Real-World Evidence Evaluation on the Lipid Profile, Therapeutic Goals, and Safety of the Fixed-Dose Combination of Rosuvastatin/Ezetimibe (Trezete®) in Dyslipidemia Patients.

Introduction: Cardiovascular diseases are the leading cause of death worldwide. The combination of statins and cholesterol-absorption inhibitors promotes the decrease in risk factors, such as high concentrations of LDL (low-density lipoproteins). The aim of the study was to evaluate changes in the lipid profile and the effect on therapeutic goals, as well as the safety of dyslipidemia patients treated with Rosuvastatin/Ezetimibe (Trezete®). Materials and Methods: A real-world evidence study was conducted with retrospective data collection through a review of clinical records from dyslipidemia patients treated with Trezete® in routine medical practice. Clinical records included results of biochemical markers before treatment and at least one follow up between weeks 8 and 16. Results: The study included 103 patients' clinical records (55.4% men) with a mean age of 56.0 ± 13.0 years. More than 57% of the patients had mixed dyslipidemia and a median disease progression of 3.1 (IQR, 1.5; 9.1) years. Regarding LDL concentrations, 72.8% of the patients achieved therapeutic goals according to cardiovascular risk (CVR), which was statistically significant. Similarly, 94.1% achieved goals for total cholesterol (<200 mg/dL) and 56.0% for triglycerides (<150 mg/dL), a p value <0.001. No cardiovascular events were observed. Conclusion: Trezete® shows an important clinical impact on CVR-related target markers during the treatment of dyslipidemia patients. It is relevant to mention that a significant percentage of patients achieved therapeutic goals during the first months of treatment. Fixed-dose combination therapy has shown to be as safe as monotherapy treatment. ClinicalTrials.gov Identifier: NCT04862962.

Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial.

The health crisis caused by the new coronavirus SARS-CoV-2 highlights the need to identify new treatment strategies for this viral infection. During the past year, over 400 coronavirus disease (COVID-19) treatment patents have been registered; nevertheless, the presence of new virus variants has triggered more severe disease presentations and reduced treatment effectiveness, highlighting the need for new treatment options for the COVID-19. This study evaluates the Metformin Glycinate (MG) effect on the SARS-CoV-2 in vitro and in vivo viral load. The in vitro study was conducted in a model of Vero E6 cells, while the in vivo study was an adaptive, two-armed, randomized, prospective, longitudinal, double-blind, multicentric, and phase IIb clinical trial. Our in vitro results revealed that MG effectively inhibits viral replication after 48 h of exposure to the drug, with no cytotoxic effect in doses up to 100 µM. The effect of the MG was also tested against three variants of interest (alpha, delta, and epsilon), showing increased survival rates in cells treated with MG. These results are aligned with our clinical data, which indicates that MG treatment reduces SARS-CoV2-infected patients´ viral load in just 3.3 days and supplementary oxygen requirements compared with the control group. We expect our results can guide efforts to position MG as a therapeutic option for COVID-19 patients.

Prevalencia de los polimorfismos de nucleótido único ARG574PRO del GEN MMP-9Y ALA38VAL del gen MMP-11 en pacientes con cáncer de mama / Prevalence of the ARG574PRO single nucleotide polymorphisms of the MMP-9 and ALA38VAL GENE of the MMP-11 gene in patients with breast cancer

El cáncer de mama (CM) es uno de los más frecuentes en Argentina y primera causa de muerte por cáncer en mujeres. Las metaloproteasas son endopeptidasas que degradan la matriz extracelular, facilitando la invasión tumoral y las metástasis. Se observó la utilidad de la MMP-9 como un marcador diagnóstico, pronóstico y de seguimiento en pacientes con CM. La MMP-11 parece tener un efecto dual en cáncer, su aumento se asocia a un incremento de tumores primarios de mama, pero con una represión en el desarrollo de metástasis. En el trabajo se analizaron los polimorfismos de nucleótido único (SNPs) Arg574Pro del gen MMP-9 y Ala38Val del MMP-11, con relación a las metástasis de CM. Se tomaron muestras de sangre de pacientes con CM metastásico y no metastásico (controles), con receptores de progesterona+, estrógeno+ y HER2-neu+/-. Se extrajo ADN de 25 muestras y se diseñaron cebadores para amplificar la región que contenían los SNPs Arg574Pro y Ala38Val. Se estandarizó la PCR para los SNPs correspondientes, aclarando que el cebador izquierdo que amplifica Arg574Pro, hibrida sobre los polimorfismos rs146961494 y rs35691798. Se realizó el análisis de las enzimas de restricción, MbiI para Arg574Pro y AatII para Ala38Val. Se concluye que para MMP-9, el polimorfismo presenta el alelo C como el G sólo en el grupo metastásico. En cuanto al gen MMP-11, se encuentra en alta frecuencia la variante alélica T, la cual no corresponde al alelo ancestral, indicando que puede estar su función/expresión relacionada con el carcinoma mamario. Estos hallazgos son preliminares (AU)

Breast cancer (BC) is one of the most common in Argentina and the leading cause of cancer death in women. Metalloproteases are endopeptidases that degrade the extracellular matrix, facilitating tumor invasion and metastases. The utility of MMP-9 was observed as a diagnostic, prognostic and follow-up marker in BC patients. MMP-11 appears to have a dual effect on cancer. High levels are associated with an increase in primary breast tumors, but with repression in the development of metastases. Arg574Pro SNPs of the MMP-9 gene and Ala38Val of MMP-11 gene were analyzed in relation to BC metastases. Blood samples were taken from patients with BC metastatic and non-metastatic (controls), with progesterone+, estrogen+ and HER2-neu+/- receptors. DNA from 25 samples was drawn and primers were designed to amplify the region containing the SNPs Arg574Pro and Ala38Val. PCR was standardized for the corresponding SNPs, clarifying that the Arg574Pro amplified left primer hybridizes to polymorphisms rs146961494 and rs35691798. The restriction enzyme analysis was performed, MbiI for Arg574Pro and AatII for Ala38Val. It is concluded that for MMP-9, the polymorphism presents the C allele as the G only in the metastatic group. As for the MMP-11 gene, the allelic variant T is found in high frequency, which does not correspond to the ancestral allele, indicating that its function/expression may be related to mammary carcinoma. These findings are preliminary (AU)

Developmental Patterns in Marital Satisfaction: Another Look at Covenant Marriage.

This study investigated differences in the trajectory of marital satisfaction in the first seven years between couples in covenant vs. standard marriages. Data on 707 Louisiana marriages from the Marriage Matters Panel Survey of Newlywed Couples, 1998 - 2004, were analyzed using multivariate longitudinal growth modeling. Restricting the sample to couples who remained married over the duration of the study, a marginal benefit of covenant status was found for husbands. This effect was largely accounted for by covenant husbands' more extensive exposure to premarital counseling. The linear decline in marital satisfaction over time that obtained for both husbands and wives was not, however, any different for covenants vs. standards. Couples characterized by more traditional attitudes toward gender roles were significantly less satisfied than others. High premarital risk factors, initial uncertainty about marrying the spouse, and the presence of preschool children in the household were all corrosive of marital satisfaction at any given time.