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1.
Clin Transl Sci ; 17(7): e13872, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38949489

RESUMO

Physiological determinants of drug dosing (PDODD) are a promising approach for precision dosing. This study investigates the alterations of PDODD in diseases and evaluates a variational autoencoder (VAE) artificial intelligence model for PDODD. The PDODD panel contained 20 biomarkers, and 13 renal, hepatic, diabetes, and cardiac disease status variables. Demographic characteristics, anthropometric measurements (body weight, body surface area, waist circumference), blood (plasma volume, albumin), renal (creatinine, glomerular filtration rate, urine flow, and urine albumin to creatinine ratio), and hepatic (R-value, hepatic steatosis index, drug-induced liver injury index), blood cell (systemic inflammation index, red cell, lymphocyte, neutrophils, and platelet counts) biomarkers, and medical questionnaire responses from the National Health and Nutrition Examination Survey (NHANES) were included. The tabular VAE (TVAE) generative model was implemented with the Synthetic Data Vault Python library. The joint distributions of the generated data vs. test data were compared using graphical univariate, bivariate, and multidimensional projection methods and distribution proximity measures. The PDODD biomarkers related to disease progression were altered as expected in renal, hepatic, diabetes, and cardiac diseases. The continuous PDODD panel variables generated by the TVAE satisfactorily approximated the distribution in the test data. The TVAE-generated distributions of some discrete variables deviated from the test data distribution. The age distribution of TVAE-generated continuous variables was similar to the test data. The TVAE algorithm demonstrated potential as an AI model for continuous PDODD and could be useful for generating virtual populations for clinical trial simulations.


Assuntos
Biomarcadores , Cardiopatias , Nefropatias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Adulto , Hepatopatias/sangue , Hepatopatias/diagnóstico , Hepatopatias/metabolismo , Idoso , Doenças Metabólicas/diagnóstico , Inteligência Artificial , Inquéritos Nutricionais , Cálculos da Dosagem de Medicamento , Modelos Biológicos
2.
J Rheumatol ; 51(Suppl 1): 3-9, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950968

RESUMO

Rheumatoid arthritis (RA) is prevalent in many Indigenous North American First Nations (FN) and tends to be seropositive, familial, and disabling, as well as associated with highly unfavorable outcomes such as early mortality. The risk of developing RA is based on a perfect storm of gene-environment interactions underpinning this risk. The gene-environment interactions include a high frequency of shared epitope encoding HLA alleles, particularly HLA-DRB1*1402, in the background population, and prevalent predisposing environmental factors such as smoking and periodontal disease. Together, these provide a compelling rationale for an RA prevention agenda in FN communities. Our research team has worked in partnership with several FN communities to prospectively follow the first-degree relatives of FN patients with RA, with the aim of better understanding the preclinical stages of RA in this population. We have focused on specific features of the anticitrullinated protein antibodies (ACPA) and other proteomic biomarkers as predictors of future development of RA. These studies have now led us to consider interventions having a favorable risk-benefit ratio if applied at a stage prior to a hypothetical "point of no return," when the autoimmunity potentially becomes irreversible. Based on a supportive mouse model and available human studies of curcumin, omega-3, and vitamin D supplements, we are undertaking studies where we screen communities using dried blood spot technology adapted for the detection of ACPA, and then enrolling ACPA-positive individuals in studies that use a combination of these supplements. These studies are guided by shared decision-making principles.


Assuntos
Artrite Reumatoide , Humanos , Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/prevenção & controle , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Interação Gene-Ambiente , Cadeias HLA-DRB1 , Indígenas Norte-Americanos
3.
Front Endocrinol (Lausanne) ; 15: 1418835, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952391

RESUMO

Background: Blood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable biomarkers in the literature. The aim of this study was to assess the causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension (PAH). Methods: A two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between blood counts and biochemical indicators with PAH. The genome-wide association study (GWAS) for blood counts and biochemical indicators were obtained from the UK Biobank (UKBB), while the GWAS for PAH were sourced from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by three sensitivity analyses to assess the robustness of the results. And we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 2003-2018 to verify the relationship. Results: The MR analysis primarily using the IVW method revealed genetic variants of platelet count (OR=2.51, 95% CI 1.56-4.22, P<0.001), platelet crit(OR=1.87, 95% CI1.17-7.65, P=0.022), direct bilirubin (DBIL)(OR=1.71, 95%CI 1.18-2.47,P=0.004), insulin-like growth factor (IGF-1)(OR=0.51, 95% CI 0.27-0.96, P=0.038), Lipoprotein A (Lp(a))(OR=0.66, 95% CI 0.45-0.98, P=0.037) and total bilirubin (TBIL)(OR=0.51, 95% CI 0.27-0.96, P=0.038) were significantly associated with PAH. In NHANES, multivariate logistic regression analyses revealed a significant positive correlation between platelet count and volume and the risk of PAH, and a significant negative correlation between total bilirubin and PAH. Conclusion: Our study reveals a causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension. These findings offer novel insights into the etiology and pathological mechanisms of PAH, and emphasizes the important value of these markers as potential targets for the prevention and treatment of PAH.


Assuntos
Biomarcadores , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/epidemiologia , Adulto , Contagem de Células Sanguíneas , Polimorfismo de Nucleotídeo Único , Idoso , Bilirrubina/sangue , Contagem de Plaquetas
4.
Front Immunol ; 15: 1400526, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38953032

RESUMO

Background: Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks. Methods: Patients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients F12 gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured. Results: Seventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6-88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for D-dimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 vs. baseline) and D-dimer in 71% (p=0.001 vs. baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p<0. 0001), ESR (p<0.0001) and D-dimer (p= 0.004). No significant differences were observed in CRP (p=0.7), ACE (p=0.67) and WCC (p=0.54). These findings remained consistent regardless of HAE type, disease activity or location of angioedema. Conclusion: The systemic increase in APR observed during HAE attacks suggests that inflammation extends beyond the localized edematous area. This finding underscores the potential involvement of inflammatory pathways in HAE and highlights the need for further investigation into their role in the pathophysiology of HAE.


Assuntos
Angioedemas Hereditários , Biomarcadores , Inflamação , Humanos , Feminino , Masculino , Adulto , Angioedemas Hereditários/sangue , Angioedemas Hereditários/diagnóstico , Pessoa de Meia-Idade , Biomarcadores/sangue , Idoso , Inflamação/sangue , Adolescente , Criança , Adulto Jovem , Idoso de 80 Anos ou mais , Proteína Inibidora do Complemento C1/genética , Proteína Inibidora do Complemento C1/metabolismo , Proteína Amiloide A Sérica/metabolismo , Fator XII/genética , Fator XII/metabolismo , Sedimentação Sanguínea , Mediadores da Inflamação/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/análise
5.
Med Sci Monit ; 30: e943375, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38956840

RESUMO

BACKGROUND The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) increases together with the epidemic of childhood obesity. An important mechanism in the phenomenon appears to be insulin resistance (IR), the assessment of which in children is problematic. The homeostatic model assessment of IR (HOMA-IR), commonly used for this, is not standardized and appears not to correlate with IR in the pediatric population. Therefore, our study aimed to evaluate potential substitute indices of IR, including the triglyceride-glucose index (TyG), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), modified TyG indices: TyG-waist circumference (TyG-WC) and TyG-body mass index (TyG-BMI) as surrogate markers of MAFLD in obese children suspected to have liver disease. MATERIAL AND METHODS The retrospective study included 264 obese children admitted to the Department to diagnose suspected liver disease. MAFLD was diagnosed according to the International Expert Consensus Statement. Anthropometric measurements and laboratory tests were made and the indices were calculated. Receiver operating characteristics analysis was performed to calculate the power of the indices. RESULTS MAFLD was diagnosed in 184 patients (70%). Obese children with MAFLD showed significantly higher activity of liver enzymes and concentration of total cholesterol, TG, WC, and waist-to-hip ratio compared to non-hepatopathic obese controls (n=80). The most important indices in identifying MAFLD were: TyG (AUC=0.641, p<0.001, cut-off =8.41, sensitivity=57.4%, specificity=68.8%), and TG/HDL-C (AUC=0.638, p<0.001, cut-off=2.5, sensitivity=48.6%, specificity=76.3%). TyG-BMI and HOMA-IR were not useful predictors. CONCLUSIONS TyG and TG/HDL-C can be considered as potential surrogate biomarkers in predicting MAFLD in obese children.


Assuntos
Índice de Massa Corporal , Resistência à Insulina , Sobrepeso , Obesidade Infantil , Triglicerídeos , Humanos , Criança , Masculino , Feminino , Triglicerídeos/sangue , Obesidade Infantil/sangue , Obesidade Infantil/complicações , Sobrepeso/sangue , Sobrepeso/complicações , Adolescente , Estudos Retrospectivos , Glicemia/metabolismo , Glicemia/análise , Obesidade/complicações , Obesidade/sangue , Obesidade/metabolismo , Antropometria/métodos , Circunferência da Cintura , HDL-Colesterol/sangue , Curva ROC , Biomarcadores/sangue , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações
6.
Scand Cardiovasc J ; 58(1): 2373090, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38957080

RESUMO

OBJECTIVES: Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE. DESIGN: All Swedish patients diagnosed with acute PE in 2005 (n = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 (n = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration. RESULTS: Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels. CONCLUSIONS: We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.


Assuntos
Biomarcadores , Dispneia , Eletrocardiografia , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Valor Preditivo dos Testes , Embolia Pulmonar , Sistema de Registros , Humanos , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/fisiopatologia , Fragmentos de Peptídeos/sangue , Masculino , Feminino , Peptídeo Natriurético Encefálico/sangue , Suécia/epidemiologia , Biomarcadores/sangue , Idoso , Estudos Prospectivos , Dispneia/sangue , Dispneia/diagnóstico , Dispneia/epidemiologia , Dispneia/fisiopatologia , Dispneia/etiologia , Pessoa de Meia-Idade , Fatores de Tempo , Prevalência , Disfunção Ventricular Direita/sangue , Disfunção Ventricular Direita/fisiopatologia , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/etiologia , Fatores de Risco , Idoso de 80 Anos ou mais , Prognóstico , Função Ventricular Direita , Bloqueio de Ramo/sangue , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/epidemiologia , Bloqueio de Ramo/fisiopatologia
7.
J Cell Mol Med ; 28(13): e18522, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957040

RESUMO

Bone non-union is a common fracture complication that can severely impact patient outcomes, yet its mechanism is not fully understood. This study used differential analysis and weighted co-expression network analysis (WGCNA) to identify susceptibility modules and hub genes associated with fracture healing. Two datasets, GSE125289 and GSE213891, were downloaded from the GEO website, and differentially expressed miRNAs and genes were analysed and used to construct the WGCNA network. Gene ontology (GO) analysis of the differentially expressed genes showed enrichment in cytokine and inflammatory factor secretion, phagocytosis, and trans-Golgi network regulation pathways. Using bioinformatic site prediction and crossover gene search, miR-29b-3p was identified as a regulator of LIN7A expression that may negatively affect fracture healing. Potential miRNA-mRNA interactions in the bone non-union mechanism were explored, and miRNA-29-3p and LIN7A were identified as biomarkers of skeletal non-union. The expression of miRNA-29b-3p and LIN7A was verified in blood samples from patients with fracture non-union using qRT-PCR and ELISA. Overall, this study identified characteristic modules and key genes associated with fracture non-union and provided insight into its molecular mechanisms. Downregulated miRNA-29b-3p was found to downregulate LIN7A protein expression, which may affect the healing process after fracture in patients with bone non-union. These findings may serve as a prognostic biomarker and potential therapeutic target for bone non-union.


Assuntos
Biomarcadores , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/sangue , Biomarcadores/sangue , Redes Reguladoras de Genes , Consolidação da Fratura/genética , Perfilação da Expressão Gênica , Biologia Computacional/métodos , Feminino , Masculino , Ontologia Genética , Regulação da Expressão Gênica , Fraturas não Consolidadas/genética , Pessoa de Meia-Idade
8.
Front Immunol ; 15: 1416476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962007

RESUMO

Human T-Lymphotropic Virus type-1 (HTLV-1) is a unique retrovirus associated with both leukemogenesis and a specific neuroinflammatory condition known as HTLV-1-Associated Myelopathy (HAM). Currently, most proposed HAM biomarkers require invasive CSF sampling, which is not suitable for large cohorts or repeated prospective screening. To identify non-invasive biomarkers for incident HAM in a large Brazilian cohort of PLwHTLV-1 (n=615 with 6,673 person-years of clinical follow-up), we selected all plasma samples available at the time of entry in the cohort (between 1997-2019), in which up to 43 cytokines/chemokines and immune mediators were measured. Thus, we selected 110 People Living with HTLV-1 (PLwHTLV-1), of which 68 were neurologically asymptomatic (AS) at baseline and 42 HAM patients. Nine incident HAM cases were identified among 68 AS during follow-up. Using multivariate logistic regression, we found that lower IL-10, IL-4 and female sex were independent predictors of clinical progression to definite HAM (AUROC 0.91), and outperformed previously suggested biomarkers age, sex and proviral load (AUROC 0.77). Moreover, baseline IL-10 significantly predicted proviral load dynamics at follow-up in all PLwHTLV-1. In an exploratory analysis, we identified additional plasma biomarkers which were able to discriminate iHAM from either AS (IL6Rα, IL-27) or HAM (IL-29/IFN-λ1, Osteopontin, and TNFR2). In conclusion, female sex and low anti-inflammatory IL-10 and IL-4 are independent risk factors for incident HAM in PLwHTLV-1,while proviral load is not, in agreement with IL-10 being upstream of proviral load dynamics. Additional candidate biomarkers IL-29/IL-6R/TNFR2 represent plausible therapeutic targets for future clinical trials in HAM patients.


Assuntos
Biomarcadores , Vírus Linfotrópico T Tipo 1 Humano , Interleucina-10 , Carga Viral , Humanos , Feminino , Masculino , Brasil/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Interleucina-10/sangue , Biomarcadores/sangue , Pessoa de Meia-Idade , Adulto , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/sangue , Infecções por HTLV-I/diagnóstico , Provírus , Estudos de Coortes , Paraparesia Espástica Tropical/sangue , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/virologia , Incidência
9.
Front Endocrinol (Lausanne) ; 15: 1308841, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962681

RESUMO

Background: Untargeted metabonomics has provided new insight into the pathogenesis of sarcopenia. In this study, we explored plasma metabolic signatures linked to a heightened risk of sarcopenia in a cohort study by LC-MS-based untargeted metabonomics. Methods: In this nested case-control study from the Adult Physical Fitness and Health Cohort Study (APFHCS), we collected blood plasma samples from 30 new-onset sarcopenia subjects (mean age 73.2 ± 5.6 years) and 30 healthy controls (mean age 74.2 ± 4.6 years) matched by age, sex, BMI, lifestyle, and comorbidities. An untargeted metabolomics methodology was employed to discern the metabolomic profile alterations present in individuals exhibiting newly diagnosed sarcopenia. Results: In comparing individuals with new-onset sarcopenia to normal controls, a comprehensive analysis using liquid chromatography-mass spectrometry (LC-MS) identified a total of 62 metabolites, predominantly comprising lipids, lipid-like molecules, organic acids, and derivatives. Receiver operating characteristic (ROC) curve analysis indicated that the three metabolites hypoxanthine (AUC=0.819, 95% CI=0.711-0.927), L-2-amino-3-oxobutanoic acid (AUC=0.733, 95% CI=0.598-0.868) and PC(14:0/20:2(11Z,14Z)) (AUC= 0.717, 95% CI=0.587-0.846) had the highest areas under the curve. Then, these significant metabolites were observed to be notably enriched in four distinct metabolic pathways, namely, "purine metabolism"; "parathyroid hormone synthesis, secretion and action"; "choline metabolism in cancer"; and "tuberculosis". Conclusion: The current investigation elucidates the metabolic perturbations observed in individuals diagnosed with sarcopenia. The identified metabolites hold promise as potential biomarkers, offering avenues for exploring the underlying pathological mechanisms associated with sarcopenia.


Assuntos
Metabolômica , Sarcopenia , Humanos , Sarcopenia/metabolismo , Sarcopenia/sangue , Masculino , Metabolômica/métodos , Feminino , Idoso , Estudos de Casos e Controles , Cromatografia Líquida/métodos , Biomarcadores/sangue , Estudos de Coortes , Metaboloma , Idoso de 80 Anos ou mais , Espectrometria de Massas/métodos , Fatores de Risco , Hipoxantina/sangue , Hipoxantina/metabolismo , Espectrometria de Massa com Cromatografia Líquida
10.
Age Ageing ; 53(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38965031

RESUMO

BACKGROUND: The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD). METHODS: In the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75 years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50-70 mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation. RESULTS: Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75 years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75 years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P < 0.001). The mean LDL-C level for three years was 65 ± 16 mg/dl in the treat-to-target strategy group and 64 ± 18 mg/dl in the high-intensity statin group (P = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61-1.38, P = 0.69). CONCLUSIONS: High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50-70 mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579499.


Assuntos
LDL-Colesterol , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Idoso , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Masculino , Feminino , LDL-Colesterol/sangue , Resultado do Tratamento , Fatores Etários , Idoso de 80 Anos ou mais , Fatores de Risco , Biomarcadores/sangue , Pessoa de Meia-Idade , Fatores de Tempo , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia
11.
Artigo em Chinês | MEDLINE | ID: mdl-38965847

RESUMO

Objective: To analyze the characteristics of patients with chronic rhinosinusitis (CRS) in the South China region based on pathological tissue biomarkers for regional comparison. Methods: The study population consisted of CRS in-patients in the First Affiliated Hospital of Sun Yat-sen University from October 2019 to June 2022. Among all the 181 cases, 123 of them were male and 58 were female, with an average age of 40. Retrospectively collected clinical data included demographic information, preoperative symptom scores, preoperative endoscopic images, preoperative paranasal sinus computed tomography scanning images, and inflammatory serological features. In addition, 52 variables of pathological tissue biomarkers including cytokines, chemokines and remodeling factors were collected for analysis. Cluster analysis was performed on the integrated data of training set through centroid-based clustering algorithm, and the inflammatory characteristics, post-operation control status, and airway diseases comorbidity of each endotype were analyzed. R project (version 4.2.2) was used in statistical analysis. Results: Cluster analysis divided 181 patients with CRS into 4 endotypes. Cluster 1 (n=101, 55.80%) showed a locally low inflammatory status. Cluster 2 (n=23, 12.71%) showed a mixed type of inflammation with predominantly neutrophilic inflammation and tissue remodeling. Cluster 3 (n=11, 6.08%) was characterized by type Ⅱ inflammation without tissue remodeling. Cluster 4 (n=46, 25.41%) was mainly characterized by type Ⅱ inflammation with tissue remodeling, showing higher comorbidity rate of asthma and allergic rhinitis. This cluster presented more severe symptoms, significant olfactory dysfunction, extensive overall inflammation based on objective examination results, a notable increase in total eosinophil count and proportion in peripheral blood, and the highest uncontrolled rate observed one year post-surgery. In comparison to other regions, the endotype classification of CRS in Southern China was characterized by a predominant pattern of locally low inflammatory status, a moderate level of type Ⅱ inflammation with tissue remodeling, and a lesser presence of neutrophilic inflammation. Conclusion: CRS distribution in Southern China is mainly characterized by low inflammatory endotype and type Ⅱ inflammation with tissue remodeling. The latter shows more severe clinical manifestations and higher uncontrol rate after surgery.


Assuntos
Biomarcadores , Inflamação , Rinite , Sinusite , Humanos , Sinusite/diagnóstico , Sinusite/classificação , Masculino , Feminino , Adulto , Doença Crônica , Biomarcadores/sangue , Estudos Retrospectivos , Rinite/classificação , China/epidemiologia , Citocinas/sangue , Citocinas/metabolismo , Análise por Conglomerados , Pessoa de Meia-Idade , Seios Paranasais/patologia , Tomografia Computadorizada por Raios X , Rinossinusite
12.
Clin Lab ; 70(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38965954

RESUMO

BACKGROUND: BNP is a sensitive and widely used biomarker for an early diagnosis of heart failure. Currently, most commercial BNP detection products use EDTA plasma samples. The aim of this study was to evaluate the clinical performance of the BNP test by using whole blood samples compared to plasma samples, and to evaluate the effect of the anticoagulant type on the BNP test result. METHODS: In total, 106 patients with different BNP levels from the Dahua Hospital volunteered for this study. Clinically homogenous samples, including EDTA anticoagulant plasma, EDTA whole blood, and heparin anticoagulant plasma, were collected and analyzed by using i-Reader S automatic immuno-analyzer and its supporting reagent kits. Pearson's correlation and weighted least squares linear regression analysis, Bland-Altman plotting, and Kappa test were used for statistical analysis. RESULTS: Correlation analysis showed that BNP concentrations, measured from EDTA anticoagulated plasma samples, had a good linear regression relationship with BNP from whole blood samples, with a slope of 0.9477, r = 0.9978, p < 0.05. A similar correlation was observed between EDTA anticoagulated plasma samples and heparin anticoagulant plasma, with a slope of 0.8413, r = 0.9793, p < 0.05. The BNP concentration measured from the heparin plasma samples were lower than of the EDTA plasma samples. Bland-Altman analysis for assessing BNP concentration agreement showed there was no outlier ratio between EDTA whole blood and EDTA plasma within the range of the detection system, as well as no outlier between EDTA anticoagulated and heparin anticoagulant plasma. Kappa coefficient of BNP concentration between homologous EDTA anticoagulated and heparin anticoagulant plasma was 0.8553 (p < 0.001), and for EDTA anticoagulated plasma and homologous whole blood it was 0.8941 (p < 0.001). CONCLUSIONS: The diagnostic performance of EDTA anticoagulated whole blood samples did not differ significantly from EDTA anticoagulated plasma samples for the BNP test. This study showed no big significant difference between EDTA anticoagulated and heparin anticoagulated plasma measurements within 2 hours. The type of anticoagulant should be carefully chosen when performing the BNP test if BNP samples were in vitro for a long time.


Assuntos
Anticoagulantes , Ácido Edético , Heparina , Peptídeo Natriurético Encefálico , Humanos , Peptídeo Natriurético Encefálico/sangue , Anticoagulantes/farmacologia , Anticoagulantes/sangue , Heparina/farmacologia , Ácido Edético/farmacologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Coleta de Amostras Sanguíneas/métodos , Biomarcadores/sangue , Modelos Lineares , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Reprodutibilidade dos Testes
13.
Clin Lab ; 70(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38965968

RESUMO

BACKGROUND: European Society of Cardiology (ESC) guidelines recommend measuring natriuretic peptides (BNP or NT-proBNP) in patients with suspected heart failure (HF) as a first-line tool. HF should be ruled-out if concen-trations of NT-proBNP are below 300 ng/L and 125 ng/L for acute HF and chronic HF, respectively. METHODS: Patients with suspected HF referred for transthoracic echocardiography (TTE) were enrolled; NT-pro-BNP concentrations were obtained from medical charts (measurement < 48 hours) or prospectively measured on the day of TTE. RESULTS: Out of 109 patients, NT-proBNP was measured by the referring department before TTE in 40 patients (36.7%), and 37.5% of these patients had NT-proBNP concentration below the rule-out threshold. NT-proBNP was measured in additional 38 patients on the day of TTE. Overall, 38.5% of the patients had a NT-proBNP concentration below the threshold value. CONCLUSIONS: Natriuretic peptides are not routinely measured in patients with suspected HF; systematic measurement would reduce unnecessary TTE by at least 38.5%.


Assuntos
Ecocardiografia , Insuficiência Cardíaca , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Humanos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Projetos Piloto , Feminino , Masculino , Ecocardiografia/métodos , Peptídeo Natriurético Encefálico/sangue , Idoso , Fragmentos de Peptídeos/sangue , Pessoa de Meia-Idade , Biomarcadores/sangue , Idoso de 80 Anos ou mais , Estudos Prospectivos , Peptídeos Natriuréticos/sangue
14.
Pediatr Allergy Immunol ; 35(7): e14187, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967090

RESUMO

BACKGROUND: The immunological mechanisms behind the clinical association between asthma and obesity in adolescence are not fully understood. This study aimed to find new plasma protein biomarkers associated specifically with coincident asthma and obesity in adolescents. METHODS: This was a cross-sectional study in children and adolescents 10-19 years old (N = 390). Relative plasma concentrations of 113 protein biomarkers related to inflammation and immune response were determined by proximity extension assay (Target 96; Olink, Uppsala, Sweden). Differences in protein concentrations between healthy controls (n = 84), subjects with asthma (n = 138), subjects with obesity (n = 107), and subjects with both asthma and obesity (AO; n = 58) were analyzed by ANCOVA, adjusting for age and sex, and in a separate model adjusting also for the sum of specific IgE antibody concentrations to a mix of food allergens (fx5) and aeroallergens (Phadiatop). Proteins elevated in the AO group but not in the obesity or asthma groups were considered specifically elevated in asthma and obesity. RESULTS: Five proteins were elevated specifically in the AO group compared to controls (here sorted from largest to smallest effect of asthma and obesity combined): CCL8, IL-33, IL-17C, FGF-23, and CLEC7A. The effects of adjusting also for specific IgE were small but IL-33, IL-17C, and FGF-23 were no longer statistically significant. CONCLUSION: We identified several new potential plasma biomarkers specifically elevated in coincident asthma and obesity in adolescents. Four of the proteins, CCL8, IL-33, IL-17C, and CLEC7A, have previously been associated with viral mucosal host defense and Th17 cell differentiation.


Assuntos
Asma , Biomarcadores , Proteínas Sanguíneas , Diferenciação Celular , Células Th17 , Humanos , Asma/imunologia , Asma/sangue , Asma/diagnóstico , Adolescente , Feminino , Masculino , Células Th17/imunologia , Criança , Estudos Transversais , Biomarcadores/sangue , Adulto Jovem , Obesidade/imunologia , Obesidade/sangue , Imunoglobulina E/sangue
15.
J Dig Dis ; 25(5): 285-297, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38946678

RESUMO

OBJECTIVES: Iron metabolism and insulin resistance (IR) are closely related to non-alcoholic fatty liver disease (NAFLD). However, the interplay between them on the occurrence and progression of NAFLD is not fully understood. We aimed to disentangle the crosstalk between iron metabolism and IR and explore its impact on NAFLD. METHODS: We analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018 to evaluate the association between serum iron metabolism indicators (ferritin, serum iron, unsaturated iron-binding capacity [UIBC], total iron-binding capacity [TIBC], transferrin saturation, and transferrin receptor) and NAFLD/non-alcoholic steatohepatitis (NASH). Mediation analysis was conducted to explore the role of IR played in these relationship. RESULTS: A total of 4812 participants were included, among whom 43.7% were diagnosed with NAFLD and 13.2% were further diagnosed with NASH. After adjusting the covariates, the risk of NAFLD increases with increasing serum ferritin (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.37-2.14), UIBC (aOR 1.45, 95% CI 1.17-1.79), and TIBC (aOR 1.36, 95% CI 1.11-1.68). Higher levels of serum ferritin (aOR 3.70, 95% CI 2.25-6.19) and TIBC (aOR 1.69, 95% CI 1.13-2.56) were also positively associated with NASH. Participants with IR were more likely to have NAFLD/NASH. Moreover, IR-mediated efficacy accounted for 85.85% and 64.51% between ferritin and NAFLD and NASH, respectively. CONCLUSION: Higher levels of serum ferritin and TIBC are closely associated with the occurrence of NAFLD and NASH. IR may be considered a possible link between NAFLD or NASH and increased serum ferritin levels.


Assuntos
Ferritinas , Resistência à Insulina , Ferro , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/metabolismo , Resistência à Insulina/fisiologia , Masculino , Feminino , Ferritinas/sangue , Ferro/sangue , Ferro/metabolismo , Pessoa de Meia-Idade , Adulto , Inquéritos Nutricionais , Análise de Mediação , Estudos Transversais , Receptores da Transferrina/sangue , Biomarcadores/sangue
16.
Hepatol Commun ; 8(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38967589

RESUMO

BACKGROUND: Novel noninvasive predictors of disease severity and prognosis in primary sclerosing cholangitis (PSC) are needed. This study evaluated the ability of extracellular matrix remodeling markers to diagnose fibrosis stage and predict PSC-related fibrosis progression and clinical events. METHODS: Liver histology and serum markers of collagen formation (propeptide of type III collagen [Pro-C3], propeptide of type IV collagen, propeptide of type V collagen), collagen degradation (type III collagen matrix metalloproteinase degradation product and type IV collagen matrix metalloproteinase degradation product), and fibrosis (enhanced liver fibrosis [ELF] score and its components [metalloproteinase-1, type III procollagen, hyaluronic acid]) were assessed in samples from baseline to week 96 in patients with PSC enrolled in a study evaluating simtuzumab (NCT01672853). Diagnostic performance for advanced fibrosis (Ishak stages 3-6) and cirrhosis (Ishak stages 5-6) was evaluated by logistic regression and AUROC. Prognostic performance for PSC-related clinical events and fibrosis progression was assessed by AUROC and Wilcoxon rank-sum test. RESULTS: Among 234 patients, 51% had advanced fibrosis and 11% had cirrhosis at baseline. Baseline Pro-C3 and ELF score and its components provided moderate diagnostic ability for discrimination of advanced fibrosis (AUROC 0.73-0.78) and cirrhosis (AUROC 0.73-0.81). Baseline Pro-C3, ELF score, and type III procollagen provided a moderate prognosis for PSC-related clinical events (AUROC 0.70-0.71). Among patients without cirrhosis at baseline, median changes in Pro-C3 and ELF score to week 96 were higher in those with than without progression to cirrhosis (both p < 0.001). CONCLUSIONS: Pro-C3 correlated with fibrosis stage, and Pro-C3 and ELF score provided discrimination of advanced fibrosis and cirrhosis and predicted PSC-related events and fibrosis progression. The results support the clinical utility of Pro-C3 and ELF score for staging and as prognostic markers in PSC.


Assuntos
Anticorpos Monoclonais Humanizados , Biomarcadores , Colangite Esclerosante , Progressão da Doença , Matriz Extracelular , Cirrose Hepática , Humanos , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/sangue , Colangite Esclerosante/patologia , Masculino , Feminino , Biomarcadores/sangue , Prognóstico , Adulto , Cirrose Hepática/sangue , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Matriz Extracelular/patologia , Índice de Gravidade de Doença , Ácido Hialurônico/sangue , Fígado/patologia
17.
Sci Rep ; 14(1): 15499, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969755

RESUMO

The triglyceride-glucose (TyG) index is a simple and inexpensive new marker of insulin resistance that is being increasingly used for the clinical prediction of metabolic syndrome (MetS). Nevertheless, there are only a few comparative studies on its predictive capacity for MetS versus those using the traditional homeostasis model assessment (HOMA). We conducted a cross-sectional study using a database from the National Health and Nutrition Examination Survey (1999 March to 2020 pre-pandemic period). Using statistical methods, we compared the predictive abilities of the TyG index and HOMA (including HOMA of insulin resistance [HOMA-IR] and HOMA of beta-cell function [HOMA-ß]) for MetS. A total of 34,195 participants were enrolled and divided into the MetS group (23.1%) or no MetS group (76.9%) according to the International Diabetes Federation (IDF) diagnostic criteria. After applying weighted data, the baseline characteristics of the population were described. Following the exclusion of medication influences, the final count was 31,304 participants. Receiver operating characteristic curve analysis revealed that while distinguishing between MetS and no MetS, the TyG index had an area under the curve (AUC) of 0.827 (sensitivity = 71.9%, specificity = 80.5%), and the cutoff was 8.75, slightly outperforming HOMA-IR (AUC = 0.784) and HOMA-ß (AUC = 0.614) with a significance of P < 0.01. The prevalence of MetS in the total population calculated using the TyG index cutoff value was 30.9%, which was higher than that reported in the IDF diagnostic criteria. Weighted data analysis using univariate and multivariate logistic regression displayed an independent association between elevated TyG and HOMA-IR with the risk of MetS. Subgroup analysis further revealed differences in the predictive ability of the TyG index among adult populations across various genders and ethnicities, whereas such differences were not observed for children and adolescents. The TyG index is slightly better than HOMA in predicting MetS and may identify more patients with MetS; thus, its applications in a clinical setting can be appropriately increased.


Assuntos
Glicemia , Homeostase , Resistência à Insulina , Síndrome Metabólica , Inquéritos Nutricionais , Triglicerídeos , Humanos , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Masculino , Feminino , Triglicerídeos/sangue , Pessoa de Meia-Idade , Glicemia/análise , Glicemia/metabolismo , Estudos Transversais , Adulto , Curva ROC , Biomarcadores/sangue , Idoso
18.
BMC Vet Res ; 20(1): 292, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970022

RESUMO

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a crucial heart disease in cats. The clinical manifestations of HCM comprise pulmonary edema, dyspnea, syncope, arterial thromboembolism (ATE), and sudden cardiac death. D-dimer and prothrombin time (PT) are powerful biomarkers used to assess coagulation function. Dysregulation in these two biomarkers may be associated with HCM in cats. This study aims to assess D-dimer levels, PT, and proteomic profiling in healthy cats in comparison to cats with symptomatic HCM. RESULTS: Twenty-nine client-owned cats with HCM were enrolled, including 15 healthy control and 14 symptomatic HCM cats. The D-dimer concentration and PT were examined. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In symptomatic cats, D-dimer levels were statistically significantly higher (mean ± SEM: 372.19 ng/ml ± 58.28) than in healthy cats (mean ± SEM: 208.54 ng/ml ± 10.92) with P-value of less than 0.01, while PT was statistically significantly lower in symptomatic cats (mean ± SEM: 9.8 s ± 0.15) compared to healthy cats (mean ± SEM: 11.08 s ± 0.23) with P-value of less than 0.0001. The proteomics analysis revealed upregulation of integrin subunit alpha M (ITGAM), elongin B (ELOB), and fibrillin 2 (FBN2) and downregulation of zinc finger protein 316 (ZNF316) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in symptomatic HCM cats. In addition, protein-drug interaction analysis identified the Ras signaling pathway and PI3K-Akt signaling pathway. CONCLUSIONS: Cats with symptomatic HCM have higher D-dimer and lower PT than healthy cats. Proteomic profiles may be used as potential biomarkers for the detection and management of HCM in cats. The use of D-dimer as a biomarker for HCM detection and the use of proteomic profiling for a better understanding of disease mechanisms remain to be further studied in cats.


Assuntos
Cardiomiopatia Hipertrófica , Doenças do Gato , Produtos de Degradação da Fibrina e do Fibrinogênio , Proteômica , Animais , Gatos , Doenças do Gato/sangue , Cardiomiopatia Hipertrófica/veterinária , Cardiomiopatia Hipertrófica/sangue , Masculino , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Coagulação Sanguínea/fisiologia , Tempo de Protrombina/veterinária , Biomarcadores/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/veterinária , Espectrometria de Massas em Tandem/veterinária
19.
Skin Res Technol ; 30(7): e13822, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38970783

RESUMO

PURPOSE: In present, the diagnosis of psoriasis is mainly based on the patient's typical clinical manifestations, dermoscopy and skin biopsy, and unlike other immune diseases, psoriasis lacks specific indicators in the blood. Therefore, we are required to search novel biomarkers for the diagnosis of psoriasis. METHODS: In this study, we analyzed the composition and the differences of intestinal fungal communities composition between psoriasis patients and healthy individuals in order to find the intestinal fungal communities associated with the diagnosis of psoriasis. We built a machine learning model and identified potential microbial markers for the diagnosis of psoriasis. RESULTS: The results of AUROC (area under ROC) showed that Aspergillus puulaauensis (AUROC = 0.779), Kazachstania africana (AUROC = 0.750) and Torulaspora delbrueckii (AUROC = 0.745) had high predictive ability (AUROC > 0.7) for predicting psoriasis, While Fusarium keratoplasticum (AUROC = 0.670) was relatively lower (AUROC < 0.7). CONCLUSION: The strategy based on the prediction of intestinal fungal communities provides a new idea for the diagnosis of psoriasis and is expected to become an auxiliary diagnostic method for psoriasis.


Assuntos
Biomarcadores , Microbioma Gastrointestinal , Metagenômica , Micobioma , Psoríase , Humanos , Psoríase/microbiologia , Psoríase/sangue , Feminino , Adulto , Masculino , Biomarcadores/sangue , Metagenômica/métodos , Pessoa de Meia-Idade , Aprendizado de Máquina , Fezes/microbiologia , Adulto Jovem , Aspergillus
20.
Int J Rheum Dis ; 27(7): e15254, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38973340

RESUMO

AIM: To evaluate whether seasonal changes influence fluctuations in serum Krebs von den Lungen-6 (KL-6) levels in systemic sclerosis-related interstitial lung disease (SSc-ILD). METHODS: Summer was defined as the period between July and September, and winter as between December and February. The study was conducted between 2015 and 2016, with a focus on these two seasons. A diagnosis of ILD and ILD progression overtime were evaluated using chest computed tomography. Among patients with SSc-ILD, those with data on serum KL-6 and lactate dehydrogenase (LDH) levels in the 2015 winter, 2015 summer, and 2016 winter seasons were included. Patients with comorbidities that could affect serum KL-6 levels were excluded. RESULTS: Of 60 patients with SSc-ILD, 52 (86.7%) had stable ILD, 5 (8.3%) had worsened ILD, and 3 (5.0%) had improved ILD. Serum KL-6 levels were significantly higher during the winter than those during the summer (2015 winter vs. 2015 summer: 649 U/mL vs. 585 U/mL, p < .0001; 2016 winter vs. 2015 summer: 690 U/mL vs. 585 U/mL, p < .0001). No significant differences were observed between the winters of 2015 and 2016 (649 U/mL vs. 690 U/mL, p = .78). However, serum LDH levels did not exhibit seasonal fluctuations (2015 winter vs. 2015 summer: 203 U/L vs. 199 U/L, p = .3; 2016 winter vs. 2015 summer: 201 U/L vs. 199 U/L, p = .6; 2015 winter vs. 2016 winter: 203 U/L vs. 201 U/L, p = .24). CONCLUSION: Seasonal fluctuations in serum KL-6 levels were observed in patients with SSc-ILD.


Assuntos
Biomarcadores , Doenças Pulmonares Intersticiais , Mucina-1 , Escleroderma Sistêmico , Estações do Ano , Humanos , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Mucina-1/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Idoso , Fatores de Tempo , Progressão da Doença , Adulto , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Regulação para Cima
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