Association between ovarian tumors and exposure to assisted reproductive technologies and ovarian stimulation: a systematic review and meta-analysis.

INTRODUCTION:  The question of whether assisted reproductive technologies (ART) and ovulation induction are related to a higher incidence of ovarian tumors (OTs) is still controversial in the literature. METHODS: We performed a comprehensive search of PubMed, Embase, and Web of Science databases for case-control and cohort studies that investigated ART and ovulation induction exposure as risk factors for OT in infertile women. Odds ratios (OR) with 95% confidence intervals (CI) were employed for all endpoints. RESULTS: A total of nine case-control and twelve cohort studies were included, encompassing 439,477 women. ART was not associated with a higher risk of OTs (OR 1.05; 95% CI 0.86-1.29; p = 0.64; I2 = 36%), nor when considering only borderline OTs (OR 1.13; 95% CI 0.84-1.51; p = 0.42; I2 = 31%). In a subgroup analysis by study type, the risk difference of OTs remained non-significant for case-control (OR 1.12; 95% CI 0.70-1.78; p = 0.65; I2 = 60%) and cohort studies (OR 1.05; 95% CI 0.87-1.27; p = 0.60; I2 = 1%). For borderline OTs, the difference between groups was also non-significant for case-control studies (OR 1.44; 95% CI 0.73-2.87; p = 0.30; I2 = 40%) and cohort studies (OR 1.00; 95% CI 0.75-1.34; p = 0.99; I2 = 24%). CONCLUSION: In this systematic review and meta-analysis, ART exposure in infertile women was not associated with a higher risk of OTs in general or borderline tumors, even when accounting for study type differences.

The decreased left ventricular ejection fraction in patients using trastuzumab deruxtecan for her2-positive breast cancer: a systematic review and meta-analysis

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.

Cardio-protective effects of statins in patients with breast cancer undergoing anthracycline-based chemotherapy: a metaanalysis of randomized controlled trials

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

Safety and efficacy of moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease: a meta-analysis

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.

Liraglutide for the Treatment of Weight Regain After Bariatric Surgery: A Systematic Review and Meta-analysis.

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.

High-Dose versus Low-Dose Oxytocin for Labor Augmentation: A Meta-Analysis of Randomized Controlled Trials.

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.

High-dose versus low-dose oxytocin for labor augmentation: a meta-analysis of randomized controlled trials

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.

Liraglutide for the treatment of weight regain after bariatric surgery: a systematic review and meta-analysis

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.

Gantenerumab for early Alzheimer's disease: a systematic review and meta-analysis.

INTRODUCTION: Gantenerumab is a monoclonal antibody targeting amyloid ß protein (Aß) in early Alzheimer's disease (AD). The authors sought to evaluate gantenerumab safety and efficacy in early AD patients. METHODS: MEDLINE, Embase, and Cochrane databases were systematically searched until 2 December 2023. Data were examined using the Mantel-Haenszel method and 95% confidence intervals (CIs). Meta-regression analysis was conducted to evaluate a possible link between baseline Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) and amyloid-related imaging abnormalities (ARIA) at follow-up. R, version 4.2.3, was used for statistical analysis. RESULTS: A total of 4 RCTs and 2848 patients were included, of whom 1580 (55%) received subcutaneous gantenerumab. Concerning clinical scores, the placebo group achieved better rates of change in the Disease Assessment Scale (ADAS-Cog13) (SMD -0.11; 95% CI -0.19- -0.03; p = 0.008569; I2 = 0%). Gantenerumab was strongly associated with the occurrence of ARIA-E and ARIA-H: (19.67% vs. 2.31%; RR 9.46; 95% CI 5.55-16.11; p = <0.000001; I2 = 10%) and (21.95% vs. 12.38%; RR 1.79; 95% CI 1.50-2.13; p = <0.000001; I2 = 0%), respectively. DISCUSSION: In this meta-analysis, consistent results suggest that gantenerumab is not safe and efficient for early AD, showing no improvement in clinical scores for AD and being associated with the occurrence of ARIA-E and ARIA-H.

Efficacy and Safety of Anti-CD38 Monoclonal Antibodies in Patients with Relapsed or Refractory Multiple Myeloma: A Meta-Analysis of Randomized Clinical Trials.

The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (CIs). Six studies comprising 2191 patients were included. Anti-CD38 monoclonal antibody significantly improved progression-free survival (HR 0.52; 95% CI 0.43-0.61; p < 0.001) and overall survival (HR 0.72; 95% CI 0.63-0.83; p < 0.001). There was a significant increase in hematological adverse events, such as neutropenia (RR 1.41; 95% CI 1.26-1.58; p < 0.01) and thrombocytopenia (RR 1.14; 95% CI 1.02-1.27; p = 0.02), in the group treated with anti-CD38 monoclonal antibody. Also, there was a significant increase in non-hematological adverse events, such as dyspnea (RR 1.72; 95% CI 1.38-2.13; p < 0.01) and pneumonia (RR 1.34; 95% CI 1.13-1.59; p < 0.01), in the group treated with anti-CD38 monoclonal antibody. In conclusion, the incorporation of an anti-CD38 monoclonal antibody demonstrated a promising prospect for reshaping the established MM treatment paradigms.

Efficacy and safety of anti-CD38 monoclonal antibodies in patients with relapsed or refractory multiple myeloma: a meta-analysis of randomized clinical trials

The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (CIs). Six studies comprising 2191 patients were included. Anti-CD38 monoclonal antibody significantly improved progressionfree survival (HR 0.52; 95% CI 0.43­0.61; p < 0.001) and overall survival (HR 0.72; 95% CI 0.63­0.83; p < 0.001). There was a significant increase in hematological adverse events, such as neutropenia (RR 1.41; 95% CI 1.26­1.58; p < 0.01) and thrombocytopenia (RR 1.14; 95% CI 1.02­1.27; p = 0.02), in the group treated with anti-CD38 monoclonal antibody. Also, there was a significant increase in non-hematological adverse events, such as dyspnea (RR 1.72; 95% CI 1.38­2.13; p < 0.01) and pneumonia (RR 1.34; 95% CI 1.13­1.59; p < 0.01), in the group treated with anti-CD38 monoclonal antibody. In conclusion, the incorporation of an anti-CD38 monoclonal antibody demonstrated a promising prospect for reshaping the established MM treatment paradigms.