Urinary L-FABP as an Early Biomarker for Pediatric Acute Kidney Injury Following Cardiac Surgery with Cardiopulmonary Bypass: A Systematic Review and Meta-Analysis.

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.

Effect of Sugar- and Polyphenol-Rich, Diluted Cloudy Apple Juice on the Intestinal Barrier after Moderate Endurance Exercise and in Ultra-Marathon Runners.

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.

Investigating the Role of FABP4 in Diabetes and Obesity and the Influence of Age and Ethnicity: A Comprehensive Analysis of a Cohort from the KEDP-Study.

Adipocyte P2 (aP2), also known as FABP4, is an adipokine that adipose tissue produces and expresses in macrophages. Its primary role is to facilitate the transportation of fatty acids across cell membranes. Numerous studies have reported associations between FABP4 and the development of metabolic disorders. However, there is limited knowledge regarding FABP4 expression in diabetes and obesity, especially about different age groups, genders, and ethnicities. This study aims to investigate the association between FABP4 levels, diabetes mellitus, and obesity within various ethnic groups. We measured plasma FABP4 concentrations in a cohort of 2083 patients from the KDEP study and gathered anthropometric data. Additionally, we collected and analyzed clinical, biochemical, and glycemic markers using multivariate regression analysis. The average FABP4 concentration was significantly higher in female participants than in males (18.8 ng/mL vs. 14.4 ng/mL, p < 0.001, respectively), and in those over 50 years old compared to those under 50 years of age (19.3 ng/mL vs. 16.2 ng/mL, p < 0.001, respectively). In this study, significant positive associations were found between the plasma level of FABP4 and obesity markers: BMI (r = 0.496, p < 0.001), hip circumference (r = 0.463, p < 0.001), and waist circumference (WC) (r = 0.436, p < 0.001). Similar observations were also seen with glycemic markers, which included HbA1c (r = 0.126, p < 0.001), fasting blood glucose (FBG) (r = 0.184, p < 0.001), fasting insulin (r = 0.326, p < 0.001), and HOMA-IR (r = 0.333, p < 0.001). Importantly, these associations remained significant even after adjusting for age, gender, and ethnicity. Furthermore, FABP4 levels were negatively associated with male gender (ß: -3.85, 95% CI: -4.92, -2.77, p < 0.001), and positively associated with age (ß: 0.14, 95% CI: 0.096, 0.183, p < 0.001), BMI (ß: 0.74, 95% CI: 0.644, 0.836, p < 0.001), and fasting insulin (ß: 0.115, 95% CI: 0.091, 0.138, p < 0.001). In this study, plasma FABP4 levels were significantly higher in diabetic and obese participants, and they were strongly influenced by age, gender, and ethnicity. These findings suggest that FABP4 may serve as a valuable prognostic and diagnostic marker for obesity and diabetes, particularly among female patients, individuals over 50 years old, and specific ethnic groups.

Gastrointestinal function following endurance exercise under different environmental temperatures.

PURPOSE: We determined the effects of different environmental temperatures on exercise-induced gastrointestinal (GI) damage and delayed gastric emptying (GE) rate. METHODS: Eleven trained males completed three trials on different days, consisting of (1) exercise in a thermoneutral environment (CON, 23 °C), (2) exercise in a hot environment (HOT, 35 °C), and (3) exercise in a cold environment (COLD, 10 °C). The subjects performed high-intensity interval-type endurance exercises in all trials. Blood intestinal fatty acid binding protein (I-FABP) levels was determine before and after exercise. We evaluated Tmax (time when the 13C-excretion/h reached a maximum level) as an indication of the GE rate during post-exercise. RESULTS: Rectal temperature during exercise was significantly higher (P < 0.001) in the HOT (38.7 ± 0.3 °C) trial compared with the CON (38.2 ± 0.3 °C) and COLD (38.2 ± 0.3 °C) trials, with no significant difference between the CON and COLD trials. Plasma I-FABP level after exercise (relative to the pre-exercise level) were significantly greater (P = 0.005) in the HOT trial (92.9 ± 69.6%) than in the CON (37.2 ± 31.6%) and COLD (37.6 ± 41.8%) trials. However, there was no significant difference between the CON and COLD trials. Moreover, the Tmax was delayed significantly (P = 0.006) in the HOT trial compared with the CON and COLD trials, with no significant difference between the CON and COLD trials. CONCLUSION: GI function following endurance exercise was similar between thermoneutral and cold environments, while endurance exercise in a hot environment exacerbated GI function compared with thermoneutral and cold environments.

Serum fatty acid binding protein 4 and Doppler of uterine artery ultrasound in the first trimester for the prediction of preeclampsia.

The objective of this study was to determine the predictive value of serum fatty acid binding protein 4 (FABP4) combined with Doppler of the uterine artery in singleton pregnancy at gestational age (GA) 11-13+6 weeks for prediction of preeclampsia. A prospective observational study included singleton pregnant women at GA 11-13+6 weeks and was conducted at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, between December 2020 and April 2022. Serum FABP4 levels and Doppler of the uterine artery were performed. Pregnancy outcomes were recorded. The predictive values of these combined tests at the optimal cut-off values were determined to predict preeclampsia. A total of 330 participants with 15 cases of preeclampsia (4.5%) and 6 cases of them had preterm preeclampsia (GA < 37 weeks) (1.8%) were analyzed. Women with preeclampsia had significantly higher serum FABP4 levels than normal pregnant women (12.9 ± 6.5 ng/ml vs 10.1 ± 4.8 ng/ml, p = 0.034) but no difference in the mean pulsatility index (PI) of the uterine artery and the presence of an early diastolic notch. When using serum FABP4 levels greater than 1.0 multiple of the median of GA as a cut-off value to predict preeclampsia, combined with abnormal Doppler PI of the uterine artery, the sensitivity, specificity, positive predictive value, and negative predictive value were 73.3%, 47.3%, 6.2%, and 97.4%, respectively. This study demonstrated that serum FABP4 levels combined with Doppler of the uterine artery at GA 11-13+6 weeks were effective in predicting preeclampsia.

Maternal serum fatty acid binding protein-4 level is upregulated in fetal growth restriction with abnormal Doppler flow patterns.

PURPOSE: This study aimed to determine fatty acid binding protein-4 (FABP-4) concentrations in maternal serum of fetal growth restriction (FGR) pregnancies and controls of normal pregnancies. Furthermore, we hypothesized that the alterations in FABP-4 levels might correlate with FGR severity. METHODS: We performed this prospective case-control study with 83 pregnant women. The study groups included 26 FGR pregnancies without abnormal fetal Doppler flow patterns and 25 pregnancies complicated with FGR accompanied by abnormal fetal Doppler flow patterns. RESULTS: The median serum FABP-4 concentrations were significantly higher in the FGR cases with abnormal Doppler flow pattern group (2.09 ng/mL) than in the FGR cases without abnormal Doppler flow pattern group (1.62 ng/mL) and the control group (1.20 ng/mL, p < 0.001). A significant negative correlation was observed between maternal serum FABP-4 levels and time to birth from blood sample collection (r = -0.356 and p = 0.001), gestational week at birth (r = -0.386 and p < 0.001), and birth weight (r = -0.394 and p < 0.001). A 1.35 ng/mL cut-off value of serum FABP-4 level could be used to discriminate FGR cases with a 78.4% sensitivity and 60.6% specificity. The optimal cut-off value of FABP-4 levels as an indicator for the diagnosis of FGR with abnormal Doppler flow pattern was estimated to be 1.76 ng/mL, which yielded a sensitivity of 84.0% and a specificity of 75.8%. CONCLUSION: FABP-4 is a crucial biomarker in the diagnosis and determining the severity of pregnancies with restricted fetal growth. We consider that FABP-4 is a powerful, reliable, and unique biomarker to diagnose FGR pregnancies.

Intestinal injury in paracetamol overdose (ATOM-8).

BACKGROUND AND AIM: Paracetamol, a widely used medication, is known for its delayed hepatotoxicity in cases of overdose. However, the potential for intestinal toxicity resulting from very high paracetamol concentrations during absorption is not well explored. This study aims to investigate the presence of intestinal toxicity and its correlation with observations in early and late paracetamol toxicity. METHODS: Serial samples of 30 patients with acute paracetamol overdose (> 10 g or 200 mg/kg) were prospectively tested. Markers of enterocyte damage, including plasma intestinal fatty acid binding protein (IFABP) and selected gut-related microRNAs (miR-21, miR-122, miR-194, and miR-215), were analyzed. Sub-analysis was performed on patients presenting with hyperlactatemia defined as a lactate greater than 2 mmol/L within 12 h post ingestion. RESULTS: In paracetamol overdose patients, median plasma IFABP was significantly elevated compared with healthy controls (720 µg/L [interquartile range, IQR, 533-1644] vs 270 µg/L [IQR 153-558], P < 0.001). Four patients had early hyperlactatemia and had significantly higher median plasma IFABP compared with those without early hyperlactatemia (3028 µg/L [IQR 1399-3556] vs 574 µg/L [IQR 526-943], P = 0.007). Furthermore, two microRNAs (miR-122 and miR-215) were downregulated in early hyperlactatemia (P = 0.019 and P = 0.006, respectively). Plasma IFABP concentrations correlated with paracetamol concentration (Spearman's r = 0.55) and lactate (r = 0.60). CONCLUSIONS: Paracetamol overdose causes concentration-related intestinal toxicity, and this is a possible explanation for the early hyperlactatemia syndrome. Intestinal toxicity has potential impacts on pharmacokinetics of other agents ingested and on the evolution of hepatotoxicity. Further studies are required to explore the mechanisms and prognostic implications of intestinal toxicity.

Elevated serum fatty acid-binding protein 4 level predicts all-cause and cardiovascular mortality in peritoneal dialysis patients: a five-year study.

BACKGROUND: To explore the prospective role of serum fatty acid-binding protein 4 (FABP4) in the outcomes of peritoneal dialysis (PD) patients. METHODS: A prospective observational study was conducted with 159 patients on PD. Demographic and clinical data at baseline were collected from medical records. Biochemical data were recorded based on blood samples measured in a central laboratory. Serum FABP4 concentrations were determined using enzyme-linked immunosorbent assay. Body composition was measured using a Body Composition Monitor. Abdominal lateral plain radiography was used to evaluate vascular calcification. The primary endpoints were all-cause and cardiovascular death. RESULTS: The median of serum FABP4 concentration was 154.6 ng/mL (interquartile range, 132.8-269.7 ng/mL). Increased serum FABP4 was associated with increased vascular calcification proportion, time on dialysis, body mass index, high-sensitivity C-reactive protein (hs-CRP), intact parathyroid hormone (iPTH), triglycerides, body fat mass, and body fat percentage (p < 0.05). Increased serum FABP4 was associated with decreased residual kidney Kt/V urea (p < 0.05). Patients with hs-CRP≥ 3 mg/L had significantly higher serum FABP4 than those with hs-CRP< 3 mg/L (p < 0.05). Patients with vascular calcification had significantly higher serum FABP4 than those without vascular calcification (p < 0.05). During a median follow-up of 58.0 months, 58 all-cause deaths and 26 cardiovascular deaths occurred. High serum FABP4 levels were independently predictive for all-cause [hazard ratio (HR), 1.003; 95% confidence interval (CI), 1.001-1.005; p = 0.016] and cardiovascular death (HR, 1.005; 95% CI, 1.001-1.008; p = 0.006) in PD patients. CONCLUSIONS: Increased serum FABP4 levels can independently predict all-cause and cardiovascular death in patients on PD.

Gastric ultrasound, citrulline, and intestinal fatty acid-binding protein as markers of gastrointestinal dysfunction in critically ill patients: A pilot prospective cohort study.

BACKGROUND: Gastrointestinal (GI) dysfunction is common in the intensive care unit (ICU), although there is no consensus on biomarkers of GI dysfunction. We aimed to evaluate ultrasound-based gastric antrum measurements and serum intestinal fatty acid-binding protein (IFABP) and citrulline levels in relation to GI dysfunction in critically ill patients. METHODS: Adult critically ill patients receiving enteral nutrition and stayed for in the ICU for ≥48 h was included. GI dysfunction was described using Gastrointestinal Dysfunction Score (GIDS). Gastric antrum measurements, including craniocaudal (CC) diameter, anteroposterior diameter, and antral-cross sectional area (CSA), as well as serum levels for IFABP and citrulline, were prospectively recorded at baseline and on day 3 and day 5 of enteral nutrition. The receiver operating characteristic (ROC) analysis was performed to evaluate gastric ultrasound parameters, serum IFABP, and citrulline concentrations in predicting GI dysfunction. RESULTS: Thirty-nine participants with a median age of 60 years were recruited and 46.2% of participants had GI dysfunction. ROC analysis revealed that the cutoff value of CSA score to predict GI dysfunction was 4.48 cm2 , which provided 72.7% sensitivity and 77.2% specificity (area under the curve = 0.768, 95% CI: 0.555-0.980). At baseline, gastric residual volume was highly correlated with CC diameter and CSA (r = 0.764, P < 0.001 and r = 0.675, P < 0.001, respectively). Serum IFABP and citrulline levels had no correlation with GI dysfunction or gastric ultrasound parameters (P > 0.05). CONCLUSION: CSA was associated with GI dysfunction in critically ill patients. Serum IFABP and citrulline concentrations were poor in predicting GI dysfunction.

Serum adipocyte fatty acid-binding protein level is positively associated with aortic stiffness in nondialysis chronic kidney disease patients: A cross-sectional study.

Aortic stiffness (AS) is a major predictor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD) and adipocyte fatty acid-binding protein (A-FABP) is a novel adipokine that is positively correlated with AS in the general population. Therefore, we investigated the correlation between serum A-FABP levels and AS in nondialysis CKD patients. Fasting blood samples and baseline characteristics were obtained in 270 patients with nondialysis CKD. Serum A-FABP concentrations were determined by enzyme immunoassay and carotid-femoral pulse wave velocity (cfPWV) measurements were acquired using a validated tonometry system. Patients with cfPWV >10 m/s formed the AS group, while those with values ≤10 m/s comprised the comparison group. Among 270 CKD patients, 92 patients (34.1%) were in the AS group. Compared to those in the comparison group, patients in the AS group were older (P < .001), had a higher prevalence of diabetes, along with higher serum A-FABP level (P < .001), larger waist circumference (P = .004), and lower estimated glomerular filtration rate (P = .001) but higher levels of body fat mass (P = .010), systolic blood pressure (P < .001), fasting glucose (P = .014), blood urea nitrogen (P = .009), and serum creatinine (P = .004). The serum log-A-FABP level was positively associated with log-cfPWV (ß = 0.178, P = .001) in nondialysis CKD patients and multivariable logistic regression analysis identified serum A-FABP (P = .006), age (P = .001), and systolic blood pressure (P = .015) as independent predictors of AS in nondialysis-dependent CKD patients. Elevated A-FABP levels may be a significant predictor of AS in nondialysis CKD patients.

The Value of Serum I-FABP Level in the Diagnosis of Acute Appendicitis.

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.

Fatty Acid-Binding Protein 4 in Patients with and without Diabetic Retinopathy.

BACKGROUND: Fatty acid-binding protein 4 (FABP4) has been demonstrated to be a predictor of early diabetic nephropathy. However, little is known about the relationship between FABP4 and diabetic retinopathy (DR). This study explored the value of FABP4 as a biomarker of DR in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 238 subjects were enrolled, including 20 healthy controls and 218 T2DM patients. Serum FABP4 levels were measured using a sandwich enzyme-linked immunosorbent assay. The grade of DR was determined using fundus fluorescence angiography. Based on the international classification of DR, all T2DM patients were classified into the following three subgroups: non-DR group, non-proliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Multivariate logistic regression analyses were employed to assess the correlation between FABP4 levels and DR severity. RESULTS: FABP4 correlated positively with DR severity (r=0.225, P=0.001). Receiver operating characteristic curve analysis was used to assess the diagnostic potential of FABP4 in identifying DR, with an area under the curve of 0.624 (37% sensitivity, 83.6% specificity) and an optimum cut-off value of 76.4 µg/L. Multivariate logistic regression model including FABP4 as a categorized binary variable using the cut-off value of 76.4 µg/L showed that the concentration of FABP4 above the cut-off value increased the risk of NPDR (odds ratio [OR], 3.231; 95% confidence interval [CI], 1.574 to 6.632; P=0.001) and PDR (OR, 3.689; 95% CI, 1.306 to 10.424; P=0.014). CONCLUSION: FABP4 may be used as a serum biomarker for the diagnosis of DR.

Serum Fatty Acid-Binding Protein 4 Levels in Adolescents: Effect of Insulin Resistance.

Background: Fatty acid-binding protein 4 (FABP4) is an adipokine that plays a causative role in obesity and diabetes. In a stratified cross-sectional study with adolescents, we explored whether changes in FABP4 are already present in lean adolescents, provided they display elements of insulin resistance (IR). Methods: Adolescents were divided in four groups according to body mass index and homeostasis model assessment-IR. Results: In metabolically unhealthy lean (MUL) adolescents (MUL, lean with IR), FABP4 was 33% higher than in healthy counterparts (metabolically healthy lean [MHL]). Obese adolescents without IR (metabolically healthy obesity [MHO]) had 50% higher levels of FABP4 than their lean counterparts (MHL), while levels of FABP4 in obese adolescents with IR (metabolically unhealthy obese [MUO]) were 220% higher than those of MUL adolescents. The differences were significant at least with P < 0.005. MUO > MHO > MUL. Our data demonstrate that the known FABP4 defect in adults with obesity also occurs in youth and even in lean adolescents, suggesting an early association between impaired glucose metabolism and FABP4 irrespective of body weight. FABP4 was more sensitive in discerning each of our 4 subgroups than either adiponectin or leptin. Moreover, evidence for a putative early adiponectin resistance in MUL suggests a combined defect in these adolescents that call for early detection and prevention of the metabolic disturbance that should stay away from concentrating only in subjects with obesity. Conclusions: Our data may serve to draw the considerable attention that is currently paid to FABP4 to the adolescent population, irrespective of the presence of obesity. Further studies with larger cohorts and analyses of visceral and liver fat are warranted.

Dynamic personalized risk prediction in chronic heart failure patients: a longitudinal, clinical investigation of 92 biomarkers (Bio-SHiFT study).

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 .

Fatty acid-binding protein 4 circulating levels in non-segmental vitiligo

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.

Urinary L-FABP is a promising prognostic biomarker of ACLF and mortality in patients with decompensated cirrhosis.

BACKGROUND & AIMS: Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC. METHODS: A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison. RESULTS: Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis. CONCLUSIONS: Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC. LAY SUMMARY: Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis.

Serum biomarkers of isoniazid-induced liver injury: Aminotransferases are insufficient, and OPN, L-FABP and HMGB1 can be promising novel biomarkers.

Isoniazid (INH)-induced liver injury is a great challenge for tuberculosis treatment. Existing biomarkers cannot accurately determine the occurrence of this injury in the early stage. Therefore, developing early specific sensitive biomarkers of INH-induced liver injury is urgent. A rat model of liver injury was established with gastric infusion of INH or INH plus rifampicin (RFP). We examined seven potential novel serum biomarkers, namely, glutamate dehydrogenase (GLDH), liver-fatty acid-binding protein (L-FABP), high-mobility group box-1 (HMGB1), macrophage colony-stimulating factor receptor (MCSF1R), osteopontin (OPN), total cytokeratin 18 (K18), and caspase-cleaved cytokeratin-18 (ccK18), to evaluate their sensitivity and specificity on INH-induced liver injury. With the increase of drug dosage, combining with RFP and prolonging duration of administration, the liver injury was aggravated, showing as decreased weight of the rats, upgraded liver index and oxidative stress level, and histopathological changes of liver becoming marked. But the activity of serum aminotransferases decreased significantly. The area under the curve (AUC) of receiver-operating characteristic (ROC) curve of OPN, L-FABP, HMGB1, MCSF1R, and GLDH was 0.88, 0.87, 0.85, 0.71, and 0.70 (≥0.7), respectively, and 95% confidence interval of them did not include 0.5, with statistical significance, indicating their potential abilities to become biomarkers of INH-induced liver injury. In conclusion, we found traditional biomarkers ALT and AST were insufficient to discover the INH-induced liver injury accurately and OPN, L-FABP, and HMGB1 can be promising novel biomarkers.

Fatty acid-binding protein 4 circulating levels in non-segmental vitiligo.

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 Acid-Binding 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.

Circulating level of fatty acid-binding protein 4 is an independent predictor of metabolic dysfunction-associated fatty liver disease in middle-aged and elderly individuals.

AIMS/INTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as hepatosteatosis with type 2 diabetes mellitus, overweight/obesity or metabolic dysregulation, has been proposed as a new feature of chronic liver disease. Fatty acid-binding protein 4 (FABP4) is expressed in adipose tissue, and secreted FABP4 is associated with the development of insulin resistance and atherosclerosis. However, the relationship between MAFLD and FABP4 has not been fully addressed. MATERIALS AND METHODS: Associations of MAFLD with metabolic markers, including FABP4, fibroblast growth factor 21 and adiponectin, were investigated in 627 individuals (men/women 292/335) in the Tanno-Sobetsu Study, a population-based cohort. RESULTS: The mean age was 65 years (range 19-98 years, median [interquartile range] 68 [56-76] years). Hepatosteatosis was determined by the fatty liver index (FLI), and FLI ≥35 for men and FLI ≥16 for women were used for detection of fatty liver, as previously reported using 14,471 Japanese individuals. FLI was positively correlated with systolic blood pressure and levels of FABP4 (r = 0.331, P < 0.001), fibroblast growth factor 21, homeostasis model assessment of insulin resistance as an insulin resistance index and uric acid, and was negatively correlated with levels of high-density lipoprotein cholesterol and adiponectin. FABP4 concentration was independently associated with FLI after adjustment of age, sex, systolic blood pressure and levels of uric acid, high-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21 in multivariable regression analysis. Logistic regression analysis showed that FABP4 was an independent predictor of MAFLD after adjustment of age, sex, presence of diabetes mellitus, hypertension and dyslipidemia, and levels of uric acid, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21. CONCLUSIONS: FABP4 concentration is independently associated with FLI and is an independent predictor of MAFLD in middle-aged and elderly individuals.

Association between enterocyte injury and fluid balance in patients with septic shock: a post hoc exploratory analysis of a prospective observational study.

BACKGROUND: The required fluid volume differs among patients with septic shock. Enterocyte injury caused by shock may increase the need for fluid by triggering a systematic inflammatory response or an ischemia-reperfusion injury in the presence of intestinal ischemia/necrosis. This study aimed to evaluate the association between enterocyte injury and positive fluid balance in patients with septic shock. METHODS: This study was a post hoc exploratory analysis of a prospective observational study that assessed the association between serum intestinal fatty acid-binding protein, a biomarker of enterocyte injury, and mortality in patients with septic shock. Intestinal fatty acid-binding protein levels were recorded on intensive care unit admission, and fluid balance was monitored from intensive care unit admission to Day 7. The association between intestinal fatty acid-binding protein levels at admission and the infusion balance during the early period after intensive care unit admission was evaluated. Multiple linear regression analysis, with adjustments for severity score and renal function, was performed. RESULTS: Overall, data of 57 patients were analyzed. Logarithmically transformed intestinal fatty acid-binding protein levels were significantly associated with cumulative fluid balance per body weight at 24 and 72 h post-intensive care unit admission both before (Pearson's r = 0.490 [95% confidence interval: 0.263-0.666]; P < 0.001 and r = 0.479 [95% confidence interval: 0.240-0.664]; P < 0.001, respectively) and after (estimate, 14.4 [95% confidence interval: 4.1-24.7]; P = 0.007 and estimate, 26.9 [95% confidence interval: 11.0-42.7]; P = 0.001, respectively) adjusting for severity score and renal function. CONCLUSIONS: Enterocyte injury was significantly associated with cumulative fluid balance at 24 and 72 h post-intensive care unit admission. Enterocyte injury in patients with septic shock may be related to excessive fluid accumulation during the early period after intensive care unit admission.