Cardiovascular outcomes and hospitalizations in Asian patients receiving immune checkpoint inhibitors: a population-based study.

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013-2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analysed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval: 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days' stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations was cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI. [Abstract copyright: Copyright © 2022. Published by Elsevier Inc.

Cardiovascular outcomes and hospitalizations in Asian patients receiving immune checkpoint inhibitors: A population-based study

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013 and 2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analyzed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval: 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days’ stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations were cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI

Towards a global partnership model in interprofessional education for cross-sector problem-solving

Objectives A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. Methods This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students’ data. Results We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest–posttest differences in students’ readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students’ social interaction anxiety after the IPE simulation. Conclusions The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education

A Wrong Fate Decision in Adipose Stem Cells upon Obesity

Progress has been made in identifying stem cell aging as a pathological manifestation of a variety of diseases, including obesity. Adipose stem cells (ASCs) play a core role in adipocyte turnover, which maintains tissue homeostasis. Given aberrant lineage determination as a feature of stem cell aging, failure in adipogenesis is a culprit of adipose hypertrophy, resulting in adiposopathy and related complications. In this review, we elucidate how ASC fails in entering adipogenic lineage, with a specific focus on extracellular signaling pathways, epigenetic drift, metabolic reprogramming, and mechanical stretch. Nonetheless, such detrimental alternations can be reversed by guiding ASCs towards adipogenesis. Considering the pathological role of ASC aging in obesity, targeting adipogenesis as an anti-obesity treatment will be a key area of future research, and a strategy to rejuvenate tissue stem cell will be capable of alleviating metabolic syndrome

Prospective relationship between duration of untreated psychosis and 13-year clinical outcome: A first-episode psychosis study

Background: The adverse effects of a long duration of untreated psychosis (DUP) have been explored in numerous short-term studies. These studies support the development of early interventions that reduce treatment delay and promote recovery. However, the enduring impact of DUP is largely unknown, partly due to the paucity of prospective long-term studies. Although the DUP-outcome relationship is commonly assumed to be linear, the threshold effect has not been adequately examined. Objective: To explore the relationship between DUP and long-term symptomatic remission. Methods: This was a prospective study of a cohort of 153 first-episode psychosis patients in Hong Kong at the 13-year follow-up. The patients were categorized into short (≤. 30. days), medium (31-180. days) and long (>. 180. days) DUP groups. Results: The long-term outcome was ascertained in 73% of the patients. Nearly half of the patients (47%) fulfilled the criteria for symptomatic remission. The short DUP group experienced a significantly higher remission rate over the course of the illness. The odds of long-term symptomatic remission was significantly reduced in the medium DUP (by 89%) and long DUP (by 85%) groups compared with the short DUP group. Further analysis showed that DUP had a specific impact on negative symptom remission. Conclusion: The findings support the threshold theory that DUP longer than 30. days adversely impacts the long-term outcome. The present study is one of the few studies that confirmed the enduring impact of DUP on long-term outcomes based on well-defined criteria and adequate statistical adjustment. © 2014 Elsevier B.V.link_to_subscribed_fulltex

Danshensu is the major marker for the antioxidant and vasorelaxation effects of Danshen (Salvia miltiorrhiza) water-extracts produced by different heat water-extractions

Some of the major components of Danshen (Salvia miltiorrhiza), a widely used Chinese herbal medicine rich in phenolic acids, are thermosensitive and may degrade to other phenolic acids during extractions with heating. The chemical profiles of Danshen water-extract may vary with different heat water extraction at different temperatures, affecting the composition and bioactivity of the extracts. In this study, six water-extracts of Danshen obtained from heat reflux water extraction and microwave-assisted extraction with water (MAE-W) at different temperatures were tested for their composition and pharmacological effects. Among these extracts, the third-round MAE-W (100 °C) extract had the highest phenolic acids and tanshinones contents, with the strongest antioxidant activity in 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay and ferric reducing/antioxidant potential (FRAP) assay. This extract also showed the strongest inhibitory effects on 2,2′-azobis-2-amidinopropane (AAPH)-induced hemolysis in human red blood cells, hydrogen peroxide-induced apoptosis in rat heart H9c2 cells and the highest relaxation effects on rat basilar artery. The antioxidant effects of Danshen water-extracts linearly correlated to their relaxation effects (r = 0.895–0.977). Through multiple linear regression analysis, danshensu was found to be the most significant marker in the antioxidant and vasodilation effects of Danshen water-extract, while tanshinone IIA as the marker on hydrogen peroxide-induced apoptosis in rat heart H9c2 cells. Danshensu is, therefore, a useful marker for the quality control of Danshen water-extracts in antioxidant and vasodilation, while tanshinone IIA for anti-apoptotic potential of different extracts

Role(s) of [Ca²⁺]_o and [Ca²⁺]_i in mediating the effects of simvastatin on AMPK and PP2A activities.

<p>(A) Effects of simvastatin (10 μM), with and without ryanodine (100 μM) pre-treatment, on [Ca²⁺]_i changes (F₁/F₀) of porcine coronary artery myocytes, estimated using Fluo-4/AM with confocal laser scanning microscope. (B) Summary of [Ca²⁺]_i changes in response to simvastatin (10 μM) before and after ryanodine (100 μM) challenges. Results are expressed (Area Under Curve, AUC) as mean ± SEM of 13–15 cells (***<i>P</i><0.001). (C) Summary of the effects of ryanodine (100 μM) on simvastatin (10 μM)- or AICAR (1 mM)-induced protein expression of p-AMPK/total AMPK in porcine coronary artery. *<i>P</i><0.05 and **<i>P</i><0.01 compared to controls (i.e. time 0). (D) Summary of the effects of caffeine (1 mM) on the protein expression of p-AMPK/total AMPK in porcine coronary artery, with and without ryanodine (100 μM). *<i>P</i><0.05 and **<i>P</i><0.01 compared to controls (i.e. time 0). (E) Effect of ryanodine (100 μM) on simvastatin (10 μM)-induced protein expression of p-PP2A/total PP2A in porcine coronary artery. *<i>P</i><0.05 and **<i>P</i><0.01 compared to controls (i.e. time 0). (F) Summary of the effect of simvastatin (10 μM), AICAR (1 mM) and caffeine (1 mM) on the protein expression of p-PP2A/total PP2A, with and without KN93 (10 μM) in porcine coronary artery. *<i>P</i><0.05 and **<i>P</i><0.01 compared to controls (i.e. time 0).</p

Effects of simvastatin and AICAR on [Glucose]_o uptake and the role(s) of [glucose]_o and [Na⁺]_o in mediating simvastatin effects on AMPK and PP2A activities.

<p>(A) Effects of simvastatin (10 μM) and AICAR (1 mM) on [³H]-2-deoxy-glucose uptake, with and without compound C (10 μM), of porcine coronary artery myocytes (n = 6 for each treatment). *<i>P</i><0.05 and **<i>P</i><0.01 compared to controls. Summary of the effect of simvastatin and AICAR on the protein expression of p-PP2A/total PP2A in (B) [glucose]_o-free, (C) [Na⁺]_o-free, (D) with phloridzin (1 mM) and (E) with ouabain (10 μM) in porcine coronary artery. *<i>P</i><0.05 and **<i>P</i><0.01 compared to controls (i.e. time 0).</p

Effects of simvastatin on K_ATP channel openers-induced vasorelaxation.

<p>(A) Effect of simvastatin (1, 3 and 10 μM) (n = 6 to 8) on cromakalim-induced relaxation of U46619 (10 nM) pre-contracted porcine coronary artery (endothelium-denuded). (B) Effect of simvastatin (1, 3 and 10 μM) (n = 6 to 8) on pinacidil-induced relaxation of U46619 (10 nM) pre-contracted porcine coronary artery (endothelium-denuded). (C) Effect of okadaic acid (10 nM) (n = 6 to 8) on simvastatin-inhibited cromakalim-induced relaxation of U46619 (10 nM) pre-contracted porcine coronary artery (endothelium-denuded). (D) Effect of okadaic acid (10 nM) (n = 6 to 8) on simvastatin-inhibited pinacidil-induced relaxation of U46619 (10 nM) pre-contracted porcine coronary artery (endothelium-denuded). *<i>P</i><0.05, **<i>P</i><0.01 and ***<i>P</i><0.001 compared to controls.</p

Biochemical existence of HMG-CoA reductase, and the effects of simvastatin and simvastatin Na⁺ on the protein expression of HMG-CoA reductase and p-HMG-CoA reductase.

<p>(A) Biochemical existence of HMG-CoA reductase in porcine liver, porcine coronary artery (endothelium-denuded) and human left internal mammary artery (endothelium-denuded). Beta actin was used as loading control. (B) Effects of simvastatin (SIM) (10 μM) and simvastatin Na⁺ (SIM Na⁺) (10 μM) (incubation, 2 to 30 min) on the protein expression of p-HMG-CoA reductase-Ser⁸⁷¹ and HMG-CoA reductase of porcine coronary artery.</p