RESUMO
BACKGROUND/AIMS: Liver fatty acid-binding protein (LFABP) controls hepatocyte lipid metabolism and can be a biomarker in liver diseases. We compared the correlation of LFABP levels with liver histology in viral hepatitis and nonalcoholic fatty liver disease (NAFLD) and investigated the utility of serum LFABP as a biomarker for liver damage. MATERIALS AND METHODS: We included 142 patients (60 chronic viral hepatitis B [CHB], 35 chronic viral hepatitis C [CHC], 47 NAFLD) and 40 healthy controls. LFABP levels were determined in all participants, and a liver biopsy was performed on patients. The nonalcoholic steatohepatitis (NASH) activity score (NAS), hepatosteatosis, liver inflammation, and fibrosis were evaluated for NAFLD patients. Ishak's histological scores were used for viral hepatitis. The correlation between LFABP levels and histologic scores was assessed in each group. RESULTS: Serum LFABP levels in CHB, CHC, NAFLD, and control groups were 2.2, 3.5, 7.6, and 2.1 ng/mL, respectively. LFABP levels were significantly higher in the NAFLD group compared to the control, CHC, and CHB groups. LFABP was significantly higher in the NASH group than in nonalcoholic steatohepatitis, 8 ng/mL and 5.4 ng/mL, respectively (P = .001). In the NAFLD group, LFABP levels showed a moderate positive correlation with NAS score (r = 0.58, P <.001), ballooning degeneration (r = 0.67, P <.001), and lobular inflammation (r = 0.62, P <.001). A logistic regression study showed that the level of LFABP was predictive of NASH independent of age, gender, homeostasis model of IR, body mass index, aspartate aminotransferase, and alanine aminotransferase (OR = 1.869, P = .01). CONCLUSION: LFABP specifically correlates with liver histology in NAFLD compared to viral hepatitis. Additionally, it can distinguish NASH from simple steatosis. LFABP may be a valuable biomarker for hepatocyte injury in NASH.
Assuntos
Biomarcadores , Proteínas de Ligação a Ácido Graxo , Hepatite C Crônica , Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Biomarcadores/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Proteínas de Ligação a Ácido Graxo/sangue , Fígado/patologia , Hepatite C Crônica/complicações , Hepatite C Crônica/sangue , Estudos de Casos e Controles , Hepatite B Crônica/complicações , Hepatite B Crônica/sangue , Biópsia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.
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Adipocinas , Deficiência de Vitamina D , Vitamina D , Humanos , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/sangue , Masculino , Feminino , Criança , Estudos de Casos e Controles , Adipocinas/sangue , Adolescente , Vitamina D/sangue , Vitamina D/análogos & derivados , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/análise , Resistina/sangue , Nucleobindinas/sangue , Adiponectina/sangue , Adiponectina/deficiência , Proteínas de Ligação ao Cálcio/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a DNA/sangue , Biomarcadores/sangue , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/complicaçõesRESUMO
INTRODUCTION: Acute kidney injury (AKI) defined by a substantial decrease in kidney function within hours to days and is often irreversible with higher risk to chronic kidney disease (CKD) transition. AREAS COVERED: The authors discuss the diagnostic and predictive utilities of serum and urinary biomarkers on AKI and on the risk of AKI-to-CKD progression. The authors focus on the relevant literature covering evidence of circulating and urinary biomarkers' capability to predict the transition of AKI to CKD. EXPERT OPINION: Based on the different modalities of serum and urinary biomarkers, multiple biomarker panel seems to be potentially useful to distinguish between various types of AKI, to detect the severity and the risk of AKI progression, to predict the clinical outcome and evaluate response to the therapy. Serum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary uromodulin, serum extracellular high mobility group box-1 (HMGB-1), serum cystatin C and urinary liver-type fatty acid-binding protein (L-FABP) were the most effective in the prediction of AKI-to-CKD transition regardless of etiology and the presence of critical state in patients. The current clinical evidence on the risk assessments of AKI progression is mainly based on the utility of combination of functional, injury and stress biomarkers, mainly NGAL, L-FABP, HMGB-1 and cystatin C.
Assuntos
Injúria Renal Aguda , Biomarcadores , Progressão da Doença , Insuficiência Renal Crônica , Humanos , Biomarcadores/urina , Biomarcadores/sangue , Injúria Renal Aguda/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Insuficiência Renal Crônica/urina , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Lipocalina-2/urina , Lipocalina-2/sangue , Prognóstico , Proteínas de Ligação a Ácido Graxo/urina , Proteínas de Ligação a Ácido Graxo/sangueRESUMO
OBJECTIVE: Neonatal necrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease. We investigated intestinal fatty acid binding protein (I-FABP), I-FABP mRNA, and interleukin-6 (IL-6) as potential diagnostic biomarkers in NEC. METHODS: Forty mice were subjected to hypoxic-ischemic intestinal injury, and then serum I-FABP protein and mRNA levels were quantified. Ileal tissue pathological scores were determined by hematoxylin and eosin staining. I-FABP expression levels and translocation in these tissues were detected using western blotting and immunofluorescence, respectively. Samples from 30 human neonates with NEC and 30 healthy neonates had serum I-FABP protein/mRNA and IL-6 levels measured. RESULTS: The mouse ileal tissue pathological score and I-FABP levels, as well as serum I-FABP and I-FABP mRNA levels, were significantly higher in the model group than in the control group. Serum I-FABP, I-FABP mRNA, and IL-6 levels were significantly higher in human neonates with NEC than in the healthy group. Logistic regression and receiver operating curve analyses revealed that I-FABP protein/mRNA and IL-6 levels could be diagnostic biomarkers for NEC. CONCLUSIONS: I-FABP protein/mRNA and IL-6 levels are useful biomarkers of intestinal ischemic injury in neonates with NEC. The combined detection of I-FABP protein/mRNA and IL-6 is recommended rather than using a single biomarker.
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Biomarcadores , Modelos Animais de Doenças , Enterocolite Necrosante , Proteínas de Ligação a Ácido Graxo , Interleucina-6 , Camundongos Endogâmicos BALB C , RNA Mensageiro , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/sangue , Enterocolite Necrosante/patologia , Enterocolite Necrosante/genética , Enterocolite Necrosante/diagnóstico , Animais , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Interleucina-6/sangue , Interleucina-6/genética , Recém-Nascido , Humanos , Biomarcadores/sangue , Biomarcadores/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/sangue , Camundongos , Masculino , Feminino , Animais Recém-Nascidos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Íleo/metabolismo , Íleo/patologia , Estudos de Casos e Controles , Curva ROCRESUMO
OBJECTIVES: Estrogens may protect the gut barrier and reduce microbial translocation and immune activation, which are prevalent in HIV infection. We investigated relationships of the menopausal transition and estrogens with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV. DESIGN: Longitudinal and cross-sectional studies nested in the Women's Interagency HIV Study. METHODS: Intestinal fatty acid binding protein, lipopolysaccharide binding protein, and soluble CD14 (sCD14) levels were measured in serum from 77 women (43 with HIV) before, during, and after the menopausal transition (â¼6 measures per woman over â¼13 years). A separate cross-sectional analysis was conducted among 72 postmenopausal women with HIV with these biomarkers and serum estrogens. RESULTS: Women in the longitudinal analysis were a median age of 43 years at baseline. In piecewise, linear, mixed-effects models with cutpoints 2 years before and after the final menstrual period to delineate the menopausal transition, sCD14 levels increased over time during the menopausal transition (Beta [95% CI]: 38 [12 to 64] ng/mL/yr, P = 0.004), followed by a decrease posttransition (-46 [-75 to -18], P = 0.001), with the piecewise model providing a better fit than a linear model (P = 0.0006). In stratified analyses, these results were only apparent in women with HIV. In cross-sectional analyses, among women with HIV, free estradiol inversely correlated with sCD14 levels (r = -0.26, P = 0.03). Lipopolysaccharide binding protein and intestinal fatty acid binding protein levels did not appear related to the menopausal transition and estrogen levels. CONCLUSIONS: Women with HIV may experience heightened innate immune activation during menopause, possibly related to the depletion of estrogens.
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Translocação Bacteriana , Biomarcadores , Estrogênios , Proteínas de Ligação a Ácido Graxo , Infecções por HIV , Receptores de Lipopolissacarídeos , Menopausa , Humanos , Feminino , Infecções por HIV/imunologia , Infecções por HIV/sangue , Adulto , Estudos Transversais , Receptores de Lipopolissacarídeos/sangue , Menopausa/sangue , Biomarcadores/sangue , Pessoa de Meia-Idade , Estudos Longitudinais , Estrogênios/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Glicoproteínas de Membrana/sangue , Proteínas de Fase Aguda , Proteínas de TransporteRESUMO
BACKGROUND: Exercise and the consumption of sugars result in a dysfunction of the intestinal barrier (IB). Here, we determined the effect of sugar in a natural matrix on the intestinal barrier after moderate (A) and intensive endurance exercise (B). METHOD: The IB function was determined before (pre) and after running (post), and 120 and 180 min after consuming the drink by measuring serum endotoxin concentrations (lipopolysaccharides-LPS), IL-6, CD14, and i-FABP. In study A, nonspecifically trained participants (n = 24, males and females, age 26 ± 4) ran for one hour at 80% of their individual anaerobic threshold (IAT). After finishing, the runners consumed, in a crossover setup, either 500 mL of water, diluted cloudy apple juice (test drink), or an identical drink (placebo) without the fruit juice matrix (FJM). In study B, the participants (n = 30, males and females, age 50 ± 9) completed an ultra-marathon run, were divided into groups, and consumed one of the above-mentioned drinks. RESULTS: Study A: Exercise resulted in a significant increase in serum LPS, i-FABP, and IL-6, which decreased fast after finishing. No impact of the different drinks on LPS i-FABP, or IL-6 could be observed, but there was an impact on CD14. Study B: The ultra-marathon resulted in a strong increase in serum LPS, which decreased fast after finishing in the water and test drink groups, but not in the placebo group. CONCLUSIONS: The consumed drinks did not affect the kinetics of IB regeneration after moderate exercise, but impacted CD14 serum concentrations, indicating possible beneficial effects of the FJM on the immune system. After an ultra-marathon, IB function regenerates very fast. The intake of sugar (placebo) seems to have had a negative impact on IB regeneration, which was diminished by the presence of the FJM.
Assuntos
Estudos Cross-Over , Sucos de Frutas e Vegetais , Interleucina-6 , Receptores de Lipopolissacarídeos , Malus , Corrida de Maratona , Resistência Física , Polifenóis , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Polifenóis/farmacologia , Polifenóis/administração & dosagem , Resistência Física/efeitos dos fármacos , Resistência Física/fisiologia , Interleucina-6/sangue , Receptores de Lipopolissacarídeos/sangue , Corrida de Maratona/fisiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Lipopolissacarídeos/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Corrida/fisiologia , Adulto JovemRESUMO
Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in the early diagnosis and prediction of CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on 12 November 2023, using the MeSH terms "Children", "CPB", "L-FABP", and "Acute Kidney Injury". Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p < 0.05. Of 508 studies assessed, nine were included, comprising 1658 children, of whom 561 (33.8%) developed CPB-AKI. Significantly higher uL-FABP levels in AKI versus non-AKI patients first manifested at baseline to 6 h post-CPB. At 6 h, uL-FABP correlated with CPB duration (r = 0.498, p = 0.036), postoperative serum creatinine (r = 0.567, p < 0.010), and length of hospital stay (r = 0.722, p < 0.0001). Importantly, uL-FABP at baseline (AUC = 0.77, 95% CI: 0.64-0.89, n = 365), 2 h (AUC = 0.71, 95% CI: 0.52-0.90, n = 509), and 6 h (AUC = 0.76, 95% CI: 0.72-0.80, n = 509) diagnosed CPB-AKI earlier. Hence, higher uL-FABP levels associate with worse clinical parameters and may diagnose and predict CPB-AKI earlier.
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Injúria Renal Aguda , Biomarcadores , Ponte Cardiopulmonar , Proteínas de Ligação a Ácido Graxo , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/sangue , Ponte Cardiopulmonar/efeitos adversos , Proteínas de Ligação a Ácido Graxo/urina , Proteínas de Ligação a Ácido Graxo/sangue , Biomarcadores/urina , Criança , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/urina , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Pré-EscolarRESUMO
BACKGROUND: This study aimed to investigate the association between intestinal fatty acid-binding protein (I-FABP), acute gastrointestinal injury (AGI) grade, and gastrointestinal (GI) complications after fenestrated or branched endovascular aortic aneurysm repair. METHODS: A total of 17 patients undergoing endovascular aortic repair for thoracoabdominal, juxtarenal, suprarenal, or pararenal aneurysm between May 2017 and September 2018 were enrolled. Blood samples were collected preoperatively and during postoperative intensive care. The blood samples were analyzed for I-FABP with enzyme-linked immunosorbent assay. Gastrointestinal function was assessed according to the AGI grade every day during postoperative intensive care. RESULTS: Higher concentrations of I-FABP at 24 hr and 48 hr correlated to higher AGI grade on postoperative days 1, 2, and 3 (P = 0.032 and P = 0.048, P = 0.040 and P = 0.018, and P = 0.012 and P = 0.016, respectively). Patients who developed a GI complication within 90 days postoperatively had a higher overall AGI grade than those who did not develop a GI complication (P < 0.001), as well as higher concentrations of I-FABP at 48 hrs (P = 0.019). Patients developing GI dysfunction (AGI grade ≥2) had a higher frequency of complications (P = 0.009) and longer length of stay in the intensive care unit (P = 0.008). CONCLUSIONS: In patients undergoing endovascular aortic repair for complex aneurysm increased postoperative plasma I-FABP concentrations and postoperative GI dysfunction, evaluated using the AGI grade, were associated with GI complications, indicating that these measures may be useful in the postoperative management of these patients.
Assuntos
Aneurisma Aórtico , Biomarcadores , Implante de Prótese Vascular , Procedimentos Endovasculares , Proteínas de Ligação a Ácido Graxo , Gastroenteropatias , Valor Preditivo dos Testes , Humanos , Biomarcadores/sangue , Masculino , Procedimentos Endovasculares/efeitos adversos , Feminino , Idoso , Proteínas de Ligação a Ácido Graxo/sangue , Implante de Prótese Vascular/efeitos adversos , Resultado do Tratamento , Fatores de Tempo , Aneurisma Aórtico/cirurgia , Aneurisma Aórtico/sangue , Gastroenteropatias/sangue , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/cirurgia , Idoso de 80 Anos ou mais , Fatores de Risco , Pessoa de Meia-Idade , Regulação para Cima , Estudos Prospectivos , Medição de RiscoRESUMO
OBJECTIVE: Prognostic tools for individuals with peripheral artery disease (PAD) remain limited. We developed prediction models for 3-year PAD-related major adverse limb events (MALE) using demographic, clinical, and biomarker data previously validated by our group. METHODS: We performed a prognostic study using a prospectively recruited cohort of patients with PAD (n = 569). Demographic/clinical data were recorded including sex, age, comorbidities, previous procedures, and medications. Plasma concentrations of three biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], fatty acid binding protein 3 [FABP3], and FABP4) were measured at baseline. The cohort was followed for 3 years. MALE was the primary outcome (composite of open/endovascular vascular intervention or major amputation). We trained three machine learning models with 10-fold cross-validation using demographic, clinical, and biomarker data (random forest, decision trees, and Extreme Gradient Boosting [XGBoost]) to predict 3-year MALE in patients. Area under the receiver operating characteristic curve (AUROC) was the primary model evaluation metric. RESULTS: Three-year MALE was observed in 162 patients (29%). XGBoost was the top-performing predictive model for 3-year MALE, achieving the following performance metrics: AUROC = 0.88 (95% confidence interval [CI], 0.84-0.94); sensitivity, 88%; specificity, 84%; positive predictive value, 83%; and negative predictive value, 91% on test set data. On an independent validation cohort of patients with PAD, XGBoost attained an AUROC of 0.87 (95% CI, 0.82-0.90). The 10 most important predictors of 3-year MALE consisted of: (1) FABP3; (2) FABP4; (3) age; (4) NT-proBNP; (5) active smoking; (6) diabetes; (7) hypertension; (8) dyslipidemia; (9) coronary artery disease; and (10) sex. CONCLUSIONS: We built robust machine learning algorithms that accurately predict 3-year MALE in patients with PAD using demographic, clinical, and novel biomarker data. Our algorithms can support risk stratification of patients with PAD for additional vascular evaluation and early aggressive medical management, thereby improving outcomes. Further validation of our models for clinical implementation is warranted.
Assuntos
Amputação Cirúrgica , Biomarcadores , Proteína 3 Ligante de Ácido Graxo , Proteínas de Ligação a Ácido Graxo , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Doença Arterial Periférica , Valor Preditivo dos Testes , Humanos , Masculino , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Biomarcadores/sangue , Idoso , Medição de Risco , Fatores de Risco , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Proteína 3 Ligante de Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Fatores de Tempo , Técnicas de Apoio para a Decisão , Aprendizado de Máquina , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Salvamento de Membro , Reprodutibilidade dos Testes , Idoso de 80 Anos ou maisRESUMO
PURPOSE: We aimed to investigate the POAF rate and blood FABP4 levels after perioperative L-carnitine administration in patients with esophageal cancer. METHODS: L-carnitine (3 g in three divided doses) was administered to 15 patients 2 days before and 3 days after surgery. POAF during the study period and blood FABP4 levels (ELISA) before and after L-carnitine administration were evaluated. Accurate 95% confidence intervals (CI) for POAF incidence and changes in blood FABP4 levels were calculated. The preoperative predicted POAF rate was calculated using an application for esophageal cancer. The correlation between FABP4 levels and the predicted POAF rate was analyzed using Pearson's coefficient (r). RESULTS: Thirteen patients completed this study. The predicted POAF rate was 24% (17%, 34%) (median; interquartile range). The actual incidence of POAF was 7.7% (95% CI: 0.2-36%). Blood FABP4 levels changed from 10.3 to 7.0 ng/mL; the average change was - 3.3 (95% CI: - 6.6 to - 0.1). A positive correlation was found between preoperative FABP4 levels and the predicted POAF rates (r = 0.564). CONCLUSIONS: The POAF rate after esophageal surgery was 7.7% for L-carnitine. L-carnitine may reduce blood FABP4 levels. This preliminary study will contribute to the planning of sample sizes in future randomized trials.
Assuntos
Fibrilação Atrial , Carnitina , Neoplasias Esofágicas , Proteínas de Ligação a Ácido Graxo , Complicações Pós-Operatórias , Humanos , Carnitina/administração & dosagem , Neoplasias Esofágicas/cirurgia , Incidência , Masculino , Feminino , Fibrilação Atrial/etiologia , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Idoso , Pessoa de Meia-Idade , Proteínas de Ligação a Ácido Graxo/sangue , Esofagectomia/efeitos adversos , Assistência Perioperatória/métodosRESUMO
BACKGROUND: Acute appendicitis is one of the most common abdominal emergencies worldwide. Biomarkers and imaging are valuable adjuncts to history and examination. Differentiating complicated and uncomplicated appendicitis is essential. Our aim is to investigate whether serum I-FABP could be a suitable diagnostic biomarker in diagnosing acute appendicitis in which inflammation and ischemia play a role in the pathophysiology. METHODS: Sixty-six patients with histopathologically confirmed acute appendicitis were included in the study. Blood samples were taken from the patient and control groups to examine serum I-FABP, white blood cell (WBC) counts, C-reactive protein (CRP), and procalcitonin (PCT) levels. RESULTS: Twenty-six patients (39.3%) had complicated appendicitis. When the patient and control groups were compared in terms of I-FABP, WBC, neutrophil-lymphocyte ratio, (NLR) CRP, and PCT values, a significant difference was found in all biochemical parameters (p < 0.001). We compared the levels of patients with uncomplicated and complicated appendicitis in terms of serum I-FABP, WBC, NLR, CRP, and PCT levels and found that only the I-FABP level was significantly different (p < 0.001), and the diagnostic sensitivity was higher in patients with complicated appendicitis compared with uncomplicated patients (AUC; 0.89 for I-FABP, 0.55, 0.57, 0.61, and 0.59 for WBC, NLR, CRP, and PCT respectively). CONCLUSIONS: I-FABP has no diagnostic advantage over WBC, CRP, and PCT to diagnose acute appendicitis. However, it is more sensitive than other biomarkers in differentiating complicated from uncomplicated appendicitis.
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Apendicite , Proteínas de Ligação a Ácido Graxo/sangue , Doença Aguda , Apendicite/diagnóstico , Biomarcadores , Proteína C-Reativa/análise , Humanos , Contagem de Leucócitos , Pró-Calcitonina , Estudos RetrospectivosRESUMO
The aim of our observational study was to derive a small set out of 92 repeatedly measured biomarkers with optimal predictive capacity for adverse clinical events in heart failure, which could be used for dynamic, individual risk assessment in clinical practice. In 250 chronic HFrEF (CHF) patients, we collected trimonthly blood samples during a median of 2.2 years. We selected 537 samples for repeated measurement of 92 biomarkers with the Cardiovascular Panel III (Olink Proteomics AB). We applied Least Absolute Shrinkage and Selection Operator (LASSO) penalization to select the optimal set of predictors of the primary endpoint (PE). The association between repeatedly measured levels of selected biomarkers and the PE was evaluated by multivariable joint models (mvJM) with stratified fivefold cross validation of the area under the curve (cvAUC). The PE occurred in 66(27%) patients. The optimal set of biomarkers selected by LASSO included 9 proteins: NT-proBNP, ST2, vWF, FABP4, IGFBP-1, PAI-1, PON-3, transferrin receptor protein-1, and chitotriosidase-1, that yielded a cvAUC of 0.88, outperforming the discriminative ability of models consisting of standard biomarkers (NT-proBNP, hs-TnT, eGFR clinically adjusted) - 0.82 and performing equally well as an extended literature-based set of acknowledged biomarkers (NT-proBNP, hs-TnT, hs-CRP, GDF-15, ST2, PAI-1, Galectin 3) - 0.88. Nine out of 92 serially measured circulating proteins provided a multivariable model for adverse clinical events in CHF patients with high discriminative ability. These proteins reflect wall stress, remodelling, endothelial dysfunction, iron deficiency, haemostasis/fibrinolysis and innate immunity activation. A panel containing these proteins could contribute to dynamic, personalized risk assessment.Clinical Trial Registration: 10/05/2013 https://clinicaltrials.gov/ct2/show/NCT01851538?term=nCT01851538&draw=2&rank=1 .
Assuntos
Biomarcadores/sangue , Insuficiência Cardíaca/sangue , Imunidade Inata/genética , Medicina de Precisão , Idoso , Antígenos CD/sangue , Arildialquilfosfatase/sangue , Doença Crônica/epidemiologia , Doença Crônica/prevenção & controle , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Galectina 3/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/patologia , Hexosaminidases/sangue , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Receptores da Transferrina/sangue , Medição de Risco , Fatores de RiscoRESUMO
Abstract Background: Vitiligo is an acquired and progressive mucocutaneous disease resulting from the loss of active epidermal melanocytes. Metabolic syndrome (MetS) affects about 25% of the world's population and is linked to inflammatory skin diseases including vitiligo. Fatty AcidBinding Protein 4 (FABP4) is an intracellular lipid chaperone. FABP4 is closely associated with MetS. Objectives: To evaluate the serum level of FABP4 in vitiligo patients and its relation to MetS in the investigated cases. Methods: This case control study was conducted on 45 patients having non segmental vitiligo and 45 matched controls. Their lipid profile, blood glucose and serum FABP4 levels were measured. Results: There were significant elevations in FABP4 (p < 0.001), cholesterol (p < 0.001), triglycerides (p = 0.005), and glucose (fasting [p = 0.001] and 2 hours post prandial [p < 0.001]) levels in patients in comparison with controls. MetS was significantly more prevalent among vitiligo patients (p < 0.001) and associated with high FABP4 serum levels (p = 0.037). In vitiligo patients, there were significant positive correlations between FABP4 serum levels and triglycerides (p = 0.047), cholesterol (p = 0.001) and LDL (p = 0.001) levels and negative correlation regarding HDL level (p = 0.009). FABP4 level was a significantly good diagnostic test for early detection of vitiligo (p < 0.001). Study limitations: The small number of studied subjects. Conclusions: FABP4 may play an active role in the disease process of vitiligo that could be mediated through associated dyslipidemia and hyperglycemia. FABP4 may be a marker of vitiligo helping in its early diagnosis, but it does not appear to be useful for determining vitiligo severity, activity or associated MetS.
Assuntos
Humanos , Síndrome Metabólica , Proteínas de Ligação a Ácido Graxo/sangue , Triglicerídeos , Vitiligo , Estudos de Casos e ControlesRESUMO
Fatty acid binding protein 4 (FABP4) has been associated with insulin resistance. Gestational diabetes mellitus (GDM) impairs fetal insulin sensitivity. Female newborns are more insulin resistant than male newborns. We sought to evaluate the association between GDM and cord blood FABP4, and explore potential sex dimorphic associations and the roles of sex hormones. This was a nested case-control study in the Shanghai Birth Cohort, including 153 pairs of newborns in GDM vs. euglycemic pregnancies matched by infant sex and gestational age at delivery. Cord plasma FABP4, leptin, total and high-molecular-weight adiponectin, testosterone and estradiol concentrations were measured. Adjusting for maternal and neonatal characteristics, cord plasma FABP4 (Mean ± SD: 27.0 ± 19.6 vs. 18.8 ± 9.6 ng/mL, P=0.045) and estradiol (52.0 ± 28.6 vs. 44.2 ± 26.6, ng/mL, P=0.005) concentrations were higher comparing GDM vs. euglycemic pregnancies in males, but similar in females (all P>0.5). Mediation analyses showed that the positive association between GDM and cord plasma FABP4 in males could be partly mediated by estradiol (P=0.03), but not by testosterone (P=0.72). Cord plasma FABP4 was positively correlated with total adiponectin in females (r=0.17, P=0.053), but the correlation was in the opposite direction in males (r=-0.11, P=0.16) (test for difference in r, P=0.02). Cord plasma FABP4 was not correlated with leptin in both sexes. The study is the first to demonstrate sex-dimorphic associations between GDM and cord plasma FABP4 or estradiol, and between FABP4 and adiponectin in newborns. GDM may affect fetal circulating FABP4 and estradiol levels in males only.
Assuntos
Diabetes Gestacional/metabolismo , Estradiol/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Medula Espinal/metabolismo , Adiponectina/sangue , Estudos de Casos e Controles , Estudos de Coortes , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Humanos , Recém-Nascido , Leptina/sangue , Masculino , Gravidez , Caracteres Sexuais , Testosterona/sangueRESUMO
INTRODUCTION: Adult-onset autoimmune enteropathy (AIE) is a rare cause of severe chronic diarrhea because of small intestinal villous atrophy. We report on patients with adult-onset AIE in an European referral center. METHODS: Retrospective study including patients diagnosed with AIE in the Amsterdam UMC, location VUmc, between January 2003 and December 2019. Clinical, serological, and histological features and response to treatment were reported. The specificity of antienterocyte antibodies (AEA) was evaluated by examining the prevalence of AEA in (i) controls (n = 30) and in patients with (ii) AIE (n = 13), (iii) celiac disease (CD, n = 52), (iv) refractory celiac disease type 2 (n = 18), and (v) enteropathy-associated T-cell lymphoma (EATL, n = 10). RESULTS: Thirteen AIE patients were included, 8 women (62%), median age of 52 years (range 23-73), and 6 (46%) with an autoimmune disease. AEA were observed in 11 cases (85%), but were also found in CD (7.7%), refractory celiac disease type 2 (16.7%), and EATL (20%). Ten patients (77%) were human leukocyte antigen DQ2.5 heterozygous. Total parenteral nutrition was required in 8 cases (62%). Steroids induced clinical remission in 8 cases (62%). Step-up therapy with rituximab, cyclosporine, infliximab, and cladribine in steroid-refractory patients was only moderately effective. Four patients died (31%), but 4 (31%) others are in long-term drug-free remission after receiving immunosuppressive treatment, including 1 patient who underwent autologous stem cell transplantation. DISCUSSION: Adult-onset AIE is a rare but severe enteropathy that occurs in patients susceptible for autoimmune disease. Four patients (31%) died secondary to therapy-refractory malabsorption, while immunosuppressive therapy leads to a long-lasting drug-free remission in one-third of patients.
Assuntos
Autoanticorpos/análise , Enterócitos/imunologia , Poliendocrinopatias Autoimunes/diagnóstico , Poliendocrinopatias Autoimunes/imunologia , Adulto , Idoso , Atrofia , Doença Crônica , Diarreia/etiologia , Duodeno/patologia , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Antígenos HLA-DQ/sangue , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Países Baixos , Nutrição Parenteral , Poliendocrinopatias Autoimunes/tratamento farmacológico , Poliendocrinopatias Autoimunes/patologia , Estudos Retrospectivos , Subpopulações de Linfócitos T/metabolismo , Centros de Atenção Terciária , Adulto JovemRESUMO
OBJECTIVE: To investigate whether serum levels of fibroblast growth factor 21 (FGF21) and fatty acid-binding protein-4 (FABP4) are associated with missed abortion (MA) in humans. DESIGN: Cross-sectional study. SETTING: University-affiliated hospital. PATIENT(S): Patients with MA at 8-12 weeks of gestation. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Serum levels of FGF21 and FABP4 were tested by enzyme-linked immunosorbent assay. Placental samples were collected during dilation and curettage surgery, and the expression of FGF21 and its related genes were measured using quantitative polymerase chain reaction. RESULT(S): In the discovery cohort, 78 patients with MA and 79 healthy pregnant women matched for maternal age and body mass index were nested from a prospective cohort. Circulating levels of FGF21 and FABP4 were significantly and independently elevated in patients with MA relative to the levels in the healthy controls. A single measurement of FGF21 serum level effectively discriminated MA with an area under the receiver operating characteristics curve of 0.80 (95% confidence interval: 0.73-0.87). Importantly, in our external validation cohort that comprised subjects with MA (n = 34) or induced abortion (n = 27), the FGF21 serum levels achieved an area under the receiver operating characteristics curve of 0.85 (95% confidence interval: 0.75-0.96) when identifying those with MA. Nevertheless, expression of FGF21 in the placenta was not associated with its serum concentration. Placental tissues from patients with MA exhibited impaired FGF21 signaling. CONCLUSION(S): Our results suggested that serum levels of FGF21 and FABP4 were associated with MA. Circulating FGF21 may serve as a potential biomarker for the recognition of MA.
Assuntos
Aborto Retido/sangue , Fatores de Crescimento de Fibroblastos/sangue , Aborto Retido/diagnóstico , Aborto Retido/genética , Adulto , Biomarcadores/sangue , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Fatores de Crescimento de Fibroblastos/genética , Idade Gestacional , Humanos , Placenta/química , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND: Diagnosing internal herniation (IH) in Roux-en-Y gastric bypass (RYGB) patients with acute abdominal pain poses a diagnostic challenge. Diagnostic laparoscopy is often required for a definitive diagnosis. We hypothesized that intestinal ischemia biomarkers would aid in the diagnosing of IH. OBJECTIVES: To explore intestinal ischemia biomarkers in diagnosing IH. SETTING: University Hospital, Sweden. METHODS: Prospective inclusion of 46 RYGB patients admitted for acute abdominal pain between June 2015 and December 2017. Blood samples for analysis of citrulline, intestinal fatty acid-binding protein (I-FABP), and D-dimer were drawn <72 hours from admission and compared between patients with IH (n = 8), small bowel obstruction (SBO) (n = 5), other specified diagnoses (n = 12), or unspecified abdominal pain (n = 21). Levels of white blood cell count (WBC), C-reactive protein (CRP), and lactate at admission were compared. A prospective pain questionnaire for time of pain onset and level of pain at onset and at admission was analyzed. RESULTS: None of the investigated biomarkers differed significantly between diagnosis categories. Most patients with IH had normal CRP, WBC, and D-dimer levels while their lactate levels were significantly lower (P = .029) compared with the rest of the cohort. Neither pain level nor pain duration differed between the groups. CONCLUSION: This study shows that citrulline, I-FABP, and D-dimer cannot be used to diagnose IH and indicates that CRP, D-dimer, and lactate are rarely elevated by an IH. Furthermore, pain intensity and duration cannot differentiate patients with IH. A diagnostic laparoscopy remains the gold standard to diagnose and rule out an IH.
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Dor Abdominal/diagnóstico , Derivação Gástrica , Obesidade Mórbida , Dor Abdominal/etiologia , Biomarcadores/sangue , Citrulina/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Derivação Gástrica/efeitos adversos , Humanos , Laparoscopia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Fatty acid binding protein 5 (FABP5) is elevated in psoriatic keratinocytes and could be involved in systemic metabolic disturbances in psoriasis. The aim of the study was to evaluate serum FABP5 in obese and non-obese psoriatic patients, to assess the relationship between FABP5 and the duration, severity of the disease, inflammatory and metabolic markers and influence of treatment with narrowband-ultraviolet B (NB-UVB). Seventy-four patients (30 treated with NB-UVB) with psoriasis were enrolled in the study. The serum concentrations of FABP5 were measured using Human FABP5 Enzyme-Linked Immunosorbent Assay kit. Serum fatty acids were measured by gas-liquid chromatography. Serum FABP5 levels in psoriatic patients were higher versus control group (P < 0.001). FABP5 in patients with PASI > 20 was higher compared to the mild group (PASI < 10) (P < 0.001) and serum FABP5 correlated positively with PASI score (r = 0.41, P < 0.001). There was also positive correlation between FABP5 and basic inflammation indices. Decrease of PASI after NB-UVB treatment (P < 0.001) was observed and accompanied by decrease of the serum FABP5 (P = 0.007). FABP5 is a potential marker of psoriasis, its severity and clinical outcome after therapy with NB-UVB. FABP5 may reflect metabolic disturbances in psoriatic patients.
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Proteínas de Ligação a Ácido Graxo/sangue , Obesidade/complicações , Psoríase/sangue , Psoríase/complicações , Índice de Gravidade de Doença , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/sangue , Inflamação/complicações , Inflamação/radioterapia , Masculino , Pessoa de Meia-Idade , Psoríase/radioterapia , Resultado do Tratamento , Terapia Ultravioleta/métodos , Adulto JovemRESUMO
Gastrointestinal disturbances are one of the most common issues for endurance athletes during training and competition in the heat. The relationship between typical dietary intake or nutritional interventions and perturbations in or maintenance of gut integrity is unclear. Twelve well-trained male endurance athletes (peak oxygen consumption = 61.4 ± 7.0 ml·kg-1·min-1) completed two trials in a randomized order in 35 °C (heat) and 21 °C (thermoneutral) conditions and kept a detailed nutritional diary for eight consecutive days between the two trials. The treadmill running trials consisted of 15 min at 60% peak oxygen consumption, 15 min at 75% peak oxygen consumption, followed by 8 × 1-min high-intensity efforts. Venous blood samples were taken at the baseline, at the end of each of the three exercise stages, and 1 hr postexercise to measure gut integrity and the permeability biomarker concentration for intestinal fatty-acid-binding protein, lipopolysaccharide, and lipopolysaccharide-binding protein. The runners self-reported gut symptoms 1 hr postexercise and 3 days postexercise. The heat condition induced large (45-370%) increases in intestinal fatty-acid-binding protein, lipopolysaccharide-binding protein, and lipopolysaccharide concentrations compared with the baseline, but induced mild gastrointestinal symptoms. Carbohydrate and polyunsaturated fat intake 24 hr preexercise were associated with less lipopolysaccharide translocation. Protein, carbohydrate, total fat, and polyunsaturated fat intake (8 days) were positively associated with the percentage increase of intestinal fatty-acid-binding protein in both conditions (range of correlations, 95% confidence interval = .62-.93 [.02, .98]). Typical nutrition intake partly explained increases in biomarkers and the attenuation of symptoms induced by moderate- and high-intensity exercise under both heat and thermoneutral conditions.
Assuntos
Ingestão de Alimentos , Trato Gastrointestinal/fisiologia , Temperatura Alta , Esforço Físico/fisiologia , Corrida/fisiologia , Adulto , Biomarcadores/sangue , Intervalos de Confiança , Estudos Cross-Over , Registros de Dieta , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Ingestão de Energia , Proteínas de Ligação a Ácido Graxo/sangue , Ácidos Graxos Insaturados/administração & dosagem , Humanos , Lipopolissacarídeos/sangue , Masculino , Consumo de Oxigênio , Condicionamento Físico Humano/fisiologia , Resistência Física , Fenômenos Fisiológicos da Nutrição Esportiva , Fatores de TempoRESUMO
BACKGROUND: Adipocytokines participate in regulating the inflammatory response in glucose homeostasis and type 2 diabetes. However, among these peptides, the role of adipocyte-specific fatty-acid-binding protein (AFABP), chemerin, and secreted protein acidic and rich in cysteine (SPARC) in gestational diabetes (GDM) has not been fully investigated. METHOD: The maternal fasting level of adipocytokines of 53 subjects with GDM and 43 normal pregnant (NGDM) was measured using multiplex immunoassay at 24-28 weeks, before delivery, immediate postpartum, and 2-6 months postpuerperium. RESULTS: Higher levels of AFABP were associated with a 3.7-fold higher risk of GDM. Low chemerin levels were associated with a 3.6-fold higher risk of GDM. Interleukin-10 (IL-10) was inversely associated with the risk of GDM. SPARC had no association with GDM. AFABP was directly correlated to interleukin-6 (r = 0.50), insulin resistance index (r = 0.26), and body mass index (r = 0.28) and inversely correlated to C-reactive protein (r = -0.27). Chemerin levels were directly and strongly correlated with IL-10 (r = 0.41) and interleukin-4 (r = 0.50) and inversely correlated to insulin resistance index (r = -0.23) in GDM but not NGDM. In the longitudinal assessment, there were no significant differences in AFABP and chemerin concentrations of both studied groups. CONCLUSION: AFABP and chemerin were associated with a higher risk of GDM. These adipocytokines were related to insulin resistance, body mass index, and inflammation in pregnant women diagnosed with GDM.