scholarly journals Impairment of Cardiac Autonomic Nerve Function in Pre-school Children With Intractable Epilepsy

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhao Yang ◽  
Tung-Yang Cheng ◽  
Jin Deng ◽  
Zhiyan Wang ◽  
Xiaoya Qin ◽  
...  

Objective: Intractable epilepsy and uncontrolled seizures could affect cardiac function and the autonomic nerve system with a negative impact on children's growth. The aim of this study was to investigate the variability and complexity of cardiac autonomic function in pre-school children with pediatric intractable epilepsy (PIE).Methods: Twenty four-hour Holter electrocardiograms (ECGs) from 93 patients and 46 healthy control subjects aged 3–6 years were analyzed by the methods of traditional heart rate variability (HRV), multiscale entropy (MSE), and Kurths–Wessel symbolization entropy (KWSE). Receiver operating characteristic (ROC) curve analysis was used to estimate the overall discrimination ability. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) models were also analyzed.Results: Pre-school children with PIE had significantly lower HRV measurements than healthy controls in time (Mean_RR, SDRR, RMSSD, pNN50) and frequency (VLF, LF, HF, LF/HF, TP) domains. For the MSE analysis, area 1_5 in awake state was lower, and areas 6_15 and 6_20 in sleep state were higher in PIE with a significant statistical difference. KWSE in the PIE group was also inferior to that in healthy controls. In ROC curve analysis, pNN50 had the greatest discriminatory power for PIE. Based on both NRI and IDI models, the combination of MSE indices (wake: area1_5 and sleep: area6_20) and KWSE (m = 2, τ = 1, α = 0.16) with traditional HRV measures had greater discriminatory power than any of the single HRV measures.Significance: Impaired HRV and complexity were found in pre-school children with PIE. HRV, MSE, and KWSE could discriminate patients with PIE from subjects with normal cardiac complexity. These findings suggested that the MSE and KWSE methods may be helpful for assessing and understanding heart rate dynamics in younger children with epilepsy.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 209-209
Author(s):  
Izumi Ohno ◽  
Shuichi Mitsunaga ◽  
Motoyasu Kan ◽  
Masafumi Ikeda ◽  
Hironobu Tsubouchi ◽  
...  

209 Background: There is a clear need to identify a non-invasive biomarker for early diagnosis of PaCa, in order to improve the overall survival of PaCa patients. Secretion of large amounts of proteases is a hallmark of PaCa, which results in an abundance of protease-induced cleavage products being excreted in the urine. This has led to speculation that measurement of PaCa-specific fragments in the urine might be useful as a tool for discrimination between PaCa patients and healthy controls. Herein, we introduce urinary KNG fragments as a promising biomarker for early diagnosis of PaCa. Methods: Urine samples were collected from PaCa patients and healthy volunteers, with the written informed consent, from January 2014 to July 2016. Urinary protein tryptic fragments derived from protein C-termini were measured using isobaric tags (iTRAQ) for their relative quantitation, and the diagnostic ability of the urinary levels of these fragments was evaluated by receiver operating characteristic (ROC) curve analysis. The fragments which showed an area-under-the-curve (AUC) of over 0.8 were selected as candidate fragments for further validation by the multiple-reaction-monitoring technique (MRM) combined with high-speed liquid chromatography. The urinary level of each candidate fragment was quantified by MRM, and the diagnostic capability of each for discriminating PaCa patients from healthy controls was evaluated by ROC curve analysis. Results: Urine samples of 39 PaCa patients (7 resectable, 32 unresectable) and 42 healthy controls were examined by iTRAQ to find 12,783 fragments. ROC curve analysis was carried out to select two candidate fragments (fragments A, B), both of which turned out to be KNG cleavage products. The urinary levels of the two fragments were measured in 23 resectable PaCa, 118 unresectable PaCa patients, and 42 healthy volunteers using high-speed-LC-/MRM. The AUCs of serum CA19-9 and urinary levels of fragments A and B for discriminating patients of PaCa from healthy controls were 0.89, 0.81 and 0.70, respectively. Conclusions: Urinary KNG fragments showed favorable diagnostic capability and were considered as promising, noninvasively measurable biomarkers of PaCa.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 214-214
Author(s):  
Motoyasu Kan ◽  
Shuichi Mitsunaga ◽  
Masafumi Ikeda ◽  
Izumi Ohno ◽  
Hironobu Tsubouchi ◽  
...  

214 Background: Non PDAC tissue-originated proteins are cleaved by proteases derived from PDAC, which can result in abnormal cleavage patterns in the urine of PDAC patients. Urinary proteomic analysis for quantifying the ratios of the abnormal protein fragments to the non-fragmented protein levels in the urine may be useful to distinguish early PDAC from healthy controls. This proof-of-concept study was planned to determine the usefulness of measuring the protein fragments from non PDAC tissue-originated proteins in the urine using the multiple-reaction-monitoring technique (MRM) for discriminating resectable PDAC from healthy controls. Methods: Urinary proteins were digested with trypsin, and resultant peptides were measured by MRM analysis and the ratio of the level of each fragment to the non-fragmented protein level (fragmentation ratio) was calculated. Fragments for which the fragmentation ratios were higher in the PDAC group than those in the healthy group were defined as abnormal protein fragments. The diagnostic capability of each abnormal protein fragment for discriminating cases of PDAC from healthy controls was evaluated by receiver operating characteristic (ROC) curve analysis. Results: A total of 21 patients with resectable PDAC and 30 healthy control subjects were enrolled in this study. All the PDAC patients were treated by pancreatic resection. Urine samples for this study were collected prior to the surgery from the PDAC patients. The non PDAC tissue-originated protein was determined as a liver-originated protein. The fragmentation ratios for six fragments were found to be higher in the PDAC group as compared to those in the healthy control group, and these fragments were determined as abnormal protein fragments. ROC curve analysis was performed for each of the abnormal fragments to determine the areas under the curve (AUCs) for discriminating cases of PDAC from healthy controls. The best AUC was 0.81 (95% CI, 0.68-0.91). Conclusions: The urinary fragmentation ratios showed the ability to discriminate cases of resectable PDAC from a healthy control group; abnormal fragmentation ratios may be promising, noninvasively measurable biomarkers of early PDAC.


2017 ◽  
Vol 45 (4) ◽  
pp. 1310-1317 ◽  
Author(s):  
Yuantao Cui ◽  
Yuan Xue ◽  
Shangwen Dong ◽  
Peng Zhang

Purpose Emerging evidence indicates that circulating microRNAs (miRs) might act as noninvasive biomarkers for cancer diagnosis and prognosis. We examined the expression pattern and clinical significance of plasma miR-9 in patients with esophageal squamous cell carcinoma (ESCC). Methods Venous blood samples (6 mL) were collected from 131 patients with ESCC and 131 healthy controls, and the plasma miR-9 concentration was detected by reverse transcription polymerase chain reaction. The association of plasma miR-9 expression with clinicopathologic factors and survival of patients with ESCC was evaluated. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the clinical value of plasma miR-9 for ESCC diagnosis. Results The plasma miR-9 expression levels in patients with ESCC were significantly upregulated compared with normal controls. High plasma miR-9 concentrations were significantly correlated with poor tumor differentiation, large tumor size, deep local invasion, lymph node metastasis, advanced clinical stage, and poor survival. ROC curve analysis showed that the plasma miR-9 concentration could efficiently distinguish patients with ESCC from healthy controls. Multivariate survival analysis confirmed plasma miR-9 as an independent prognostic factor for ESCC. Conclusions Plasma miR-9 expression was upregulated in ESCC and might act as a novel diagnostic and prognostic biomarker.


2019 ◽  
Author(s):  
Jing Li ◽  
Min Ming ◽  
Yonghong Han

Abstract Background This study aimed to investigate the predictive value of JNK pathway-associated phosphatase (JKAP) level for severe acute pancreatitis (SAP) risk, and its association with disease severity, inflammation and in-hospital mortality in SAP patients. Methods Our study recruited 50 SAP patients, 50 moderate-severe acute pancreatitis (MSAP) patients, 50 mild acute pancreatitis (MAP) patients and 50 healthy controls. And the serum samples were obtained from all acute pancreatitis patients within 24 hours after admission and from health controls at their enrollment to detect JKAP level by enzyme-linked immunosorbent assay. Results JKAP level was decreased in SAP patients compared with healthy controls, MSAP and MAP patients. And receiver operating characteristics (ROC) curve analysis revealed that JKAP could not only distinguish SAP patients from healthy controls (AUC: 0.914, 95%CI: 0.857-0.971), but also differentiate SAP patients from MAP patients (AUC: 0.869, 95%CI: 0.802-0.937) and MSAP patients (AUC: 0.712, 95%CI: 0.610-0.813). In SAP patients, JKAP was negatively correlated with Ranson score, acute physiology and chronic health care evaluation II (APACEH II) score, sequential organ failure assessment (SOFA) score and C-reactive protein (CRP). And lower JKAP level, higher CRP level, Ranson score, APACEH II score and SOFA score were associated with increased in-hospital mortality in SAP patients. Additionally, ROC curve analysis showed that JKAP could predict decreased in-hospital mortality in SAP patients (AUC: 0.720, 95%CI: 0.526-0.914). Conclusions JKAP might serve as a biomarker for disease risk and management for SAP.


2021 ◽  
Author(s):  
Yuanyuan Hu ◽  
Xuzhao Bian ◽  
Chao Wu ◽  
Yan Wang ◽  
Yang Wu ◽  
...  

Abstract Background: Cerebral palsy (CP) is a spectrum of non-progressive motor disorders caused by brain injury during fetal or postnatal periods. Current diagnosis of CP mainly relies on neuroimaging and motor assessment. Here, we aimed to explore novel biomarkers for early diagnosis of CP. Methods: Blood plasma from five CP children and their healthy twin brothers/sisters was analyzed by gene microarray to screen out differentially expressed RNAs. Selected differentially expressed circular RNAs (circRNAs) were further validated using quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the value of using hsa_circ_0086354 as a biomarker of CP.Results: 43 up-regulated circRNAs and 2 down-regulated circRNAs were obtained by difference analysis (fold change>2, p<0.05), among which five circRNAs related to neuron differentiation and neurogenesis were chosen for further validation. Additional 30 pairs of CP children and healthy controls were recruited and five selected circRNAs were further detected, showing that hsa_circ_0086354 was significantly down-regulated in CP plasma compared with control, which was highly in accord with microarray analysis. ROC curve analysis showed that the area under curve (AUC) to discriminate CP children and healthy controls using hsa_circ_0086354 was 0.967, the sensitivity was 0.833 and the specificity was 0.966. Moreover, hsa_circ_0086354 was predicted as a competitive endogenous RNA for miR-181a, miR-4741 and miR-4656, and much literature evidence suggested that miR-181a may be a key target of hsa_circ_0086354 to regulate neuronal survival and neuronal differentiation. Conclusion: Hsa_circ_0086354 was significantly down-regulated in blood plasma of CP children, which may be a novel competent biomarker for early diagnosis of CP.


2021 ◽  
Author(s):  
Yuanyuan Hu ◽  
Xuzhao Bian ◽  
Chao Wu ◽  
Yan Wang ◽  
Yang Wu ◽  
...  

Abstract Background: Cerebral palsy (CP) is a spectrum of non-progressive motor disorders caused by brain injury during fetal or postnatal periods. Current diagnosis of CP mainly relies on neuroimaging and motor assessment. Here, we aimed to explore novel biomarkers for early diagnosis of CP. Methods: Blood plasma from five CP children and their healthy twin brothers/sisters was analyzed by gene microarray to screen out differentially expressed RNAs. Selected differentially expressed circular RNAs (circRNAs) were further validated using quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the value of using hsa_circ_0086354 as a biomarker of CP.Results: 43 up-regulated circRNAs and 2 down-regulated circRNAs were obtained by difference analysis (fold change>2, p<0.05), among which five circRNAs related to neuron differentiation and neurogenesis were chosen for further validation. Additional 30 pairs of CP children and healthy controls were recruited and five selected circRNAs were further detected, showing that hsa_circ_0086354 was significantly down-regulated in CP plasma compared with control, which was highly in accord with microarray analysis. ROC curve analysis showed that the area under curve (AUC) to discriminate CP children and healthy controls using hsa_circ_0086354 was 0.967, the sensitivity was 0.833 and the specificity was 0.966. Moreover, hsa_circ_0086354 was predicted as a competitive endogenous RNA for miR-181a, miR-4741 and miR-4656, and much literature evidence suggested that miR-181a may be a key target of hsa_circ_0086354 to regulate neuronal survival and neuronal differentiation. Conclusion: Hsa_circ_0086354 was significantly down-regulated in blood plasma of CP children, which may be a novel competent biomarker for early diagnosis of CP.


2020 ◽  
Author(s):  
Lili Wang ◽  
Hongguang Song ◽  
Shiming Yang

Abstract Background: It had been suggested that microRNA-101 (miR-101) was involved in carcinogenesis and progression of various human tumors. The purpose of this study was to investigate the diagnostic value of miR-101 in oral cancer.Methods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the serum mRNA level of miR-101 in 130 oral cancer cases and 82 healthy individuals. The association of miR-101 with clinical characteristics of oral cancer patients was estimated using chi-square test. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic significance of miR-101 in oral cancer.Results: Compared with healthy controls, serum miR-101 level was significantly down-regulated in oral cancer patients (P<0.001). Furthermore, low expression of miR-101 was closely associated with histological grade (P=0.037), TNM stage (P=0.018) and lymph node metastasis (P=0.023). ROC curve analysis indicated that serum miR-101 could effectively distinguish oral cancer patients from healthy controls with an area under the curve (AUC) of 0.878 (95%CI=0.834-0.922, P<0.001). The cutoff level of miR-101 expression for oral cancer diagnosis was 1.46, with the sensitivity of 82.9% and the specificity of 74.6%.Conclusions: Decreased expression of miR-101 is correlated with the aggressive progression of oral cancer. Serum miR-101 may be a promising bio-marker for early diagnosis of oral cancer.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ken-ichiro Konishi ◽  
Tatsuki Mizuochi ◽  
Hajime Takei ◽  
Ryosuke Yasuda ◽  
Hirotaka Sakaguchi ◽  
...  

AbstractDiagnosis of biliary atresia (BA) can involve uncertainties. In the present prospective multicenter study, we considered whether urinary oxysterols represent a useful marker for diagnosis of BA in Japanese children. Subjects under 6 months old at 7 pediatric centers in Japan were prospectively enrolled, including patients with cholestasis and healthy controls (HC) without liver disease. Patients with cholestasis constituted 2 groups representing BA patients and others with cholestasis from other causes (non-BA). We quantitatively analyzed 7 oxysterols including 4β-, 20(S)-, 22(S)-, 22(R)-, 24(S)-, 25-, and 27-hydroxycholesterol by liquid chromatography/electrospray ionization-tandem mass spectrometry. Enrolled subjects included 14 with BA (median age 68 days; range 26–170) and 10 non-BA cholestatic controls (59; 14–162), as well as 10 HC (57; 25–120). Total urinary oxysterols were significantly greater in BA (median, 153.0 μmol/mol creatinine; range 24.1–486.7; P < 0.001) and non-BA (36.2; 5.8–411.3; P < 0.05) than in HC (2.7; 0.8–7.6). In patients with BA, urinary 27-hydroxycholesterol (3.61; 0.42–11.09; P < 0.01) was significantly greater than in non-BA (0.71; 0–5.62). In receiver operating characteristic (ROC) curve analysis for distinguishing BA from non-BA, the area under the ROC curve for urinary 27-hydroxycholesterol was 0.83. In conclusion, this first report of urinary oxysterol analysis in patients with BA indicated that 27-hydroxycholesterol may be a useful marker for distinguishing BA from other causes of neonatal cholestasis.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Santos ◽  
S Paula ◽  
I Almeida ◽  
H Santos ◽  
H Miranda ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients (P) with acute heart failure (AHF) are a heterogeneous population. Risk stratification at admission may help predict in-hospital complications and needs. The Get With The Guidelines Heart Failure score (GWTG-HF) predicts in-hospital mortality (M) of P admitted with AHF. ACTION ICU score is validated to estimate the risk of complications requiring ICU care in non-ST elevation acute coronary syndromes. Objective To validate ACTION-ICU score in AHF and to compare ACTION-ICU to GWTG-HF as predictors of in-hospital M (IHM), early M [1-month mortality (1mM)] and 1-month readmission (1mRA), using real-life data. Methods Based on a single-center retrospective study, data collected from P admitted in the Cardiology department with AHF between 2010 and 2017. P without data on previous cardiovascular history or uncompleted clinical data were excluded. Statistical analysis used chi-square, non-parametric tests, logistic regression analysis and ROC curve analysis. Results Among the 300 P admitted with AHF included, mean age was 67.4 ± 12.6 years old and 72.7% were male. Systolic blood pressure (SBP) was 131.2 ± 37.0mmHg, glomerular filtration rate (GFR) was 57.1 ± 23.5ml/min. 35.3% were admitted in Killip-Kimball class (KKC) 4. ACTION-ICU score was 10.4 ± 2.3 and GWTG-HF was 41.7 ± 9.6. Inotropes’ usage was necessary in 32.7% of the P, 11.3% of the P needed non-invasive ventilation (NIV), 8% needed invasive ventilation (IV). IHM rate was 5% and 1mM was 8%. 6.3% of the P were readmitted 1 month after discharge. Older age (p &lt; 0.001), lower SBP (p = 0,035) and need of inotropes (p &lt; 0.001) were predictors of IHM in our population. As expected, patients presenting in KKC 4 had higher IHM (OR 8.13, p &lt; 0.001). Older age (OR 1.06, p = 0.002, CI 1.02-1.10), lower SBP (OR 1.01, p = 0.05, CI 1.00-1.02) and lower left ventricle ejection fraction (LVEF) (OR 1.06, p &lt; 0.001, CI 1.03-1.09) were predictors of need of NIV. None of the variables were predictive of IV. LVEF (OR 0.924, p &lt; 0.001, CI 0.899-0.949), lower SBP (OR 0.80, p &lt; 0.001, CI 0.971-0.988), higher urea (OR 1.01, p &lt; 0.001, CI 1.005-1.018) and lower sodium (OR 0.92, p = 0.002, CI 0.873-0.971) were predictors of inotropes’ usage. Logistic regression showed that GWTG-HF predicted IHM (OR 1.12, p &lt; 0.001, CI 1.05-1.19), 1mM (OR 1.10, p = 1.10, CI 1.04-1.16) and inotropes’s usage (OR 1.06, p &lt; 0.001, CI 1.03-1.10), however it was not predictive of 1mRA, need of IV or NIV. Similarly, ACTION-ICU predicted IHM (OR 1.51, p = 0.02, CI 1.158-1.977), 1mM (OR 1.45, p = 0.002, CI 1.15-1.81) and inotropes’ usage (OR 1.22, p = 0.002, CI 1.08-1.39), but not 1mRA, the need of IV or NIV. ROC curve analysis revealed that GWTG-HF score performed better than ACTION-ICU regarding IHM (AUC 0.774, CI 0.46-0-90 vs AUC 0.731, CI 0.59-0.88) and 1mM (AUC 0.727, CI 0.60-0.85 vs AUC 0.707, CI 0.58-0.84). Conclusion In our population, both scores were able to predict IHM, 1mM and inotropes’s usage.


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