Serum concentration of taurochenodeoxycholic acid predicts clinically significant portal hypertension.

BACKGROUND & AIMS: Severity of portal hypertension is usually quantified by measuring the hepatic venous pressure gradient (HVPG). However, due to its invasiveness, alternative markers are being sought. Bile acids (BA), being synthesized, metabolized, and transported by the liver, seem to have the potential to serve as endogenous markers. The aim of the present study was to determine whether serum BA reflect the severity of portal hypertension. METHODS: We correlated serum concentrations of individual BA with portal pressure (as HVPG) in an exploratory cohort of 21 cirrhotic patients with portal hypertension. The predictive potential of selected candidates was then confirmed in an independent validation cohort (n = 214). Additionally, nine previously published noninvasive markers were added to the stepwise logistic regression model to identify the most relevant ones, which were eventually used to create a prognostic index of portal hypertension. RESULTS: Serum levels of taurochenodeoxycholic acid (TCDCA) significantly correlated with HVPG and showed a high potential to predict clinically significant portal hypertension (HVPG ≥ 10 mm Hg: AUROC = 0.97 ± 0.06). This was confirmed in the validation cohort (AUROC = 0.96 ± 0.01). The predictive index (constructed based on AST/ALT, spleen diameter, and TCDCA concentration) was able to distinguish clinically significant portal hypertension with 95% sensitivity and 76% specificity. CONCLUSIONS: TCDCA seems to be a promising noninvasive marker of clinically significant portal hypertension. Its predictive potential may be further enhanced when it is combined with both the AST/ALT ratio and spleen diameter.

Diagnostic and prognostic value of presepsin vs. established biomarkers in critically ill patients with sepsis or systemic inflammatory response syndrome.

BACKGROUND: Inflammatory biomarkers may aid to distinguish between systemic inflammatory response syndrome (SIRS) vs. sepsis. We tested the hypotheses that (1) presepsin, a novel biomarker, can distinguish between SIRS and sepsis, and (2) higher presepsin levels will be associated with increased severity of illness and (3) with 28-day mortality, outperforming traditional biomarkers. METHODS: Procalcitonin (PCT), C-reactive protein (CRP), presepsin, and lactate were analyzed in 60 consecutive patients (sepsis and SIRS, n=30 per group) on day 1 (D1) to D3 (onset sepsis, or after cardiac surgery). The systemic organ failure assessment (SOFA) score was determined daily. RESULTS: There was no difference in mortality in sepsis vs. SIRS (12/30 vs. 8/30). Patients with sepsis had higher SOFA score vs. patients with SIRS (11±4 vs. 8±5; p=0.023), higher presepsin (AUC=0.674; p<0.021), PCT (AUC=0.791; p<0.001), CRP (AUC=0.903; p<0.0001), but not lactate (AUC=0.506; p=0.941). Unlike other biomarkers, presepsin did not correlate with SOFA on D1. All biomarkers were associated with mortality on D1: presepsin (AUC=0.734; p=0.0006; best cutoff=1843 pg/mL), PCT (AUC=0.844; p<0.0001), CRP (AUC=0.701; p=0.0048), and lactate (AUC=0.778; p<0.0001). Multiple regression analyses showed independent associations of CRP with diagnosis of sepsis, and CRP and lactate with mortality. Increased neutrophils (p=0.002) and decreased lymphocytes (p=0.007) and monocytes (p=0.046) were also associated with mortality. CONCLUSIONS: Presepsin did not outperform traditional sepsis biomarkers in diagnosing sepsis from SIRS and in prognostication of mortality in critically ill patients. Presepsin may have a limited adjunct value for both diagnosis and an early risk stratification, performing independently of clinical illness severity.

Corrigendum to: Assessment of the degree of adherence of medical laboratories to KDIGO 2012 guideline for evaluation and management of CKD in Czechia and Slovakia.

[This corrects the article DOI: 10.11613/BM.2019.030704.].

Dynamic genetic architecture of metabolic syndrome attributes in the rat.

The polydactylous rat strain (PD/Cub) is a highly inbred (F > 90) genetic model of metabolic syndrome. The aim of this study was to analyze the genetic architecture of the metabolic derangements found in the PD/Cub strain and to assess its dynamics in time and in response to diet and medication. We derived a PD/Cub x BN/Cub (Brown Norway) F2 intercross population of 149 male rats and performed metabolic profiling and genotyping and multiple levels of genetic linkage and statistical analyses at five different stages of ontogenesis and after high-sucrose diet feeding and dexamethasone administration challenges. The interval mapping analysis of 83 metabolic and morphometric traits revealed over 50 regions genomewide with significant or suggestive linkage to one or more of the traits in the segregating PD/Cub x BN/Cub population. The multiple interval mapping showed that, in addition to "single" quantitative train loci, there are more than 30 pairs of loci across the whole genome significantly influencing the variation of particular traits in an epistatic fashion. This study represents the first whole genome analysis of metabolic syndrome in the PD/Cub model and reveals several new loci previously not connected to the genetics of insulin resistance and dyslipidemia. In addition, it attempts to present the concept of "dynamic genetic architecture" of metabolic syndrome attributes, evidenced by shifts in the genetic determination of syndrome features during ontogenesis and during adaptation to the dietary and pharmacological influences.

Diagnostic and prognostic value of presepsin in preterm deliveries.

PROBLEM: To evaluate the association between serum presepsin (soluble CD14 antigen subtype, sCD14-ST) levels soon after the appearance of signs of preterm delivery and preterm delivery within 48 h, before the 34th and 37th gestational weeks and the possible additional value of concurrently evaluated ultrasound vaginal cervicometry with serum presepsin measurement. METHODOLOGY: A total of 60 females were included. Serum presepsin was measured by a chemiluminescent immunoassay. Sonographic evaluation of cervical length in all females was conducted by transvaginal ultrasound. RESULTS: Patients who delivered within 48 h after analysis showed significantly higher presepsin concentrations compared to females with later deliveries. Higher presepsin was proven also for deliveries before/after weeks 34 and 37. A combined finding of cervical length shortening below 18 mm and presepsin level increasing above 623.5 pg/mL could point to the significantly high risk of preterm delivery. CONCLUSION: Elevated maternal serum concentration of sCD14-ST could be an independent and relevant risk factor for preterm delivery.

Performance characteristics of seven neuron-specific enolase assays.

BACKGROUND/AIMS: The determination of neuron-specific enolase (NSE) is relatively frequently requested in the differential diagnosis of small-cell lung carcinoma and non-small-cell lung carcinoma. The individual results of different immunoassays are often not comparable, which has been confirmed by long-term external quality assessments. In this study, we assessed the possible sources of these differences. METHODS: More than 3,000 NSE analyses were performed using seven different immunoassays: DELFIA (PerkinElmer), Elecsys 2010 or Modular Analytics E 170 (Roche), Kryptor (B.R.A.H.M.S.), the enzyme-linked immunosorbent assay DRG and three assays based on immunoradiometric assays (DiaSorin, Immunotech and Schering-CIS). The following parameters were evaluated: precision profile of the individual methods, linearity on dilution and modified recovery, comparability and discrimination of immunoassays, sensitivity, and specificity. RESULTS: There were differences in the correlation of values of certain low-concentration specimens. Some assays correlate well while others do not (up to fivefold difference), especially in the case of controls prepared synthetically. Therefore, the current non-standardized preparation of controls is questionable in our opinion. In the cutoff range, the difference in the results of native samples did not exceed its double value. The variation in values >100 microg/l obtained with different assays is <40%. CONCLUSION: Our results confirmed expected matrix interferences especially in the range of normal and cutoff NSE concentrations. Another source of discrepancies can be attributed to different antibody affinity to alphagamma- and gammagamma-enolase isoenzymes. Finally, improper settings of cutoff values also contribute to the different discrimination of the methods.

Advanced glycation end-products in patients with chronic alcohol misuse.

AIMS: The aim of our study was to determine serum levels of advanced glycation end-products (AGE) in patients with chronic alcohol misuse and to examine their relationship to markers of nutrition and inflammation. METHODS: The study group consisted of 23 heavy alcohol drinkers treated for chronic alcohol misuse and 22 healthy controls. Studied parameters included AGE (fluorescence, CML - carboxymethyllysine and pentosidine), lipids, glucose, albumin, leptin, prealbumin, C-reactive protein (CRP) and pregnancy-associated plasma protein A (PAPP-A). RESULTS: AGE fluorescence was significantly higher in chronic alcoholic patients than in healthy subjects (4.3 +/- 0.7 x 10(3) vs 3.7 +/- 0.5 x 10(3) AU/g protein, P < 0.005), while CML was only slightly but not significantly elevated (569.1 +/- 106.6 vs 545.5 +/- 85.8 microg/l) and pentosidine levels did not differ (105.4 +/- 29 vs 102.2 +/- 23 nmol/l). In alcoholics, AGE correlate significantly negatively with leptin (r = -0.46, P < 0.05) and pentosidine with prealbumin (r = -0.43, P < 0.05), otherwise there was no relationship between AGE and other biochemical parameters (glucose, cholesterol, albumin, CRP, PAPP-A). CONCLUSION: Our findings suggest a more complex relationship among advanced glycation, oxidative stress and metabolism of ethanol and their link to nutrition and nutrition-associated parameters. AGE as a result of oxidative stress might be similarly linked to increased cardiovascular risk of heavy alcohol drinkers, as are malnutrition and inflammation; however, further studies are needed to confirm this hypothesis.