubMed, Embase, and the Cochrane databases, focusing on studies that compared the effects of moderate-intensity statins plus ezetimibe with high-intensity statin monotherapy in ASCVD patients. RESULTS In the 13 included studies, involving 8,592 patients, 4,525 (52.67%) of which received moderate-intensity statin plus ezetimibe treatment. The follow-up period ranged from 4 to 156 weeks, with participant ages varying LDL-C from 55.2 to 71 years old. Analysis revealed significant MIS+EZT-associated with greater percentages of patients achieved the goal in Low-Density Lipoprotein (LDL-C) < 70 (Odds Ratio (OR) 1.76; 95% CI [1.26; 2.45]; p=0.001; I²=73%), LDL-C reduction (Mean Difference (MD) -5.05 mg/dL; 95% CI [-9.02;-1.07]; p<0.013; I²=56%;); Total Cholesterol reduction (MD -7.91 mg/ dL; 95% CI [-14.90; -0.91]; p<0.027; I²=60%); Triglycerides reduction (MD -8.20 mg/ dL; 95% CI [-13.05; -3.35]; p<0.001; I²=2%;); There was no statistical difference between groups in Drug Adverse reaction (Risk Ratio (RR) 1.19; 95% CI [0.79; 1.78]; p=0.404; I²=0%); and Drug intolerance (RR 0.78; 95% CI [0.32; 1.92]; p=0.584; I²=35%). CONCLUSIONS This meta-analysis highlights the effectiveness of MIS+EZT in improving significant lipid profile components for ASCVD patients, as can been seen through the greater percentage of patients achieving the LDL-C <70 mg/dL target and lower LDL-C, total cholesterol and triglycerides levels. Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between the two groups.
Assuntos
Combinação Ezetimiba e Simvastatina , Inibidores de Hidroximetilglutaril-CoA Redutases , EzetimibaRESUMO
Lorlatinib has been FDA-approved as a systemic therapy for ALK/ROS1-positive non-small cell lung cancer (NSCLC) patients. However, it has been associated with an increased frequency of neurocognitive adverse events (NAEs). Therefore, we conducted a systematic review and meta-analysis to assess the NAEs related to lorlatinib therapy in NSCLC patients. PubMed, Scopus, the Cochrane Library, and prominent conference proceedings were searched for eligible studies of lorlatinib in NSCLC patients. NAEs included cognitive, mood, speech, and psychotic effects. A total of 1147 patients from 12 studies were included; 62% had brain metastases. A pooled analysis of NAEs showed frequencies of cognitive effects of 14.57% (95% CI, 8.37 to 24.14, I2 = 84%), mood effects of 11.17% (95% CI, 5.93 to 20.07, I2 = 84%), speech effects of 7.24% (95% CI, 3.39 to 15.20, I2 = 72%), and psychotic effects of 4.97% (95% CI, 3.27 to 7.49, I2 = 21%). Clinical trials reported a significantly higher frequency of mood effects than was indicated by real-world data. These results highlight the importance of educating patients and healthcare professionals about lorlatinib-related NAEs for early detection and management to improve NSCLC patients' quality of life.
RESUMO
Background/Objectives: Although oxytocin administration is recommended for delayed labor progress, there is no consensus over the preferred optimal dose of oxytocin. We aimed to perform a meta-analysis of pregnancy outcomes comparing high-dose versus low-dose oxytocin regimens for augmentation of delayed labor. Methods: PubMed, Embase, and Cochrane databases were systematically searched for studies comparing high-dose with low-dose oxytocin for labor augmentation from inception up to May 2023. The outcomes assessed were cesarean rate, instrumental delivery rate, postpartum hemorrhage, neonatal death, and uterine tachysystole. Subgroup analysis was performed with randomized controlled trials (RCTs) and propensity-matched studies. Statistical analysis was performed using Rstudio. Heterogeneity was assessed with I2 statistics, and a random-risk effect was used if I2 > 50%. Results: Twenty-one studies met inclusion criteria, and eighteen were RCTs. A total of 14.834 patients were included, of whom 7.921 (53.3%) received high-dose and 6.913 (46.6%) received low-dose oxytocin during labor augmentation. No statistical differences were found in cesarean delivery, neonatal mortality, postpartum hemorrhage and vaginal instrumentation rate. However, uterine tachysystole incidence was significantly higher with high-dose oxytocin (95% Cl, 1.30-1.94, p = 0.3; 0.6; I2 = 9%). Conclusions: Labor augmentation with a low-dose oxytocin regimen is effective as with a high-dose regimen, but with significantly less uterine tachysystole events, which can lead to intrauterine and neonatal complications. Our findings suggest that a low-dose regimen may be safe and effective for labor augmentation in medical practice.
RESUMO
INTRODUCTION: The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. RESULTS: A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55 years, with a mean body mass index (BMI) of 39.4 kg/m2, and had BS surgery 5 years prior. Over a mean follow-up time ranging from 3 months to 4 years, it was observed a statistically significant reduction in BMI (MD - 8.56 kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03 kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. CONCLUSIONS: Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.
Assuntos
Cirurgia Bariátrica , Liraglutida , Obesidade Mórbida , Aumento de Peso , Redução de Peso , Humanos , Liraglutida/uso terapêutico , Aumento de Peso/efeitos dos fármacos , Redução de Peso/efeitos dos fármacos , Feminino , Obesidade Mórbida/cirurgia , Obesidade Mórbida/tratamento farmacológico , Adulto , Índice de Massa Corporal , Pessoa de Meia-Idade , Masculino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND/OBJECTIVES: Although oxytocin administration is recommended for delayed labor progress, there is no consensus over the preferred optimal dose of oxytocin. We aimed to perform a meta-analysis of pregnancy outcomes comparing high-dose versus low-dose oxytocin regimens for augmentation of delayed labor. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for studies comparing high-dose with low-dose oxytocin for labor augmentation from inception up to May 2023. The outcomes assessed were cesarean rate, instrumental delivery rate, postpartum hemorrhage, neonatal death, and uterine tachysystole. Subgroup analysis was performed with randomized controlled trials (RCTs) and propensity-matched studies. Statistical analysis was performed using Rstudio. Heterogeneity was assessed with I2 statistics, and a random-risk effect was used if I2 > 50%. RESULTS: Twenty-one studies met inclusion criteria, and eighteen were RCTs. A total of 14.834 patients were included, of whom 7.921 (53.3%) received high-dose and 6.913 (46.6%) received low-dose oxytocin during labor augmentation. No statistical differences were found in cesarean delivery, neonatal mortality, postpartum hemorrhage and vaginal instrumentation rate. However, uterine tachysystole incidence was significantly higher with high-dose oxytocin (95% Cl, 1.30-1.94, p = 0.3; 0.6; I2 = 9%). CONCLUSIONS: Labor augmentation with a low-dose oxytocin regimen is effective as with a high-dose regimen, but with significantly less uterine tachysystole events, which can lead to intrauterine and neonatal complications. Our findings suggest that a low-dose regimen may be safe and effective for labor augmentation in medical practice.
Assuntos
Gravidez , Ocitocina/administração & dosagem , Interpretação Estatística de DadosRESUMO
INTRODUCTION: The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. RESULTS: A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55 years, with a mean body mass index (BMI) of 39.4 kg/m2, and had BS surgery 5 years prior. Over a mean follow-up time ranging from 3 months to 4 years, it was observed a statistically significant reduction in BMI (MD - 8.56 kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03 kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. CONCLUSIONS: Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.
Assuntos
Redução de Peso , Índice de Massa Corporal , Cirurgia Bariátrica , Liraglutida/administração & dosagem , Interpretação Estatística de DadosRESUMO
INTRODUCTION: Incorporation of AKT inhibitors into adjuvant therapy for advanced or metastatic breast cancer has improved clinical outcomes. However, the safety of AKT inhibitors should be better evaluated, given the possibility of prolonging survival and impacting patient quality of life. Our aim was to assess how the addition of AKT inhibitors to adjuvant therapy affects treatment-related adverse events. METHODS: We evaluated binary outcomes with risk ratios (RRs), with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses. RESULTS: A total of seven RCTs comprising 1619 patients with BC. The adverse effects that show significance statistical favoring the occurrence of adverse effects in AKT inhibitor were diarrhea (RR 3.05; 95% CI 2.48-3.75; p < 0.00001; I2 = 49%), hyperglycemia (RR 3.4; 95% CI 1.69-6.83; p = 0.00058; I2 = 75%), nausea (RR 1.69; 95% CI 1.34-2.13; p = 0.000008; I2 = 42%), rash (RR 2.79; 95% CI 1.49-5.23; p = 0.0013; I2 = 82%), stomatitis (RR 2.24; 95% CI 1.69-2.97; p < 0.00001; I2 = 16%) and vomiting (RR 2.99; 95% CI 1.85-4.86; p = 0.00009; I2 = 42%). There was no significant difference between the groups for alopecia (p = 0.80), fatigue (p = 0.087), and neuropathy (p = 0.363380). CONCLUSION: The addition of AKT inhibitors to adjuvant therapy was associated with an increase in treatment-related adverse events. These results provide safety information for further clinical trials evaluating AKT inhibitor therapy for patients with metastatic BC. Clinicians should closely monitor patients for treatment-related adverse events to avoid discontinuation of therapy and morbidity caused by these early-stage therapies.
Assuntos
Neoplasias da Mama , Proteínas Proto-Oncogênicas c-akt , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Neoplasias da Mama/tratamento farmacológico , Feminino , Quimioterapia Adjuvante , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêuticoRESUMO
INTRODUCTION: New therapies for resistant hypertension (RH), including renal denervation (RDN), have been studied. AIM: Access the safety and effectiveness of radiofrequency-based RDN vs pharmacological treatment for RH. METHODS: A thorough literature search was conducted across PubMed, EMBASE, and the Cochrane databases, focusing on studies that compared the effects of radiofrequency-based RDN versus pharmacological treatment for RH. Treatment effects for binary and continuous endpoints were pooled and used, respectively, odds-ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) to analyze continuous outcomes. RESULTS: In the 10 included studies, involving 1.182 patients, 682 received radiofrequency-based RDN. The follow-up period ranged from 6 to 84 months. Analysis revealed that the RDN group had a significant reduction in office systolic blood pressure (BP) (MD - 9.5 mmHg; 95% CI - 16.81 to - 2.29; P = 0.01), office diastolic BP (MD - 5.1 mmHg; 95% CI - 8.42 to - 2.80; P < 0.001), 24 h systolic BP (MD - 4.8 mmHg; 95% CI - 7.26 to - 2.42; P < 0.001). For 24 h diastolic BP RDN did not have a significant reduction (MD - 2.3 mmHg; 95% CI - 4.19 to - 0.52; P = 0.012). The heterogeneity between the studies was high, visible in the funnel and Baujat plots. The OR was non-significant for non-serious adverse events, but also clinically significant for hypertensive crises and strokes for the RDN group. CONCLUSIONS: While the pharmacological regimen of 3 or more anti-hypertensive, including a diuretic, still be the first-line option for RH treatment, our results support that radiofrequency-based RDN is superior in reducing global BP and is safe.
Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Ablação por Cateter , Resistência a Medicamentos , Hipertensão , Rim , Simpatectomia , Humanos , Resultado do Tratamento , Hipertensão/fisiopatologia , Hipertensão/cirurgia , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Ablação por Cateter/efeitos adversos , Rim/inervação , Pessoa de Meia-Idade , Simpatectomia/efeitos adversos , Simpatectomia/métodos , Feminino , Masculino , Idoso , Fatores de Risco , Artéria Renal/inervação , Artéria Renal/cirurgia , Fatores de Tempo , AdultoRESUMO
Imatinib is the tyrosine kinase inhibitor used as the gold standard for the treatment of Chronic Myeloid Leukemia. However, about 30% of patients do not respond well to this therapy. Variants in drug administration, distribution, metabolism and excretion (ADME) genes play an important role in drug resistance especially in admixed populations. We investigated 129 patients diagnosed with Chronic Myeloid Leukemia treated with imatinib as first choice therapy. The participants of the study are highly admixed, populations that exhibit genetic diversity and complexity due to the contributions of multiple ancestral groups. Thus, the aim of this work was to investigate the association of 30 SNVs in genes related to response to treatment with Imatinibe in CML. Our results indicated that for the rs2290573 of the ULK3 gene, patients with the recessive AA genotype are three times more likely to develop resistance over time (secondary resistance) (p = 0.019, OR = 3.19, IC 95%= 1.21-8.36). Finally, we performed interaction analysis between the investigated variants and found several associations between SNVs and secondary resistance. We concluded that the variant rs2290573 of the ULK3 gene may be relevant for predicting treatment response of CML with imatinib, as well as possible treatment resistance. The use of predictive biomarkers is an important tool for therapeutic choice of patients, improving their quality of life and treatment efficacy.
Assuntos
Antineoplásicos , Resistencia a Medicamentos Antineoplásicos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva , Polimorfismo de Nucleotídeo Único , Inibidores de Proteínas Quinases , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Resistencia a Medicamentos Antineoplásicos/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Inibidores de Proteínas Quinases/uso terapêutico , Antineoplásicos/uso terapêutico , Idoso , Farmacogenética , Genótipo , Adulto JovemRESUMO
INTRODUCTION: New therapies for resistant hypertension (RH), including renal denervation (RDN), have been studied. AIM: Access the safety and effectiveness of radiofrequency-based RDN vs pharmacological treatment for RH. METHODS: A thorough literature search was conducted across PubMed, EMBASE, and the Cochrane databases, focusing on studies that compared the effects of radiofrequency-based RDN versus pharmacological treatment for RH. Treatment effects for binary and continuous endpoints were pooled and used, respectively, odds-ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) to analyze continuous outcomes. RESULTS: In the 10 included studies, involving 1.182 patients, 682 received radiofrequency-based RDN. The follow-up period ranged from 6 to 84 months. Analysis revealed that the RDN group had a significant reduction in office systolic blood pressure (BP) (MD − 9.5 mmHg; 95% CI − 16.81 to − 2.29; P = 0.01), office diastolic BP (MD − 5.1 mmHg; 95% CI − 8.42 to − 2.80; P < 0.001), 24 h systolic BP (MD − 4.8 mmHg; 95% CI − 7.26 to − 2.42; P < 0.001). For 24 h diastolic BP RDN did not have a significant reduction (MD − 2.3 mmHg; 95% CI − 4.19 to − 0.52; P = 0.012). The heterogeneity between the studies was high, visible in the funnel and Baujat plots. The OR was non-significant for non-serious adverse events, but also clinically significant for hypertensive crises and strokes for the RDN group. CONCLUSIONS: While the pharmacological regimen of 3 or more anti-hypertensive, including a diuretic, still be the first-line option for RH treatment, our results support that radiofrequency-based RDN is superior in reducing global BP and is safe.
RESUMO
BACKGROUND: Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR. METHODS: In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I2 statistic and employed the R statistical software (version 4.2.3) for all analyses. RESULTS: Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I2 = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I2 = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I2 = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I2 = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I2 = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I2 = 0%). CONCLUSION: This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice.
Assuntos
Neoplasias Retais/terapia , Análise de Sobrevida , Resultado do Tratamento , Quimioterapia Adjuvante , Terapia NeoadjuvanteRESUMO
COVID-19 is a systemic disease caused by the etiologic agent SARS-CoV-2, first reported in Hubei Province in Wuhan, China, in late 2019. The SARS-CoV-2 virus has evolved over time with distinct transmissibility subvariants from ancestral lineages. The clinical manifestations of the disease vary according to their severity and can range from asymptomatic to severe. Due to the rapid evolution to a pandemic, epidemiological studies have become essential to understand and effectively combat COVID-19, as the incidence and mortality of this disease vary between territories and populations. This study correlated epidemiological data on the incidence and mortality of COVID-19 with frequencies of important SNPs in GWAS studies associated with the susceptibility and mortality of this disease in different populations. Our results indicated significant correlations for 11 genetic variants (rs117169628, rs2547438, rs2271616, rs12610495, rs12046291, rs35705950, rs2176724, rs10774671, rs1073165, rs4804803 and rs7528026). Of these 11 variants, 7 (rs12046291, rs117169628, rs1073165, rs2547438, rs2271616, rs12610495 and rs35705950) were positively correlated with the incidence rate, these variants were more frequent in EUR populations, suggesting that this population is more susceptible to COVID-19. The rs2176724 variant was inversely related to incidence rates; therefore, the higher the frequency of the allele is, the lower the incidence rate. This variant was more frequent in the AFR population, which suggests a protective factor against SARS-CoV-2 infection in this population. The variants rs10774671, rs4804803, and rs7528026 showed a significant relationship with mortality rates. SNPs rs10774671 and rs4804803 were inversely related to mortality rates and are more frequently present in the AFR population. The rs7528026 variant, which is more frequent in the AMR population, was positively related to mortality rates. The study has the potential to identify and correlate the genetic profile with epidemiological data, identify populations that are more susceptible to severe forms of COVID-19, and relate them to incidence and mortality.
RESUMO
Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included - 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42-0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52-0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51-6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28-2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19-1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44-0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Neoplasias Colorretais , Combinação de Medicamentos , Pirrolidinas , Timina , Trifluridina , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Trifluridina/uso terapêutico , Trifluridina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pirrolidinas/uso terapêutico , Pirrolidinas/administração & dosagem , Metástase Neoplásica , Intervalo Livre de Progressão , Uracila/análogos & derivados , Uracila/uso terapêutico , Uracila/administração & dosagem , Resistencia a Medicamentos AntineoplásicosRESUMO
BACKGROUND: Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR. METHODS: In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I2 statistic and employed the R statistical software (version 4.2.3) for all analyses. RESULTS: Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I2 = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I2 = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I2 = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I2 = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I2 = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I2 = 0%). CONCLUSION: This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice.
Assuntos
Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/mortalidade , Neoplasias Retais/tratamento farmacológico , Quimioterapia Adjuvante , Resultado do Tratamento , Análise de Sobrevida , Intervalo Livre de Doença , Terapia NeoadjuvanteRESUMO
BACKGROUND: Female gynecological cancers represent a serious public health problem, with 1,398,601 new diagnoses and 671,875 deaths per year worldwide. Antipsychotics are often used in psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. It is estimated that the prescription of these drugs is linked to 1,800 deaths a year in the United States, but their association with cancer remains controversial. METHODS: We searched PubMed, Scopus, and Web of Science databases for studies reporting the correlation in the incidence risk of gynecological cancer by antipsychotic use. We used DerSimonian and Laird random-effect models to compute logit transformed odds ratio (OR) for the primary binary endpoint with 95% confidence interval (CI). Heterogeneity was assessed through effect size width along with I-squared and Tau-squared statistics. Review Manager 5.4.1. was used for statistical analyses. A p-value of < 0.05 denoted statistically significant. RESULTS: 50,402 patients were included, of whom 778 (1,54%) took antipsychotic medication for at least 1 year. 1,086 (2,15%) with ovarian cancer and 49,316 (97,85%) with endometrial cancer. Antipsychotic use (OR 1.50; 1.06 to 2.13 95% CI; p-value 0.02), hypertension (OR 1.50; 95% CI 1.06 to 2.13; p-value < 0.01), nulliparity (OR 1.98; 95% CI 1.53 to 2.57; p-value < 0.01) and multiparity (OR 0.53; 95% CI 0.41 to 0.69; p-value < 0.01) showed significantly different distributions between groups of cancer and cancer-free patients. The primary endpoint of incidence risk of gynecological cancer by antipsychotic therapy showed a statistically significant difference (OR 1.67; 95% CI 1.02 to 2.73; p-value < 0.05) against the use of antipsychotic drugs. CONCLUSIONS: Our meta-analysis showed that the use of antipsychotic drugs increases the risk of gynecological cancers, particularly endometrial cancer. This result should be weighed against the potential effects of treatment for a balanced prescribing decision.
Assuntos
Antipsicóticos , Neoplasias dos Genitais Femininos , Humanos , Feminino , Incidência , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/tratamento farmacológico , Fatores de Risco , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/induzido quimicamente , Razão de Chances , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/tratamento farmacológicoRESUMO
PURPOSE: Approximately 45% of anaplastic thyroid cancer (ATC) patients harbor a BRAFV600E mutation and are eligible for target therapy (TT) with BRAF and MEK inhibitors (BRAFi/MEKi), nevertheless, few data advocate for this. Hence, we've conducted a systematic review and meta-analysis investigating the effectiveness and safety of BRAFi/MEKi in BRAFV600E ATC patients. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for BRAFi/MEKi TT in BRAFV600E ATC patients. Outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), duration of response (DOR) and adverse events (AEs). RESULTS: Nine studies with 168 patients were included. Median follow-up ranged from 2.0 to 47.9 months. 75% of patients had stage IVc. In a pooled analysis, ORR was 68.15% (95% CI 55.31-80.99, I2 = 47%) and DCR was 85.39% (95% CI 78.10-92.68, I2 = 0), with a median DOR of 14.4 months (95% CI 4.6-14.4) and a median PFS of 6.7 months (95% CI 4.7-34.2). Moreover, 1-year OS rate was 64.97% (95% CI 48.76-81.17, I2 = 84%) and 2-years OS rate was 52.08% (95% CI 35.71-68.45, I2 = 79%). Subgroup analysis showed patients in the neoadjuvant setting had higher rates of 1 and 2-years OS and observational studies tended to report higher rates of ORR than clinical trials. No new or unexpected adverse events were found. CONCLUSIONS: Our study demonstrated BRAFi/MEKi have a decent activity for BRAFV600E ATC patients, especially in the neoadjuvant setting, with a tolerable safety profile. However, further clinical trials are warranted to investigate these findings.