Effects of febuxostat therapy on circulating adipokine profiles in patients with overweight or obesity and asymptomatic hyperuricemia: A randomized controlled study.

INTRODUCTION: Elevated levels of serum uric acid (SUA) are strongly associated with several components of the metabolic syndrome, particularly obesity. Previous studies have reported the correlation between SUA levels, xanthine oxidoreductase (XOR) activity, and the imbalanced adipokine levels that are characteristic of obesity. In this study, we explored the effect of febuxostat on circulating adipokine profiles in patients with overweight or obesity and asymptomatic hyperuricemia. METHODS: This study was a single-center, randomized and controlled clinical trial that enrolled 130 participants with asymptomatic hyperuricemia and obesity. 117 participants were included in the final analysis, with 60 participants in the febuxostat group and 57 in the control group. We compared the circulating adipokine levels at 3 and 6 months, including high molecular weight (HMW) adiponectin, chemerin, omentin, (monocyte chemotactic protein-1) MCP-1, asprosin, fibroblast growth factor 21 (FGF21), neuregulin-4 (Nrg4), leptin, resistin, vaspin, visfatin, adipsin, and assessed the correlation between changes in adipokine levels (Δadipokines) and changes in XOR activity (ΔXOR) after febuxostat treatment. RESULTS: The results showed that an increase in HMW adiponectin and omentin levels and a decrease in chemerin and asprosin levels at 3 or 6 months compared to the control group. Additionally, a positive correlation was observed between ΔXOR activity and Δasprosin. Furthermore, after adjusting for ΔTG (triglyceride) and ΔSUA (serum uric acid) in multiple linear regression analyses, we found that ΔXOR activity was independently correlated with Δasprosin. CONCLUSION: This study may provide important evidence that febuxostat could alleviate the imbalance in circulating adipokine levels in patients with overweight or obesity and asymptomatic hyperuricemia. Furthermore, we observed a positive correlation between changes in asprosin levels and changes in XOR activity after febuxostat treatment.

U-shaped association between low-density lipoprotein cholesterol levels and risk of futile reperfusion mediated by stroke-associated pneumonia in acute ischemic stroke after endovascular thrombectomy.

OBJECTIVE: Futile reperfusion (FR) is becoming a major challenge in the treatment of patients with acute ischaemic stroke (AIS) undergoing endovascular thrombectomy. This study aims to determine the dose-response relationship between low-density lipoprotein cholesterol (LDL-C) levels and the risk of FR in patients with AIS undergoing endovascular thrombectomy and to investigate potential mediators. METHODS: A total of 614 patients with AIS undergoing endovascular thrombectomy were enrolled and divided into five groups according to quintiles of LDL-C levels: Q1(≤2.27 mmol/l), Q2 (2.27-2.5 mmol/l), Q3 (2.5-2.59 mmol/l), Q4 (2.59-2.97 mmol/l) and Q5 (≥2.97 mmol/l). Associations between LDL-C levels and the risk of FR and stroke-associated pneumonia (SAP) were estimated using multivariate logistic regression models. Restricted cubic spline curves were used to describe the dose-response relationship between LDL-C levels and the risk of FR and SAP. Mediation effect analysis was performed in R software with 100 bootstrap samples. RESULTS: After adjustment for confounders, both low and high LDL-C levels were significantly associated with a higher risk of FR compared with the reference group (Q3). We observed a U-shaped association between LDL-C levels and the risk of FR (P for nonlinear =0.012). Mediation analysis showed that the association between LDL-C levels and the risk of FR was 29.7 % (95 % CI: 2.96 %-75.0 %, P=0.02) mediated by SAP. CONCLUSIONS: We found a U-shaped association between LDL-C levels and the risk of FR that was mediated by SAP. Clinicians should note that in AIS patients undergoing endovascular thrombectomy, lower LDL-C levels are not always better.

A CT texture-based nomogram for predicting futile reperfusion in patients with intraparenchymal hyperdensity after endovascular thrombectomy for acute anterior circulation large vessel occlusion.

Background: Post-thrombectomy intraparenchymal hyperdensity (PTIH) in patients with acute anterior circulation large vessel occlusion is a common CT sign associated with a higher incidence of futile reperfusion (FR). We aimed to develop a nomogram to predict FR specifically in patients with PTIH. Methods: We retrospectively collected information on patients with acute ischemic stroke who underwent endovascular thrombectomy (EVT) at two stroke centers. A total of 398 patients with PTIH were included to develop and validate the nomogram, including 214 patients in the development cohort, 92 patients in the internal validation cohort and 92 patients in the external validation cohort. The nomogram was developed according to the independent predictors obtained from multivariate logistic regression analysis, including clinical factors and CT texture features extracted from hyperdense areas on CT images within half an hour after EVT. The performance of the nomogram was evaluated with integrated discrimination improvement (IDI), category-free net reclassification improvement (NRI), the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analyses for discrimination, calibration ability, and clinical net benefits, respectively. Results: Our nomogram was constructed based on three clinical factors (age, NIHSS score and ASPECT score) and two CT texture features (entropy and kurtosis), with AUC-ROC of 0.900, 0.897, and 0.870 in the development, internal validation, and external validation cohorts, respectively. NRI and IDI further validated the superior predictive ability of the nomogram compared to the clinical model. The calibration plot revealed good consistency between the predicted and the actual outcome. The decision curve indicated good positive net benefit and clinical validity of the nomogram. Conclusion: The nomogram enables clinicians to accurately predict FR specifically in patients with PTIH within half an hour after EVT and helps to formulate more appropriate treatment plans in the early post-EVT period.

Alterations in the gut mycobiome with coronary artery disease severity.

BACKGROUND: Coronary artery disease (CAD) is a prevalent cardiovascular condition, and numerous studies have linked gut bacterial imbalance to CAD. However, the relationship of gut fungi, another essential component of the intestinal microbiota, with CAD remains poorly understood. METHODS: In this cross-sectional study, we analyzed fecal samples from 132 participants, split into 31 healthy controls and 101 CAD patients, further categorized into stable CAD (38), unstable angina (41), and acute myocardial infarction (22) groups. We conducted internal transcribed spacer 1 (ITS1) and 16S sequencing to examine gut fungal and bacterial communities. FINDINGS: Based on ITS1 analyses, Ascomycota and Basidiomycota were the dominant fungal phyla in all the groups. The α diversity of gut mycobiome remained unaltered among the control group and CAD subgroups; however, the structure and composition of the mycobiota differed significantly with the progression of CAD. The abundances of 15 taxa gradually changed with the occurrence and progression of the disease and were significantly correlated with major CAD risk factor indicators. The mycobiome changes were closely linked to gut microbiome dysbiosis in patients with CAD. Furthermore, disease classifiers based on gut fungi effectively identified subgroups with different degrees of CAD. Finally, the FUNGuild analysis further categorized these fungi into distinct ecological guilds. INTERPRETATION: In conclusion, the structure and composition of the gut fungal community differed from healthy controls to various subtypes of CAD, revealing key fungi taxa alterations linked to the onset and progression of CAD. Our study highlights the potential role of gut fungi in CAD and may facilitate the development of novel biomarkers and therapeutic targets for CAD. FUNDING: This work was supported by the grants from the National Natural Science Foundation of China (No. 82170302, 92168117, 82370432), National clinical key specialty construction project- Cardiovascular Surgery, the Reform and Development Program of Beijing Institute of Respiratory Medicine (No. Ggyfz202417, Ggyfz202308), the Beijing Natural Science Foundation (No. 7222068); and the Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (No. CYFH202209).

Regio- and Diastereoselective Annulation of α,ß-Unsaturated Aldimines with Alkenes via Allylic C(sp3)-H Activation by Rare-Earth Catalysts.

The [3 + 2] or [4 + 2] annulation of α,ß-unsaturated aldimines with alkenes via ß'- or γ-allylic C(sp3)-H activation is, in principle, an atom-efficient route for the synthesis of five- or six-membered-ring cycloalkylamines, which are important structural motifs in numerous natural products, bioactive molecules, and pharmaceuticals. However, such a transformation has remained undeveloped to date probably due to the lack of suitable catalysts. We report herein for the first time the regio- and diastereoselective [3 + 2] and [4 + 2] annulations of α,ß-unsaturated imines with alkenes via allylic C(sp3)-H activation by half-sandwich rare-earth catalysts having different metal ion sizes. The reaction of α-methyl-substituted α,ß-unsaturated aldimines with alkenes by a C5Me4SiMe3-ligated scandium catalyst took place in a trans-diastereoselective [3 + 2] annulation fashion via C(sp3)-H activation at the α-methyl group (ß'-position), exclusively affording alkylidene-functionalized cyclopentylamines with excellent trans-diastereoselectivity. In contrast, the reaction of ß-methyl-substituted α,ß-unsaturated aldimines with alkenes by a C5Me5-ligated cerium catalyst proceeded in a cis-diastereoselective [4 + 2] annulation fashion via γ-allylic C(sp3)-H activation, selectively yielding multisubstituted 2-cyclohexenylamines with excellent cis-diastereoselectivity. The mechanistic details of these transformations have been elucidated by deuterium-labeling experiments, kinetic isotope effect studies, and the isolation and transformations of key reaction intermediates. This work offers an efficient and selective protocol for the synthesis of a new family of cycloalkylamine derivatives, featuring 100% atom efficiency, high regio- and diastereoselectivity, broad substrate scope, and an unprecedented reaction mechanism.

Association between uric acid levels and the risk of futile reperfusion in stroke after thrombectomy: A propensity score matching study.

INTRODUCTION: Currently, futile reperfusion (FR) is becoming a major challenge in the endovascular treatment of patients with acute ischemic stroke (AIS). The relationship between serum uric acid (SUA) and FR has not been investigated. This study aims to determine the relationship between SUA and FR using propensity score matching (PSM) analysis. METHODS: A total of 441 patients with AIS undergoing mechanical thrombectomy (MT) between August 2017 and January 2023 were included and divided into two groups based on the median SUA (297.4 µmol/L). Two groups were balanced using PSM analysis at a 1:1 ratio. The standardized mean difference (SMD) were used to assess the efficacy of the matching. Finally, 158 patients with low SUA (≤ 297.4 µmol/L) were matched with 158 patients with high SUA (>297.4 µmol/L). Predictors of FR were analyzed by multivariate logistic regression analysis in the PSM cohort. RESULTS: After PSM, patients with low SUA (≤ 297.4 µmol/L) had a significant higher incidence of FR (72.8 %, 115/158) than patients with high SUA (>297.4 µmol/L) (48.1 %, 76/158) (P<0.001). Multivariate logistic regression analysis in the PSM cohort showed that low SUA (≤ 297.4 µmol/L) was an independent risk factor for the efficacy of reperfusion (OR: 6.403, 95 % CI: 3.123-13.129, P<0.001), suggesting that patients with SUA ≤ 297.4 µmol/L have a 6.403 times higher risk of FR than patients with SUA>297.4 µmol/L. CONCLUSION: The results of this study suggest that low SUA (≤ 297.4 µmol/L) at admission increases the risk of FR in AIS patients undergoing MT by PSM analysis.

CT Texture-Based Nomogram in Ischemic Stroke to Differentiate Intracerebral Hemorrhage from Contrast Extravasation after Thrombectomy.

INTRODUCTION: Post-thrombectomy intraparenchymal hyperdensity (PTIH) in patients with acute ischemic stroke is a common CT sign, making it difficult for physicians to distinguish intracerebral hemorrhage in the early post-thrombectomy period. The aim of this study was to develop an effective model to differentiate intracerebral hemorrhage from contrast extravasation in patients with PTIH. METHODS: We retrospectively collected information on patients who underwent endovascular thrombectomy at two stroke centers between August 2017 and January 2023. A total of 222 patients were included in the study, including 118 patients in the development cohort, 52 patients in the internal validation cohort, and 52 patients in the external validation cohort. The nomogram was constructed using R software based on independent predictors derived from the multivariate logistic regression analysis, including clinical factors and CT texture features extracted from hyperdense areas on CT images. The performance and accuracy of the derived nomogram were assessed by the area under the receiver operating characteristic curve (AUC-ROC) and calibration curves. Additionally, decision curve analysis was conducted to appraise the clinical utility of the nomogram. RESULTS: Our nomogram was derived from two clinical factors (ASPECT score and onset to reperfusion time) and two CT texture features (variance and uniformity), with AUC-ROC of 0.943, 0.930, and 0.937 in the development, internal validation, and external validation cohorts, respectively. Furthermore, the calibration plot exhibited a strong agreement between the predicted outcome and the actual outcome. In addition, the decision curve analysis revealed the clinical utility of the nomogram in accurately predicting hemorrhage in patients with PTIH. CONCLUSION: The developed nomogram, based on clinical factors and CT texture features, proves to be effective in distinguishing intracerebral hemorrhage from contrast extravasation in patients with PTIH.