Prognostic Biomarker In Children Research Articles

The Neutrophil-to-Lymphocyte Ratio (NLR) as a Prognostic Biomarker in Children with Guillain-Barre Syndrome (GBS): A Systematic Review (P9-11.003)

The Neutrophil-to-Lymphocyte Ratio (NLR) as a Prognostic Biomarker in Children with Guillain-Barre Syndrome (GBS): A Systematic Review (P9-11.003)

Long Non-coding RNA RP11-252C15.1 is a Potential Biomarker of Prognosis and Hallmark for Leukemogenesis in Children with B-cell Precursor Acute Lymphoblastic Leukemia.

Improved understanding of the prognostic biomarkers associated with childhood acute lymphoblastic leukemia (ALL) is needed for accurate risk group stratification. This study aimed to identify potential long-non coding RNA (lncRNA) markers and evaluate their prognostic value in children with ALL. We selected 50 children with newly diagnosed ALL and 20 age-matched patients with idiopathic immune thrombocytopenia (controls). RNA sequencing was performed to identify differentially expressed lncRNAs between the ALL and control groups. Correlation analysis was performed to determine the relationships between candidate lncRNAs, clinical features, and the risk of leukemogenesis. A total of 1,019 differentially expressed lncRNAs were identified between the ALL and control groups. Reverse-transcriptase (RT-qPCR) revealed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 were significantly upregulated in patients with ALL. Furthermore correlation analysis showed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 represent potential predictors of leukemogenesis; however, only lncRNA RP11-252C15.1 was associated with clinical features and outcome in children with B-cell precursor ALL (BCP-ALL). In vitro experiments confirmed that lncRNA RP11-252C15.1 was significantly overexpressed in BCP-ALL cell lines and promoted proliferation, and repressed apoptosis in MHH-CALL-3 cells. LncRNA RP11-252C15.1 is a potential oncogene in BCP-ALL pathogenesis and a prognostic biomarker in children with BCP-ALL.

Neutrophil-to-lymphocyte ratio as a predictive and prognostic marker in children with dilated cardiomyopathy.

We aimed to evaluate neutrophil-to-lymphocyte ratio in children with acute heart failure due to dilated cardiomyopathy, to assess the predictive and prognostic values of neutrophil-to-lymphocyte ratio, and to correlate its levels with brain natriuretic peptide and other various data in these patients. We included 50 children with acute heart failure due to dilated cardiomyopathy as the patient group. Fifty healthy children of matched age and sex served as the control group. Patients were evaluated clinically and by echocardiography. A complete blood count with differentiation to evaluate neutrophil-to-lymphocyte ratio was done, and the serum level of brain natriuretic peptide was also measured. All patients were followed up for death or readmission for a period of one year. Neutrophil-to-lymphocyte ratio was significantly higher in patient group as compared to the control group. Neutrophil-to-lymphocyte ratio was significantly increased in patients with higher severity of heart failure. There was a significant increase in neutrophil-to-lymphocyte ratio in patients with bad prognoses compared to those with good prognoses. There was a significant positive correlation between neutrophil-to-lymphocyte ratio and both brain natriuretic peptide and clinical stage of heart failure while there was a significant negative correlation between neutrophil-to-lymphocyte ratio and left ventricular systolic function. The best cut-off of neutrophil-to-lymphocyte ratio to predict adverse outcomes in children with dilated cardiomyopathy was >3.6 with 87% sensitivity and 79% specificity. The cut-off of neutrophil-to-lymphocyte ratio to predict patients who will not respond to conventional treatment was ≥3.85 with 85% sensitivity and 100% specificity. Neutrophil-to-lymphocyte ratio is a cheap good predictive and prognostic biomarker in children with dilated cardiomyopathy.

Differences in Cerebellar Volume as a Diagnostic and Prognostic Biomarker in Children and Adolescents With Epilepsy of Unknown Etiology.

Epilepsy is one of the most common brain diseases during childhood and adolescence. Atrophy in different brain areas is possible during epilepsy. This study aimed to verify whether cerebellar volume differences could be detected by volume analysis using magnetic resonance imaging (MRI) in children with epilepsy. In this retrospective study, 41 children (3.1-18.8 years) with epilepsy of unknown etiology were included (duration of epilepsy 1.9 ± 3 years). A cranial MRI with a volumetric 3-dimensional, T1-weighted sequence was used for volume analysis. The MRIs of 26 patients with headache (5.3-17.1 years) were analyzed for comparison. A volume analysis of the cerebellum was performed using region-based morphometry. Total cerebellar volume, total white and gray matter volume, and 48 regional lobules (L), separated into white and gray matter, were calculated. Cerebellar volumes are presented in relative ratios as the volume fraction of cerebellar volume to total intracranial volume: CV/TIV. The ratio of overall white matter volume was significantly lower in the case group (23.93 × 10-3, P = .039). A significantly lower ratio of regional white matter volume was detected in LV right (P = .031) and left (P = .014), in LVIIIB right (P = .011) and left (P = .019), and in LVIIIA left (P = .009). Our results emphasize that volume analysis of the total cerebellar volume alone is insufficient to characterize cerebellar differences in children with epilepsy. Rather, in specific cerebellar region volume analysis using region-based morphometry, children with epilepsy showed significantly lower regional volumes of lobules, which are important for sensorimotor function (LV, LVIII) and higher cognitive function (crus I).

High levels of blood circulating immune checkpoint molecules in children with new-onset type 1 diabetes are associated with the risk of developing an additional autoimmune disease.

We assessed the levels of blood circulating immune checkpoint molecules (ICMs) at diagnosis of type 1 diabetes, and determined their association with the risk of developing an additional autoimmune disorder over time. Children with new-onset type 1 diabetes (n = 143), without biological and/or clinical signs of additional autoimmune disorders, and healthy children (n = 75) were enrolled, and blood circulating levels of 14 ICMs were measured. The children with type 1 diabetes were divided into two groups on the basis of the development of an additional autoimmune disease in the 5years after diabetes onset. Differences in soluble ICM levels between the groups were assessed, and a Cox regression analysis was used to evaluate their association with the risk of development of an additional autoimmune disease over time. To validate the data, circulating ICMs were measured in an independent cohort of 60 children with new-onset type 1 diabetes stratified into two groups. We found that the levels of circulating ICMs were significantly higher in children with new-onset diabetes compared with healthy children. Further, we observed that children with type 1 diabetes who developed a second autoimmune disease over time (T1D-AAD+ children) had higher levels of soluble ICMs than children with type 1 diabetes who did not (T1D-AAD- children). Cox regression models revealed that high circulating levels of CD137/4-1BB and PD-1 molecules at diabetes diagnosis were associated with the risk of developing an additional autoimmune disease in both type 1 diabetes cohorts. Our findings suggest that soluble CD137/4-1BB and PD-1 molecules may be used as prognostic biomarkers in children with type 1 diabetes, and may pave the way for novel immunological screening at diabetes onset, allowing early identification of children at higher risk of developing other autoimmune conditions over time.

B type natriuretic peptide (BNP) as diagnostic and prognostic biomarker in children with congestive heart failure

Background: Pediatric acute heart failure is now being increasingly recognized as an important source of healthcare resource utilization. B-type natriuretic peptide (BNP) continues to be the dominant biomarker in pediatric heart failure. This study aimed to prove the role of BNP in diagnosis and prognosis of congestive heart failure in children. Method: This case control study was performed in Zagazig University Hospitals and include 60 infants and children who divided into 2 groups, group 1 consists of 30 children diagnosed by congestive heart failure and group 2 consists of 30 age and sex-matched apparently healthy children. Serum BNP level measured for both groups with assessment to the cardiac function, CBC, CRP and serum creatin level. Result: BNP and is significantly higher among CHF patients compared to controls. BNP is found to be higher in patients with sever heart failure compared to moderate and mild HF patients with significance correlation. BNP is found to be higher among congestive heart disease patients with sensitivity 93.3% and specificity 76%. BNP is a significant independent diagnostic parameter for CHF. BNP is found to be non-significant prognostic factors for children with CHF. Conclusion: BNP continues to be the dominant biomarker in pediatric heart failure. BNP is a significant diagnostic marker in diagnosis of heart failure, while it found to be non-significant prognostic factor in CHF.

Circulating miR-26a as Potential Prognostic Biomarkers in Pediatric Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) arises from myogenic precursors that fail to complete muscle differentiation and represents the most frequent soft tissue sarcoma in children. Two major histological subtypes are recognized: alveolar RMS, characterized by a more aggressive behavior and a greater proneness to metastasis, and embryonal RMS which accounts for the 80% of cases and carries a better prognosis. Despite the survival of patients with localized tumors has progressively improved, RMS remains a challenging disease especially for metastatic patients and in case of progressive or recurrent disease after front-line therapy. MicroRNAs, a class of small non-coding RNA, have emerged as crucial players in cancer development and progression, and their detection in plasma (circulating miRNAs) represents a promising minimally invasive approach that deserve to be exploited in clinical practice. We evaluated the utility of circulating miRNAs as diagnostic and prognostic biomarkers in children with RMS profiling miRNAs from plasma of a small cohort of RMS patients and healthy donors (HD) using a qPCR Cancer Panel. An assessment of hemolysis status of plasma using miR-451/miR-23a ratio was performed as pre-analytical analysis. Statistical analysis revealed that miRNAs expression pattern clearly distinguished RMS patients from HD (p < 0.05). Interestingly, plasma levels of muscle-specific miR-206 were found to be significantly increased in RMS patients compared to HD, whereas levels of three potential tumor-suppressor miRNAs, miR-26a and miR-30b/30c, were found lower. Reduced levels of circulating miR-26a and miR-30b/c were further measured in an independent larger cohort of patients (validation set) by digital droplet PCR. In particular, we evidenced that miR-26a absolute plasma levels were associated with fusion status and adverse outcome (p < 0.05). Taken together, these findings demonstrate the potential of circulating miRNA as diagnostic and prognostic biomarker in children affected by this malignancy and enforced the key role of miR-26a in pediatric rhabdomyosarcoma.

Cardiac Myosin Binding Protein C Plasma Level as a Diagnostic and Prognostic Biomarker in Heart Failure in Children

Background: Heart failure is one of the cardiovascular diseases that have high morbidity and mortality especially among children. It accounts for 2% of all pediatric inpatient admission. Cardiac Myosin Binding Protein-C (cMyBP-C) is cardiomyocyte specific sarcomeric protein that regulates sarcomeric structure and its function where it is released in circulation in response to cardiac injury. Objective: To explore the role of cMyBP-C as a biomarker in heart failure in children. Patients and Methods: This prospective cohort study was carried out during the period from October 2017 to October 2018 in Pediatric Cardiology Unit, Zagazig University Hospital. It included 26 selected patients with heart failure diagnosed clinically and by echocardiography. Results: The study revealed that the most common cause pf heart failure in our patients was VSD (30.8%) then DCM (26.9%). 57.7% of studied patients were grade III of ROSS classification while 30.8% were grade IV and 11.5% were grade II. In ECHO findings, mean EF% was 52.3% while mean FS% was 33 % with negative correlation between plasma level of cMyBP-C and EF% and FS%. There was high statistical significant difference in cMyBP-C plasma level at time of admission and after treatment (123.5 ng/ml and 78.8 ng/ml respectively). There was high statistical significant difference in level of cMyBP-C among improved cases before and after treatment. There was no statistical significant difference in level of cMyBP-C before and after treatment among cases with bad prognosis. Conclusion: cMyBP-C could be a prognostic biomarker in children with HF and may be used as a tool to help in HF diagnosis in children as a marker of disease severity.

Anti-Saccharomyces cerevisiae Antibodies as a Prognostic Biomarker in Children With Crohn Disease.

Although anti-Saccharomyces cerevisiae antibodies (ASCAs) could be a useful biomarker in differentiating Crohn disease (CD) from ulcerative colitis (UC), their role as prognostic markers in children with CD has been underinvestigated. This longitudinal prospective observational study aimed to assess the prognostic value of ASCA status among children with CD managed using biologics. The study population comprised children with inflammatory bowel disease diagnosed with CD from 2012 to 2018. Cox regression model with adjustment for a priori covariates was used to examine the response to anti-tumor necrosis factor (TNF) biological therapy among ASCA-positive patients in comparison to ASCA-negative patients. There were 273 measurements available from the study cohort comprising children with CD, who were followed up for a median duration of 14 months (interquartile range 5-42). ASCA-positive patients had a higher risk for moderate to severe clinical disease (odds ratio 2.88; 95% confidence interval [CI] 1.2-7.55) and extensive endoscopic distribution (odds ratio 3.30; CI 1.12-9.74) at baseline in comparison to ASCA-negative patients, respectively. In comparison to ASCA immunoglobulin G (IgG)-negative patients, ASCA IgG-positive patients who were treated with biologics had a significantly lower relapse rate (adjusted hazard ratio 0.12; CI 0.02-0.93). Ten (14%) patients had an unstable ASCA value with either ASCA immunoglobulin A or ASCA IgG status changing from positive to negative or vice versa. ASCA-positive children with CD present with more extensive (endoscopic) and clinically severe disease. ASCA IgG is a useful prognostic marker among children with CD who receive biologics.

Circulating MicroRNA-21, MicroRNA-23a, and MicroRNA-125b as Biomarkers for Diagnosis and Prognosis of Burkitt Lymphoma in Children.

BackgroundThe aim of this study was to investigate the diagnostic and prognostic value of microRNA (miRNA)-21, miRNA-23a, and miRNA-125b in Burkitt lymphoma (BL) in children.Material/MethodsWe recruited 41 children with BL for the case group, 56 children with lymph node inflammation for the positive control group, and 60 healthy children for the negative control group. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was conducted for detection of circulating miRNA-21, miRNA-23a, and miRNA-125b. A receiver operating characteristic (ROC) curve was drawn to compare the diagnostic value of miRNA-21, miRNA-23a, and miRNA-125b. Kaplan-Meier method and log-rank test were used for prognostic analyses.ResultsMiRNA-21 and miRNA-23a had significantly higher expression in cases than in positive and negative controls (all P<0.05). Overexpression of miRNA-21 and miRNA-23a were associated with staging, WBC, upregulated serum lactate dehydrogenase (LDH) level, presence of lymphoma size ≥6 cm, and cluster of differentiation 10 (CD10) expression, while miRNA-125b expression had an association with staging and upregulated serum LDH level (both P<0.05). ROC curves of miRNA-21, miRNA-23a, and miRNA-125b presented an area under curve (AUC) of 0.759, 0.853 and 0.615, respectively. MiRNA-21 and miRNA-23a in combination had an AUC of 0.869. After treatment, both miRNA-21 and miRNA-23a expression were significantly decreased (both P<0.05). Advanced clinical stage, upregulated LDH, and lymphoma size of ≥6 cm were related to low complete remission rate (all P<0.05).ConclusionsPatients with high expression of miRNA-21 and miRNA-23a had significantly lower complete remission rates and survival rates than those with low expression. Expression of miRNA-21 and miRNA-23a may serve as useful diagnostic and prognostic biomarkers in children with BL.

Diagnostic and Prognostic Value of Plasma Levels of Cardiac Myosin Binding Protein-C as a Novel Biomarker in Heart Failure.

Heart failure (HF) has high morbidity and mortality in children. This study aimed to investigate the value of cardiac myosin binding protein-C (cMyBP-C) as a diagnostic and prognostic biomarker in children with heart failure. This study was a prospective case-control study that involved 50 children with acute HF and 25 healthy children of matched age and sex as a control group. cMyBP-C plasma levels were measured in patients with HF at the time of admission and 1month after treatment. Echocardiographic assessment was done for all children. All patients were followed up for a period of 3months. There was a significant increase in plasma levels of cMyBP-C (ng/ml) in patients with HF at admission (122.44±41.01) as compared to patients after treatment (71.38±49.68) and to control group (24.40±9.83). This increase was associated with increased severity of HF according to pediatric Ross classification of HF. Significant increase in plasma levels of cMyBP-C at admission and its persistent increase after treatment were associated with adverse outcome of mortality and readmission. Plasma levels of cMyBP-C were significantly correlated with echocardiographic and clinical assessment of heart failure. Plasma levels of cMyBP-C were a good biomarker for diagnosis of HF with sensitivity 100% and specificity 96% at cutoff point of 45ng/ml. Its value in predicting adverse outcome in HF patients was obtained by ROC curve with sensitivity of 90% and specificity 93% at a cutoff point of 152ng/ml cMyBP-C at admission. cMyBP-C may be a novel useful diagnostic and prognostic biomarker in children with heart failure and determination of severity of HF in these patients.

OP0187 Developing Prognostic Biomarkers from Whole Blood Expression Profiling in Juvenile Idiopathic Arthritis: Influence of Early Therapy on Treatment Outcome

BackgroundWe have recently demonstrated the feasibility of developing prognostic biomarkers from whole blood gene expression profiles in children with newly diagnosed juvenile idiopathic arthritis (JIA). However, determining disease status at...

Serum levels of amino terminal of probrain natriuretic peptide (NT-Pro BNP) as a diagnostic and prognostic biomarker in children with dilated cardiomyopathy

Background The amino terminal fragment of proB-type natriuretic peptide (NT-proBNP) has become commonly utilized as a sensitive marker for cardiac dysfunction in adults. However, its value in children with dilated cardiomyopathy (DCM) has not been widely investigated. We aimed to evaluate the serum levels of NT-proBNP as a diagnostic and prognostic biomarker of left ventricular dysfunction in children with DCM. Patients and methods The level of NT-proBNP was measured in 20 critically ill children with DCM and in 20 age-matched control children. Results There was highly significant increase in serum NT-proBNP level in patients with DCM as compared with the control group. At cutoff level of 1500 pg/ml, the sensitivity of NT-proBNP as a diagnostic biomarker in children with DCM was 85% and the specificity was 100%. There were significant positive correlations between serum NT-proBNP level and left ventricular systolic and diastolic diameters, whereas significant negative correlations were present between serum NT-proBNP level and ejection fraction and fraction shortening in children with DCM. Conclusion Serum NT-proBNP levels could play a role as a diagnostic and prognostic biomarker (with high sensitivity and specificity) of left ventricular systolic dysfunction in children with DCM.