Novel Biomarker In Patients Research Articles

Thermal heterogeneity of carotid arteries as a novel biomarker in patients with diabetes mellitus assessed for coronary artery disease

BackgroundVulnerable plaque plays crucial role in prognosis of diabetes mellitus (DM). Microwave radiometry (MWR) allows measurement of the temperature of tissues, thus indirectly reflecting inflammation, a characteristic of atherosclerotic plaque stability. Aim of the study was to evaluate the relation of carotid artery inflammation with glycemic control and presence of coronary artery disease (CAD). MethodsWe included 112 patients (65 ± 9 years, 30 ± 5 kg/m2, 74 DM and 38 non-DM, with a 2:1 ratio) that were referred for scheduled coronary angiography (CA) for evaluation of their clinical condition. We measured thermal heterogeneity, expressed as temperature difference (ΔT) along each carotid artery, with MWR and maximum temperature difference between the 2 carotid arteries (ΔΤmax). ResultsPatients with DM presented higher ΔTmax comparing to patients without DM (0.91 ± 0.29 vs 0.71 ± 0.25 °C, p < 0.001). Glycaemia over time was associated with thermal heterogeneity of carotids (HbA1c: <6.5: 0.78 ± 0.23, HbA1c: 6.5–7: 0.87 ± 0.24, HbA1c: 7–8: 0.99 ± 0.30, HbA1c: >8: 1.15 ± 0.35 °C, p = 0.003). Patients with CAD presented higher ΔΤmax comparing to patients with normal CA (0.93 ± 0.24 vs 0.68 ± 0.25 °C, p < 0.001) and patients that underwent coronary revascularization presented higher ΔTmax (0.95 ± 0.25 vs 0.76 ± 0.26 °C, p < 0.001). A ΔTmax ≥ 0.9 (received by ROC analysis) was an independent predictor for revascularization in DM patients (odds ratio 3.29, 95% CI: 1.07–10.16; p = 0.039) when adjusted for sex, age and the established risk factors of CAD. ConclusionLocal inflammatory activation of carotid arteries is more pronounced in patients with DM and is associated with the glycemic control. Carotids' thermal heterogeneity is associated with need for revascularization supporting its predictive value in DM patients assessed for CAD.

A novel biomarker in patients with knee osteoarthritis: adropin.

Adropin is newly discovered peptide hormone. Osteoarthritis (OA) is a kind of joint disease characterized by progressive joint cartilage loss and joint pain. The present study was carried out to investigate adropin and tumor necrosis factor alpha (TNF-α) levels and the relationship between adropin in patients with knee OA classified by Kellgren-Lawrence (KL). A total of 60 knee OA patients and 30 healthy controls were included in this study. KL grading was carried out using the radiographic findings. Demographic characteristics and laboratory parameters were recorded. Adropin and TNF-α levels were determined by using enzyme-linked immunosorbent assay (ELISA). Adropin level was lower in the knee OA patients compared with the healthy controls (p < 0.001), whereas TNF-α level was higher (p < 0.001). Adropin level was negatively correlated with TNF-α level, blood white blood cell (WBC) count, and neutrophil-lymphocyte ratio (NLR). However, there was a significant decrease in adropin level and an increase in TNF-α level parallel to the increase in the KL grade. In addition, serum adropin level was found to be significantly lower in KL grade 1 groups compared with healthy controls (p < 0.01). There was a decrease in adropin level parallel to the increase in the body mass index (BMI), and there was a statistically significant decrease in adropin level in knee OA patients higher than BMI > 30 (p < 0.01). Mean NLR of KL grade 4 was significantly increased compared with other grades (p < 0.05). The consequence of the present study suggested that serum adropin level could be used as a new biomarker indicating the early grade of knee OA.

Soluble urokinase plasminogen activator receptor (suPAR) as a novel serum biomarker for patients undergoing resection of colorectal liver metastases.

309 Background: In colorectal cancer (CRC), the liver is the most common site of metastasis. Surgical resection represents the standard potentially curative therapy for patients with colorectal liver metastases (CRLM). However, 5-year survival rates after resection do not exceed 50%, and despite existing preoperative stratification algorithms it is still not fully understood which patients benefit most from surgery. The soluble urokinase plasminogen activator receptor (suPAR) has recently evolved as a promising biomarker for distinct clinical conditions. Here, we examined a potential role of circulating suPAR as a biomarker in patients undergoing resection of CRLM. Methods: Expression levels of uPAR, the membrane-bound source of circulating suPAR, were analysed in tissue samples of CRLM using RT-PCR and IHC. SuPAR serum levels were measured by ELISA in 104 patients undergoing surgical resection of CRLM as well as 50 healthy controls. Results were correlated with clinical data. Results: In line with an upregulation of uPAR in the CRLM tissue, serum levels of suPAR were significantly elevated in patients with CRLM compared to healthy controls. Patients with preoperative suPAR serum levels above our defined ideal cut-off value of 4.83 ng/ml showed a strikingly reduced overall survival after resection of CRLM, which could be confirmed for right- and left-sided primary CRC. Importantly, none of these patients reached long-term survival compared to patients with preoperative suPAR serum concentrations below the cut-off value. Moreover, multivariate Cox-regression analysis revealed preoperative suPAR serum levels as an independent prognostic factor in this setting. Additionally, elevated preoperative suPAR but not creatinine levels were a predictor of acute kidney injury after CRLM resection, correlating with a longer postoperative hospitalization. Conclusions: Serum levels of suPAR represent a promising novel biomarker in patients with resectable CRLM that might help to guide preoperative treatment decisions with regards to patients’ outcome and the identification of patients particularly susceptible to postoperative acute kidney injury.

Nasal IL-25 predicts the response to oral corticosteroids in chronic rhinosinusitis with nasal polyps

Nasal IL-25 predicts the response to oral corticosteroids in chronic rhinosinusitis with nasal polyps

Plasma CRABP2 as a Novel Biomarker in Patients with Non-Small Cell Lung Cancer.

BackgroundLung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC).MethodsBlood samples that were collected from 122 patients with NSCLC between September 2009 and September 2013 were selected for the analysis, along with samples from age- (± 5 years), sex-, and cigarette smoking history (± 10 pack-years [PY])-matched controls from the Korea Biobank Network. The control specimens were from patients who were without malignancies or pulmonary diseases. We measured plasma levels of CRABP2 using commercially available enzyme-linked immunosorbent assay kits.ResultsThe mean age of the NSCLC patients was 71.8 ± 8.9 years, and the median cigarette smoking history was 32 PY (range, 0–150 PY). Plasma CRABP2 levels were significantly higher in patients with NSCLC than in the matched controls (37.63 ± 28.71 ng/mL vs. 24.09 ± 21.09 ng/mL, P < 0.001). Higher plasma CRABP2 levels were also correlated with lower survival rates in NSCLC patients (P = 0.014).ConclusionPlasma CRABP2 levels might be a novel diagnostic and prognostic marker in NSCLC.

Soluble urokinase plasminogen activator receptor (suPAR) represents a novel biomarker for patients undergoing resection of colorectal liver metastases

Soluble urokinase plasminogen activator receptor (suPAR) represents a novel biomarker for patients undergoing resection of colorectal liver metastases

Spot Testing Urine pH, a Novel Biomarker for Patients with ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention

Spot Testing Urine pH, a Novel Biomarker for Patients with ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention

Prognostic value of a microRNA signature as a novel biomarker in patients with lower-grade gliomas.

MicroRNAs (miRNAs) may act as prognostic biomarkers in a variety of cancers. The aim of this study was to identify and evaluate a prognostic miRNA signature in patients with lower-grade gliomas (LGGs). miRNA expression profiles and clinical data of patients with LGGs from the Chinese Glioma Genome Atlas (CGGA; the training cohort) and The Cancer Genome Atlas (TCGA; the validation cohort) were analyzed, and the least absolute shrinkage and selection operator Cox regression model was used to identify the miRNA signature, which was combined with clinical prognostic factors to develop an individualized survival prediction model. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to reveal the biological implications of the signature. We identified a four-miRNA signature that stratified patients in the training cohort into low- or high-risk groups according to overall survival time, a finding that was verified in the validation cohort. Multivariate Cox regression analysis indicated that the four-miRNA signature was an independent prognostic biomarker, and a nomogram combining this miRNA signature with clinicopathological and molecular factors showed high prognostic accuracy for individualized survival prediction in both TCGA (C-index = 0.83) and CGGA (C-index = 0.68) cohorts. Functional annotation indicated that the major biological processes of this prognostic miRNA signature were enriched in cell cycle and DNA repair-associated biological processes. Our findings indicated that our newly discovered four-miRNA signature may be an effective independent prognostic factor for the prediction of patients with LGGs.

TCT-685 Thermal heterogeneity of carotid arteries as a novel biomarker in patients undergoing coronary angiography

TCT-685 Thermal heterogeneity of carotid arteries as a novel biomarker in patients undergoing coronary angiography

Nasal interleukin 25 as a novel biomarker for patients with chronic rhinosinusitis with nasal polyps and airway hypersensitiveness: A pilot study

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airway and is tightly linked with airway hyperresponsiveness (AHR) and asthma. However, the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP remain elusive. ObjectiveTo investigate the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP. MethodsIn this study, sinonasal tissues were collected from 42 patients with CRSwNP (asthma, n = 17; asymptomatic AHR, n = 11; non-AHR, n = 14), 11 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 13 controls. The protein and messenger RNA levels of interleukin (IL) 25 and other cytokines in nasal polyp (NP) and control sinonasal tissues were determined by quantitative real-time polymerase chain reaction and multiplex immunoassay, respectively. Multivariate logistic regression and receiver operating characteristic curve analysis were performed to assess the clinical relevance of IL-25. ResultsWe found that the protein and messenger RNA levels of IL-25 were significantly increased in NP tissues compared with the control sinonasal tissues from patients with CRSwNP, patients with CRSsNP, and controls. Multivariate logistic regression revealed that the nasal IL-25 protein level and nasal and blood eosinophil counts were independent risk factors for AHR in patients with CRSwNP. According to receiver operating characteristic curve analysis, nasal tissue IL-25 had a sensitivity of 91.4% and a specificity of 62.8% (area under the curve, 0.845) at the cutoff level of 5 pg/μL for indicating AHR in this CRSwNP cohort. ConclusionOur findings indicated that IL-25 was significantly increased in NP tissues and may be considered as the molecular indicator for AHR in patients with CRSwNP. Trial RegistrationClinicalTrials.gov Identifier: NCT02110654.

Plasma lipidomics identifies novel biomarkers in patients with hepatitis B virus-related acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) is a fatal syndrome that presents with acute deterioration of liver function in chronic hepatitis B virus (HBV) patients. However, reliable diagnostic and prognostic biomarkers are scarce. The aim of this study to identify lipid species associated with HBV infection as well as novel lipid biomarkers for HBV-ACLF. High performance liquid chromatography–tandem mass spectrometry was used for targeted lipidomic analyses of 147 lipid species. Fasting-state plasma samples from 74 HBV-ACLF patients, 86 HBV-non-ACLF patients [30 HBV-immune tolerant (HBV-IT) and 56 chronic hepatitis B] and 20 healthy controls. Univariate and multivariate analyses examined changes in lipid species among patient groups. The HBV-ACLF and HBV-non-ACLF groups had distinctly different lipid profiles, while the HC and HBV-IT groups had similar lipid profiles. Further, lysophosphatidylcholine (LPC) 22:6, cholesterol ester (CE) 22:6, CE 20:4, CE 18:2 and CE 18:1 could be used as potential biomarkers for the early prediction of ACLF. Meanwhile, univariate and multivariate analyses identified CE 20:4, LPC 16:0, LPC 18:0, phosphatidylcholine (PC) 40:6 and PC 32:0 as putative diagnostic biomarkers of HBV-ACLF. Moreover, LPC 16:0 and LPC 18:0 were significantly associated with model for end stage liver disease (MELD) scores, and the two lipid species combined with MELD score had significant capability to predict the 6-month mortality. Our study revealed that lipid metabolism disorders were significantly associated with the severity of liver inflammatory injury rather than HBV infection in patients with chronic HBV infection, and specific lipid species could be used as potentially biomarkers for diagnosis and prognosis in HBV-ACLF.

Regorafenib inhibited gastric cancer cells growth and invasion via CXCR4 activated Wnt pathway.

AimRegorafenib is an oral small-molecule multi kinase inhibitor. Recently, several clinical trials have revealed that regorafenib has an anti-tumor activity in gastric cancer. However, only part of patients benefit from regorafenib, and the mechanisms of regorafenib’s anti-tumor effect need further demonstrating. In this study, we would assess the potential anti-tumor effects and the underlying mechanisms of regorafenib in gastric cancer cells, and explore novel biomarkers for patients selecting of regorafenib.MethodsThe anti-tumor effects of regorafenib on gastric cancer cells were analyzed via cell proliferation and invasion. The underlying mechanisms were demonstrated using molecular biology techniques.ResultsWe found that regorafenib inhibited cell proliferation and invasion at the concentration of 20μmol/L and in a dose dependent manner. The anti-tumor effects of regorafenib related to the decreased expression of CXCR4, and elevated expression and activation of CXCR4 could reverse the inhibition effect of regorafenib on gastric cancer cells. Further studies revealed that regorafenib reduced the transcriptional activity of Wnt/β-Catenin pathway and led to decreased expression of Wnt pathway target genes, while overexpression and activation of CXCR4 could attenuate the inhibition effect of regorafenib on Wnt/β-Catenin pathway.ConclusionsOur findings demonstrated that regorafenib effectively inhibited cell proliferation and invasion of gastric cancer cells via decreasing the expression of CXCR4 and further reducing the transcriptional activity of Wnt/β-Catenin pathway.

Circulating miR-21 serves as a serum biomarker for hepatocellular carcinoma and correlated with distant metastasis.

Serum miRNAs have gained great popularity to act as circulating biomarkers of several cancers. In this study, we aimed to evaluate the diagnostic efficiency of serum miR-21 as novel biomarkers for patients with hepatocellular carcinoma (HCC) and other controls. A total of 533 individuals were recruited and conducted in a two-step analysis. The pilot group included 40 HCC patients and 40 healthy donors. The expression levels of miR-21 were significantly higher in primary HCC tissues than in adjacent noncancerous tissues (P<0.0001). HCC patients exhibited significantly higher serum levels of miR-21 than HD (P<0.0001). In the verification group, the mean serum levels of miR-21 in 175 patients with HCC were significantly higher than in 64 with CHB, 78 with LC and 136 HD (all P<0.0001). ROC curves demonstrated that the AUC of miR-21 was 0.849, sensitivity 82.1% and specificity 83.9%. Furthermore, serum miR-21 maintained its diagnostic efficiency in AFP-negative HCC subgroups with AUC 0.831, sensitivity 81.2% and specificity 83.2%. The serum levels of miR-21 could distinguish HCC from CHB and LC (AUC 0.789, sensitivity 76.9%, specificity 85.7% and AUC 0.814, sensitivity 80.8%, specificity 72.9%, respectively). In addition, the serum levels of miR-21 were significantly associated with clinical stage (P=0.006) and distant metastasis (P=0.000). Thus, our findings suggest that miR-21 together with AFP may help enhance the diagnosis of HCC, especially of AFP-negative HCC, and could distinguish HCC from CHB and LC.

HOTAIR is a promising novel biomarker in patients with thyroid cancer.

Thyroid cancer (TC) is the most common endocrine malignancy. Lack of effective early diagnostic tools is one of the clinical obstacles for TC treatment. Thus, enhanced comprehension of the molecular changes in TC tumorigenesis is urgently needed to develop novel strategies for the diagnosis and treatment of TC. Long non-coding RNAs (lncRNAs) manage fundamental biochemical and cellular processes in tumorigenesis and development. One of the best-described lncRNAs, HOX transcript antisense RNA (HOTAIR), functions as a regulatory molecule in a wide variety of biological processes, and represses gene expression through recruitment of the chromatin modifying complex. However, the function of HOTAIR in TC remains unclear. In the current study, the expression of HOTAIR is elevated in TC and correlates with metastasis and poor prognosis. Furthermore, the expression of HOTAIR is significantly upregulated in human thyroid carcinoma cells compared with normal human thyroid cells. Furthermore, knockdown of HOTAIR significantly inhibited cell growth and invasion in TPC-1 and SW579 human thyroid carcinoma. In summary, HOTAIR is a promising novel biomarker in patients with TC.

Novel biomarkers for patients with idiopathic acute anterior uveitis: neutrophil to lymphocyte ratio and platelet to lymphocyte ratio.

To assess the levels of the neutrophil to lymphocyte ratio (N/L) and the platelet to lymphocyte ratio (P/L) in patients with idiopathic acute anterior uveitis (AAU) and to compare with healthy controls. Thirty-six male patients with idiopathic AAU and 36 male healthy subjects were enrolled in this retrospective study. Complete ophthalmological examination and complete blood count measurements results of all subjects were evaluated. There was a significant difference in N/L and P/L between idiopathic AAU and control groups (P=0.006, P=0.022). Also, correlation analysis revealed a significant correlation between C-reactive protein (CRP) and N/L (P=0.002; r=0.461). Our study for the first time provides evidence of N/L and P/L may be useful biomarkers in patients with idiopathic AAU. N/L is correlated with CRP, so it can be a useful biomarker to predict the prognosis in idiopathic AAU.

Soluble ST2 predicts 1‐year outcome in patients undergoing transcatheter aortic valve implantation

Soluble ST2 (sST2) has been introduced as a novel biomarker in patients suffering from heart failure for risk stratification. In this study, we sought to investigate whether sST2 is useful for risk stratification and prediction of mortality in patients undergoing transcatheter aortic valve implantation (TAVI). A total of 274 patients undergoing TAVI were included in this study (149 female; age 81±1years; EUROSCORE 25±1; STS score 3·8±0·2). Plasma samples were obtained preinterventional and analysed for sST2. Patients were followed up 1month and 1year after TAVI. In a Cox regression analysis, sST2 plasma concentration was associated with increased mortality (changes per pg/mL sST2 concentration; HR 1·00006 95% (1·00004-1·00009); P<0·001). A cut-off by means of the Youden Index was calculated (10070·27pg/mL), and patients were retrospectively divided into two cohorts, in those above (31·3%) and those below (68·7%) this value. These two groups were then compared regarding mortality both after 30days and 1year: whereas 1-month mortality did not differ (7·0% vs. 10·3%, OR 1·50 95% CI (0·60-3·79; P=0·46)), patients with a sST2 concentration above the cut-off of 10070·27pg/mL showed a significantly worse outcome after 1year (49·2% vs. 23·2%; OR 3·21 95% CI (1·70-6·04); P<0·001). After correction for confounders in a multivariate Cox regression analysis, sST2 (1·0002 95% CI (1·0001-1·0003); P=0·001) concentration remained associated with mortality. sST2 levels were associated with 1-year mortality after TAVI. Based on these results, we assume that sST2 might help to identify patients at high risk for death in whom conservative treatment should be considered.

ALCAM a novel biomarker in patients with type 2 diabetes mellitus complicated with diabetic nephropathy

Background & AimActivated leukocyte cell adhesion molecule (ALCAM/CD166) functions analogue to the receptor of advanced glycation end products, which has been implicated in the development of diabetic nephropathy (DN). We investigated the expression of ALCAM and its ligand S100B in patients with DN. MethodsA total of 34 non-diabetic patients, 29 patients with type 2 diabetes and normal albuminuria and 107 patients with type 2 diabetes complicated with DN were assessed for serum concentration of soluble ALCAM (sALCAM) by ELISA. Expression of ALCAM and S100B in kidney histology from patients with DN was determined by immunohistochemistry. Cell expression of ALCAM and S100B was analyzed through confocal immunofluorescence microscopy. ResultsSerum concentration of sALCAM was increased in diabetic patients with DN compared to non-diabetic (59.85±14.99ng/ml vs. 126.88±66.45ng/ml, P<0.0001). Moreover sALCAM correlated positively with HbA1c (R=0.31, P<0.0001), as well as with the stages of chronic kidney disease and negatively correlated with eGFR (R=−0.20, P<0.05). In diabetic patients with normal albuminuria sALCAM was increased compared to patients with DN (126.88±66.45ng/ml vs. 197.50±37.17ng/ml, P<0.0001). In diabetic patients, ALCAM expression was significantly upregulated in both the glomeruli and tubules (P<0.001). ALCAM expression in the glomeruli correlated with presence of sclerosis (R=0.25, P<0.001) and localized mainly in the podocytes supporting the hypothesis that membrane bound ALCAM drives diabetic nephropathy and thus explaining sALCAM decrease in diabetic patients with DN. The expression of S100B was increased significantly in the glomeruli of diabetic patients (P<0.001), but not in the tubules. S100B was as well localized in the podocytes. ConclusionsThis study identifies for the first time ALCAM as a potential mediator in the late complications of diabetes in the kidney.

Evaluation of urinary desmosines as a noninvasive diagnostic biomarker in patients with idiopathic pleuroparenchymal fibroelastosis (PPFE)

BackgroundPleuroparenchymal fibroelastosis (PPFE) is a rare interstitial pneumonia with upper lobe predominance and fibroelastosis. Although definite diagnosis requires surgical lung biopsy (SLB), SLB is often difficult because of its complications such as refractory pneumothorax. ObjectiveTo evaluate urinary desmosines (degradation product of mature elastin) as a novel biomarker in patients with PPFE. MethodsBiopsy-proven patients with PPFE (n = 14) were prospectively enrolled. Levels of urinary desmosines in patients with PPFE were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared with those in patients with idiopathic pulmonary fibrosis (IPF), patients with chronic obstructive pulmonary disease (COPD), and controls. ResultsLevels of urinary desmosines were significantly higher in patients with PPFE than those in patients with IPF (48.4 vs. 28.6 ng/mg creatinine, p = 0.034), patients with COPD (8.0 ng/mg creatinine, p < 0.001), or controls (17.4 ng/mg creatinine, p < 0.001). Desmosines discriminated between PPFE and IPF (area under the curve [AUC] = 0.708), and between PPFE and controls (AUC = 0.956). However, levels of desmosines were not correlated with physiological parameters in patients with PPFE. ConclusionsUrinary desmosines may be a useful diagnostic biomarker in patients with PPFE. Measurement of desmosines combined with specific clinical and radiological features of PPFE may lead to an accurate diagnosis without SLB in patients with PPFE.

Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction.

BackgroundInsulin-like growth factor binding protein-7 (IGFBP-7) modulates the biological activities of insulin-like growth factor-1 (IGF-1). Previous studies demonstrated the prognostic value of IGFBP-7 and IGF-1 among patients with systolic heart failure (HF). This study aimed to evaluate the IGF1/IGFBP-7 axis in HF patients with preserved ejection fraction (HFpEF).MethodsSerum IGF-1 and IGFBP-7 levels were measured in 300 eligible consecutive patients who underwent comprehensive cardiac assessment. Patients were categorized into 3 groups including controls with normal diastolic function (n = 55), asymptomatic left ventricular diastolic dysfunction (LVDD, n = 168) and HFpEF (n = 77).ResultsIGFBP-7 serum levels showed a significant graded increase from controls to LVDD to HFpEF (median 50.30 [43.1-55.3] vs. 54.40 [48.15-63.40] vs. 61.9 [51.6-69.7], respectively, P < 0.001), whereas IGF-1 levels showed a graded decline from controls to LVDD to HFpEF (120.0 [100.8-144.0] vs. 112.3 [88.8-137.1] vs. 99.5 [72.2-124.4], p < 0.001). The IGFBP-7/IGF-1 ratio increased from controls to LVDD to HFpEF (0.43 [0.33-0.56] vs. 0.48 [0.38-0.66] vs. 0.68 [0.55-0.88], p < 0.001). Patents with IGFB-7/IGF1 ratios above the median demonstrated significantly higher left atrial volume index, E/E’ ratio, and NT-proBNP levels (all P ≤ 0.02).ConclusionIn conclusion, this hypothesis-generating pilot study suggests the IGFBP-7/IGF-1 axis correlates with diastolic function and may serve as a novel biomarker in patients with HFpEF. A rise in IGFBP-7 or the IGFBP-7/IGF-1 ratio may reflect worsening diastolic function, adverse cardiac remodeling, and metabolic derangement.

Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

To date, the value of fasting plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) as potential novel biomarkers in patients with neuroendocrine tumors (NETs) is unknown. The aims of this study are to (i) compare fasting AG and UAG levels between nonobese, nondiabetic NET patients (N=28) and age- (±3 years) and sex-matched nonobese, nondiabetic controls (N=28); and (ii) study the relationship between AG, UAG, and AG/UAG ratios and biochemical (chromogranin-A (CgA) and neuron-specific enolase (NSE) levels) and clinical parameters (age at diagnosis, sex, primary tumor location, carcinoid syndrome, ENETS TNM classification, Ki-67 proliferation index, grading, prior incomplete surgery) in NET patients. Fasting venous blood samples (N=56) were collected and directly stabilized with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride after withdrawal. Plasma AG and UAG levels were determined by ELISA. Expression of ghrelin was examined in tumor tissue by immunohistochemistry. There were no significant differences between NET patients and controls in AG (median: 62.5 pg/mL, IQR: 33.1–112.8 vs median: 57.2pg/mL, IQR: 26.7–128.3, P=0.66) and UAG in levels (median: 76.6pg/mL, IQR: 35.23–121.7 vs median: 64.9, IQR: 27.5–93.1, P=0.44). No significant correlations were found between AG, UAG, and AG/UAG ratios versus biochemical and clinical parameters in NET patients with the exception of age at diagnosis (AG: ρ= −0.47, P=0.012; AG/UAG ratio: ρ= −0.50, P=0.007) and baseline chromogranin-A levels (AG/UAG ratio: ρ= −0.44, P=0.019). In our view, fasting plasma acylated and unacylated ghrelin appear to have no value as diagnostic biomarkers in the clinical follow-up of patients with NETs.