The beneficial role of simple inflammatory blood indices in pediatric cardiology.

Simple whole blood analysis can effectively demonstrate complex changes in inflammatory responses to cardiovascular disorders in adults and enable the prediction of adverse outcomes or diminished survival. Such inflammatory activation has also been detected in the pediatric population. Blood analysis results are repeatable and readily available, which gives the method an advantage over others. Inflammatory phenomena such as a high leukocyte count and an increased neutrophil-to-lymphocyte ratio (NLR) are related to a poor prognosis of advanced heart defects and worse outcomes after pediatric cardiac surgery in the advanced stages of the disease. Surgery-associated inflammation exacerbates these diseases, and the inflammatory response may further complicate the postoperative period. Simple blood cell counts and indices may be beneficial for evaluating cardiac surgery outcomes and cardiovascular disorder prognosis in infants and children. This review summarizes current knowledge on inflammatory markers in pediatric cardiovascular diseases and surgery.

Heart Rate Asymmetry in Healthy Children.

Heart rate asymmetry (HRA) is a physiological phenomenon characterized by an unequal contribution of heart rate decelerations and accelerations to different heart rate variability (HRV) features. While HRA has been demonstrated in adults' ECGs of different duration, a similar investigation in healthy children has not been conducted. This study investigated the variance- and number-based HRA features in 96 healthy children (50 girls and 46 boys, aged 3-18 years) using 24-h ECGs. Additionally, we studied sex differences in HRA. To quantify HRA, variance-based and relative contributions of heart rate decelerations to short-term (C1d), long-term (C2d), and total (CTd) HRV, and the number of all heartbeats (Nd) were computed. Heart rate decelerations contributed more to C1d, but less to C2d and CTd, and were less frequent than heart rate accelerations. Short-term HRA was better expressed in boys. The majority of children (93.7%) had short-term HRA, 88.5% had long-term HRA, 88.5% had total HRA, and 99.0% had more accelerations than decelerations. No sex differences were observed for the rate of various HRA features. Heart rate asymmetry is a common phenomenon in healthy children, as observed in 24-h ECGs. Our findings can be used as reference data for future clinical studies on HRA in children.

Neutrophil Count as Atrioventricular Block (AVB) Predictor following Pediatric Heart Surgery.

Neutrophils play a significant role in immune and inflammatory reactions. The preoperative inflammatory activation may have a detrimental effect on postoperative outcomes. The aim of the study was to investigate the relation between preoperative hematological indices on postoperative complications' risk in pediatric cardiac congenital surgery. The retrospective single center analysis included 93 pediatric patients (48 (65%) males and 45 (35%) females), mean age of 7 (3−30) months referred for cardiac surgery in cardiopulmonary bypass due to functional single ventricle disease (26 procedures), shunts lesions (40 procedures) and cyanotic disease (27 procedures). Among simple hematological indices, the receiver-operating-characteristic curve showed that a neutrophil count below 2.59 K/uL was found as an optimal cut-off point for predicting postoperative atrioventricular block following pediatric cardiac surgery (AUC = 0.845, p < 0.0001) yielding a sensitivity of 100% and a specificity of 65.62%. Preoperative values of neutrophil count below 2.59 K/uL in whole blood analysis can be regarded as a predictive factor (AUC = 0.845, p < 0.0001) for postoperative atrioventricular block in pediatric cardiac surgery.

Multiples of Median-Transformed, Normalized Reference Ranges of Steroid Profiling Data Independent of Age, Sex, and Units.

BACKGROUND/AIMS: The high complexity of pediatric reference ranges across age, sex, and units impairs clinical application and comparability of steroid hormone data, e.g., in congenital adrenal hyperplasia (CAH). We developed a multiples-of-median (MoM) normalization tool to overcome this major drawback in pediatric endocrinology. METHODS: Liquid chromatography tandem mass spectrometry data comprising 10 steroid hormones representing 905 controls (555 males, 350 females, 0 to > 16 years) from 2 previous datasets were MoM transformed across age and sex. Twenty-three genetically proven CAH patients were included (21-hydroxylase deficiency [21OHD], n = 19; 11ß-hydroxylase deficiency [11OHD], n = 4). MoM cutoffs for single steroids predicting 21OHD and 11OHD were computed and validated through new, independent patients (21OHD, n = 8; adrenal cortical carcinoma, n = 6; obesity, n = 40). RESULTS: 21OHD and 11OHD patients showed disease-typical, easily recognizable MoM patterns independent of age, sex, and concentration units. Two single-steroid cutoffs indicated 21OHD: 3.87 MoM for 17-hydroxyprogesterone (100% sensitivity and 98.83% specificity) and 12.28 MoM for 21-deoxycortisol (94.74% sensitivity and 100% specificity). A cutoff of 13.18 MoM for 11-deoxycortisol indicated 11OHD (100% sensitivity and 100% specificity). CONCLUSIONS: Age- and sex-independent MoMs are straightforward for a clinically relevant display of multi-steroid patterns. In addition, defined single-steroid MoMs can serve alone as predictors of 21OHD and 11OHD. Finally, MoM transformation offers substantial enhancement of routine and scientific steroid hormone data exchange due to improved comparability.

Is growth without IGF1 possible? A case report.

According to the growth hormone - insulin-like growth factor 1 axis (GH/IGF1 axis) theory, the actions of GH on promoting growth are mediated by IGF1. In the blood, IGF1, insulin-like growth factor 1 binding protein 3 (IGFBP3) and acid-labile subunit (ALS) form ternary complexes, hence the accumulation of IGF1. We report a case of 10-year-old male with short stature due to GH deficiency diagnosed with hypopituitarism. Therapy with recombinant human GH (rhGH) was initiated at 11 years and 4 months. After twenty three months on treatment clinical effects were as follows: increase in the patient's height by 19.2 cm (initial height 12.4 cm vs. 140.6 cm; hSDS -4.35 vs. -2.7; predicted adult height 176 cm vs. 182 cm, respectively). Despite good clinical response to the therapy, serum levels of IGF1 and IGFBP3 remained diminished: IGF1 - 28 ng/ml initially, vs. 23 ng/ml 19 months on therapy and IGFBP3 - 1116 ng/ml initially, vs. 1888 ng/ml after 11 months on therapy. We attempt to justify this phenomenon by reconsidering the IGF1-independent GH actions, assessing the endocrine role of hepatic IGF1 in comparison to the autocrine/paracrine role of its bone tissue fraction, and evaluating the functions of ALS. The exact explanation for the positive response to rhGH treatment without the expected increase in IGF1 in our patient remains unknown. Serum levels of IGF1 and IGFBP3 seem not always to be reliable markers of the response to rhGH treatment in GH-deficient patients.

Permanent atrial fibrillation in heart failure patients as another condition with increased reverse triiodothyronine concentration.

OBJECTIVE: To fully investigate the thyroid hormonal function in patients with the most common arrhythmia - atrial fibrillation. MATERIALS AND METHODS: 120 patients (aged 55-85 yrs) with symptoms of congestive heart failure exacerbation and no other concomitant disorders (inclusion criteria: normal cardiac troponin T at admission and 12 hours after, normal renal, hepatic and respiratory function; exclusion criteria: inflammatory state, history of myocardial infarction). Depending on the presence of permanent atrial fibrillation (PAF), patients were divided into two groups: PAF (34 females, 26 males) and regular sinus heart rhythm (43 females, 17 males), the groups did not differ in terms of heart rate, blood pressure, presence of overt/subclinical thyroid dysfunction, and medical therapy used. In all subjects thyroid stimulating hormone, free thyroxine, free triiodothyronine, reverse triiodothyronine were measured; echocardiography was performed. RESULTS: PAF group showed higher FT4 and rT3 (1.41 vs. 1.27 ng/dl, p=0.0007; 0.61 vs. 0.32 ng/ml, p<0.0001, respectively). With ROC curve analysis the biochemical thyroid related factor of the highest prognostic value for PAF occurrence (with the highest sensitivity and specificity: 77% and 72%, respectively) was rT3 with the cut-off of above 0.3 ng/ml. Also, a positive correlation between rT3 levels and left ventricular posterior wall diameter was observed (Spearman's correlation coefficient 0.33, p=0.0093). CONCLUSIONS: PAF is another condition where an increase in rT3 is observed. rT3 concentration above 0.3 ng/ml may be a novel biochemical sign associated with the presence of PAF in patients with chronic heart failure.