Serum TP53 Protein Level as a Sensitive Biomarker for the Diagnosis of Myocardial Damage in Children.

BACKGROUND High levels of TP53 protein can lead to apoptosis of myocardial cells. However, TP53 protein influence of myocardial damage remains unclear. This prospective study investigated the involvement of TP53 protein in secondary myocardial damage in children up to 18 years of age. MATERIAL AND METHODS Serum TP53 protein, N-terminal prohormone B-type natriuretic peptide (NT-ProBNP), cardiac troponin-I (cTnI), and creatine kinase isoenzyme MB (CK-MB) concentrations were measured in 50 hospitalized patients with secondary myocardial damage, 50 hospitalized patients without myocardial damage, and 50 healthy individuals (control). Cardiac damage was diagnosed based on cTnI, NT-ProBNP, and CK-MB levels, with electrocardiographic evidence as the reference. The appropriate cut-off value of TP53 protein for secondary myocardial damage was analyzed by receiver operating characteristic (ROC) curves. RESULTS The serum TP53 protein, NT-ProBNP, cTnI, and CK-MB concentrations of the patients with and without myocardial damage were 10.20±1.20 and 0.30±0.10 ng/L, 505.30 and 107.8 ng/L, 0.23±0.13 and 0.02±0.01 µg/L, and 28.30±5.13 and 12.24±4.29 IU/L, respectively. For the 50 patients with myocardial damage, the area under the ROC curve for serum TP53 protein, NT-ProBNP, cTnI, and CK-MB concentrations were 0.89 (95% CI: 0.81-0.95), 0.83 (95% CI: 0.77-0.91), 0.92 (95% CI: 0.84-0.97), and 0.85 (95% CI: 0.78-0.93), respectively, and the diagnostic cut-off values were 12.00 ng/L, 500.00 ng/L, 0.16 µg/L, and 27.00 IU/L, respectively, with positive likelihood ratios of 20.8, 13.2, 24.6, and 15.6. CONCLUSIONS TP53 protein is a valid biomarker of secondary myocardial damage in pediatric patients and can be diagnostic.

Age-Stratified Cut-Off Values for Serum Levels of N-Terminal ProB-Type Natriuretic Peptide and Mortality from Sepsis in Children Under Age 18 Years: A Retrospective Study from a Single Center.

BACKGROUND The N-terminal fragment of proB-type natriuretic peptide (NT-proBNP) is an established predictive marker for sepsis-related mortality in adult. This retrospective study aimed to determine age-stratified cut-off values for serum levels of NT-proBNP and mortality from sepsis in children under 18 years. MATERIAL AND METHODS Patients were stratified by age as follows: <1 year, 1-3 years, 4-6 years, and 7-18 years (age groups). The control group consisted of age- and sex-matched healthy children. Serum NT-proBNP levels were detected by laboratory assays in the participants. The appropriate serum NT-proBNP cut-off values for predicting short-term mortality of the sepsis patients were calculated via receiver operating characteristic (ROC) curve analyses. RESULTS Among 327 pediatric patients with sepsis, the serum NT-proBNP cut-off concentrations for predicting sepsis-related mortality in the <1 year, 1-3 years, 4-6 years, and 7-18 years age groups were 5000 ng/L, 4500 ng/L, 4100 ng/L, and 3800 ng/L, respectively (P<0.001). The area under the ROC curve (AUC) values for these were 0.815, 0.812, 0.806 and 0.725, respectively (P<0.001). CONCLUSIONS This retrospective study provided the age range-specific serum NT-proBNP cut- off concentrations for predicting short-term mortality in children. In children <1 year, 1-3 years, 4-6 years, and 7-18 years, age-stratified cut-off values that predicted sepsis-associated mortality were 5000 ng/L, 4500 ng/L, 4100 ng/L, and 3800 ng/L, respectively.

Bronchiolitis Associated with Mycoplasma pneumoniae Infection in Infants in Foshan China: An Epidemiologic Study.

BACKGROUND Bronchiolitis is common in infants under 2 years of age. Most infections are caused by respiratory syncytial virus (RSV), but the importance of Mycoplasma pneumoniae (MP) in the etiology of bronchiolitis is unclear. MATERIAL AND METHODS We investigated the clinical characteristics of bronchiolitis caused by MP in 79 infants admitted to Shunde Women's and Children's Hospital of Guangdong Medical University and Sanshui Women's and Children's Healthcare Hospital from January 2016 to December 2018. Infection with MP was confirmed by the presence of serum immunoglobulin M. RESULTS The peak detection rates of MP in the years 2016, 2017, and 2018 were 19.2%, 21.3%, and 24.0%, respectively. In each year, the peak of MP infections occurred during June and July. MP-associated bronchiolitis was mainly seen in infants from 6 to 12 months of age. Compared with RSV-associated bronchiolitis, the age of patients with bronchiolitis associated with MP was significantly older and they had a shorter hospital stay (all P<0.01 or P<0.05). CONCLUSIONS Our study indicated that MP is an important cause of bronchiolitis, with peaks of occurrence during June and July every year. Pulmonary interstitial infiltration was a characteristic of this infection. Azithromycin treatment can shorten the course of MP-associated bronchiolitis. Investigation of the epidemiological characteristics of pediatric MP-associated bronchiolitis can help diagnose and treat the disease correctly.

Involvement of p53, p21, and Caspase-3 in Apoptosis of Coronary Artery Smooth Muscle Cells in a Kawasaki Vasculitis Mouse Model.

BACKGROUND Overexpression of p53, p21, and caspase-3 promotes apoptosis of vascular smooth muscle cells. However, the mechanisms that lead to apoptosis of coronary artery smooth muscle cells (CASMCs) is unclear in Kawasaki disease (KD). This study investigated involvement of p53, p21, and caspase-3 in the apoptosis of CASMCs from a Kawasaki vasculitis mouse model. MATERIAL AND METHODS The Kawasaki vasculitis mouse model with coronary artery lesions was generated via administration of Lactobacillus casei cell wall extract. In 2 groups of mice (healthy control and KD vasculitis mice), the levels of p53, p21, and caspase-3 protein in the root of the coronary artery were evaluated via immunohistochemistry. Receiver operating characteristic curves were plotted for determination of area under the curve, 95% confidence interval, sensitivity, specificity, and cutoff values for the ability of p53, p21, and caspase-3 expression to predict CASMC apoptosis and coronary artery lesion formation in KD vasculitis mice. RESULTS Compared with healthy mice, KD vasculitis mice had a significantly higher apoptosis index and upregulated p53, p21, and caspase-3 expression. Also, the immunoreactive score for caspase-3 was positively correlated with the immunoreactivity scores for p53 and p21. The optimal cutoff values for p53, p21, and caspase-3 expression for predicting the presence of coronary artery lesions were 4.15, 4.18, and 4.22, respectively. CONCLUSIONS Upregulated levels of p53, p21, and caspase-3 promoted apoptosis of CASMCs in KD vasculitis mice. Thus, the levels of p53, p21, and caspase-3 may serve as valuable predictors of coronary artery lesion formation in KD.

Determining the optimal cutoff values of plasma N-terminal pro-B-type natriuretic peptide levels for the diagnosis of heart failure in children of age up to 14 years.

BACKGROUND: Plasma N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of heart failure (HF). However, the optimal cutoff value of plasma NT-proBNP for the diagnosis of HF in children is unknown. The objective of this study was to determine the appropriate cutoff value of plasma NT-proBNP for the diagnosis of HF in children ≤14 years old. METHODS AND RESULTS: Plasma NT-proBNP concentrations were detected in pediatric HF patients using standard clinical assays. Patients were stratified into 4 groups by age: 0-1 year, 1-3 years, 4-7 years, and 8-14 years. Case-matched healthy children were recruited as control subjects. HF was diagnosed with the use of the modified Ross score. The optimal cutoff value of plasma NT-proBNP for the diagnosis of HF was determined by analyzing receiver operating characteristic (ROC) curves and the resulting sensitivity, specificity, and Youden index (J). In healthy children, plasma NT-proBNP level and age were negatively correlated (r = -0.739; P < .001). In HF patients aged 0-1 year, 1-3 years, 4-7 years, and 8-14 years, respectively, areas under the ROC curves were 0.795, 0.786, 0.783, and 0.696; 95% confidence intervals were 0.689-0.901, 0.669-0.903, 0.662-0.904, and 0.487-0.905; and J values were 0.715, 0.708, 0.706, and 0.679. Optimal cutoff values of plasma NT-proBNP for the diagnosis of HF were 502 ng/L, 456 ng/L, 445 ng/L, and.355 ng/L. CONCLUSIONS: Age-stratified analysis of plasma NT-proBNP levels in children provides new parameters for diagnosing HF.

[Clinical importance of preoperative measurement of plasma amino-terminal pro-B-type natriuretic peptide in infants with congenital heart disease].

OBJECTIVE: To define cut-off values of plasma amino-terminal pro-B-type natriuretic peptide (NT-ProBNP) for the diagnosis of congenital heart failure (CHF) and evaluate the importance of plasma NT-ProBNP measurement in the assessment of cardiac function prior to heart surgery in infants with congenital heart disease (CHD). METHODS: Plasma levels of NT-proBNP were measured in 120 infants with CHD before heart surgery and in 100 age-matched healthy infants between June 2010 and June 2013. The data were stratified based on the presence or absence of CHF in the whole group of CHD infants and on age (i.e., <1 year and ≥1 year) and time (i.e., before surgery) within the subgroup of CHF infants. RESULTS: Of the 120 infants with CHD, 41 met the criteria for CHF defined in the Ross Classification for Heart Failure in Infants.The cut-off values of plasma NT-ProBNP were ≥498 ng/L for infants of all ages, 557 ng/L for <1 year age group and 452 ng/L for ≥1 year age group, respectively, in the 41 CHF patients. In CHF infants, plasma NT-proBNP was significantly decreased after protecting of cardiac function (P<0.001). CONCLUSIONS: The cut-off values of plasma NT-ProBNP for CHF differ between infants <1 year and infants ≥1 year. Moreover, plasma NT-ProBNP can be used as an additional parameter in the preoperative assessment of cardiac function in CHD infants.

Insulin therapy is not associated with improved clinical outcomes in critically ill infants with stress hyperglycemia.

The aim of the present study was to examine the benefits of insulin use and non-use in critically ill infants with stress-induced hyperglycemia. The present retrospective study used clinical data from 302 critically ill infants with stress hyperglycemia admitted to pediatric intensive care units (PICUs). The patients were recruited randomly and divided into three groups: The tight glycemic control, conventional insulin therapy and control groups. Correlations between insulin therapy and improved clinical outcomes were assessed according to key parameters (length of PICU stay, total length of stay, occurrence of organ dysfunction and mortality). Correlations between blood glucose level and these parameters in the three groups were also examined. Blood glucose levels following insulin therapy were not correlated with the length of PICU stay, total length of stay, mortality, secondary coma, or secondary hepatic or renal dysfunction in the three groups. At 96 h following PICU admission, blood glucose levels were statistically similar (5.0±1.2, 4.9±1.3 and 5.1±0.9 mmol/l, respectively; P>0.05). Insulin therapy was revealed to have no benefit on the length of hospitalization, the occurrence of organ dysfunction or mortality in critically ill pediatric patients with stress hyperglycemia. Even with no insulin use, the blood glucose level could spontaneously return to normal, with no associated risk of organ dysfunction or fatality.

Reduced environmental stimuli is associated with improved insulin-like growth factor-1 levels and physical growth in very low birth weight premature infants.

Standard environmental features of the neonatal intensive care unit (NICU) may be stressful and not optimal for the maturation of very low birth weight premature infants (VLBWPIs). The present study investigated whether structured no-touch periods and reducing periods of light and sound stimulation may influence the developmental indices of VLBWPIs. Between June 2012 and June 2013, 60 consecutive VLBWPIs were equally apportioned to either an experimental or control group. The groups were statistically comparable with regard to sex ratio, gestational age and birth weight. Each group received routine nursing care, but infants in the experimental group were additionally cared for in a separate room with 3 h of rest every 8 h, and reduced light and sound from staff and instruments. At 7 and 14 days following birth, plasma insulin-like growth factor 1 (IGF-1) levels of the experimental group were significantly higher than that of the control group. Furthermore, at day 7 and 14, the body weight and crown-to-heel lengths were significantly increased in the experimental group compared with the control group. In summary, during the first 2 weeks following birth, the reduction of touch, sound and light stimulation in the NICU were associated with higher plasma IGF-1 levels and physical growth of VLBWPIs. These results may have implications for the better management of VLBWPIs in the NICU.

Role of E-selectin for diagnosing myocardial injury in paediatric patients with mycoplasma pneumoniae pneumonia.

Backgrounds Effects of myocardial injury on E-selectin remain unclear. Thus, we investigated the diagnostic value of E-selectin for myocardial injury in paediatric patients with mycoplasma pneumoniae pneumonia. Methods In this prospective and blinded clinical study, plasma E-selectin, cardiac troponin I, creatine kinase isoenzyme MB, interleukin-6 and tumor necrosis factor alpha concentrations were measured in paediatric patients with mycoplasma pneumoniae pneumonia (MPP group, n = 138). The control group comprised 120 healthy children. The definition of cardiac injury was based on cardiac troponin I or CK-MB (with or possibly without abnormal electrocardiogram evidence). Diagnostic value of E-selectin for myocardial injury was determined by analysing receiver operating characteristic curves. Results Among the 138 mycoplasma pneumoniae pneumonia patients, 40 patients were identified with myocardial injury, while 98 patients were identified without myocardial injury. Plasma E-selectin concentrations were: 40.22 ± 4.80 ng/mL, in patients with myocardial injury; 18.55 ± 2.16 ng/mL, in patients without myocardial injury and 12.39 ± 3.27 ng/mL, in healthy children. For the 40 patients identified with myocardial injury, area under the receiver operating characteristic curve value for plasma E-selectin concentrations was 0.945 (95% CI: 0.899-0.991), and optimal diagnostic cut-off value was 29.93 ng/mL (positive likelihood ratio = 72.5). Conclusion E-selectin was shown to be an effective index for myocardial injury in paediatric patients with mycoplasma pneumoniae pneumonia, and its role in other causes of myocardial injury warrants further investigation.

Diagnostic Accuracy of NT-ProBNP for Heart Failure with Sepsis in Patients Younger than 18 Years.

This clinical study investigated plasma NT-proBNP levels as a potential predictor of heart failure in pediatric patients with sepsis. Plasma NT-ProBNP levels of 211 pediatric patients with sepsis and 126 healthy children were measured. Patients were stratified as with heart failure (HF) or without heart failure (non-HF). Patients were graded as having sepsis, severe sepsis, or septic shock. The optimal cut-off values of plasma NT-ProBNP for heart failure were determined by analyzing the receiver operating characteristic (ROC). In the HF, non-HF and control groups, the median plasma NT-proBNP levels were 3640, 656, and 226 ng/L, respectively. For all patients with sepsis, the optimal diagnostic cut-off value was 1268 ng/L for differentiating heart failure. In the severe sepsis patients and septic shock patients, the optimal diagnostic cut-off values were 1368 ng/L and 1525 ng/L, respectively. This report is the first one to reveal that NT-proBNP may predict heart failure in children with sepsis. It provides an important clinical reference for the diagnosis of heart failure in pediatric patients with sepsis, and enables monitoring septic children for cardiac involvement.

Role of E-selectin for diagnosis of myocardial injury in children of age up to 14 years.

BACKGROUND: Effects of myocardial injury on E-selectin remain unclear. Thus, we investigated the diagnostic value of E-selectin for myocardial injury in children of no more than 14 years of age, which determined the scoring method of myocardial injury. METHODS: In this prospective study, plasma E-selectin, cardiac troponin I (cTnI) and creatine kinase isoenzyme MB (CK-MB) concentrations in pediatric patients with myocardial injury (myocardial injury group, n=85) were measured. The control group comprised 80 patients without myocardial injury, and the case-control study method was selected at the same time. The definition of cardiac injury was based on cTnI and CK-MB (with or possibly without abnormal ECG evidence). Diagnostic value of E-selectin for myocardial injury was determined by analyzing receiver operating characteristic (ROC) curves. RESULTS: The differences between the two groups were of statistical significance (P<0.001). For the 85 patients with myocardial injury, the area under the ROC curve (AUC) value for plasma E-selectin levels was 0.945 with a 95% CI of 0.899-0.991 and the optimal diagnostic cut-off value 29.67 ng/ml (positive likelihood ratio (positive LR=72.5); AUC value for plasma cTnI level was 0.848 with a 95% CI: 0.737-0.960 and the optimal diagnostic cut-off value was 0.155 µg/L (positive LR=12.3); AUC value for plasma CK-MB levels was 0.946 with a 95% CI: 0.903-0.989 and the optimal diagnostic cut-off value 24.26 IU/L (positive LR=72.5). CONCLUSIONS: E-selectin is more effective than cTnI in diagnosing myocardial injury as an important biological marker of myocardial injury- an important index of pediatric cardiac injury score.

A multiple logistic regression analysis of complications following microsurgical breast reconstruction.

BACKGROUND: Although we practice in an era of high flap success rates following microsurgical breast reconstruction, complications can still occur. Several studies have evaluated the impact of risk factors on microvascular outcomes in the setting of a particular type of patient or with a particular type of flap. However, few studies that have evaluated a consecutive series of high-risk patients will all types of microvascular breast reconstruction. Our goal was to gain a better understanding of the relationship between risk factors and complications in order to provide useful information for patients and surgeons considering free flap breast reconstruction in high-risk patients. METHODS: We performed a retrospective review of all patients who underwent microsurgical breast reconstruction by the senior author (M.Y.N) from July 2005 July 2010. Patient records were analyzed for risk factors (age, BMI, smoking history, medical history, adjunct therapies, timing of reconstruction, type of reconstruction), and complications (hematoma, seroma, infection, wound dehiscence, pulmonary embolism (PE), deep venous thrombosis (DVT), pneumonia, fat necrosis, leech use, partial flap loss, total flap loss). Statistical methods were employed to determine statistically significant relationships. RESULTS: A total of 352 patients underwent 490 microvascular breast reconstructions during the study period. Active smoking was found to be a statistically significant risk factor for seroma [P<0.0001; odds ratio (OR) =36; 95% confidence interval (CI), 5.9-193.9], infection (P=0.0081; OR =4.3; 95% CI, 1.3-14.1), and pneumonia (P<0.0001; OR =17.1; 95% CI, 3.3-89.9). Unilateral reconstruction was found to be a statistically significant factor for fat necrosis (P=0.0083; OR =4; 95% CI, 1.4-11.4). Additionally, BMI was found to be a statistically significant risk factor for infection (P<0.00001). CONCLUSIONS: This study corroborates findings from previous studies. Tobacco use was demonstrated to be a significant risk factor for infection, seroma, and pneumonia. Obesity was demonstrated to be a significant risk factor for infection. Unilateral reconstruction was demonstrated to pose additional risk for fat necrosis compared to bilateral reconstruction. Patients who choose to have microsurgical breast reconstruction should be informed of the complication profile associated with certain risk factors.

Role of the NT-proBNP level in the diagnosis of pediatric heart failure and investigation of novel combined diagnostic criteria.

The aim of this study was to investigate the modified Ross criteria score and the diagnostic cut-off level for plasmatic amino-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of pediatric heart failure, by analyzing the receiver operating characteristic (ROC) curve. The plasma NT-proBNP level was measured in 80 children diagnosed with heart failure according to the modified Ross criteria, 80 children with non-cardiogenic dyspnea and 80 healthy children. The NT-proBNP levels were then compared using an F-test. The cut-off score for heart failure in the modified Ross criteria and the diagnostic cut-off level for plasmatic NT-proBNP in pediatric heart failure were determined by ROC curve analysis. The results demonstrated that the NT-proBNP level was markedly increased in 76 of the 80 children with heart failure, and the correlation with the modified Ross criteria was 95%. Based on ROC curve analysis, the diagnosis of pediatric heart failure was most accurate when the modified Ross criteria score was ≥4 and the plasmatic NT-proBNP level was ≥598 ng/l. The NT-proBNP level was normal (0-300 ng/l) in the children with non-cardiogenic dyspnea and the healthy children. Significant differences were observed in the comparison of the three groups (P<0.01). In conclusion, a NT-proBNP level of ≥598 ng/l, combined with a modified Ross criteria score ≥4, is highly diagnostic of heart failure in children.

The pendulum test for evaluating spasticity of the elbow joint.

OBJECTIVE: To develop a modification of the pendulum test to allow evaluation of elbow spasticity. DESIGN: The main difficulties of directly applying the conventional pendulum test to the elbow were the small inertia of the forearm and the uncomfortable posture. We designed an experimental apparatus similar to a clock pendulum and developed an elbow biomechanic model to measure objectively spasticity of the elbow joint. The model consisted of linear stiffness and damping and gravity contribution. SETTING: A referral medical center in Taiwan. PARTICIPANTS: Eleven stable stroke patients and 11 able-bodied subjects. INTERVENTIONS: A custom-designed accessory apparatus to facilitate the pendulum test in elbow joints. MAIN OUTCOME MEASURES: By using an optimization technique, we estimated parameters of the proposed elbow biomechanic model as the candidate indicators of spasticity. RESULTS: The stiffness constant remained relatively consistent in all groups. Both the damping coefficient and damping ratio increased in the affected side of stroke patients and tended to increase with the severity of spasticity. Damping ratio had marginally better differentiation capability than the damping coefficient. CONCLUSIONS: The damping ratio derived from the proposed model differentiated spasticity from normotonus and increased as spasticity increased.