Higher Levels Of Inflammatory Biomarkers Research Articles

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial

Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Clinical presentation, ICU management and outcome in severe COVID-19 disease – A prospective observational study

Aim: We conducted a prospective, observational study to describe the clinical characteristics, management, and outcomes of patients with moderate to severe coronavirus disease admitted to the Intensive Care Unit (ICU). Methods: The study was conducted from 1st July 2020 to 31st December 2020. The criteria for ICU admission included a positive Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) for the novel Coronavirus (SARS-CoV-2) and oxygen saturation of less than 90% with or without oxygen. Results: A total of 621 patients were included (median age, 59 years [interquartile range {IQR}, 48-68]; 75.8% were males. The common comorbidities were hypertension (323 [52%]), and diabetes mellitus. 96 (15.5%) patients underwent mechanical ventilation, 18 (2.9%) received renal replacement therapy, and 223 (36%) died. The median age in non-survivors was significantly higher [63 years (IQR 55-71)] vs. 57 years (IQR 46-66)] (p < 0.001). Hypoxia (oxygen saturation (SpO2 < 90%) and shortness of breath suggestive of impending respiratory failure were the most common symptoms necessitating ICU admission. A low absolute lymphocyte count (ALC), and high levels of inflammatory biomarkers which persisted for seven days after diagnosis were significantly associated with non-survival. Multivariate logistic regression analysis showed shortness of breath (SOB), hypoxia (SpO2 < 90% on oxygen), use of neuromuscular blockers, and chronic kidney disease as independent risk factors associated with mortality as were the severity scores (APACHE and SOFA). Conclusion: This single-center case series provides clinical characteristics and outcomes of patients with confirmed COVID-19 disease admitted to the COVID ICU. These findings are important for guiding research and preparing for future pandemics.

The role of inflammatory biomarkers in the development and progression of pre-eclampsia: a systematic review and meta-analysis.

Pre-eclampsia (PE) is a pregnancy complication associated with maternal and fetal morbidity and mortality. Among the potential pathogenesis discussed, inflammation is considered an essential initiator of PE. Previous studies have compared the levels of various inflammatory biomarkers that indicate the existence of PE; however, the relative levels of pro-inflammatory and anti-inflammatory biomarkers and their dynamic changes during PE progression remain unclear. This knowledge is essential to explain the occurrence and progression of the disease. We aimed to identify the relationship between inflammatory status and PE using inflammatory biomarkers as indicators. We also discussed the underlying mechanism by which inflammatory imbalance contributes to PE by comparing the relative levels of pro-inflammatory and anti-inflammatory biomarkers. Furthermore, we identified additional risk factors for PE. We reviewed PubMed, Embase, and the Cochrane Library for articles published until 15th September 2022. Original articles that investigated inflammatory biomarkers in PE and normal pregnancy were included. We selected healthy pregnant women as controls. The inflammatory biomarkers in the case and control groups were expressed as standardized mean differences and 95% confidence intervals using a random-effects model. Study quality was assessed using the Newcastle-Ottawa Scale. Publication bias was assessed using Egger's test. Thirteen articles that investigated 2,549 participants were included in this meta-analysis. Patients with PE had significantly higher levels of C-reactive protein (CRP), interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) than the controls. CRP and pro-inflammatory cytokine levels were higher than those of anti-inflammatory cytokines. Patients with gestational age > 34 weeks had significantly higher IL-6 and TNF levels. Patients with higher systolic blood pressure had significantly higher IL-8, IL-10, and CRP levels. Inflammatory imbalance is an independent risk factor for PE development. Impairment of the anti-inflammatory system is a crucial initiating factor for PE development. Failed autoregulation, manifested as prolonged exposure to pro-inflammatory cytokines, leads to PE progression. Higher levels of inflammatory biomarkers suggest more severe symptoms, and pregnant women after 34 weeks of gestation are more susceptible to PE.

144 Occupational Exposure to Particles Measured by Nanoparticles Tracking Analysis (NTA) in Exhaled Breath Condensate (EBC).

Abstract The production of paints, coatings and construction materials may generate nanoparticles (NP) with potential adverse health effects. We carried out a study aimed at investigating exposure biomarkers reflecting the internal dose of inhaled particles and NP. NTA was used to quantify particle number concentration and size in EBC collected at the end of shift in 81 workers employed in companies producing technological materials. External exposure was characterized in terms of particle number concentration, size and lung deposited surface area (LDSA) in the near operational field by using a set of DiSCmini. Three subgroups were identified: Low-Exposure (LE, n=30), High-Exposure (HE n=35), and non-occupationally exposed (UC, n=16). Comparisons between groups were made using non-parametric analyses. LE and HE workers showed significantly higher number of NP in EBC (p=0.024, p=0.041, respectively) as compared to UC. The HE groups showed higher levels of inflammatory biomarkers, such as IL-1β and IL-10 as compared to LE and UC (p=0.02, p<0.01, respectively). Positive correlations were observed between particle number concentration recorded by DiscMini and NTA data (Rho=0,225, p=0.04) and between the NTA and IL-10 and IL-1β (Rho=0.246, p=0.012; Rho=0.223, p=0.022, respectively). In contrast, LDSA did not correlate with NTA data. These findings provide evidence of the relationship between increasing exposure to NP and the burden of particles in the airways which, in turn, results in sustained inflammation. Given the lack of exposure biomarkers for dusts, these results are promising to investigate the relationship between internal dose of particles and changes in lung pathobiology.

Solute carrier family 11 member 1 genetic polymorphisms rs17235409 and rs3731865 associate with susceptibility to extremity post-traumatic osteomyelitis in a Chinese Han population.

Genetic variations in the solute carrier family 11 member 1 (SLC11A1) gene have been implicated in developing inflammatory disorders. However, it is still unclear whether such polymorphisms contribute to the pathogenesis of post-traumatic osteomyelitis (PTOM). Therefore, this study investigated the roles of genetic variations of the SLC11A1 gene (rs17235409 and rs3731865) in PTOM development in a Chinese Han cohort. The SNaPshot method was used for genotyping 704 participants (336 patients and 368 controls) for rs17235409 and rs3731865. Outcomes revealed that rs17235409 increased the risk of PTOM occurrence by dominant (p=.037, odds ratio [OR]=1.44) and heterozygous models (p=.035, OR=1.45), implying AG genotype as a risk factor for PTOM development. In addition, patients with AG genotype had relatively higher levels of inflammatory biomarkers than those with AA and GG genotypes, especially for the white blood cell count and C-reactive protein. Despite no statistically significant differences achieved, rs3731865 may reduce the PTOM susceptibility, suggested by the results of dominant (p=.051, OR=0.67) and heterozygous (p=.068, OR=0.69) models. In short, rs17235409 confers an elevated chance of developing PTOM, with AG genotype as a risk factor. Whether rs3731865 involves in the pathogenesis of PTOM requires further investigations.

MP05-17 RISKS OF CAROTID ARTERY STENOSIS AND ATHEROSCLEROTIC CARDIOVASCULAR DISEASE IN PATIENTS WITH CALCIUM KIDNEY STONE: ASSESSMENT OF SYSTEMIC INFLAMMATORY BIOMARKERS

You have accessJournal of UrologyCME1 Apr 2023MP05-17 RISKS OF CAROTID ARTERY STENOSIS AND ATHEROSCLEROTIC CARDIOVASCULAR DISEASE IN PATIENTS WITH CALCIUM KIDNEY STONE: ASSESSMENT OF SYSTEMIC INFLAMMATORY BIOMARKERS Chang Te Wang, Chan Jung Liu, Hau Chern Jan, and Ho Shiang Huang Chang Te WangChang Te Wang More articles by this author , Chan Jung LiuChan Jung Liu More articles by this author , Hau Chern JanHau Chern Jan More articles by this author , and Ho Shiang HuangHo Shiang Huang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003216.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To assess the clinical significance of preoperative inflammatory biomarkers combined with atherosclerotic cardiovascular disease (ASCVD) risk score to evaluate carotid artery stenosis in patients with calcium kidney stones. METHODS: We conducted a prospective observational case-control study, enrolling seventy four patients with calcium kidney stones and sixty six age- and sex-matched healthy controls. We calculated the inflammatory biomarkers including the neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI). Ultrasound of the carotid arteries was performed on all participants to identify the severity of the stenosis. RESULTS: All inflammatory biomarkers and the severity of carotid artery stenosis were higher in the calcium kidney stone group than in controls. After stratification of ASCVD, inflammatory biomarkers and carotid artery stenosis severity were still significantly higher in the calcium kidney stone group. Multivariate analyses showed that calcium kidney stones significantly increased the risk of ASCVD and carotid artery stenosis. In multivariate linear logistic regression analyses, calcium kidney stone and ASCVD score had a significant association with carotid artery occlusion, but SIRI did not. CONCLUSIONS: Calcium kidney stone is associated with higher levels of inflammatory biomarkers and carotid artery stenosis. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e50 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chang Te Wang More articles by this author Chan Jung Liu More articles by this author Hau Chern Jan More articles by this author Ho Shiang Huang More articles by this author Expand All Advertisement PDF downloadLoading ...

Potential Role of Oleanolic and Ursolic Acids from Food and Plant Materials as Natural Ingredients for the Cosmetic Industry: A Review

Cosmeceuticals have emerged as health and beauty aid products that integrate active ingredients from natural sources. Phytochemicals have prevailed in this market as an effective alternative toward different skin conditions. This is mainly due to the increasing demand for natural products that overcome the side effects of conventional treatments. Alopecia, acne, and skin aging are prevalent skin-related conditions worldwide. These conditions are characterized by high levels of inflammatory biomarkers and oxidative stress conditions. Oleanolic and ursolic acids are two biologically active pentacyclic triterpenoid isomeric compounds. They have shown strong potential for the prevention and treatment of diverse skin-related conditions through their effective antioxidant and anti-inflammatory capacity. This review presents the latest available information on the biological potential of oleanolic and ursolic acids, highlighting their cosmeceutical potential. In the pursuit of a better understanding of their potential as natural ingredients of dermatological relevance, graphical analysis is provided to propose the molecular mechanisms involved in the effects of each skin-related condition.

COVID-19 severity and in-hospital mortality in an area with high HIV prevalence.

HIV infection causes immune dysregulation affecting T-cell and monocyte function, which may alter coronavirus disease 2019 (COVID-19) pathophysiology. We investigated the associations among clinical phenotypes, laboratory biomarkers, and hospitalisation outcomes in a cohort of people hospitalised with COVID-19 in a high HIV prevalence area. We conducted a prospective observational cohort study in Tshwane, South Africa. Respiratory disease severity was quantified using the respiratory oxygenation score. Analysed biomarkers included inflammatory and coagulation biomarkers, CD4 T-cell counts, and HIV-1 viral loads (HIVVL). The analysis included 558 patients, of whom 21.7% died during admission. The mean age was 54 years. A total of 82 participants were HIV-positive. People living with HIV (PLWH) were younger (mean age 46 years) than HIV-negative people; most were on antiretroviral treatment with a suppressed HIVVL (72%) and the median CD4 count was 159 (interquartile range: 66-397) cells/µL. After adjusting for age, HIV was not associated with increased risk of mortality during hospitalisation (age-adjusted hazard ratio = 1.1, 95% confidence interval: 0.6-2.0). Inflammatory biomarker levels were similar in PLWH and HIV-negative patients. Detectable HIVVL was associated with less severe respiratory disease. In PLWH, mortality was associated with higher levels of inflammatory biomarkers. Opportunistic infections, and other risk factors for severe COVID-19, were common in PLWH who died. PLWH were not at increased risk of mortality and those with detectable HIVVL had less severe respiratory disease than those with suppressed HIVVL. This study advances our understanding of severe COVID-19 in PLWH.

Revascularization of Peripheral Arteries in Patients with Intermittent Claudication Decreases Inflammatory Biomarkers.

Patients with intermittent claudication have significantly higher levels of inflammatory biomarkers, particularly interleukins, which is also a consequence of exercise limitation. Physical activity, which is one of the preventive measures against atherosclerosis, is associated with a decrease in inflammatory biomarkers. Therefore, in our study, we investigated the effects of revascularization of peripheral arteries in patients with intermittent claudication on functional capacity and levels of inflammatory markers. The study included 26 patients with intermittent claudication who underwent percutaneous transluminal angioplasty (PTA). Before the procedure and 2-4 months after successful revascularization, the ankle-brachial index (ABI), functional capacity using the treadmill test, and the walking impairment questionnaire (WIQ) were determined. Inflammatory biomarkers were also measured before and after procedures. Successful revascularization was associated with an increase in intermittent claudication: 120 (20-315) versus 300 (100-1000 m), P < 0.001. Treadmill testing showed a significant increase in initial and maximal walking distance. After revascularization, ABI increased significantly (0.55 vs 0.82, P < 0.003). Improvement in functional performance was also demonstrated by WIQ. Two to three months after revascularization, some inflammatory biomarkers decreased significantly: fibrinogen, interleukin-6 (IL-6), and interleukin-8 (IL-8). The high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-alpha (TNFα) also did not decrease significantly. The levels of some inflammatory markers: IL-6, TNFα, and fibrinogen were significantly related to the improvement in patients' functional capacity. The results of our study show that successful revascularization of the lower limb arteries not only improves the functional capacity of patients with intermittent claudication, but also reduces the systemic inflammatory response and may have a preventive effect on local and concomitant other atherosclerotic diseases.

507: PLASMA BIOMARKERS AS PROGNOSTICATION IN PATIENTS RECEIVING EXTRACORPOREAL MEMBRANE OXYGENATION

Introduction: Neurological complications in VA-ECMO beget a 7-15% mortality rate; however, existing literature demonstrates that neuromonitoring reduces the rate of complications. There is an increasing need for easily measured, accurate markers that can predict neurological injury. We propose that plasma biomarkers such as Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NFL), and Tau can be utilized for prognostication of neurologic outcomes on ECMO. We hypothesised that patients with higher levels of inflammatory biomarkers will be at higher risk for neurologic complications. Methods: In this pilot prospective, cohort study, patients were consented within 24 hours of cannulation and followed over duration of VA-ECMO course. Peak concentrations of plasma biomarkers were used for analysis. Samples were taken daily for first 7 days and every other day afterwards as long as patient remained in the ICU. Outcomes were determined by the modified Rankin Scale (mRS) with a favorable outcome of mRS < 4. Statistical analyses used STATA v17 to calculate the Area Under ROC curves to determine sensitivity and specificity. Results: 20 patients were enrolled. Median age was 48.5 (41.5-62 IQR) yrs, and patients were 55% female. The median peak concentration values of GFAP, NFL, and Tau were 382.3 pg/ml (100.8-5,516.4), 8,306.7 pg/ml (2,338.9-13,577.2), and 1,278.4 pg/ml (318.7-3,447.4), respectively. There were 15 patients (75%) with unfavourable neurologic outcome at discharge, 17 patients had acute brain injury (85%), 10 patients had thromboembolic events (50%), and 14 patients had hemorrhagic events (70%). In prognostication of acute brain injury in patients, the plasma biomarkers GFAP, NFL and Tau achieved an AUC of 0.84, 0.73, and 0.73 respectively. Furthermore, GFAP, NFL and Tau achieved an AUC of 0.70, 0.81, and 0.70 for prediction of hemorrhagic events on ECMO. Conclusions: We identify three key plasma biomarkers, GFAP, NFL and Tau, that have the groundbreaking potential to assist prognostication of acute brain injury and hemorrhagic events on ECMO. We strongly recommend further research to identify feasibility and utility of novel biomarkers in the context of VA-ECMO and neurological complications to understand which combination of plasma biomarkers has the highest clinical yield.

Persistent Asthma Is Associated With Carotid Plaque in MESA.

Background Asthma and atherosclerotic cardiovascular disease share an underlying inflammatory pathophysiology. We hypothesized that persistent asthma is associated with carotid plaque burden, a strong predictor of atherosclerotic cardiovascular disease events. Methods and Results The MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults free of known atherosclerotic cardiovascular disease at baseline. Subtype of asthma was determined at examination 1. Persistent asthma was defined as asthma requiring use of controller medications, and intermittent asthma was defined as asthma without controller medications. B-mode carotid ultrasound was performed to detect carotid plaques (total plaque score [TPS], range 0-12). Multivariable regression modeling with robust variances evaluated the association of asthma subtype and carotid plaque burden. The 5029 participants were a mean (SD) age of 61.6 (10.0) years (53% were women, 26% were Black individuals, 23% were Hispanic individuals, and 12% were Chinese individuals). Carotid plaque was present in 50.5% of participants without asthma (TPS, 1.29 [1.80]), 49.5% of participants with intermittent asthma (TPS, 1.25 [1.76]), and 67% of participants with persistent asthma (TPS, 2.08 [2.35]) (P≤0.003). Participants with persistent asthma had higher interleukin-6 (1.89 [1.61] pg/mL) than participants without asthma (1.52 [1.21] pg/mL; P=0.02). In fully adjusted models, persistent asthma was associated with carotid plaque presence (odds ratio, 1.83 [95% confidence interval, 1.21-2.76]; P<0.001) and TPS (β=0.66; P<0.01), without attenuation after adjustment for baseline interleukin-6 (P=0.02) or CRP (C-reactive protein) (P=0.01). Conclusions Participants with persistent asthma had higher carotid plaque burden and higher levels of inflammatory biomarkers, compared with participants without asthma. Adjustment for baseline inflammatory biomarkers did not attenuate the association between carotid plaque and asthma subtype, highlighting the increased atherosclerotic cardiovascular disease risk among those with persistent asthma may be multifactorial.

Sex differences in a double-blind randomized clinical trial with minocycline in treatment-resistant depressed patients: CRP and IL-6 as sex-specific predictors of treatment response

BackgroundInflammation is a well-known risk factor for depression. Specifically, patients who do not respond to antidepressant treatment show higher levels of inflammatory biomarkers compared with responders. Thus, several studies have investigated the efficacy of anti-inflammatory add-on treatment in this population. However, major depressive disorder is more prevalent in females than in males, with sex differences present in antidepressant treatment response and in immune system regulation. To explore sex differences in inflammatory profiles and treatment responses, we investigated a cohort of patients with treatment resistant depression (TRD), for which they received an adjunctive, anti-inflammatory treatment with minocycline – the Minocycline in Depression (MINDEP) study. MethodsThe MINDEP study is a 4-week double-blind, randomised, placebo-controlled clinical trial (stratified by sex) with 39 TRD participants, which demonstrated the efficacy of minocycline, an antibiotic with anti-inflammatory properties, in TRD patients with major depressive disorder (MDD) and evidence of low-grade inflammation measured with C-reactive protein (CRP) ≥ 3 mg/L. In these secondary analyses, we investigated the differential effects of minocycline in females (N = 22, 10 randomised to minocycline and 12 randomised to placebo) and in males (N = 17, 8 randomised to minocycline and 9 randomised to placebo) on changes in depressive symptoms (Δ- Hamilton Rating Scale for Depression (HAMD)-17), taking also into consideration CRP levels (CRP ≥3 mg/L vs. CRP <3 mg/L). Additionally, we investigated the role of serum IL-6 in predicting treatment response to minocycline, using sex-specific medians of IL-6, in novel exploratory analyses. ResultsSex differences in Δ-HAMD-17 indicate that only females (F = 10.49, p = 0.005), but not males (F = 1.64, p = 0.22), presented an effect of CRP levels on the response to minocycline. Also, we detected sex differences in the relationship between serum CRP and IL-6 levels: CRP was strongly correlated with IL-6 in females (Spearman's ρ = 0.658, P < 0.001) but not in males (ρ = 0.007, p = 0.979). Exploratory analyses found that IL-6 was indeed a better predictor of response than minocycline than CRP, as we found an interaction between study arms and IL-6 groups (above and below the IL-6 sex-specific median) in females (F = 4.435 p = 0.050) and, at trend statistical level, in males (F = 4.258 p = 0.060). Moreover, Δ-HAMD-17 was numerically comparable in the two high-IL-6 group taking minocycline (females, mean 9.20 ± SD 7.80; males, mean 8.80 ± SD 5.97), confirming that high IL-6, differently from high CRP, identified responders to minocycline both in males and females. ConclusionOur findings highlight the need of sex-specific inflammatory biomarkers in predicting antidepressant response to anti-inflammatories in TRD patients, with the possibility of CRP being a relevant predictor of treatment response only for females, and IL-6 being relevant for both sexes.

Risks of Carotid Artery Stenosis and Atherosclerotic Cardiovascular Disease in Patients with Calcium Kidney Stone: Assessment of Systemic Inflammatory Biomarkers.

(1) Background: To assess the clinical significance of preoperative inflammatory biomarkers combined with atherosclerotic cardiovascular disease (ASCVD) risk score to evaluate carotid artery stenosis in patients with calcium kidney stones; (2) Methods: We conducted a prospective observational case-control study, enrolling 74 patients with calcium kidney stones and 66 age- and sex-matched healthy controls. We calculated the inflammatory biomarkers including the neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI). An ultrasound of the carotid arteries was performed on all participants to identify the severity of the stenosis; (3) Results: All inflammatory biomarkers and the severity of carotid artery stenosis were higher in the calcium kidney stone group than in controls. After stratification of ASCVD, inflammatory biomarkers and carotid artery stenosis severity were still significantly higher in the calcium kidney stone group. Multivariate analyses showed that calcium kidney stones significantly increased the risk of ASCVD and carotid artery stenosis. In multivariate linear logistic regression analyses, calcium kidney stone and ASCVD score had a significant association with carotid artery occlusion, but SIRI did not; (4) Conclusions: Calcium kidney stone is associated with higher levels of inflammatory biomarkers and carotid artery stenosis. Calcium kidney stone is associated with higher levels of inflammatory biomarkers and carotid artery stenosis.

Prevalence and outcomes of peripheral artery disease in a real-world cohort of patients with acute coronary syndrome: insights from the prospective SPUM registry

Abstract Background Despite substantial improvement in secondary preventive therapy, the burden of recurrent cardiovascular (CV) events remains high. Peripheral artery disease (PAD), is a potential marker of increased residual ischemic risk in acute coronary syndrome (ACS) patients suggesting greater net clinical benefit from intensified individualized therapy. Purpose We aimed to assess the prevalence and cardiovascular (CV) outcomes of peripheral arterial disease (PAD) in 4'787 patients with acute coronary syndromes (ACS) in the Swiss prospective multicenter SPUM study. Methods PAD was defined according to international guidelines. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), i.e., stroke, myocardial infarction (MI) and death at 1 year. Adjusted Cox proportional hazards regression models were used to estimate the risk associated with PAD and outcomes. Results Out of 4'787 ACS patients, 285 patients (6.0%) had PAD. These patients were older (70.1±10.6 vs 63.3±12.4, p&amp;lt;0.001), presented all traditional CV risk factors (all p&amp;lt;0.001) and were more likely to have a complex history of CV disease, such as previous MI (24.3% vs 11.4%, p&amp;lt;0.001), prior percutaneous (32.3% vs 13.8%, p&amp;lt;0.001) or surgical (12.6% vs 3.5%, p&amp;lt;0.001) coronary revascularization. PAD-patients presented also higher levels of inflammatory biomarkers, such as hs-CRP, and GRACE 2.0 score (all p&amp;lt;0.001). At 1 year, patients with PAD had a higher rate of MACCE compared to those presenting without PAD. Rates of the individual components of the primary endpoint and CV-death were all significantly higher in patients with PAD (all p&amp;lt;0.001), except for a numerical increase in MI (5.3% vs 3.3%, p=0.060). This enhanced risk persisted after adjustment for differences in baseline characteristics, with a 53% (Adj. HR 1.53, CI95% 1.14–2.08, p=0.005) increase in MACCE. In spite of high-intensity anti-thrombotic therapy, PAD patients presented the same rate (Adj. HR 1.03, CI95% 0.68–1.54, p=0.901) of major bleeding events at 1 year. Conclusions Among a real-world cohort of ACS patients, the coexistence of PAD, a very-high CV risk phenotype, is associated with significantly increased rates of MACCE, but no difference in major bleeding events. These observations might help clinicians to further stratify this very-high risk population and to identify patients who may derive the greatest benefit from more intense secondary prevention therapies. Funding Acknowledgement Type of funding sources: None.

Stroke-associated infections in patients with and without cancer.

Cancer in stroke patients is associated with higher levels of inflammatory biomarkers and unfavorable poststroke outcomes. We thus explored whether there is a link between cancer and stroke-associated infections. Medical records of patients with ischemic stroke in 2014-2016 registered in the Swiss Stroke Registry of Zurich were retrospectively analyzed. Incidence, characteristics, treatment, and outcome of stroke-associated infections diagnosed within 7 days after stroke onset were tested for an association with cancer. Among 1181 patients with ischemic stroke, 102 patients with cancer were identified. Stroke-associated infections occurred in 179 and 19 patients (17% and 19%) without and with cancer (P = .60), respectively, among them pneumonia in 95 and 10 patients (9% and 10%) and urinary tract infections in 68 and 9 patients (6% and 9%) (P = .74 and P = .32). Use of antibiotics was similar between groups. Levels of C-reactive protein (CRP) (P < .001), erythrocyte sedimentation rate (ESR) (P = .014) and procalcitonin (P = .015) were higher and levels of albumin (P = .042) and protein (P = .031) were lower in patients with cancer than without cancer. Among patients without cancer, higher CRP (P < .001), ESR (P < .001) and procalcitonin (P = .04) and lower albumin (P < .001) were associated with stroke-associated infections. Among cancer patients with or without infections, no significant differences in these parameters were observed. In-hospital mortality was associated with cancer (P < .001) and with stroke-associated infections (P < .001). However, among patients with stroke-associated infections, cancer was not associated with in-hospital mortality (P = .24) or 30-day mortality (P = .66). Cancer does not represent a risk factor for stroke-associated infections in this patient cohort.

Duration, timing, and consistency of sleep in relation to inflammatory cytokines in Mexican adolescents

ObjectiveTo evaluate whether sleep duration, timing, and variability were associated with inflammatory cytokines in a cohort of Mexico City adolescents. MethodsThe analytic sample comprised >500 adolescents who were part of an ongoing longitudinal study in Mexico City. At two time points during mid-to-late puberty (average age 14, n = 391) and late-to-post puberty (average age 16, n = 345), adolescents completed a follow-up visit that included 7-day wrist actigraphy and clinical assessment of plasma inflammatory cytokines (high-sensitivity C-reactive protein, Interleukin 1β, Interleukin 6, and Tumor Necrosis Factor ɑ). Sleep characteristics included weekday and weekend sleep duration and midpoint (median of bed and wake time), as well as sleep variability (SD of sleep duration across 7 days) and social jetlag (midpoint difference from weekdays to weekends). At each time point, multivariable linear regression models were run with log inflammatory levels as the outcome and categories of sleep characteristics as predictors, while adjusting for potential confounders (specific to each model). Analyses were run unstratified and sex-stratified. ResultsIn the mid-to-late pubertal visit, weekday sleep duration was inversely associated with natural log hs-CRP after adjustment (Q4 vs Q1: β = -0.41, 95% Confidence Interval (CI) −0.81 to −0.01) and later sleep midpoint was positively associated with log hs-CRP (Q4 vs Q1: β = 0.55, 95% CI 0.13 to 0.97). Sleep duration variability was associated with higher IL-1β among boys, while in girls social jetlag was associated with higher IL-1β and weekend sleep duration was inversely associated with IL-6. At the late-to-post pubertal visit, there were few associations except for a positive association between weekday sleep duration and hs-CRP among boys (β = 0.60, 95% CI 0.04 to 1.16) and a non-linear positive association between social jetlag and hs-CRP among girls (β = 0.80, 95% CI 0.22 to 1.37 comparing 2 to 3 h of social jetlag vs <1 h). ConclusionLater timing, shorter duration, and inconsistency of sleep were related to higher levels of inflammatory biomarkers, but associations were more evident at the mid-to-late pubertal visit than the late-to-post pubertal visit.

The genetics of ME: A commentary on Hajdarevic et al.

Depression is characterized by altered neurobiological responses to threat and inflammation may be involved in the development and maintenance of symptoms. However, the mechanistic pathways underlying the relationship between the neural underpinnings of threat, inflammation and depressive symptoms remain unknown.Twenty participants with major depressive disorder (MDD) and 17 healthy controls (HCs) completed this study. Peripheral blood mononuclear cells (PBMCs) were collected and stimulated ex vivo with lipopolysaccharide (LPS). We then measured a broad array of secreted proteins and performed principal component analysis to compute an aggregated immune reactivity score. Subjects completed a well-validated emotional face processing task during functional magnetic resonance imaging (fMRI). Amygdala activation was measured during perception of threat for the main contrast of interest: fear > happy face. Participants completed the Mood and Anxiety Symptom Questionnaire (MASQ) and the Perceived Stress Scale (PSS). Correlation analyses between amygdala activation, the aggregate immune score, and symptom were computed across groups. A mediation analysis was also performed across groups to further explore the relationship between these three variables.In line with our hypotheses and with prior work, the MDD group showed greater amygdala activation in response to threat compared to the HC group [t35 = -2.038, p = 0.049]. Internal consistency of amygdala activation to threat was found to be moderate. Response to an ex vivo immune challenge was greater in MDD than HC based on the computed immune reactivity score (PC1; t35 = 2.674, p = 0.011). Amygdala activation was positively correlated with the immune score (r = 0.331, p = 0.045). Moreover, higher amygdala activation was associated with greater anxious arousal measured by the MASQ (r = 0.390, p = 0.017). Exploring the role of stress, we found that higher perceived stress was positively associated with both inflammatory response (r = 0.367, p = 0.026) and amygdala response to threat (r = 0.325, p = 0.050). Mediation analyses showed that perceived stress predicted anxious arousal, but neither inflammation nor amygdala activation fully accounted for the effect of perceived stress on anxious arousal.These data highlight the potential importance of threat circuitry hyperactivation in MDD, consistent with prior reports. We found that higher levels of inflammatory biomarkers were associated with higher amygdala activation, which in turn was associated with anxious arousal. Future research utilizing larger sample sizes are needed to replicate these preliminary results.

Development of a nomogram to assess the impact of the myocardial injury on the prognosis of COVID-19 patients.

Coronavirus disease 2019 (COVID-19) has been spreading worldwide. Many COVID-19 patients were accompanied by myocardial injury during the course of the disease. To evaluate the association of cardiac injury with clinical outcomes in COVID-19 patients, we recruited 261 COVID-19 cases admitted to Tongji Hospital of Huazhong University of Science and Technology in this study. Compared with patients without myocardial injury, those with myocardial injury were older, with shorter hospital stays and lower survival rates. They also had higher levels of inflammatory biomarkers (Interleukin-6,8,10 and C-reactive protein), coagulation biomarkers, liver and kidney function markers. Kaplan-Meier analysis demonstrated that patients with myocardial injury had a higher mortality rate. The multivariate Cox regression model and the nomogram revealed that myocardial injury, co-morbidity, and abnormal procalcitonin (PCT) levels were independent risk factors of the mortality of COVID-19 patients. The linear correlation analysis and the ROC curve suggested a predictive value of the neutrophil-lymphocyte ratio (NLR) in cardiac injury. Summarily, myocardial injury in COVID-19 patients is associated with a higher mortality risk. Attention should be paid to monitoring myocardial injury in patients with significantly elevated myocardial markers and NLR at admission.

Exaggerated amygdala response to threat and association with immune hyperactivity in depression

BackgroundDepression is characterized by altered neurobiological responses to threat and inflammation may be involved in the development and maintenance of symptoms. However, the mechanistic pathways underlying the relationship between the neural underpinnings of threat, inflammation and depressive symptoms remain unknown. MethodsTwenty participants with major depressive disorder (MDD) and 17 healthy controls (HCs) completed this study. Peripheral blood mononuclear cells (PBMCs) were collected and stimulated ex vivo with lipopolysaccharide (LPS). We then measured a broad array of secreted proteins and performed principal component analysis to compute an aggregated immune reactivity score. Subjects completed a well-validated emotional face processing task during functional magnetic resonance imaging (fMRI). Amygdala activation was measured during perception of threat for the main contrast of interest: fear > happy face. Participants completed the Mood and Anxiety Symptom Questionnaire (MASQ) and the Perceived Stress Scale (PSS). Correlation analyses between amygdala activation, the aggregate immune score, and symptom were computed across groups. A mediation analysis was also performed across groups to further explore the relationship between these three variables. ResultsIn line with our hypotheses and with prior work, the MDD group showed greater amygdala activation in response to threat compared to the HC group [t35 = -2.038, p = 0.049]. Internal consistency of amygdala activation to threat was found to be moderate. Response to an ex vivo immune challenge was greater in MDD than HC based on the computed immune reactivity score (PC1; t35 = 2.674, p = 0.011). Amygdala activation was positively correlated with the immune score (r = 0.331, p = 0.045). Moreover, higher amygdala activation was associated with greater anxious arousal measured by the MASQ (r = 0.390, p = 0.017). Exploring the role of stress, we found that higher perceived stress was positively associated with both inflammatory response (r = 0.367, p = 0.026) and amygdala response to threat (r = 0.325, p = 0.050). Mediation analyses showed that perceived stress predicted anxious arousal, but neither inflammation nor amygdala activation fully accounted for the effect of perceived stress on anxious arousal. ConclusionThese data highlight the potential importance of threat circuitry hyperactivation in MDD, consistent with prior reports. We found that higher levels of inflammatory biomarkers were associated with higher amygdala activation, which in turn was associated with anxious arousal. Future research utilizing larger sample sizes are needed to replicate these preliminary results.

Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19.

Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.