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1.
PLoS One ; 19(3): e0296668, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38507367

RESUMO

OBJECTIVES: Patients with COVID-19 infection appear to develop virus-induced hypercoagulability resulting in numerous thrombotic events. The aim of the present study was to determine the relationship between the thrombophilia genes mutations (prothrombin G20210A, factor V Leiden, and methyltetrahydrofolate reductase (MTHFR)) and the severity of COVID-19 patients. DESIGN: Prospective cross-sectional study. METHOD: One hundred and forty patients (80 adults and 60 children) were included in the current study. They were divided into the severe COVID-19 group and the mild COVID-19 group, with each group comprising 40 adults and 30 children. The patients were assessed for FV R506Q, FV R2H1299R, MTHFR A1298C, MTHFR C677T, and prothrombin gene G20210A polymorphisms. CBC, D-dimer, renal and liver function tests, hs-CRP, ferritin, and LDH were also assessed. Thrombotic events were clinically and radiologically documented. RESULTS: Severe COVID-19 cases were significantly more frequent to have a heterozygous mutation for all the studied genes compared to mild COVID-19 cases (p<0.05 for all). Being mutant to gene FV R506Q carried the highest risk of developing a severe disease course (p<0.0001). Patients with abnormally high D-dimer levels were significantly more frequent to be heterozygous for FV R506Q, FV R2H1299R, and prothrombin gene G20210A (p = 0.006, 0.007, and 0.02, respectively). CONCLUSION: We concluded that there is an evident relationship between severe COVID-19 and inherited thrombophilia. In the current study, FV R506Q gene mutation carried the highest risk of developing a severe COVID-19 disease course.


Assuntos
COVID-19 , Trombofilia , Trombose , Adulto , Criança , Humanos , Estudos Prospectivos , Protrombina/genética , Estudos Transversais , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , COVID-19/genética , Mutação , Trombofilia/complicações , Trombofilia/genética , Trombose/genética , Gravidade do Paciente , Fator V/genética
2.
Cancer Med ; 13(3): e6825, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38361401

RESUMO

AIM: The aim of our study was to evaluate the accuracy of serum biomarkers (AFP/PIVKA-II) and their combination in HCC diagnosis among Caucasian cirrhotic patients. METHODS: Serum AFP/PIVKA-II levels were evaluated in 218 cirrhotics (163 males, 118 CTP-A, 66 ALBI-I, 111 with varices, 63 with diabetes) with (n = 90) or without (n = 128) HCC. Patients with HCC were categorized to BCLC Stage 0/A (n = 12), B (n = 21), C (n = 48), and D (n = 9). RESULTS: The two groups were comparable for all baseline parameters except for age, platelets, and diabetes presence. Median levels of AFP (239.1 vs. 4.0 ng/mL) and PIVKA-II (4082.7 vs. 45.8 mAU/mL) were both significantly higher in HCC group compared to controls (p < 0.001). AUROC and cutoff value for HCC diagnosis were 88%/12.35 ng/mL (AFP) and 84.4%/677.13 mAU/mL (PIVKA-II), whereas their combination showed better diagnostic accuracy (AUROC = 90.2%). The diagnostic accuracy of each biomarker separately was moderate or good in BCLC-0/A/B and was excellent only for BCLC-C patients (AFP: AUROC = 94.3%, cutoff = 12.35 ng/mL and PIVKA-II: 91.3%, 253.51 mAU/mL) whereas their combination presented quite acceptable results in BCLC-B (AUROC = 92.4%) and BCLC-C (AUROC = 95.7%). Excluding HCC patients with high AFP (above 400 ng/mL), the diagnostic accuracy of each biomarker separately and their combination was moderate/good in all groups, except for their combination in BCLC-C (AUROC = 90.5%). CONCLUSIONS: Each biomarker separately showed acceptable accuracy for detecting HCC in cirrhotic patients and excellent for those in BCLC-C stage. The combination of the biomarkers presented excellent results in BCLC-B/C patients. The diagnostic accuracy of PIVKA-II and the combination of the two biomarkers in patients expressing low/non-diagnostic AFP levels was good in BCLC-B and excellent in BCLC-C patients.


Assuntos
Biomarcadores , Carcinoma Hepatocelular , Diabetes Mellitus , Neoplasias Hepáticas , Precursores de Proteínas , Protrombina , Masculino , Humanos , Vitamina K , Carcinoma Hepatocelular/diagnóstico , alfa-Fetoproteínas , Neoplasias Hepáticas/diagnóstico , Proteínas Sanguíneas , Vitaminas , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico
3.
Rheumatology (Oxford) ; 63(SI): SI64-SI71, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320588

RESUMO

In 2006, at a meeting in Sydney, Australia, consensus was reached by an international group of specialists to establish a number of serological criteria that identify patients with a history of thrombosis or pregnancy complications as having antiphospholipid syndrome (APS). These criteria were originally formulated for research purposes and to compare clinical trials in different centres. However, these same criteria are now generally used and accepted for the diagnosis and treatment of patients. The practice of using these criteria for direct patient care requires that these criteria are based on sound scientific evidence. Indeed, for all the autoantibodies that are officially included in the serological criteria, it has been shown that they induce thrombosis and fetal loss when infused into mice. There are also a number of additional autoantibodies that have been identified in these patients but for these antibodies there was not enough evidence to meet the official APS criteria in 2006. Seventeen years have now passed since the consensus meeting, therefore, this review examines whether additional studies performed with these 'non-criteria' autoantibodies have provided sufficient results to suggest the inclusion of these autoantibodies in the official serological criteria of APS.


Assuntos
Síndrome Antifosfolipídica , Trombose , Gravidez , Feminino , Humanos , Animais , Camundongos , Anticorpos Antifosfolipídeos , Autoanticorpos , Cuidado Pré-Natal , Protrombina
4.
PLoS One ; 19(2): e0296850, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38330059

RESUMO

Staphylococcus schleiferi and Staphylococcus coagulans are opportunistic pathogens of animals and humans. They were previously classified as Staphylococcus schleiferi subs. schleiferi and Staphylococcus schleiferi subs. coagulans, respectively, and recently reclassified as separate species. S. coagulans, is frequently associated with dogs, whereas S. schleiferi is more commonly isolated from humans. Coagulase activity status is a defining characteristic of the otherwise closely related species. However, the use of coagulase tests originally developed to distinguish S. aureus from non-coagulase-producing staphylococci, for this purpose is questionable and the basis for their host preference has not been elucidated. In the current study, a putative coa gene was identified and correlated with coagulase activity measured using a chromogenic assay with human and bovine prothrombin (closely related to canine prothrombin). The results of the tests performed with human prothrombin showed greater reactivity of S. coagulans isolates from humans than isolates obtained from dogs with the same substrate. Our data suggest that unlike S. coagulans isolates from humans, isolates from dogs have more coagulase activity with bovine prothrombin (similar to canine prothrombin) than human prothrombin. Differences in nuc and 16s rRNA genes suggest a divergence in S. coagulans and S. schleiferi. Phenotypic and genotypic variation based on the number of IgG binding domains, and the numbers of tandem repeats in C-terminal fibronectin binding motifs was also found in protein A, and fibronectin-binding protein B respectively. This study identified a coa gene and associated phenotypic activity that differentiates S. coagulans and S. schleiferi and identified key phylogenetic and phenotypic differences between the species.


Assuntos
Doenças do Cão , Infecções Estafilocócicas , Animais , Humanos , Cães , Bovinos , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Coagulase/genética , Coagulase/metabolismo , RNA Ribossômico 16S/genética , Fibronectinas/genética , Filogenia , Protrombina , Staphylococcus/metabolismo , Infecções Estafilocócicas/veterinária
5.
Clin Immunol ; 261: 109926, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38355030

RESUMO

Our study aimed to evaluate the presence, clinical associations, and potential mechanistic roles of non-criteria antiphospholipid antibodies (aPL) and circulating calprotectin, a highly stable marker of neutrophil extracellular trap release (NETosis), in pediatric APS patients. We found that 79% of pediatric APS patients had at least one non-criteria aPL at moderate-to-high titer. Univariate logistic regression demonstrated that positive anti-beta-2 glycoprotein I domain 1 (anti-D1) IgG (p = 0.008), anti-phosphatidylserine/prothrombin (aPS/PT) IgG (p < 0.001), and aPS/PT IgM (p < 0.001) were significantly associated with venous thrombosis. Positive anti-D1 IgG (p < 0.001), aPS/PT IgG (p < 0.001), and aPS/PT IgM (p = 0.001) were also associated with non-thrombotic manifestations of APS, such as thrombocytopenia. Increased levels of calprotectin were detected in children with APS. Calprotectin correlated positively with absolute neutrophil count (r = 0.63, p = 0.008) and negatively with platelet count (r = -0.59, p = 0.015). Mechanistically, plasma from pediatric APS patients with high calprotectin levels impaired platelet viability in a dose-dependent manner.


Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Humanos , Criança , Biomarcadores , beta 2-Glicoproteína I , Imunoglobulina G , Imunoglobulina M , Protrombina , Complexo Antígeno L1 Leucocitário
6.
Clin Chim Acta ; 556: 117831, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38378104

RESUMO

BACKGROUND: Volatile organic compounds (VOCs) have been shown as promising biomarkers for hepatocellular carcinoma (HCC) diagnosis. We aimed to investigate the performance of VOCs for diagnosing early-stage HCC in patients at-risk for HCC. METHODS: VOCs were identified in exhaled breath samples collected from 87 early-stage HCC patients, 90 cirrhotic patients, and 72 HBV-infected patients using thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry. The VOC levels were compared between the three groups. An association between VOCs and HCC was determined using logistic regression analysis. Diagnostic performance of VOCs was estimated using the AUROC and compared to serum alpha-fetoprotein (AFP). RESULTS: The levels of acetone monomer, dimethyl sulfide, 1,4-pentadiene, isopropyl alcohol, and acetone dimer were significantly different between the three groups. After adjusting for liver function test and AFP, acetone dimer was significantly associated with HCC. Acetone dimer significantly outperformed AFP with 86.2 % vs. 61.2 % sensitivity, 87.6 % vs. 66.2 % specificity, 86.9 % vs. 63.5 % for accuracy, and AUROC of 0.908 vs. 0.665, p = 0.007, <0.001, <0.001, and 0.001, respectively, for differentiating between HCC and cirrhosis. CONCLUSION: Acetone showed a better performance than AFP for diagnosing early HCC in at-risk patients. Further studies to validate the utility of VOCs as an HCC surveillance tool are needed.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , alfa-Fetoproteínas/análise , Acetona/análise , Curva ROC , Precursores de Proteínas , Protrombina , Cromatografia Gasosa-Espectrometria de Massas , Cirrose Hepática , Biomarcadores Tumorais
7.
J Ethnopharmacol ; 325: 117890, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38336186

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dang-Gui-Si-Ni (DGSN) decoction is a classic prescription in the clinical practice of traditional Chinese Medicine (TCM). DGSN decoction is often used to relieve symptoms of cold coagulation and blood stasis recorded by Treatise on Febrile Diseases (Shang Han Lun) and treat Raynaud's disease, dysmenorrhea, arthritis, migraine in TCM clinic. Accumulated evidences have suggested that this diseases are related to microcirculation disturbance. However, the anticoagulant activity and underlying mechanisms of DGSN decoction responsible for the therapeutic not well understood. AIM OF THE STUDY: The fingerprint and anticoagulant activity in vivo-in vitro of DGSN decoction were evaluated to strengthen the quality control and activity study of formulas. MATERIALS AND METHODS: The chemical components of DGSN decoction were analyzed by HPLC and its fingerprint similarity were evaluated by "Chinese Medicine Chromatographic Fingerprint Similarity Evaluation Software (2012 Edition)". The anticoagulant activity of DGSN decoction was assessed by measuring four coagulation factors (PT, TT, APTT, FIB) in vitro. Zebrafish thrombosis model induced by punatinib was established to evaluate the activity of improving microvascular hemodynamics in vivo. Quantitative real-time polymerase chain reaction (q-PCR) were adopted to compare the changes in the RNA expression levels of coagulation factor II (FII), VII (FVII), IX (FIX) and X (FX) in zebrafish thrombosis model. RESULTS: The fingerprint similarity evaluation method of DGSN decoction was established. The results showed that 18 samples had higher similarity (S1-S18 > 0.878). Pharmacodynamic results showed that DGSN decoction could extend PT, TT and APTT, and reduce FIB content in vitro. Meanwhile, it markedly enhanced the cardiac output and blood flow velocity at low dosage (500 µg mL-1) in vivo. q-PCR data demonstrated that DGSN decoction (500 µg mL-1) could downregulate the RNA expression of FII, FVII, FIX and FX. Interestingly, there were a bidirectional regulation of FII, FIX and FX in a certain concentration range. In general, DGSN decoction can significantly improve hemodynamics and downregulate coagulation factors, and the results were consistent both in vitro - in vivo. CONCLUSION: The fingerprint study provide a new perspective for improving the quality control of DGSN decoction. DGSN decoction possess anticoagulant activity by regulating multiple coagulation factors simultaneously. Thus, it has the potential to develop into the novel raw material of anticoagulant drugs.


Assuntos
Angelica sinensis , Medicamentos de Ervas Chinesas , Trombose , Feminino , Animais , Peixe-Zebra , Fatores de Coagulação Sanguínea , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Protrombina , Trombose/tratamento farmacológico , RNA
8.
Biomarkers ; 29(2): 55-67, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361436

RESUMO

BACKGROUND: The conventional markers for hepatocellular carcinoma (HCC), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), have several limitations; both have low sensitivity in patients with early-stage HCC; low sensitivity for AFP with HCC after eliminating hepatitis C virus (HCV); low specificity for DCP in patients with non-viral HCC, which is increasing worldwide; low specificity for AFP in patients with liver injury; and low specificity for DCP in patients treated with warfarin. To overcome these issues, the identification of novel biomarkers is an unmet need. OBJECTIVE: This study aimed to assess the usefulness of serum protein kinase C delta (PKCδ) for detecting these HCCs. METHODS: PKCδ levels were measured using a sandwich enzyme-linked immunosorbent assay in 363 chronic liver disease (CLD) patients with and without HCC. RESULTS: In both viral and non-viral CLD, PKCδ can detect HCCs with high sensitivity and specificity, particularly in the very early stages. Notably, the value and sensitivity of PKCδ were not modified by HCV elimination status. Liver injury and warfarin administration, which are known to cause false-positive results for conventional markers, did not modify PKCδ levels. CONCLUSIONS: PKCδ is an enhanced biomarker for the diagnosis of HCC that compensates for the drawbacks of conventional markers.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas , Biomarcadores Tumorais , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Proteína Quinase C-delta , Varfarina , Sensibilidade e Especificidade , Precursores de Proteínas , Biomarcadores , Protrombina/metabolismo
9.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(1): 131-139, 2024 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38310085

RESUMO

OBJECTIVES: To assess the value of serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) and glypican-3 (GPC-3) in the diagnosis of hepatocellular carcinoma (HCC). METHODS: Studies of AFP, PIVKA-Ⅱ, GPC-3 or in combination for the diagnosis of HCC since 2002 were searched in PubMed, Web of Science and Embase databases. The literature was screened according to the inclusion and exclusion criteria, the quality of the included articles was evaluated by QUADAS checklist, and relevant data were extracted by Meta DiSc, Review Manager 5.4 and Stata 15.1. The diagnostic values of AFP, PIVKA-Ⅱ and GPC-3 alone or in combination for HCC were assessed with receiver operating characteristic (ROC) curve. RESULTS: A total of 32 articles were included in the study. Meta-analysis showed that when a single marker was used to diagnose HCC, the area under the ROC curve (AUC) of PIVKA-Ⅱ was the highest (0.88, 95%CI: 0.85-0.91), followed by GPC-3 and AFP. The AUC of combination of serum markers was higher than that of a single marker, and the AUC of PIVKA-Ⅱ combined with GPC-3 was the highest (0.90, 95%CI: 0.87-0.92). When a single marker was used for diagnosis, the sensitivity of PIVKA-Ⅱ and GPC-3 were relatively high (0.75 and 0.76), while the specificity of PIVKA-Ⅱ (0.88) and AFP (0.87) were higher than that of GPC-3 (0.81). The sensitivity of the combination of serum markers was higher than that of a single marker, while the specificity was not significantly improved. When a single marker is used to diagnose HCC, the diagnostic odds ratio (DOR) of PIVKA-Ⅱ was the highest (22, 95%CI: 13-36), followed by GPC-3 and AFP. The DOR of the combination of two markers in the diagnosis of HCC was higher than that of a single marker, and the DOR of AFP combined with GPC-3 was the highest (25, 95%CI: 9-67). The DOR of the combination of the three markers was significantly reduced to 10 (95%CI: 7-45). CONCLUSIONS: When a single marker is used, PIVKA-Ⅱ has a higher diagnostic value for HCC. The combination of two markers can significantly improve the diagnostic sensitivity, and AFP combined with PIVKA-Ⅱ is recommended for the diagnosis of HCC. The combination of all three markers failed to further improve the diagnostic value.


Assuntos
Biomarcadores , Carcinoma Hepatocelular , Neoplasias Hepáticas , Precursores de Proteínas , Protrombina , Humanos , alfa-Fetoproteínas , Carcinoma Hepatocelular/diagnóstico , Glipicanas , Neoplasias Hepáticas/diagnóstico
10.
Int J Hematol ; 119(4): 407-415, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38334914

RESUMO

Age is a significant risk factor for ischemic stroke. However, the influence of aging on coagulation parameters in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOACs) remains unclear. A total of 775 samples were collected from 224 NVAF patients receiving apixaban, edoxaban or rivaroxaban. The samples were categorized into three age groups: (i) ≤ 64 years, (ii) 65-74 years, and (iii) ≥ 75 years (apixaban: N = 48, 108, 119; edoxaban: N = 63, 68, 126; rivaroxaban: N = 115, 90, 38, respectively). Coagulation parameters including fibrinogen (Fbg), factor II, factor V, factor VII, factor X, and D-dimer, were compared between the three age groups for each drug. The slopes in the correlation between drug concentrations and modified diluted prothrombin time (mdPT) were also assessed. Fbg and factor V increased with age, while factor II and factor X decreased. Factor VII and D-dimer showed no significant differences across age categories. The slope in response to drug concentrations was similar between the age groups. In NVAF patients treated with apixaban, edoxaban and rivaroxaban, some coagulation parameters exhibited age-related variation. However, the response of mdPT to drug concentration was consistent across age categories.


Assuntos
Fibrilação Atrial , Piridinas , Acidente Vascular Cerebral , Tiazóis , Humanos , Pessoa de Meia-Idade , Rivaroxabana/efeitos adversos , Varfarina , Anticoagulantes , Hemorragia/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/induzido quimicamente , Dabigatrana/efeitos adversos , Fator X/uso terapêutico , Fator VII/uso terapêutico , Protrombina , Fator V , Piridonas/uso terapêutico , Administração Oral
12.
Sci Rep ; 14(1): 2468, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291086

RESUMO

Coagulation factor 2 thrombin receptor (F2R), a member of the G protein-coupled receptor family, plays an important role in regulating blood clotting through protein hydrolytic cleavage mediated receptor activation. However, the underlying biological mechanisms by which F2R affects the development of gastric adenocarcinoma are not fully understood. This study aimed to systematically analyze the role of F2R in gastric adenocarcinoma. Stomach adenocarcinoma (STAD)-related gene microarray data and corresponding clinicopathological information were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential expression genes (DEGs) associated with F2R were analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks. F2R mRNA expression data were utilized to estimate stromal cell and immune cell scores in gastric cancer tissue samples, including stromal score, immune score, and ESTIMATE score, derived from single-sample enrichment studies. Analysis of TCGA and GEO databases revealed significantly higher F2R expression in STAD tissues compared to normal tissues. Patients with high F2R expression had shorter survival times than those with low F2R expression. F2R expression was significantly correlated with tumor (T) stage, node (N) stage, histological grade and pathological stage. Enrichment analysis of F2R-related genes showed that GO terms were mainly related to circulation-mediated human immune response, immunoglobulin, cell recognition and phagocytosis. KEGG analysis indicated associations to extracellular matrix (ECM) receptor interactions, neuroactive ligand-receptor interactions, the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K-AKT) signaling pathway, the Wnt signaling pathway and the transforming growth factor-beta (TGF-ß) signaling pathway. GSEA revealed connections to DNA replication, the Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway and oxidative phosphorylation. Drug sensitivity analysis demonstrated positive correlations between F2R and several drugs, including BEZ235, CGP-60474, Dasatinib, HG-6-64-1, Aazopanib, Rapamycin, Sunitinib and TGX221, while negative correlation with CP724714, FH535, GSK1904529A, JNK-9L, LY317615, pyrimidine, rTRAIL and Vinorelbine. Knocking down F2R in GC cell lines resulted in slowed proliferation, migration, and invasion. All statistical analyses were performed using R software (version 4.2.1) and GraphPad Prism 9.0. p < 0.05 was considered statistically significant. In conclusion, this study underscores the significance of F2R as a potential biomarker in gastric adenocarcinoma, shedding light on its molecular mechanisms in tumorigenesis. F2R holds promise for aiding in the diagnosis, prognosis, and targeted therapy of STAD.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Protrombina/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Fosfatidilinositol 3-Quinases/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores , Adenocarcinoma/genética , Adenocarcinoma/patologia , Biologia Computacional/métodos
13.
Am J Hematol ; 99(4): 577-585, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38291601

RESUMO

In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of cancer-associated venous thromboembolism (VTE) remains controversial. Our objective was to determine the risk of VTE in cancer patients with inherited thrombophilia. We conducted a systematic review and meta-analysis of studies reporting on VTE after a cancer diagnosis in adult patients who were tested for inherited thrombophilia. In September 2022, we searched Medline, EMBASE, and Cochrane Central. Two reviewers screened the abstracts/full texts and assessed study quality using the Quality in Prognostic Studies tool. We used Mantel-Haenszel random-effects models to estimate pooled odds ratios (OR) of VTE and 95% confidence intervals (95%CI). We included 37 and 28 studies in the systematic review and meta-analysis, respectively. Most studies focused on specific cancer types and hematologic malignancies were rare. The risk of VTE was significantly higher in cancer patients with non-O (compared with O) blood types (OR: 1.56 [95% CI: 1.28-1.90]), Factor V Leiden, and Prothrombin Factor II G20210A mutations compared with wild types (OR: 2.28 [95% CI: 1.51-3.48] and 2.14 [95% CI: 1.14-4.03], respectively). Additionally, heterozygous and homozygous methylenetetrahydrofolate reductase C677T had ORs of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively. Among those with Plasminogen-Activator Inhibitor-1 4G/5G, Vascular Endothelial Growth Factor (VEGF) A C634G, and VEGF C2578A mutations, there was no significant association with VTE. In conclusion, this meta-analysis provided evidence that non-O blood types, Factor V Leiden, and Prothrombin Factor II G20210A mutations are important genetic risk factors for VTE in cancer patients.


Assuntos
Neoplasias , Trombofilia , Tromboembolia Venosa , Adulto , Humanos , Tromboembolia Venosa/genética , Fator A de Crescimento do Endotélio Vascular , Protrombina/genética , Trombofilia/genética , Mutação , Neoplasias/complicações , Neoplasias/genética , Fator V/genética , Fatores de Risco
14.
Bratisl Lek Listy ; 125(2): 102-106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38219063

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common forms of cancer significantly affecting the mortality and morbidity rates. The increasing incidence of HCC is a great concern across the globe. The current methods of HCC screening, detection and diagnosis depend mainly on imaging techniques. However, biomarkers represent a relatively easy and noninvasive way to detect and estimate the disease prognosis. New potential biomarkers such as α-fetoprotein (AFP), des­Î³­carboxyprothrombin (DCP), α-fetoprotein L3 (AFP-L3), glypican 3 (GCP3), micro-RNA, and Golgi-protein 73 (GP73) are being used more often in the diagnosis and prognosis of HCC. The lack of prudent diagnostic measures makes early detection of HCC nearly impossible. The use of biomarkers to detect cancer has helped to screen for the disease. However, the most commonly used biomarkers for HCC have inadequate performance characteristics. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker for HCC. In this paper the main biomarkers for the surveillance, diagnosis and prognosis of HCC are reviewed. The advantages and limitations of these biomarkers are summarized, and the future development directions are proposed (Tab. 1, Ref. 30). Keywords: hepatocellular carcinoma, biomarkers, AFP, DCP, diagnosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Biomarcadores Tumorais , Precursores de Proteínas , Protrombina , Biomarcadores
15.
Clin Chim Acta ; 554: 117761, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38195020

RESUMO

BACKGROUND AND AIMS: Several non-criteria (NC) anti-phospholipid antibodies (APLA) have been proposed as candidates for antiphospholipid antibody syndrome (APS) diagnosis. The objectives of this study were 1) to determine the association of five different NC-APLA with positivity for Lupus anti-coagulant (LAC) and the criteria antibodies anti-cardiolipin (aCL) and anti-beta glycoprotein (aB2GPI), and 2) to assess the ability of NC-APLA to predict LAC presence and clinical APS diagnoses. MATERIAL AND METHODS: Results from 486 patients tested for LAC and APLA were retrieved. Patients were grouped according to LAC and serology positivity into three groups: Single-positives (SP) for LAC, aCL or aB2GPI; Double-positives for aCL and aB2GPI; Triple-positives (TP) for LAC, aCL and aB2GPI. NC-ALPA titers were compared between LAC-positive and negative and APS and non-APS patients. RESULTS: Forty-two of 486 patients were LAC-positive and 28 were diagnosed with APS. All criteria and NC-APLA titers were significantly higher in TP than SP patients. ROC analyses based on LAC status showed highest area under the curve (AUC, 95% CI) for aPS/PT IgG (0.75, 0.65-0.85) and aPS/PT IgM (0.73, 0.63-0.82). Based on APS diagnosis, aPS/PT IgM achieved highest AUC (0.87; 0.79-0.95). CONCLUSION: Anti-phosphatidyl-serine/prothrombin (aPS/PT) antibodies are superior predictors of LAC presence and APS diagnoses.


Assuntos
Síndrome Antifosfolipídica , Humanos , Protrombina , Fosfatidilserinas , Anticorpos Antifosfolipídeos , Anticorpos Anticardiolipina , Imunoglobulina M , Serina , Inibidor de Coagulação do Lúpus
16.
Vet Ophthalmol ; 27(1): 40-52, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37144658

RESUMO

OBJECTIVE: The objective of this study was to use shotgun label-free tandem mass spectrometry (LF-MS/MS) to evaluate aqueous humor (AH) from horses with uveitis (UH) compared to ophthalmologically healthy horses (HH). ANIMALS STUDIED: Twelve horses diagnosed with uveitis based on ophthalmic examination and six ophthalmologically healthy horses (postmortem) purchased for teaching purposes. PROCEDURES: All horses received a complete ophthalmic examination and physical exam. Aqueous paracentesis was performed on all horses and AH total protein concentrations were measured with nanodrop (TPn) and refractometry (TPr). AH samples were analyzed with shotgun LF-MS/MS and proteomic data were compared between groups using Wilcoxon rank-sum test. RESULTS: A total of 147 proteins were detected, 11 proteins had higher abundance in UH, and 38 proteins had lower abundance in UH. Proteins with higher abundance included apolipoprotein E, alpha-2-macroglobulin (A2M), alpha-2-HS-glycoprotein, prothrombin, fibrinogen, complement component 4 (C4), joining chain for IgA and IgM, afamin, and amine oxidase. There were positive correlations between TPn (p = .003) and TPr (p = .0001) compared to flare scores. CONCLUSION: Differential abundance of A2M, prothrombin, fibrinogen, and C4 indicate upregulation of the complement and coagulation cascade in equine uveitis. Proinflammatory cytokines and the complement cascade have potential as therapeutic targets for equine uveitis.


Assuntos
Doenças dos Cavalos , Uveíte , Animais , Cavalos , Humor Aquoso/metabolismo , Protrombina/metabolismo , Protrombina/uso terapêutico , Proteômica , Espectrometria de Massas em Tandem/veterinária , Uveíte/veterinária , Uveíte/tratamento farmacológico , Fibrinogênio/metabolismo , Fibrinogênio/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico
17.
Rheumatology (Oxford) ; 63(3): 891-900, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37382568

RESUMO

OBJECTIVE: This study investigates the positivity and relevance of non-criteria aPLs with clinical phenotypes in patients highly suspected of or diagnosed with APS. METHODS: Outpatient cases were included from a prospectively maintained database, and patients were grouped into APS (n = 168), seronegative APS (SNAPS, n = 9), those meeting the diagnostic criteria for clinical events without laboratory results (only-event, n = 15), those that had aPL positivity without clinical manifestations (asymptomatic APA, n = 39), and healthy controls (n = 88). Criteria aPL results and APS-related clinical features were extracted. Sixteen non-criteria aPLs were tested and analysed. RESULTS: LA, aCL and anti-ß2 glycoprotein-I were positive in 84.5%, 61.3% and 74.4% of APS patients, and 61.5%, 59.0% and 74.4% of asymptomatic APA patients, respectively. In patients negative for criteria serological tests, 23 out of 24 were positive for at least one non-criteria aPL. Triple-positive patients also had significantly higher tests of some aPLs in comparison with other groups. Stroke was associated with anti-phosphatidyl-inositol (aPI) IgG and anti-phosphatidyl-glycerol (aPG) IgG. Late embryonic loss correlated with aPI IgM, and premature birth/eclampsia was associated with aPI IgG and aPG IgG. There were also positive associations between heart valve lesions and anti-phosphatidylserine-prothrombin (aPS/PT) IgM, APS nephropathy and anti-phosphatidyl-choline IgG or aPS/PT IgG, and livedo reticularis and anti-phosphatidyl-ethanolamine IgM. CONCLUSION: The prevalence of non-criteria aPLs differed from diagnostic biomarkers in patients diagnosed with or suspected of APS. Detection of aPLs provided additive value in the evaluation of APS-related clinical manifestations.


Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Feminino , Gravidez , Humanos , Síndrome Antifosfolipídica/complicações , Relevância Clínica , Protrombina , Imunoglobulina G , Imunoglobulina M
18.
Br J Clin Pharmacol ; 90(3): 828-836, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37953511

RESUMO

AIMS: Genotype-guided dosing algorithms can explain about half of the interindividual variability in prothrombin time-international normalized ratio (PT-INR) under warfarin treatment. This study aimed to refine a published kinetic-pharmacodynamic model and guide warfarin dosage for an optimal PT-INR based on renal function. METHODS: Using a retrospective cohort of adult patients (>20 years) who were administered warfarin and underwent PT-INR measurements, we refined the kinetic-pharmacodynamic model with age and the genotypes of cytochrome P450 2C9 and vitamin K epoxide reductase complex subunit 1 using the PRIOR subroutine in the nonlinear-mixed-effect modelling programme. We searched the significant covariates for parameters, such as the dose rate for 50% inhibition of coagulation (EDR50 ), using a stepwise forward and backward method. Monte Carlo simulation determined a required daily dose of warfarin with a target range of PT-INR (2.0-3.0 or 1.6-2.6) based on the significant covariates. RESULTS: A total of 350 patients with 2762 PT-INR measurements were enrolled (estimated glomerular filtration rate [eGFR]: 47.5 [range: 2.6-199.0] mL/min/1.73 m2 ). The final kinetic-pharmacodynamic model showed that the EDR50 changed power functionally with body surface area, serum albumin level and eGFR. Monte Carlo simulation revealed that a lower daily dose of warfarin was required to attain the target PT-INR range as eGFR decreased. CONCLUSIONS: Model-informed precision dosing of warfarin is a valuable approach for estimating its dosage in patients with renal impairment.


Assuntos
Anticoagulantes , Varfarina , Adulto , Humanos , Anticoagulantes/farmacocinética , Citocromo P-450 CYP2C9/genética , Genótipo , Coeficiente Internacional Normatizado , Japão , Protrombina , Tempo de Protrombina , Estudos Retrospectivos , Vitamina K Epóxido Redutases/genética , Varfarina/farmacocinética
20.
Int J Gynaecol Obstet ; 165(1): 148-154, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38112221

RESUMO

OBJECTIVE: The aim of our study was that to assess the allelic and genotype frequencies of nine prothrombotic gene variants in patients with a history of pregnancy loss and recurrent pregnancy loss (RPL). Women who underwent assisted reproductive technology (ART) with ongoing pregnancy and those with recurrent implantation failure (RIF) were also included. METHODS: Nine prothrombotic gene variants were evaluated: factor V Leiden (FVL), factor V, H1299R variant (FVR2), factor II (FII) G20210A, methylene-tetrahydrofolate reductase (MTHFR) C677T and A1298C, beta-fibrinogen -455G>A, factor XIII (FXIII) V34L, human platelet antigen-1 (HPA-1) L33P variants, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G. The following study groups were assessed: (1) women who experienced one (n = 334) or two (n = 264) episodes of pregnancy loss; (2) 468 women who experienced RPL; (3) 214 women who underwent ART followed by ongoing pregnancies; and (4) 282 women who experienced RIF after ART, that is, three or more consecutive implantation failures following high-quality embryo transfers to the uterus with an appropriate endometrium. As control group, 430 subjects from the general population were enrolled. RESULTS: FVL, the -455G>A variant of beta-fibrinogen, and PAI-1 4G were associated with a higher risk of developing RPL compared with the general population. Furthermore, FVL, FVR2, FII G20210A and MTHFR C677T conferred a significantly higher risk of RIF in women who performed ART compared with the general population. No statistical differences between the general population and other study groups were observed. CONCLUSIONS: Specific prothrombotic genetic variants are more frequently expressed in women with RPL and RIF, supporting their role in the development of polimicrothrombosis and impairing the invasion during embryo implantation.


Assuntos
Aborto Habitual , Trombofilia , Gravidez , Humanos , Feminino , Inibidor 1 de Ativador de Plasminogênio/genética , Estudos Retrospectivos , Aborto Habitual/genética , Fator V/genética , Implantação do Embrião/genética , Protrombina/genética , Fibrinogênio/genética , Trombofilia/genética
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