Growth differentiation factor-15 combined with N-terminal prohormone of brain natriuretic peptide increase 1-year prognosis prediction value for patients with acute heart failure: a prospective cohort study / 中华医学杂志(英文版)

Background@#Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers. The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15 (GDF-15) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in assessing hospitalized patients with acute heart failure (AHF).@*Methods@#In total, 260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016. Medical history and blood samples were collected within 24 h after the admission. The primary endpoint was the all-cause mortality within 1 year. The patients were divided into survival group and death group based on the endpoint. With established mortality risk factors and serum GDF-15 level, receiver-operator characteristic (ROC) analyses were performed. Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15.@*Results@#Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors (P < 0.001). In ROC analyses, area under curve (AUC) for GDF-15 to predict 1-year mortality was 0.707 (95% confidence interval [CI]: 0.648–0.762, P < 0.001), and for NT-proBNP was 0.682 (95% CI: 0.622–0.738, P < 0.001). No statistically significant difference was found between the two markers (P = 0.650). Based on the optimal cut-offs (GDF-15: 4526.0 ng/L; NT-proBNP: 1978.0 ng/L), the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction (AUC = 0.743, 95% CI: 0.685–0.795, P < 0.001).@*Conclusions@#GDF-15, as a prognostic marker in patients with AHF, is not inferior to NT-proBNP. Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis.@*Clinical trial registration@#ChiCTR-ONC-12001944, http://www.chictr.org.cn.

The Prognostic Value of Serum Levels of Heart-Type Fatty Acid Binding Protein and High Sensitivity C-Reactive Protein in Patients With Increased Levels of Amino-Terminal Pro-B Type Natriuretic Peptide

BACKGROUND: Amino-terminal pro-B type natriuretic peptide (NT-proBNP) is a well-established prognostic factor in heart failure (HF). However, numerous causes may lead to elevations in NT-proBNP, and thus, an increased NT-proBNP level alone is not sufficient to predict outcome. The aim of this study was to evaluate the utility of two acute response markers, high sensitivity C-reactive protein (hsCRP) and heart-type fatty acid binding protein (H-FABP), in patients with an increased NT-proBNP level. METHODS: The 278 patients were classified into three groups by etiology: 1) acute coronary syndrome (ACS) (n=62), 2) non-ACS cardiac disease (n=156), and 3) infectious disease (n=60). Survival was determined on day 1, 7, 14, 21, 28, 60, 90, 120, and 150 after enrollment. RESULTS: H-FABP (P<0.001), NT-proBNP (P=0.006), hsCRP (P<0.001) levels, and survival (P<0.001) were significantly different in the three disease groups. Patients were divided into three classes by using receiver operating characteristic curves for NT-proBNP, H-FABP, and hsCRP. Patients with elevated NT-proBNP (≥3,856 pg/mL) and H-FABP (≥8.8 ng/mL) levels were associated with higher hazard ratio for mortality (5.15 in NT-proBNP and 3.25 in H-FABP). Area under the receiver operating characteristic curve analysis showed H-FABP was a better predictor of 60-day mortality than NT-proBNP. CONCLUSIONS: The combined measurement of H-FABP with NT-proBNP provides a highly reliable means of short-term mortality prediction for patients hospitalized for ACS, non-ACS cardiac disease, or infectious disease.

The value of N-terminal pro-B type natriuretic peptide in predicting the outcome of spontaneous breathing trials in elderly renal dysfunction patients / 中华危重病急救医学

Objective To investigate the value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in predicting the outcome of spontaneous breathing trial (SBT) in ventilated elderly renal dysfunction patients. Methods The clinical data of patients who received mechanical ventilation in the Department of Critical Care Medicine of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease from January 2011 to December 2014 were analyzed retrospectively. AU the patients conformed to the following criteria: age > 65 years, endogenous creatinine clearance rate (CCr) 72 hours and undergone at least one SBT. The patients were assigned to a SBT success group and a SBT failure group according to the outcome of first SBT. The following factors were recorded: gender, age, the underlying disease [chronic obstructive pulmonary disease (COPD), heart failure (HF) and others], body mass index (BMI), serum pre-albumin (pre-ALB), and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, CCr and the concentration of the plasma NT-proBNP before SBT. Receiver operator characteristic curve (ROC) was plotted, and the predict value of NT-proBNP for the outcome of SBT in elder patients with kidney dysfunction was determined. Results A total of 58 patients with complete data were enrolled, with 41 cases in SBT success group, and 17 in SBT failure group. There were no significant differences in gender [male/female (cases): 26/15 vs. 13/4, χ2 = 0.930, P = 0.335], age (years: 70.2±7.4 vs. 74.6±10.1, t = 0.833, P = 0.339), the stratification of underlying diseases [COPD/HF/COPD+HF/others (cases): 15/9/13/4 vs. 7/3/5/2, χ2 = 0.242, P = 0.971], BMI (kg/m2: 25.2±11.3 vs. 27.4±6.43, t = 1.038, P = 0.221), pre-ALB (mg/L: 201.0±13.2 vs. 189.0±7.6, t = 0.688, P = 0.519), and APACHE Ⅱ score (12.2±3.2 vs. 13.5±6.3, t = 1.482, P = 0.147) and CCr (mL·min-1·1.73 m-2: 51.3±7.7 vs. 54.2±6.4, t = 0.711, P = 0.487) before SBT between SBT success group and SBT failure group. The concentration of plasma NT-proBNP in SBT failure group was significantly higher than that of the SBT success group (μg/L: 4.162±1.128 vs. 2.284±1.399, t = 4.905, P = 0.000). The area under ROC curve for plasma NT-proBNP in predicting successful SBT among elder patients with kidney dysfunction was 0.878, with 95% confidence interval (95%CI) 0.786 - 0.970. The cut-off method was used, and it was identified that the concentration of NT-proBNP < 3.350 μg/L as a predictor for successful SBT, with sensitivity of 82.4%, specificity of 87.8%, positive prediction value of 88.1% and negative predictive value of 76.5%. Conclusion The concentration of plasma NT-proBNP may increase in elderly kidney dysfunction patients undergoing ventilation, and NT-proBNP < 3.350 μg/L can serve as a good predictor for SBT success.

Increased L-arginine Production by Site-directed Mutagenesis of N-acetyl-L-glutamate Kinase and proB Gene Deletion in Corynebacterium crenatum / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>In Corynebacterium crenatum, the adjacent D311 and D312 of N-acetyl-L-glutamate kinase (NAGK), as a key rate-limiting enzyme of L-arginine biosynthesis under substrate regulatory control by arginine, were initially replaced with two arginine residues to investigate the L-arginine feedback inhibition for NAGK.</p><p><b>METHODS</b>NAGK enzyme expression was evaluated using a plasmid-based method. Homologous recombination was employed to eliminate the proB.</p><p><b>RESULTS</b>The IC50 and enzyme activity of NAGK M4, in which the D311R and D312R amino acid substitutions were combined with the previously reported E19R and H26E substitutions, were 3.7-fold and 14.6% higher, respectively, than those of the wild-type NAGK. NAGK M4 was successfully introduced into the C. crenatum MT genome without any genetic markers; the L-arginine yield of C. crenatum MT-M4 was 26.2% higher than that of C. crenatum MT. To further improve upon the L-arginine yield, we constructed the mutant C. crenatum MT-M4 proB. The optimum concentration of L-proline was also investigated in order to determine its contribution to L-arginine yield. After L-proline was added to the medium at 10 mmol/L, the L-arginine yield reached 16.5 g/L after 108 h of shake-flask fermentation, approximately 70.1% higher than the yield attained using C. crenatum MT.</p><p><b>CONCLUSION</b>Feedback inhibition of L-arginine on NAGK in C. crenatum is clearly alleviated by the M4 mutation of NAGK, and deletion of the proB in C. crenatum from MT to M4 results in a significant increase in arginine production.</p>

Comparison of N-terminal Pro-B type Natriuretic Peptide and Tissue Doppler in Diagnosing Diagstoic Heart Failure.

Background: Heart failure (HF) has become a main cardiac problem. Doppler echocardiography has been used to examine left ventricular (LV) diastolic filling dynamics. Limitations of this modality suggest the need for other objective measures of diastolic HF. Aim of the Study: The hypothesis of this study is to assess the utility of N-terminal pro-B type natriuretic peptide (NTproBNP) in the diagnostic evaluation of diastolic HF in comparison with tissue Doppler imaging (TDI) recordings. Methods: A prospective study was carried out between May 2010 and December 2011. Patients with signs and symptoms of HF with normal LV systolic function by 2D-echocardiography were recruited. M-mode and 2-dimensional images, left atrial volume index (LAVI), spectral and TDI of the mitral annulus were obtained for all the patients. NTproBNP levels were measured with a bedside immunoassay. Results: We found linear correlation between NTproBNP levels and grade of diastolic dysfunction (DD), LAVI, ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/E’) [r=0.72, p<0.001]. Patients with elevated left ventricular end diastolic pressure, defined as E/E’>15 (n =18), had the highest NTproBNP levels (3028±2674pg/mL). NTproBNP levels (4146±2887.43 pg/mL) were highest in patients with grade III DD. A receiver operator characteristic curve showed NTproBNP value, 286 pg/mL, the best cut-off for diagnosing diastolic HF with a sensitivity of 89% and a specificity of 100%. Conclusions: Plasma NTproBNP levels can reliably estimate LV filling pressures in patients with HF and normal systolic function which might help to reinforce the diagnosis of “diastolic HF”.

Therapeutic effect of trimetazidine on patients with ischemic cardiomyopathy heart failure and significance of plasma level of N-terminal pro-B type natriuretic peptide / 中国基层医药

Objective To observe the therapeutic effect of trimetazidine on patients with ischemic cardiomyopathy heart failure and the changes of plasma level of N-terminal pro-B type natriuretic peptide(NT-proBNP).Methods 62 patients with ischemic cardiomyopathy heart failure were randomly assigned to regular treatment group(3 1)and trimetazidine treatment group(31).All of them were given either regular medicine treatment or trimetazidine for 4 weeks.Concentration of NT-proBNP and echocardiography were detected before and after treatment and the correlation between NT-pmBNP and ultra-sound values was studied.Results There was no statistic difference in the NT-proBNP level between two groups before treatment,but after 4-week treatment the NT-proBNP level in both groups were deCreased(P＜0.05),the decline in the trimetazidine group was more significant.The NT-proBNP level was significantly correlated to LVEF and LVEDD(γ=-0.472、0.45 1;P＜0.05).Conclusions Trimetazidine has a positive effect on patients with ischemic cardiomyopathy heart failure,and decreases the plasma NT-proBNP level.NT-proBNP Can be used as a follow-up index.

Caracterización biológica y clínica de pacientes pediátricos con leucemia linfoide aguda pro-B / Biological and clinical characterization of pediatric patients with pro-B acute lymphocytic leukemia

Se estudiaron las características biológicas y clínicas de 19 niños con leucemia linfoide aguda (LLA) pro-B en un periodo de 14 años. El inmunofenotipaje celular se realizó mediante el ultramicrométodo inmunocitoquímico. Se observó una mayor incidencia en el grupo de 2-5 años. La distribución por raza en este trabajo fue la misma que en la población normal. Los niños varones de piel blanca fueron los más afectados. El 73,7 % de los pacientes mostró leucocitos < 20 x109 /L al inicio de la enfermedad y el 57,9 % mostró hepatomegalia y esplenomegalia. Se observaron adenopatías y manifestaciones hemorrágicas en el 47,4 % y en el 2 %, respectivamente. El antígeno CD19 se expresó en el 100 % de los pacientes, el CD22 citoplasmático en el 89,5 %, la enzima Tdt en el 68,4 % y el HLA-DR en el 57,9 %. Del total de pacientes estudiados, 4 (21 %) expresaron antígenos mieloides y fueron clasificados como LLA pro-B Mi+. Los antígenos mieloides expresados fueron, en un paciente el CD13 y CD33 (5,3 %), y el CD15 en 2 enfermos (10,5 %). Estos resultados demuestran que la LLA es una enfermedad heterogénea con subtipos biológicos y clínicos diferentes.

The biological and clinical characteristics of 19 children with pro-B acute lymphocytic leukemia were studied during 14 years. The cellular immunophenotyping was performed by the immunocytochemical ultramicrornethod. A higher incidence was observed in a group aged 2-5 years old. The distribution by race was the same as in the normal population. The white boys were the most affected. 73.7 % of the patients presented leukocytes < 20x10 9 /L at the onset of the disease, and 57.9 % had hepatomegaly and splenomegaly. Adenopathies and hemorrhagic manifestations were observed in 47.4 % and in 2 %, respectively. The CD19 antigen was expressed in 100 % of the patients, the CD22 plasmatic antigen in 89.5 %, the Tdt enzyme in 68.4 % and HLA-DR in 57.9 %. Of the total of studied patients, 4 (21 %) expressed myeloid antigens and were classified as pro-B LLA-Mi+. The expressed myeloid antigens were CD13 and CD33 (5.3 %) in a patient, and CD15 in 2 patients (10.5 %). These results show that LLA is a heterogenous disease with different biological and clinical subtypes.