Importance of cytochrome 3A4 and 2D6-mediated drug-drug interactions in oxycodone consumption among older adults hospitalized for hip fracture: a cross-sectional study.

Hip fracture is a common injury and represents a major health problem with an increasing incidence. In older adults, opioids such as oxycodone are often preferred to other analgesics such as tramadol because of a lower risk of delirium. Different parameters, such as inhibition of cytochrome P450 (CYP450) 2D6 and/or 3A4, can potentially lead to pharmacokinetic variations of oxycodone representing a risk of adverse drugs effects or lack of drug response. There is a risk of drug-drug interactions involving CYP450 in older adults due to the high prevalence of polypharmacy. This study sought to identify patient characteristics that influence oxycodone administration. A single-center observational study included 355 patients with a hip fracture hospitalized in a geriatric postoperative unit. Composite endpoint based on form, duration, and timing to intake separated patients into three groups: "no oxycodone", "low oxycodone ", and "high oxycodone ". CYP450 interactions were studied based on a composite variable defining the most involved CYP450 pathways between CYP2D6 and CYP3A4. CYP450 interactions with CYP2D6 pathway involved were associated with the risk of "high oxycodone" [odds ratio adjusted on age and the type of hip fracture (OR*) 4.52, 95% confidence interval (CI) 1.39-16.83, p = 0.02)], as well as serum albumin levels (OR* 1.09, 95% CI 1.02-1.17, p = 0.01). Cognitive impairment was negatively associated with the risk of "high oxycodone" (OR* 0.38, 95% CI 0.18-0.77, p = 0.02). This study showed an association between CYP2D6 interactions and higher oxycodone consumption indirectly reflecting the existence of uncontrolled postoperative pain.

Expression of immune checkpoint on subset of monocytes in old patients.

BACKGROUND: Immune checkpoints and their ligands are important actors of lymphocytes and monocytes activation's regulation. Their expression level within T cells changes with aging. Despite the major impact of aging on monocytes, there is no data about the expression of ICs on monocytes from old patients. The objective of our study is to describe the expression of ICs and their ligands on monocytes from young individuals compared to old patients. METHODS: We included 18 old control (>75 years old), 10 young control (<55 years old) and 45 old patients with hip fracture (HF). Phenotypical and functional analyses were performed on cryopreserved PBMCs. RESULTS: There is a differential expression of immune checkpoints and their ligands within monocyte subtypes regardless of age at baseline. After stimulation, a differential expression of immune checkpoints in young subjects but not in old subjects was observed which would be in favor of a regulation defect in old subjects. We hypothesize that this lack of regulation could partially explain the excess production of pro-inflammatory cytokines by the stimulated monocytes in old subjects. In HF, we also observe a differential expression of immune checkpoints, especially in old patients with a poor prognosis. CONCLUSION: Our results suggest that the immune regulation which should take place post-acute stress may be affected in old individuals.

Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients.

Highlights: Innate immune activation during Covid-19 infection is associated with pernicious clinical outcome. Background: Coronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity. Methods: We measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death. Results: Severe and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity. Conclusion: We propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.

Liver fibrosis evaluation using real-time shear wave elastography: applicability and diagnostic performance using methods without a gold standard.

BACKGROUND & AIMS: Real-time shear wave elastography (SWE) is a new two-dimensional transient elastography which had no assessment of factors associated with reliability, and had limited comparisons with other validated fibrosis biomarkers. The aim was to assess the applicability and performances of SWE for the diagnosis of fibrosis as compared with FibroTest (FT) and liver stiffness measurement (LSM) by transient elastography using two probes (TE-M and TE-XL). METHODS: Without a gold standard, the strength of concordance, discordance analysis and latent class analysis (LCM) were applied. RESULTS: 422 patients were included. The applicability of SWE (90.0%) was significantly lower than that of FT (97.9%; p <0.0001) and did not differ from those of TE-M (90.5%) and TE-XL (90.3%); it was higher though for SWE (86%) in 22 patients with ascites vs. 55% using TE-M (p=0.04). For the diagnosis of all fibrosis stages as presumed by FT, the performance of SWE was highly significant (Obuchowski measure 0.807 ± 0.013 [m ± se]), but lower than those of TE-M (0.852; p=0.0007) and TE-XL (0.834; p=0.046). SWE had a low performance for discrimination between F0 and F1. For the diagnosis of cirrhosis using LCM, SWE specificities were all equal to 99%, and SWE sensitivities ranged from 0.47 to 0.64. For the diagnosis of non-cirrhotic stages, the results were heterogeneous. CONCLUSIONS: The performance of SWE for the diagnosis of cirrhosis was similar to those of FT and TE. SWE applicability was lower than that of FT, but greater than that of TE in patients with ascites.