Impact of CT-apelin and NT-proBNP on identifying non-responders to cardiac resynchronization therapy

Context: Assessment of response to cardiac resynchronization therapy (CRT) is essential.

Objective: To assess the predictive value of CT-apelin together with NT-proBNP in patients undergoing CRT.

Methods: Serum CT-apelin and NT-proBNP were measured by ELISA before, and six months after CRT. Primary endpoint was non-response (<4% increase in LVEF) after six months.

Results: From 81 patients, 15 proved to be non-responders. Six-month CT-apelin was superior compared to NT-proBNP in identifying non-responders by multivariate ROC (CT-apelin: p?=?0.01, NT-proBNP: p?=?0.13) and by logistic regression (CT-apelin: p?=?0.01, NT-proBNP: p?=?0.41) analyses.

Conclusion: Six-month CT-apelin might be a valuable novel biomarker in identifying non-responders to CRT that was superior to NT-proBNP.     

Low YKL-40 in chronic heart failure may predict beneficial effects of statins: analysis from the controlled rosuvastatin multinational trial in heart failure (CORONA)

Context and objective: To evaluate if YKL-40 can provide prognostic information in patients with ischemic heart failure (HF) and identify patients who may benefit from statin therapy.

Materials and methods: The association between serum YKL-40 and predefined outcome was evaluated in 1344 HF patients assigned to rosuvastatin or placebo.

Results: YKL-40 was not associated with outcome in adjusted analysis. In YKL-40 tertile 1, an effect on the primary outcome (HR 0.50, p?=?0.006) and CV death (HR 0.54, p?=?0.040) was seen by rosuvastatin in adjusted analysis.

Conclusions: A beneficial modification of outcome was observed with statin therapy in patients with low YKL-40 levels.     

Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project

Purpose: Elevation of high-sensitivity cardiac troponin T (hs-cTnT) is associated with an increased risk of cardiovascular disease (CVD). This study determined whether hs-cTnT was detectable with N-terminal pro-b-type natriuretic peptide (NT-proBNP) and related to CV risk factors in a general Japanese population.

Materials and methods: The Tohoku Medical Megabank Organization pooled individual participant data for a population-based cohort study in the Iwate prefecture (n?=?30,193, age = 60.2?±?11.5?year).

Results: Hs-cTnT levels were higher in participants with hypertension, diabetes mellitus than in participants without these conditions (all ps < 0.001). Logistic regression analysis demonstrated that NT-proBNP was strongly associated with elevation of hs-cTnT (OR = 3.35, 95% CI = 2.90–3.89, p?<?0.001). The receiver operating characteristic curve analysis showed that hs-cTnT was one of useful biomarker for the differentiation of high risk for CVD (the Suita score ≥ 56) from a general population. Logistic regression analysis demonstrated hs-cTnT levels were related to the CVD high risk group (OR = 2.67, 95% CI = 2.28–3.14, p?<?0.001).

Conclusions: Hs-cTnT levels are associated with elevation of NT-proBNP and high Suita score, which suggests that elevated hs-cTnT is related to subclinical myocardial damage and indicates CV risk.     

Circulating levels of apoptotic markers and oxidative stress parameters in women with polycystic ovary syndrome: a case-controlled descriptive study

Context: Apoptotic dysregulation plays a role in the pathogenesis of polycystic ovary syndrome (PCOS).

Objective: To evaluate circulatory apoptotic markers and oxidative stress in patients with PCOS.

Materials and methods: Forty-four women with PCOS, and 44 healthy women as controls were enrolled in the study. Oxidative stress parameters and caspases levels were measured in serum.

Results: The caspase 9 level was significantly lower and related with oxidant status in patients with PCOS, while the circulating levels of caspases 3 and 7 were statistically similar in both groups.

Discussion: This study is the first report demonstrating the circulating levels of apoptotic markers and their relationship with oxidant status in PCOS.

Conclusion: The circulating caspase 9 and oxidant status might contribute to apoptotic dysregulation in PCOS.     

Prognostic prediction in acute heart failure patients with extreme BNP values

Background: Some patients have good prognosis despite elevated B-type natriuretic peptide (BNP), while others have ominous outcome with low BNP. We aimed at characterising these groups of patients.

Methods: We analysed patients prospectively included in an acute HF registry. Vital status within 1-year post discharge was ascertained. A receiver–operating characteristic curve was used to define discharge BNP cut-offs for 1-year death prediction. Among survivors, we compared patients with low and not-low BNP (cut-off 400?pg/mL); and among non-survivors those with high vs not-high BNP (cut-off 2000?pg/mL). In the specific subgroups of patients with low and high BNP, mortality predictors were assessed with multivariate Cox-regression analysis.

Results: We studied 584 patients, median age 78 years, 62.5% had HF with reduced ejection fraction; and 199 (34.1%) died during the first year. Non-survivors were very homogeneous irrespective of BNP, survivors were substantially different. In patients discharged with BNP <400?pg/mL, increasing age independently predicted death; when BNP ≥2000?pg/mL death predictors were higher NYHA class, and non-use of evidence-based therapy. BNP was outcome associated in both groups.

Conclusions: Different prognostic predictors may play a role in different BNP levels. We suggest that risk stratification in HF would probably be more accurate if made on top of BNP knowledge.     

Plasma myostatin levels are related to the extent of right ventricular dysfunction in exacerbation of chronic obstructive pulmonary disease

Objective: To investigate the relationship between plasma myostatin levels and right ventricle (RV) dysfunction (RVD) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods: The study recruited 84 patients with AECOPD. Plasma myostatin was analyzed and tricuspid annular plane systolic excursion (TAPSE)?<?16?mm was used as the main indicator for RVD.

Results: Plasma myostatin levels were significantly higher in 47 patients with RVD than 37 ones without (P?<?0.005). Multivariate regression analysis revealed that myostatin levels correlated significantly with TAPSE values and RV myocardial performance index (p?<?0.001) among the study patients.

Conclusion: Plasma myostatin is a potential biomarker for improving diagnosis of RVD in AECOPD.     

Soluble CD40 ligand in haemodialysis patients: survival impact and cardiovascular prognostic role

Context: Soluble CD40 ligand (sCD40l) can predict cardiovascular events (CVE) and mortality in haemodialysis (HD) patients (short-, medium-term follow-up studies).

Objective: To evaluate the relationship between sCD40l and survival, CVE and mortality in HD patients on long-term follow-up.

Methods: We registered 46?HD patients’ baseline characteristics, mortality and CVE for 108 months.

Results: SCD40l correlated positively with C-reactive protein, was higher in survivors, but had no impact on survival and was not predictive for CVE or CV mortality.

Conclusion: The levels of sCD40l have no influence on survival or CVE and mortality in HD patients in a long-term follow-up.     

Prognostic significance of insulin-like growth factor-I serum levels in acute decompensation of cirrhosis

Context: IGF-I serum levels are suppressed in cirrhosis, but its prognostic significance is unknown.

Objectives: To investigate the prognostic value of IGF-I in patients admitted for acute decompensation of cirrhosis.

Materials and methods: Cohort study that included 103 patients. IGF-I was measured by enzyme-linked immunosorbent assay (ELISA).

Results: Ninety-day mortality was 26.2% and it was independently associated with MELD, age and IGF-I. The Kaplan–Meier survival probability at 90 days was 94.3% in patients with IGF-I?≥13?ng/mL and 63.2% for patients with IGF-I?<13?ng/mL (p?=?.001).

Discussion and conclusion: IGF-I levels are independently associated with mortality in acute decompensation of cirrhosis.     

Soluble TREM-1 as a diagnostic and prognostic biomarker in patients with septic shock: an observational clinical study

Objectives: The impact of TREM-1-mediated inflammation was investigated in different inflammatory settings.

Methods: Secondary analyses of an observational clinical pilot study, including 60 patients with septic shock, 30 postoperative controls and 30 healthy volunteers.

Results: Plasma levels of sTREM-1 were found to identify patients with septic shock more effectively than procalcitonin and C-reactive protein. Moreover, sTREM-1 was identified to be an early predictor for survival in patients with septic shock.

Conclusion: Due to its diagnostic as well as prognostic value in sepsis syndrome, implementation of sTREM-1 measurements in routine diagnostics should be taken into account.     

Association of IL-10 (-819T/C, -592A/C and -1082A/G) and IL-6 -174G/C gene polymorphism and the risk of pneumonia-induced sepsis

Context: Association between inherited variants and the risks of sepsis is controversial.

Objective: To evaluate the risk of pneumonia-induced sepsis by examining its linkage with polymorphisms of IL-6 and IL-10.

Materials and methods: Samples were obtained from 188 pneumonia-induced sepsis patients, 162 pneumonia patients and 200 healthy controls.

Results: Subjects with IL-10 -1082 AA genotypes and IL-6 -174?CC genotype had a higher risk of sepsis and increased mRNA levels.

Conclusion: The variants of IL-10 -1082 A allele and IL-6 -174 C allele contributed to an increased risk of pneumonia-induced sepsis.     

Circulating adiponectin as a biomarker in renal cell carcinoma: a systematic review and meta-analysis

Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels.

Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC.

Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan.

Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels.

Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.     

Release kinetics of high-sensitivity cardiac troponins I and T and troponin T upstream open reading frame peptide (TnTuORF) in clinically induced acute myocardial infarction

Context: Troponin T upstream open reading frame peptide (TnTuORF) may be useful as a novel biomarker in acute cardiac syndromes.

Objective: The study examined the early release kinetics of TnTuORF.

Materials and methods: We analyzed the time course of the release of cardiac troponins I and T and TnTuORF in patients (n?=?31) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH).

Results: Fifteen minutes after TASH, the levels of both troponins increased significantly (cTnT median: 18?ng/L versus 27?ng/L; cTnI median: 15?ng/L versus 25?ng/L). TnTuORF showed no variation.

Discussion: We observed a significantly greater increase in cTnI compared with cTnT.

Conclusion: Our results demonstrate that troponin assays allow early detection of myocardial injury, whereas TnTuORF levels remain unchanged in this setting.     

Nickel exposure and plasma levels of biomarkers for assessing oxidative stress in nickel electroplating workers

Context: The mechanism of nickel-induced pathogenesis remains elusive.

Objective: To examine effects of nickel exposure on plasma oxidative and anti-oxidative biomarkers.

Materials and methods: Biomarker data were collected from 154 workers with various levels of nickel exposure and from 73 controls. Correlations between nickel exposure and oxidative and anti-oxidative biomarkers were determined using linear regression models.

Results: Workers with a exposure to high nickel levels had significantly lower levels of anti-oxidants (glutathione and catalase) than those with a lower exposure to nickel; however, only glutathione showed an independent association after multivariable adjustment.

Discussion and conclusion: Exposure to high levels of nickel may reduce serum anti-oxidative capacity.     

Beta-2-glycoprotein-1 and alpha-1-antitrypsin as urinary markers of renal cancer in von Hippel–Lindau patients

Context: Von Hippel–Lindau disease (VHLD) is a rare inherited neoplastic syndrome. Among all the VHLD-associated tumors, clear cell renal cell carcinoma (ccRCC) is the major cause of death.

Objective: The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients.

Materials and methods: We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers.

Results: Among all differentially expressed proteins, alpha-1-antitrypsin (A1AT) and APOH (beta-2-glycoprotein-1) are strongly over-abundant only in the urine of VHLD patients with a history of ccRCC.

Discussion and conclusion: A1AT and APOH could be promising non-invasive biomarkers.     

Identification of circulating protein biomarkers in patients with hepatocellular carcinoma concomitantly infected with chronic hepatitis C virus

Context: The incidence rate of hepatocellular carcinoma (HCC) is higher in developing countries, and most cases are associated with chronic hepatitis C virus (HCV) infection.

Objective: To evaluate the circulating proteins as liver biomarkers for the identification of HCC associated with HCV infection in Egyptian patients using LC-MS/MS analysis.

Methods: Blood sera were collected from 31 HCC patients and the fractionated proteins were subjected to LC-MS/MS analysis. Protein candidates were validated by enzyme-linked immunosorbent assay (ELISA).

Results: Thirty-three proteins were significantly identified in the sera of HCC patients with persistent HCV infection. These proteins are involved in several biological processes including acute phase response, complement activation, hemostasis process and lipid metabolism. The level of lectin galactoside-binding soluble 3 binding protein (LGALS3BP), Kininogen-1 (KNG1), serum amyloid A2 (SAA2) and paraoxonase 1 (PON1) and alpha-fetoprtoein (AFP) were elevated in serum.

Conclusion: In HCC patients with chronic HCV infection, we identified a group of differentially expressed circulating proteins involved in regulating different cellular mechanisms.     

The prognostic value of MR-proadrenomedullin in patients with acute coronary syndrome complicated by cardiogenic shock

Context: Cardiogenic shock (CS) still remains one of the main causes of death in acute myocardial infarction (AMI).

Objective: The aim of this study was to evaluate the prognostic value of midregional (MR)-proadrenomedullin in AMI complicated by CS.

Methods: Forty-seven consecutive patients were included in our prospective observational study. All patients underwent coronarography and successful percutaneous coronary intervention (PCI). Plasma levels of MR-proADM were measured by a immunofluorescence method. The primary endpoint of the study, defined as cardiovascular death, occurred in 17 patients (36%).

Results and conclusion: Elevated plasma level of MR-proADM, determined 24?h after diagnosis of CS could be a predictor of in-hospital mortality in patients with AMI complicated by CS.     

Positive effects of plantar vibration training for the treatment of diabetic peripheral neuropathy: A pilot study

Purpose: To evaluate the effectiveness of 8-week low-frequency plantar vibration training on patients with sensorimotor diabetic peripheral neuropathy (DPN).

Participants: Twelve patients took part in the investigation.

Results: An increase of the nerve conductive velocity of soral and peroneal nerves of feet, increased postural stability, and disappearance of the pain and tingling were observed.

Conclusion: The obtained results provide evidence for beneficial effects of 8-week plantar vibration training in patients with DPN.     

Propeptide big-endothelin,N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study

Context: The endothelin system (Big-ET-1) is a key regulator in cardiovascular (CV) disease and congestive heart failure (CHF).

Objectives: We have examined the incremental value of Big-ET-1 in predicting total and CV mortality next to the well-established CV risk marker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP).

Methods: Big-ET-1 and NT-proBNP were determined in 2829 participants referred for coronary angiography (follow-up 9.9 years).

Results: Big-ET-1 is an independent predictor of total, CV mortality and death due to CHF.

Discussion: The conjunct use of Big-ET-1 and NT-proBNP improves the risk stratification of patients with intermediate to high risk of CV death and CHF.

Conclusions: Big-ET-1improves risk stratification in patients referred for coronary angiography.     

Kallistatin levels in HIV-infected patients and effects of statin therapy

Background: Kallistatin, a serine proteinase inhibitor, has vasodilatory and anti-inflammatory properties and is increased in other inflammatory conditions. We measured kallistatin in HIV for the first time, examined its relationship with inflammation, and determined if statin therapy affected levels.

Methods: Kallistatin levels were measured in subjects from a randomized, double-blinded, placebo-controlled trial.

Results: One hundred and thirty-five HIV-infected subjects were included. Kallistatin levels were 28.4?μg/mL at baseline and not affected by rosuvastatin. Levels were correlated with high-sensitivity C-reactive protein (hsCRP), interleukin-6, fibrinogen and insulin resistance.

Conclusions: Kallistatin levels were correlated with some markers of systemic inflammation and should be further explored in the HIV population.     

Validation of a protein panel for the noninvasive detection of recurrent non-muscle invasive bladder cancer

Context: About 50–70% of patients with non-muscle invasive bladder cancer (NMIBC) experience relapse of disease.

Objective: To establish a panel of protein biomarkers incorporated in a multiplexed microarray (BCa chip) and a classifier for diagnosing recurrent NMIBC.

Materials and methods: Urine samples from 45 patients were tested. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis.

Results: A multi biomarker panel (ECadh, IL8, MMP9, EN2, VEGF, past recurrences, BCG therapies and stage at diagnosis) was identified yielding an area under the curve of 0.96.

Discussion and conclusion: This biomarker panel represents a potential diagnostic tool for noninvasive diagnosis of recurrent NMIBC.