Fluoropyrimidines are chemotherapy drugs utilized to treat a variety of solid tumors. These drugs predominantly rely on the enzyme dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, for their metabolism. Genetic mutations affecting this gene can cause DPYD deficiency, disrupting pyrimidine metabolism and increasing the risk of toxicity in cancer patients treated with 5-fluorouracil. The severity and type of toxic reactions are influenced by genetic and demographic factors and, in certain instances, can result in patient mortality. Among the more than 50 identified variants of DPYD, only a subset has clinical significance, leading to the production of enzymes that are either non-functional or impaired. The study aims to examine treatment-related mortality in cancer patients undergoing fluoropyrimidine chemotherapy, comparing those with and without DPD deficiency. The meta-analysis selected and evaluated 9685 studies from Pubmed, Cochrane, Embase and Web of Science databases. Only studies examining the main DPYD variants (DPYD*2A, DPYD p.D949V, DPYD*13 and DPYD HapB3) were included. Statistical Analysis was performed using R, version 4.2.3. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed with I2 statistics. There were 36 prospective and retrospective studies included, accounting for 16,005 patients. Most studies assessed colorectal cancer, representing 86.49% of patients. Other gastrointestinal cancers were evaluated by 11 studies, breast cancer by nine studies and head and neck cancers by five studies. Four DPYD variants were identified as predictors of severe fluoropyrimidines toxicity in literature review: DPYD*2A (rs3918290), DPYD p.D949V (rs67376798), DPYD*13 (rs55886062) and DPYD Hap23 (rs56038477). All 36 studies assessed the DPYD*2A variant, while 20 assessed DPYD p.D949V, 7 assessed DPYD*13, and 9 assessed DPYDHap23. Among the 587 patients who tested positive for at least one DPYD variant, 13 died from fluoropyrimidine toxicity. Conversely, in the non-carrier group there were 14 treatment-related deaths. Carriers of DPYD variants was found to be significantly correlated with treatment-related mortality (OR = 34.86, 95% CI 13.96–87.05; p < 0.05). This study improves our comprehension of how the DPYD gene impacts cancer patients receiving fluoropyrimidine chemotherapy. Identifying mutations associated with dihydropyrimidine dehydrogenase deficiency may help predict the likelihood of serious side effects and fatalities. This knowledge can be applied to adjust medication doses before starting treatment, thus reducing the occurrence of these critical outcomes.

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. 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. 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 %). 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.

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.