Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an integrated safety analysis of the SELECT phase 3 clinical program

Clinical Rheumatology - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by ongoing inflammation and degradation of synovial joints. The oral JAK inhibitor, upadacitinib, is...     

Inflammatory Markers after Switching to a Dual Drug Regimen in HIV-Infected Subjects: A Two-Year Follow-Up

Objective: Immunadapt is a study evaluating the impact of combination antiretroviral treatment (cART) simplification on immune activation. We previously showed that switching to dual therapies could be associated six months later with macrophage activation. Followup continued up to 24 months after treatment simplification. Materials and Methods: Immunadapt is a prospective single arm study of successfully treated subjects simplifying cART from triple to dual regimens. Before cART change, at 6 months, and between 18 and 24 months following the switch, we measured IP-10, MCP-1, soluble CD14 (sCD14), soluble CD163 (sCD163), and lipopolysaccharide binding protein. Patients were stratified according to lower or greater likelihood of immune activation (CD4 nadir < 200, previous AIDS-defining event or very-low-level viremia during follow-up). Variables were compared using matched Wilcoxon tests. Results: From April 2019 to September 2021, 14 subjects were included (mean age 60 years, 12 men, 26 years since HIV infection, CD4 nadir 302 cells/mm³, 18 years on cART, 53 months on last cART). Twenty-one months following the switch, all but one subject maintained their viral load < 50 cp/mL. One subject had two viral blips. For the entire population, the sCD163 values increased significantly from baseline (+36%, p = 0.003) and from 6 months after the switch. The other markers did not change. After 6 months, the sCD163 increase was more pronounced in subjects with greater likelihood of immune activation (+53% vs. +19%, p = 0.026) Conclusions: cART simplification to dual therapy was associated with macrophage activation despite successful virological control after almost two years’ follow-up. This was more pronounced in those at risk of immune activation.     

Single-access dual-injection technique (SADIT) for high-risk PCI with Impella CP

The use of two arterial vascular accesses is now the standard of care in chronic total occlusion (CTO) percutaneous coronary interventions (PCI). When Impella support is needed, an additional vascular access may be necessary. We describe the first-in-man single-access, dual injection technique (SADIT). The Impella CP device was inserted in the left ventricle in the standard fashion. Subsequently, a 6 French sheath was placed at the “10 o clock” position and a second 4 French sheath was at the “5 o clock” position. This technique obviates the need for additional arterial access sites and potentially risk of complications. The SADIT technique is a simple way to perform high-risk, Impella-assisted coronary revascularization procedures necessitating dual coronary injections like CTO interventions. This strategy avoids unnecessary vascular complications from multiple access sites.     

Anti-Candida,docking studies,and in vitro metabolism-mediated cytotoxicity evaluation of Eugenol derivatives

The high morbidity and mortality rates of Candida infections, especially among immunocompromised patients, are related to the increased resistance rate of these species and the limited therapeutic arsenal. In this context, we evaluated the anti-Candida potential and the cytotoxic profile of eugenol derivatives. Anti-Candida activity was evaluated on C. albicans and C. parapsilosis strains by minimum inhibitory concentration (MIC), scanning electron microscopy (SEM), and molecular docking calculations at the site of the enzyme lanosterol-14-α-demethylase active site, responsible for ergosterol formation. The cytotoxic profile was evaluated in HepG2 cells, in the presence and absence of the metabolizing system (S9 system). The results indicated compounds 1b and 1d as the most active ones. The compounds have anti-Candida activity against both strains with MIC ranging from 50 to 100 μg ml⁻¹. SEM analyses of 1b and 1d indicated changes in the envelope architecture of both C. albicans and C. parapsilosis like the ones of eugenol and fluconazole, respectively. Docking results of the evaluated compounds indicated a similar binding pattern of fluconazole and posaconazole at the lanosterol-14-α-demethylase binding site. In the presence of the S9 system, compound 1b showed the same cytotoxicity profile as fluconazole (1.08 times) and compound 1d had 1.23 times increase in cytotoxicity. Eugenol and other evaluated compounds showed a significant increase in cytotoxicity. Our results suggest compound 1b as a promising starting point candidate to be used in the design of new anti-Candida agent prototypes.     

Intrauterine exposure to omeprazole increases the risk of teeth morphological anomalies in the offspring of a murine model

Odontology - Conditions experienced in early life have long-lasting effects on offspring health. Despite this, little is known about how maternal exposure to drugs during pregnancy affects...