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Background: Systemic immune-inflammation index (SII) is a novel comprehensive inflammatory marker. Inflammation is associated with impaired lung function. We aimed to explore the possible relationship between SII and lung function to examine the potential of SII in predicting lung function decline. Methods: A cross-sectional survey was conducted using the data of the NHANES from 2007 to 2012. Multiple linear regression models were used to analyze the linear relationship between SII and pulmonary functions. Sensitivity analyses, subgroup analyses, and interaction tests were used to examine the robustness of this relationship across populations. Fitted smooth curves and threshold effect analysis were used to describe the nonlinear relationships. Results: A total of 10,125 patients were included in this study. After adjusting for all covariates, multiple linear regression model analysis showed that high Log2-SII level was significantly associated with decreased FVC(ß, -23.4061; 95% CI, -42.2805- -4.5317), FEV1(ß, -46.7730; 95% CI, -63.3371- -30.2089), FEV1%(ß, -0.7923; 95% CI, -1.1635- -0.4211), FEV1/FVC(ß, -0.6366; 95% CI, -0.8328- -0.4404) and PEF(ß, -121.4468; 95% CI,-164.1939- -78.6998). The negative correlation between Log2-SII and pulmonary function indexes remained stable in trend test and stratified analysis. Inverted U-shaped relationships between Log2-SII and FVC, FEV1, FEV1%, and PEF were observed, while a negative linear correlation existed between FEV1/FVC and Log2-SII. The cutoff values of the nonlinear relationship between Log2-SII and FVC, FEV1, FEV1%, PEF were 8.3736, 8.0688, 8.3745, and 8.5255, respectively. When SII exceeded the critical value, the lung function decreased significantly. Conclusion: This study found a close correlation between SII and pulmonary function indicators. This study investigated the SII threshold when lung functions began to decline in the overall population. SII may become a promising serological indicator for predicting lung function decline. However, prospective studies were needed further to establish the causal relationship between these two factors.
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Mediadores de Inflamación , Inflamación , Pulmón , Encuestas Nutricionales , Valor Predictivo de las Pruebas , Humanos , Masculino , Estudios Transversales , Femenino , Persona de Mediana Edad , Pulmón/fisiopatología , Pulmón/inmunología , Volumen Espiratorio Forzado , Estados Unidos/epidemiología , Adulto , Capacidad Vital , Inflamación/fisiopatología , Inflamación/inmunología , Inflamación/diagnóstico , Inflamación/sangre , Mediadores de Inflamación/sangre , Anciano , Biomarcadores/sangre , Factores de Riesgo , Modelos LinealesRESUMEN
OBJECTIVES: This study investigated whether kidney transplant donors experience increased arterial stiffness compared with the general population and how arterial stiffness changes over time. MATERIALS AND METHODS: Our study included 59 kidney transplant donors and 27 healthy volunteers. All subjects underwent cardio-ankle vascular index measurements. We studied fibroblast growth factor23, klotho, monocyte chemoattractant protein-1, N-terminal pro-B-type natriuretic peptide, indoxyl sulfate, and p-cresyl sulfate levels. RESULTS: Cardio-ankle vascular index level was higher in donors 6 to 11 years after donation (8.02 ± 0.24 m/s) than in donors 2 to 6 years after donation (7.02 ± 0.27 m/s) and healthy volunteers (6.65 ± 0.22 m/s). Cardioankle vascular index level was positively correlated with age (r = 0.382, P < .001) and levels of triglyceride (r = 0.213, P = .049), blood urea nitrogen (r = 0.263, P = .014), creatinine (r = 0.354, P = .001), calcium (r = 0.228, P = .035), indoxyl sulfate (r = 0.219, P = .042), p-cresyl sulfate (r = 0.676, P ≤ .001), and monocyte chemoattractant protein-1 (r = 0.451, P ≤ .001) and negatively correlated with estimated glomerular filtration rate (r = -0.383, P < .001). Multiple linear regression analysis revealed that age (P = .026, B = 0.244), mean arterial blood pressure (P < .001, B = 0.446), blood urea nitrogen (P = .006, B = 0.302), creatinine (P = .032, B = 0.236), estimated glomerular filtration rate (P = .003, B = -0.323), fibroblast growth factor-23 (P = .007, B = 0.294), N-terminal pro-B-type natriuretic peptide (P = .005, B = 0.304), and monocyte chemoattractant protein-1 (P ≤ .001, B = 0.434) independently predicted cardio-ankle vascular index levels. CONCLUSIONS: Even without additional risk factors, kidney donors should be followed closely for arterial stiffness and cardiovascular disease, especially in the long-term (>5 years) after kidney transplant.
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Biomarcadores , Índice Vascular Cardio-Tobillo , Mediadores de Inflamación , Trasplante de Riñón , Valor Predictivo de las Pruebas , Calcificación Vascular , Rigidez Vascular , Humanos , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Trasplante de Riñón/efectos adversos , Adulto , Estudios de Casos y Controles , Calcificación Vascular/sangre , Calcificación Vascular/fisiopatología , Calcificación Vascular/etiología , Calcificación Vascular/diagnóstico , Factores de Tiempo , Mediadores de Inflamación/sangre , Factores de Riesgo , Factores de Crecimiento de Fibroblastos/sangre , Factor-23 de Crecimiento de Fibroblastos , Quimiocina CCL2/sangre , Uremia/sangre , Uremia/diagnóstico , Uremia/fisiopatología , Indicán/sangre , Resultado del Tratamiento , Donadores VivosRESUMEN
BACKGROUND: Severe Plasmodium falciparum malarial anemia is still the principal cause of death in children in underdeveloped countries. An imbalance between proinflammatory and anti-inflammatory cytokines is associated with malaria progression. This study evaluated circulating levels of selected inflammatory cytokines among malaria-infected children in Ghana. METHODS: This case-control study was conducted at Tamale Teaching Hospital, Ghana. One hundred and twenty children with malaria and 60 controls, aged 12-144 months were selected from April to July, 2023 for the study. Malaria was diagnosed through microscopy, full blood count was measured using hematology analyzer, and cytokines were measured using enzyme-linked immunosorbent assay. RESULTS: Malaria-infected children had higher tumor necrosis factor alpha (TNF-α) (p < .001), interferon-gamma (IFN-É£) (p < .001), interleukin (IL)-1ß (p < .001), IL-6 (p < .001), granulocyte macrophage-colony stimulating factor (GM-CSF) (p < .001), and IL-10 (p < .001) levels than controls. Participants with high parasitemia had raised TNF-α (p < .001), IFN-É£ (p < .001), IL-1ß (p < .001), IL-6 (p < .001), GM-CSF (p < .001), and IL-10 (p < .001), but reduced IL-3 (p < .001) and TGF-ß (p < .001) than those with low parasitemia. Severe malarial anemic children had elevated TNF-α (p < .001), IFN-É£ (p < .001), IL-1ß (p < .001), IL-6 (p < .001), GM-CSF (p < .001), and IL-10 (p < .001), but lower IL-3 (p < .001) and TGF-ß (p < .001) than those with uncomplicated malaria. CONCLUSION: Parasite density was the principal predictor of the cytokine levels, as parasitemia positively associated with IL-10, GM-CSF, IL-6, IL-1ß, IFN-É£, and TNF-α, but negatively associated with IL-3 and TGF-ß. Malaria is associated with enhanced secretion of pro- and anti-inflammatory cytokines in Ghanaian children. Inflammatory cytokines may be involved in the development of severe malarial anemia in children. However, IL-3 and TGF-ß may offer protection against severe malarial anemia.
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Anemia , Citocinas , Progresión de la Enfermedad , Malaria Falciparum , Humanos , Citocinas/sangre , Anemia/sangre , Anemia/inmunología , Anemia/parasitología , Masculino , Preescolar , Femenino , Estudios Prospectivos , Estudios de Casos y Controles , Lactante , Malaria Falciparum/sangre , Malaria Falciparum/inmunología , Malaria Falciparum/complicaciones , Malaria Falciparum/parasitología , Malaria Falciparum/epidemiología , Ghana/epidemiología , Niño , Parasitemia/sangre , Parasitemia/inmunología , Plasmodium falciparum/inmunología , Mediadores de Inflamación/sangreRESUMEN
OBJECTIVE: To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA). METHODS: Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12-week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL-BREF) and the treatment-emergent adverse events (TEAEs) for all the participants in the study. RESULTS: At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed (p > .05). CONCLUSION: In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
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Antirreumáticos , Artritis Reumatoide , Quimioterapia Combinada , Hidroxicloroquina , Metotrexato , Calidad de Vida , Humanos , Metotrexato/efectos adversos , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/sangre , Femenino , Antirreumáticos/efectos adversos , Antirreumáticos/administración & dosificación , Antirreumáticos/uso terapéutico , Masculino , Resultado del Tratamiento , Persona de Mediana Edad , Adulto , Factores de Tiempo , Dimensión del Dolor , Biomarcadores/sangre , Anciano , Mediadores de Inflamación/sangreRESUMEN
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the key factor promoting its development. Carotid intima-media thickening and the presence of carotid plaques are important indices of cardiovascular risk. In addition, inflammation is a major and complex factor in the development of atherosclerosis. The relationships between carotid atherosclerosis and certain inflammatory markers have rarely been studied in healthy individuals. Therefore, we aimed to investigate the associations between subclinical carotid atherosclerosis and various inflammatory biomarkers in a large Caucasian population free of evident CVD. In addition to recording study participants' demographic characteristics, anthropometric characteristics, and atherosclerotic risk factors, laboratory tests were performed to measure levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and inflammatory cytokines/chemokines, including interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP)-1. This study included 264 asymptomatic individuals with a median age of 61.7 years (interquartile range, 54.5-67.5 years); 45.7% of participants were male. Participants were divided into two groups according to their carotid status: the normal carotid group, comprising 120 participants; and the pathological carotid group, comprising 144 participants. Compared with the normal carotid group, hypertension and diabetes mellitus were significantly more common and serum levels of HbA1c, IL-8, and MCP-1 were significantly higher in the pathological carotid group. Multivariate regression analysis revealed significant positive associations between pathological carotid findings and serum levels of IL-8 (highest tertile, OR: 2.4, p = 0.030) and MCP-1 (highest tertile, OR: 2.4, p = 0.040). Our results suggest that IL-8 and MCP-1 may serve as early indicators of subclinical atherosclerosis, thereby helping to identify individuals at increased risk of CVD before the onset of clinical symptoms.
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Biomarcadores , Enfermedades de las Arterias Carótidas , Grosor Intima-Media Carotídeo , Citocinas , Inflamación , Humanos , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Anciano , Enfermedades de las Arterias Carótidas/sangre , Citocinas/sangre , Inflamación/sangre , Factores de Riesgo , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Arterias Carótidas/patología , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Quimiocina CCL2/sangre , Mediadores de Inflamación/sangre , Enfermedades AsintomáticasRESUMEN
In the context of the development of intervertebral disc degeneration (IDD), inflammatory mediators play a pivotal role. Nevertheless, due to the influence of the inflammatory microenvironment, the causal relationship between specific inflammatory mediators and the development of IDD remains uncertain. The understanding of the causal relationship between inflammatory mediators and IDD is of great importance in preventing and delaying disc degeneration in the future. We utilized genetic data concerning systemic circulating inflammatory regulators obtained from a Genome-Wide Association Study (GWAS) analyzing 41 serum cytokines in a cohort of 8293 individuals from Finland. The genetic data for IDD were derived from the most recent GWAS summary statistics conducted within the FinnGen consortium, encompassing 37,636 IDD cases and 270,964 controls. Our analysis employed bidirectional 2-sample Mendelian randomization (MR) techniques, which included several MR methods such as MR Egger, weighted median, inverse variance weighted, weighted mode, and simple mode. Additionally, the MR-PRESSO method was employed to identify horizontal pleiotropy, heterogeneity was quantified using the Cochran Q statistic, and MR-Egger intercept analysis was performed to assess pleiotropy. We established causal relationships between 3 specific inflammatory factors and IDD. Elevated levels of MIP-1ß (ORâ =â 0.956, 95% CI: -0.08 to -0.006; Pâ =â .02) and IFN-G (ORâ =â 0.915, 95% CI: -0.16 to -0.02; Pâ =â .01) expression were associated with a reduced risk of IDD. Conversely, genetic susceptibility to IDD was linked to a decrease in IL-13 levels (ORâ =â 0.967, 95% CI: -0.063 to -0.004; Pâ =â .03). In this study, we have identified inflammatory factors that exhibit a causal relationship with the onset and progression of IDD, as supported by genetic predictions.
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Estudio de Asociación del Genoma Completo , Degeneración del Disco Intervertebral , Análisis de la Aleatorización Mendeliana , Humanos , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/epidemiología , Degeneración del Disco Intervertebral/sangre , Masculino , Femenino , Finlandia/epidemiología , Citocinas/sangre , Citocinas/genética , Polimorfismo de Nucleótido Simple , Persona de Mediana Edad , Mediadores de Inflamación/sangre , Inflamación/genética , Inflamación/sangre , Predisposición Genética a la EnfermedadRESUMEN
OBJECTIVES: To assess the ability of baseline serum biomarkers to predict disease activity and remission status in juvenile idiopathic arthritis (JIA) at 18-year follow-up (FU) in a population-based setting. METHODS: Clinical data and serum levels of inflammatory biomarkers were assessed in the longitudinal population-based Nordic JIA cohort study at baseline and at 18-year FU. A panel of 16 inflammatory biomarkers was determined by multiplexed bead array assay. We estimated both univariate and multivariate logistic regression models on binary outcomes of disease activity and remission with baseline variables as explanatory variables. RESULTS: Out of 349 patients eligible for the Nordic JIA cohort study, 236 (68%) had available serum samples at baseline. We measured significantly higher serum levels of interleukin 1ß (IL-1ß), IL-6, IL-12p70, IL-13, MMP-3, S100A9 and S100A12 at baseline in patients with active disease at 18-year FU than in patients with inactive disease. Computing receiver operating characteristics illustrating the area under the curve (AUC), we compared a conventional prediction model (gender, age, joint counts, erythrocyte sedimentation rate, C reactive protein) with an extended model that also incorporated the 16 baseline biomarkers. Biomarker addition significantly improved the ability of the model to predict activity/inactivity at the 18-year FU, as evidenced by an increase in the AUC from 0.59 to 0.80 (p=0.02). Multiple regression analysis revealed that S100A9 was the strongest predictor of inactive disease 18 years after disease onset. CONCLUSION: Biomarkers indicating inflammation at baseline have the potential to improve evaluation of disease activity and prediction of long-term outcomes.
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Artritis Juvenil , Biomarcadores , Inducción de Remisión , Humanos , Artritis Juvenil/sangre , Artritis Juvenil/diagnóstico , Biomarcadores/sangre , Femenino , Masculino , Niño , Adolescente , Pronóstico , Curva ROC , Preescolar , Estudios Longitudinales , Metaloproteinasa 3 de la Matriz/sangre , Estudios de Cohortes , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Estudios de Seguimiento , Mediadores de Inflamación/sangreRESUMEN
BACKGROUND: Heart failure (HF) is a serious and common condition affecting millions of people worldwide, with obesity being a major cause of metabolic disorders such as diabetes and cardiovascular disease. This study aimed to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, on the obese- and diabetes-related cardiomyopathy. METHODS AND RESULTS: We used db/db mice and high fat diet-streptozotocin induced diabetic mice to investigate the underlying mechanisms of fenofibrate's beneficial effects on heart function. Fenofibrate reduced fibrosis, and lipid accumulation, and suppressed inflammatory and immunological responses in the heart via TNF signaling. In addition, we investigated the beneficial effects of fenofibrate on HF hospitalization. The Korean National Health Insurance database was used to identify 427,154 fenofibrate users and 427,154 non-users for comparison. During the 4.22-year follow-up, fenofibrate use significantly reduced the risk of HF hospitalization (hazard ratio, 0.907; 95% CI 0.824-0.998). CONCLUSIONS: The findings suggest that fenofibrate may be a useful therapeutic agent for obesity- and diabetes-related cardiomyopathy.
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Cardiomiopatías Diabéticas , Fenofibrato , Insuficiencia Cardíaca , Hipolipemiantes , Obesidad , Fenofibrato/uso terapéutico , Fenofibrato/farmacología , Animales , Obesidad/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Masculino , República de Corea/epidemiología , Humanos , Cardiomiopatías Diabéticas/prevención & control , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Ratones Endogámicos C57BL , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , PPAR alfa/agonistas , PPAR alfa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factores de Tiempo , Bases de Datos Factuales , Transducción de Señal/efectos de los fármacos , Miocardio/metabolismo , Miocardio/patología , Femenino , Hospitalización , Persona de Mediana Edad , Anciano , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/sangre , Factores de Riesgo , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
BACKGROUND: The maternal intrauterine immune environment may affect offspring long-term health. We aimed to investigate the association between the intrauterine placental immunological milieu and glycolipid metabolic health in children. METHODS AND RESULTS: This study enrolled 1803 mother-child pairs from the Ma'anshan birth cohort (2013-2014). Placental mRNA expression of inflammatory cytokines (interleukin-1ß [IL-1ß], IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-4, IL-6, IL-8, C-reactive protein, and interferon-γ) and oxidative stress biomarkers (heme oxygenase-1, hypoxia-inducible factor-1alpha, and glucose-related protein 78) was quantified using real-time quantitative polymerase chain reaction. Fasting blood glucose, insulin, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol were assessed at 5 to 6 years old. Statistical analyses included multiple linear regression, binary logistic regression, restricted cubic spline model, and the Bayesian kernel machine regression model. Placental inflammatory cytokines (IL-1ß, monocyte chemoattractant protein-1, C-reactive protein, IL-6, IL-8, IL-10) and oxidative stress biomarkers (heme oxygenase-1, hypoxia-inducible factor-1alpha, glucose-related protein 78) showed positive associations with children's fasting blood glucose levels. Heme oxygenase-1 and glucose-related protein 78 exhibited negative correlations with children's fasting insulin levels. Elevated IL-6, heme oxygenase-1, hypoxia-inducible factor-1alpha, and glucose-related protein 78 were associated with increased risk of prediabetes in children. Overall upregulation of placental proinflammatory cytokines and oxidative stress factors mRNA expression correlated with higher prediabetes risk in children. Bayesian kernel machine regression analysis indicated a joint positive effect of the 12 placental inflammation and oxidative stress mixtures on children's risk of high fasting blood glucose. CONCLUSIONS: This exploratory study underscores significant correlations between maternal intrauterine placental inflammation, oxidative stress markers, and offspring fasting blood glucose and insulin levels. These findings highlight the potential role of intrauterine holistic immunity in shaping offspring glucose metabolism health.
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Biomarcadores , Estrés Oxidativo , Placenta , Humanos , Femenino , Embarazo , Biomarcadores/sangre , Niño , Masculino , China/epidemiología , Preescolar , Placenta/metabolismo , Citocinas/sangre , Glucemia/metabolismo , Glucemia/análisis , Adulto , Inflamación/sangre , Lípidos/sangre , Mediadores de Inflamación/sangreRESUMEN
BACKGROUND: Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD). METHODS: In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA. RESULTS: Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR: 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively]. CONCLUSIONS: PTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs. TRIAL REGISTRATION: The study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009-016595-77). The validation date was 2010-03-09.
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Grosor Intima-Media Carotídeo , Diabetes Mellitus Tipo 2 , Progresión de la Enfermedad , Pentoxifilina , Insuficiencia Renal Crónica , Humanos , Proyectos Piloto , Masculino , Persona de Mediana Edad , Pentoxifilina/uso terapéutico , Femenino , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Estudios Prospectivos , Anciano , Resultado del Tratamiento , Factores de Tiempo , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/tratamiento farmacológico , Glucuronidasa/sangre , Glucuronidasa/genética , Biomarcadores/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Enfermedades Asintomáticas , Mediadores de Inflamación/sangre , Inhibidores de Fosfodiesterasa/uso terapéutico , Antiinflamatorios/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/diagnóstico , OsteocalcinaRESUMEN
BACKGROUND AND AIMS: Systemic low-grade inflammation, measured by plasma high-sensitivity C-reactive protein (hsCRP) levels, is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). To date, however, it is unknown whether plasma hsCRP is associated with adverse histological plaque features. METHODS: Plaques were derived during carotid endarterectomy. Patients with hsCRP levels ≥2 mg/L were evaluated for pro-inflammatory and adverse plaque characteristics, as well as future ASCVD events, and compared with patients with low hsCRP levels. Logistic and linear regression analyses in addition to subdistribution hazard ratios were conducted, adjusted for cardiovascular risk factors. RESULTS: A total of 1096 patients were included, of which 494 (46.2 %) had hsCRP levels ≥2 mg/L. Elevated hsCRP levels 2 mg/L were independently associated with levels of plaque interleukin 6, beta coefficient of 109.8 (95 % confidence interval (CI): 33.4, 186.5; p = 0.005) pg/L, interleukin 8 levels, 194.8 (110.4, 378.2; p = 0.03) pg/L and adiponectin plaque levels, -16.8 (-30.1, -3.6; p = 0.01) µg/L, compared with plaques from patients with low hsCRP levels. Histological analysis revealed increased vessel density in high hsCRP patients, odds ratio (OR) of 1.57 (1.20, 2.09; p = 0.001), larger lipid core, 1.35 (1.02, 1.73; p = 0.04), and increased macrophage content, 1.32 (1.02, 1.73; p = 0.04). Over a 3-year follow-up period, hsCRP levels ≥2 mg/L were associated with a hazard ratio of 1.81 (1.03, 3.16; p = 0.04) for coronary artery disease event risk. CONCLUSIONS: The distinct inflammatory and histological features observed in carotid plaques among individuals with hsCRP levels ≥2 mg/L underscore the utility of plasma hsCRP as a potent identifier for patients harboring high-risk plaques.
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Biomarcadores , Proteína C-Reactiva , Endarterectomía Carotidea , Inflamación , Fenotipo , Placa Aterosclerótica , Humanos , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Masculino , Placa Aterosclerótica/sangre , Femenino , Anciano , Persona de Mediana Edad , Biomarcadores/sangre , Inflamación/sangre , Mediadores de Inflamación/sangre , Factores de Riesgo , Adiponectina/sangre , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/patología , Interleucina-6/sangre , Interleucina-8/sangre , Arterias Carótidas/patología , Modelos Logísticos , Pronóstico , Receptores InmunológicosRESUMEN
INTRODUCTION: Depressive symptoms are a common concomitant of cerebral small vessel disease (CSVD), of which pathogenesis requires more study. White matter microstructural abnormalities and proteomic alternation have been widely reported regarding depression in the elderly with CSVD. Exploring the relationship between cerebral white matter microstructural alterations and serum proteins may complete the explanation of molecular mechanisms for the findings from neuroimaging research of CSVD combined with depressive symptoms. METHODS: An untargeted proteomics approach based on mass spectrometry was used to obtain serum proteomic profiles, which were clustered into co-expression protein modules. White matter microstructural integrity was measured using the FMRIB Software Library (FSL) and MATLAB to analyze diffusion tensor imaging (DTI) data and calculate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for 50 regions of interest (ROI). Integrating the proteome with the DTI results, weighted gene co-expression analysis (WGCNA) was used to identify protein modules related to white matter microstructural alterations, and the proteins of the corresponding modules were analyzed for functional enrichment through bioinformatics techniques. RESULTS: DTI measurements were analCerebral small vessel disease (CSVD); Depression; Diffusion tensor imaging (DTI); Proteomics; Inflammationyzed between individuals with CSVD and depressive symptoms (CSVD+D) (n = 24) and those without depressive symptoms (CSVD-D) (n = 35). Results showed an overall increase in MD, AD, and RD within the left hemisphere of the CSVD+D group, suggesting widespread loss of white matter integrity and axonal demyelination, including left superior longitudinal fasciculus (SLF), left posterior corona radiata (PCR) and right external capsule (EC). We identified two protein modules associated with DTI diffusivity, and functional enrichment analyses revealed that complement and coagulation cascades and immune responses participate in the alternation of white matter microstructure in the CSVD+D group. CONCLUSION: The results suggested immune- and inflammation-related mechanism was associated with white matter microstructure changes in CSVD with depressive symptoms.
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Biomarcadores , Enfermedades de los Pequeños Vasos Cerebrales , Depresión , Imagen de Difusión Tensora , Proteómica , Sustancia Blanca , Humanos , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/sangre , Enfermedades de los Pequeños Vasos Cerebrales/psicología , Depresión/sangre , Masculino , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Anciano , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Valor Predictivo de las Pruebas , Mapas de Interacción de Proteínas , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/sangre , Mediadores de Inflamación/sangre , Proteínas Sanguíneas/análisis , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease with a global prevalence rate of 1%. Patients with RA often associate specific foods like tomatoes and eggplants with adverse symptoms. These plants contain solanine, which could potentially contribute to bone and joint damage. Despite patient reports, there is a lack of randomized controlled trials (RCTs) investigating the effects of nightshades on patients with RA. This study aims to assess the effect of nightshade elimination diet (NED) on inflammatory and rheumatologic marker levels in rheumatoid arthritis patients for the first time. METHODS: A single-blinded controlled trial will be conducted to evaluate the effect of an NED on 40 participants over 8 weeks (2 months). Participants will be equally divided into intervention and placebo groups. Both groups will receive general anti-inflammatory dietary recommendations, with the intervention group undergoing an NED during the study. Clinical symptoms will be assessed using questionnaires, and blood samples will be collected to measure relevant indicators. DISCUSSION: This RCT signifies a groundbreaking exploration into NED effects on RA markers, potentially initiating crucial discussions in the field. Its outcomes could serve as a cornerstone for larger and more robust trials, offering pivotal insights to nutritionists and physicians for the nuanced management of patients with RA. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20230220057465N1 ( https://irct.behdasht.gov.ir/trial/68959 ). Registered on 8 April 2023.
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Artritis Reumatoide , Biomarcadores , Dieta de Eliminación , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Artritis Reumatoide/sangre , Artritis Reumatoide/dietoterapia , Artritis Reumatoide/inmunología , Artritis Reumatoide/diagnóstico , Biomarcadores/sangre , Mediadores de Inflamación/sangre , Método Simple Ciego , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: Considerable debate exists regarding the association between coffee consumption and C-reactive protein (CRP) levels and the shape of this association. We conducted a meta-analysis to assess the relationship between coffee consumption and CRP levels. DATA SYNTHESIS: We searched PubMed and Web of Science databases and conducted a hand search as of June 27, 2023. Meta-analyses were conducted using standardized mean differences (SMDs) with random-effects models, based on the geometric mean of CRP from included studies. We identified 13 studies for our systematic review and included 11 cross-sectional studies, involving a total of 66,691 subjects, in our meta-analysis. We found a linear inverse association between coffee consumption and CRP levels (p-value = 0.002) and did not find evidence of a non-linear association (p for non-linearity = 0.13). Compared with the lowest category of coffee consumption (median, non-drinkers), the SMDs of log-transformed CRP levels were -0.02 (95% confidence interval [CI]: -0.05 to 0.00) for the third highest (median, 0.5 cup/day), -0.09 (95% CI: -0.15 to -0.04) for the second highest (median, 2.5 cups/day), and -0.14 (95% CI: -0.25 to -0.04) for the highest category (median, 4.5 cups/day). The inverse association tended to be stronger in women, but the difference by gender was not significant. Compared to the limited number of studies not adjusting for smoking, those that adjusted showed a strong linear inverse association, although the difference was not significant. CONCLUSIONS: Our findings indicate that coffee consumption is inversely associated with CRP levels. These associations may vary with potential modifiers, including gender and smoking adjustment. PROSPERO: CRD42023445986.
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Biomarcadores , Proteína C-Reactiva , Café , Humanos , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Biomarcadores/sangre , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Medición de Riesgo , Factores Protectores , Adulto Joven , Mediadores de Inflamación/sangre , AdolescenteRESUMEN
BACKGROUND: Inflammation and immunity play important roles in the formation of coronary collateral circulation (CCC). The pan-immune-inflammation value (PIV) is a novel marker for evaluating systemic inflammation and immunity. The study aimed to investigate the association between the PIV and CCC formation in patients with chronic total occlusion (CTO). METHODS: This retrospective study enrolled 1150 patients who were diagnosed with CTO through coronary angiographic (CAG) examinations from January 2013 to December 2021 in China. The Cohen-Rentrop criteria were used to catagorize CCC formation: good CCC formation (Rentrop grade 2-3) and poor CCC formation group (Rentrop grade 0-1). Based on the tertiles of the PIV, all patients were classified into three groups as follows: P1 group, PIV ≤ 237.56; P2 group, 237.56< PIV ≤ 575.18; and P3 group, PIV > 575.18. RESULTS: A significant relationship between the PIV and the formation of CCC was observed in our study. Utilizing multivariate logistic regression and adjusting for confounding factors, the PIV emerged as an independent risk factor for poor CCC formation. Notably, the restricted cubic splines revealed a dose-response relationship between the PIV and risk of poor CCC formation. In terms of predictive accuracy, the area under the ROC curve (AUC) for PIV in anticipating poor CCC formation was 0.618 (95% CI: 0.584-0.651, P < 0.001). Furthermore, the net reclassification index (NRI) and integrated discrimination index (IDI) for PIV, concerning the prediction of poor CCC formation, were found to be 0.272 (95% CI: 0.142-0.352, P < 0.001) and 0.051 (95% CI: 0.037-0.065, P < 0.001), respectively. It's noteworthy that both the NRI and IDI values were higher for PIV compared to other inflammatory biomarkers, suggesting its superiority in predictive capacity. CONCLUSIONS: PIV was associated with the formation of CCC. Notably, PIV exhibited potential as a predictor for poor CCC formation and showcased superior predictive performance compared to other complete blood count-based inflammatory biomarkers.
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Circulación Colateral , Angiografía Coronaria , Circulación Coronaria , Oclusión Coronaria , Mediadores de Inflamación , Inflamación , Valor Predictivo de las Pruebas , Humanos , Masculino , Persona de Mediana Edad , Oclusión Coronaria/fisiopatología , Oclusión Coronaria/diagnóstico por imagen , Femenino , Estudios Retrospectivos , Enfermedad Crónica , Anciano , Inflamación/diagnóstico , Inflamación/sangre , Inflamación/inmunología , Inflamación/fisiopatología , Mediadores de Inflamación/sangre , Medición de Riesgo , China , Biomarcadores/sangre , Factores de Riesgo , PronósticoRESUMEN
Sepsis, one of the leading causes of death, is still lacking specific treatment. OXIRIS (BAXTER, Deerfield, IL, USA) is the first device allowing combined removal of endotoxins, inflammatory mediators and uremic toxins, alongside fluid balance control. Available data is very limited. This retrospective propensity score-matched cohort study of adult patients with septic shock aimed to evaluate septic shock duration and mortality in patients treated with either standard of care renal replacement therapy (RRT) or RRT with combined hemoadsorption, who were admitted to the interdisciplinary surgical intensive care unit at Heidelberg University Hospital during the years 2018 through 2021. Main outcomes were duration of shock, thirty-day mortality and plasma interleukin-6 levels before and after initiation of hemoadsorption. Included were 117 patients (female, 33%; male 67%); median age: 67 (16) years. After matching: 42 patients (female, 33%; male, 67%); mean age: 59.1 ± 13.8 years. There was no statistically significant difference in septic shock duration (p = 0.94; hazard ratio (HR) 0.97 (95% CI, 0.48-1.97)). Thirty-day survival analysis showed a non-statistically significant survival difference. (p = 0.063; HR 0.43 (95% CI, 0.17-1.09)). A post-hoc 90-day survival analysis revealed statistically significant longer survival and lower death hazard ratio in patients treated with RRT + HA (p = 0.037; HR = 0.42 (95% CI, 0.18-0.99). In conclusion, RRT with combined hemoadsorption of endotoxins, inflammatory mediators and uremic toxins is a modality worth further investigation.
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Endotoxinas , Mediadores de Inflamación , Unidades de Cuidados Intensivos , Terapia de Reemplazo Renal , Choque Séptico , Tóxinas Urémicas , Humanos , Choque Séptico/mortalidad , Choque Séptico/sangre , Choque Séptico/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Endotoxinas/sangre , Mediadores de Inflamación/sangre , Tóxinas Urémicas/sangre , Terapia de Reemplazo Renal/métodos , Interleucina-6/sangreRESUMEN
BACKGROUND: Brain injury is one of the most serious complications after cardiac arrest (CA). To prevent this phenomenon, rapid cooling with total liquid ventilation (TLV) has been proposed in small animal models of CA (rabbits and piglets). Here, we aimed to determine whether hypothermic TLV can also offer neuroprotection and mitigate cerebral inflammatory response in large animals. METHODS AND RESULTS: Anesthetized pigs were subjected to 14 minutes of ventricular fibrillation followed by cardiopulmonary resuscitation. After return of spontaneous circulation, animals were randomly subjected to normothermia (control group, n=8) or ultrafast cooling with TLV (TLV group, n=8). In the latter group, TLV was initiated within a window of 15 minutes after return of spontaneous circulation and allowed to reduce tympanic, esophageal, and bladder temperature to the 32 to 34 °C range within 30 minutes. After 45 minutes of TLV, gas ventilation was resumed, and hypothermia was maintained externally until 3 hours after CA, before rewarming using heat pads (0.5 °C-1 °C/h). After an additional period of progressive rewarming for 3 hours, animals were euthanized for brain withdrawal and histological analysis. At the end of the follow-up (ie, 6 hours after CA), histology showed reduced brain injury as witnessed by the reduced number of Fluroro-Jade C-positive cerebral degenerating neurons in TLV versus control. IL (interleukin)-1ra and IL-8 levels were also significantly reduced in the cerebrospinal fluid in TLV versus control along with cerebral infiltration by CD3+ cells. Conversely, circulating levels of cytokines were not different among groups, suggesting a discrepancy between local and systemic inflammatory levels. CONCLUSIONS: Ultrafast cooling with TLV mitigates neuroinflammation and attenuates acute brain lesions in the early phase following resuscitation in large animals subjected to CA.
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Modelos Animales de Enfermedad , Paro Cardíaco , Hipotermia Inducida , Ventilación Liquida , Animales , Hipotermia Inducida/métodos , Paro Cardíaco/terapia , Ventilación Liquida/métodos , Porcinos , Factores de Tiempo , Reanimación Cardiopulmonar/métodos , Encéfalo/patología , Encéfalo/metabolismo , Neuroprotección , Citocinas/metabolismo , Citocinas/sangre , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/sangreRESUMEN
BACKGROUND: Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers? METHODS: We examined 162 South Asian and 107 Nordic women in Norway 1-3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP. RESULTS: The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26 (15-38) vs. 42 (22-66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1-4.4) vs. 1.2 (0.3-4.2) mg/L), IL-6 (2.3 (1.5-3.2) vs. 1.5 (1.5-2.5) pg/mL), leptin (1647 (1176-2480) vs. 1223 (876-2313) pmol/L), and lower adiponectin levels (7.2 (5.3-9.3) vs. 10.0 (7.2-13.5) mg/L) and Matsuda ISI (2.4 (1.7-3.7) vs. 4.2 (2.9-6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP. CONCLUSIONS: NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.
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Pueblo Asiatico , Biomarcadores , Diabetes Gestacional , Resistencia a la Insulina , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Humanos , Femenino , Péptido Natriurético Encefálico/sangre , Diabetes Gestacional/etnología , Diabetes Gestacional/sangre , Diabetes Gestacional/diagnóstico , Biomarcadores/sangre , Resistencia a la Insulina/etnología , Adulto , Fragmentos de Péptidos/sangre , Embarazo , Noruega/epidemiología , Glucemia/metabolismo , Insulina/sangre , Mediadores de Inflamación/sangre , Factores de Riesgo Cardiometabólico , Población Blanca , Medición de Riesgo , Factores de Tiempo , Adiponectina/sangre , Leptina/sangreRESUMEN
BACKGROUND: Heart failure is a chronic and progressive disease where the heart muscle is unable to pump enough blood and oxygen to meet the body's needs. Oxidative stress and inflammation are key elements in the development and progression of heart failure. Astaxanthin, a carotenoid, has strong anti-inflammatory and antioxidant effects that may protect the cardiovascular system. A study will evaluate the effect of astaxanthin supplementation on inflammatory status, oxidative stress, lipid profile, uric acid levels, endothelial function, quality of life, and disease symptoms in people with heart failure. METHODS: The current study is a double-blind controlled randomized clinical trial for 8 weeks, in which people with heart failure were randomly assigned to two groups: intervention (one capsule containing 20 mg of astaxanthin per day, n = 40) and placebo (one capsule containing 20 mg of maltodextrin per day, n = 40) will be divided. At the beginning and end of the intervention, uric acid, lipid profile, oxidative stress indices, inflammatory markers, blood pressure, nitric oxide, and anthropometric factors will be measured, and questionnaires measuring quality of life, fatigue intensity, shortness of breath, and appetite will be completed. SPSS version 22 software will be used for statistical analysis. DISCUSSION: There is a growing global interest in natural and functional food products. This RCT contributes to the expanding body of research on the potential benefits of astaxanthin in heart failure patients, including its antioxidant, lipid-lowering, and anti-inflammatory effects. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20200429047235N3. Registered on 26 March 2024.
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Biomarcadores , Presión Sanguínea , Suplementos Dietéticos , Insuficiencia Cardíaca , Estrés Oxidativo , Calidad de Vida , Ácido Úrico , Xantófilas , Humanos , Xantófilas/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/sangre , Ácido Úrico/sangre , Método Doble Ciego , Biomarcadores/sangre , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Persona de Mediana Edad , Masculino , Lípidos/sangre , Femenino , Antioxidantes , Anciano , Resultado del Tratamiento , Mediadores de Inflamación/sangre , Adulto , Inflamación/sangre , Antiinflamatorios/uso terapéutico , IránRESUMEN
BACKGROUND: Thermal ablation is a minimally invasive treatment for non-small cell lung cancer (NSCLC). Aside from causing an immediate direct tumour cell injury, the effects of thermal ablation on the internal microenvironment are unknown. This study aimed to investigate the effects of thermal ablation on the plasma internal environment in patients with NSCLC. METHODS: 128 plasma samples were collected from 48 NSCLC (pre [LC] and after thermal ablation [LC-T]) patients and 32 healthy controls (HCs). Olink proteomics and metabolomics were utilized to construct an integrated landscape of the cancer-related immune and inflammatory responses after ablation. RESULTS: Compared with HCs, LC patients exhibited 58 differentially expressed proteins (DEPs) and 479 differentially expressed metabolites (DEMs), which might participate in tumour progression and metastasis. Moreover, 75 DEPs were identified among the HC, LC, and LC-T groups. Forty-eight highly expressed DEPs (eg, programmed death-ligand 1 [PD-L1]) in the LC group were found to be downregulated after thermal ablation. These DEPs had significant impacts on pathways such as angiogenesis, immune checkpoint blockade, and pro-tumour chemotaxis. Metabolites involved in tumour cell survival were associated with these proteins at the expression and functional levels. In contrast, 19 elevated proteins (eg, interleukin [IL]-6) were identified after thermal ablation. These proteins were mainly associated with inflammatory response pathways (NF-κB signalling and tumour necrosis factor signalling) and immune cell activation. CONCLUSIONS: Thermal ablation-induced changes in the host plasma microenvironment contribute to anti-tumour immunity in NSCLC, offering new insights into tumour ablation combined with immunotherapy. Trial registration This study was registered on the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/index.html ). ID: ChiCTR2300076517. Registration Date: 2023-10-11.