Devastating Complications of Metal Strut Migration Following Pectus Excavatum Repair.

The modified Ravitch technique with metal struts and the Nuss operation have been the dominant operative techniques for treatment of pectus excavatum in the previous decades. We present devastating postoperative complications of a 16-year-old boy after the modified Ravitch procedure for a severe deformity utilizing two metal bars. Four months following surgery, one strut was removed after the displacement noted on a regular postoperative examination. Ten days after the strut removal, the patient complained of lower limb pain but the sensations were attributed to physical inactivity. Two months later, after pain intensification, the boy was diagnosed with bilateral arterial and venous lower limb thromboses and subsequently, the migration of the remaining metal strut intracardially with the free end in the left ventricular cavity embedded in massive thrombi. An urgent cardiac procedure was performed and the bar removed. Postoperatively, the boy made a full cardiac recovery but with severe neurological complications and subsequent death. Migration of metal struts is a rare complication and, except in our case, had been dealt with successfully. This case should emphasize more attention to the postoperative follow-up management of such patients.

Experience with developing antibiotic stewardship programs in Serbia: potential model for other Balkan countries?

AIM: Antimicrobial resistance and inappropriate use of antibiotics in children are important issues. Consequently, there is a need to develop comprehensive stewardship programs even in hospitals with limited resources starting with children's hospitals. METHODS: Retrospective observational analysis of antimicrobial utilization and resistance patterns over 5 years in a tertiary care children's hospital in Serbia. RESULTS: Cumulative antimicrobial resistance decreased but was still high, with high cumulative resistance rates among the most widely used antibiotics in the hospital. Total antibiotic use decreased from 2010 to 2014 although there was still high prescribing of reserved antibiotics. CONCLUSION: Concerns with inappropriate use and high resistance rates among some antibiotics used in the hospital are being used to develop guidance on future antibiotic use in this hospital, building on the recently introduced antibiotic stewardship program, as well as encourage other hospitals in Serbia to review their policies.

The usefulness of advanced lipid and oxidative stress testing for diagnosis and management of low HDL-cholesterol phenotype: A case report.

OBJECTIVE: Plasma high-density lipoprotein cholesterol (HDL-C) level is a strong inverse predictor of cardiovascular disease (CVD) development. Tangier disease, a consequence of mutations in the ATP binding cassette transporter 1 (ABCA1) gene, is associated with very low HDL-C levels. Still, the relationship between Tangier disease and CVD is not always evident. The study investigates usefulness of lipoprotein subfractions, oxidative stress and paraoxonase 1 (PON1) status assessment for evaluation and management of patient with low HDL-C phenotype. PATIENT AND METHODS: A 12-year-old boy was hospitalised due to hypertension. Laboratory evaluation revealed low HDL-C level, and subsequent molecular diagnostic confirmed Tangier disease. Lipoprotein subfractions were assessed by gradient-gel electrophoresis. Oxidative stress status was estimated by measuring total antioxidative status, total oxidative status, prooxidative-antioxidative balance, malondialdehyde and advanced oxidation protein products levels. Activity of paraoxonase 1 in serum and its distribution within HDL subclasses was also determined (ten healthy boys aged 13.1±3.4years served as the reference group). RESULTS: Analysis of oxidative stress status biomarkers revealed a state of prolonged prooxidants activity. In turn, serum PON1 activity was substantially reduced. The majority of PON1 activity was present on HDL 2 particles. CONCLUSION: Impaired antioxidative potential of HDL may point toward hidden cardiovascular risk in isolated low HDL-phenotype.

Successful use of sirolimus for refractory atrial ectopic tachycardia in a child with cardiac rhabdomyoma.

Cardiac rhabdomyomas are common in tuberous sclerosis. We report a child who developed rhabdomyoma related arrhythmia refractory to antiarrhythmic drug therapy. Reversion of the atrial ectopic tachycardia was achieved with mammalian target of rapamycin pathway (mTOR) inhibitor sirolimus. As per our knowledge, this is the first time that sirolimus has been successfully used in this setting.

Magnesium in Pain Research: State of the Art.

Magnesium has been shown to produce an antinociceptive effect on animal models of neuropathic and inflammatory pain. It has also been shown to exert an analgesic effect on humans in conditions presenting acute (postoperative pain) and chronic (neuropathic) pain. As it is known that magnesium is a physiological antagonist of the N-methyl-Daspartate (NMDA) receptor ion channel, and that the NMDA receptor plays a key role in central sensitization, the primary mechanism through which magnesium produces its analgesic effect is believed to be blockade of the NMDA receptor in the spinal cord. In addition, magnesium blocks calcium channels and modulates potassium channels. The activation of the nitric oxide (NO) pathway could have an important role in the antinociceptive effects of systemic magnesium sulfate in the somatic, but not in the visceral model of inflammatory pain. Although it is known for some time that intramuscular, intravenous and subcutaneous injections of magnesium sulfate in humans, and intraperitoneal injection in rodents produce local pain sensation, the mechanism of this action was elucidated only recently. It was demonstrated that subcutaneous injection of an isotonic, pHadjusted (7.4) solution of magnesium sulfate (6.2%) to rats produces local peripheral pain via activation of peripheral TRPA1, TRPV1, TRPV4 and NMDA receptors and peripheral production of NO. In animal models of pain, magnesium has been shown to exert both antinociceptive and pronociceptive effects by acting on different ion channels and NO pathways, however, the precise mechanisms remain to be elucidated.

Clinical implications of prenatal diagnosis of aorto-left ventricular tunnel on postnatal treatment and final outcome.

Kosutic J, Prijic S, Stajevic M, Kalaba M, Ninic S, Mikovic Z, Vujic A, Popovic S. Clinical implications of prenatal diagnosis of aorto-left ventricular tunnel on postnatal treatment and final outcome. Turk J Pediatr 2017; 59: 342-344. There are no more than 20 antenatally diagnosed aorto-left ventricular tunnel cases reported in the literature. In most of them the diagnosis was made indirectly and only after multiple fetal scans based on findings such as thick and dilated left ventricle and grossly dilated ascending aorta. We present a patient in whom a direct tunnel visualization and aorto-left ventricular tunnel diagnosis was made at the 30th gestation week after a single fetal scan using the recently introduced `cockade sign`. Clinical implications of antenatal diagnosis on postnatal treatment and outcome are also discussed.

The Analysis of the Risk Factors in the Arterial Switch Operation for Treatment of D-Transposition of the Great Arteries in One Pediatric Cardiac Center in Serbia.

INTRODUCTION: The arterial "switch" operation has been the operation of choice for children born with D-transposition of the great arteries (D-TGA) for more than 30 years in countries with developed pediatric cardiac surgery program. After two decades of successful treatment of these children with the atrial "switch" corrections (Mustard or Senning operative techniques), the arterial "switch"operation (ASO) had been introduced as a routine technique in one pediatric cardiac center in Serbia. OBJECTIVE: The aim of this study was the analysis of the identified risk factors involved with the ASO in the preoperative, operative and postoperative period and their impact on the survival of the operated children. METHODS: A retrospective nonrandomized study of 52 operated patients with D-TGA by the ASO in the period between May 1, 2003 and December 31, 2011, divided into two groups. The data collection consisted of preoperative, operative and postoperative factors during the in-hospital stay and until the discharge from the hospital. Descriptive and differential statistical methods were used for analysis. RESULTS: Ten individual risk factors were identified as significant for the immediate survival of children operated with the ASO technique. CONCLUSION: The arterial "switch" surgical operative technique is a complex neonatal/young infant procedure in which the preoperative status carried a significant risk as well as the surgical technique itself. These results differ from the results published throughout the world and are a representation of an evolutionary process of one center in Serbia starting the ASO procedure.

Screening performances of abnormal first-trimester ductus venosus blood flow and increased nuchal translucency thickness in detection of major heart defects.

OBJECTIVE: The aim of this study was to evaluate the screening performances of abnormal ductus venosus (DV) blood flow for the detection of heart defects in chromosomally normal fetuses with increased nuchal translucency (NT) thickness at 11-13 + 6 weeks' gestational in a population of singleton pregnancies. METHODS: During an 8-year period, all singleton pregnancies from 11 + 0 to 13 + 6 weeks were scanned for NT and DV blood flow assessment. Two groups of cases with abnormal NT were evaluated: NT ≥ 95th and NT ≥ 99th centile. DV waveforms were considered to be abnormal if the a-wave was reversed or absent (R/A). RESULTS: Addition of DV R/A a-wave to either NT ≥ 95th or NT ≥ 99th percentile increased specificity (p < 0.001 and p < 0.001, respectively), but not screening performances in detection of major heart defects (p = 0.73 and p = 0.91, respectively). Combination of DV R/A a-wave with NT ≥ 95th or NT ≥ 99th centile correlated with right heart defects (p = 0.024 and p = 0.013, respectively). CONCLUSIONS: In chromosomally normal fetuses, addition of abnormal DV a-wave to increased NT does not improve screening performances of NT in detection of major hearts defects in first trimester. However, there is correlation of such parameter with right heart defects and AV septal defects.

Balloon dilation and surgical valvotomy comparison in non-critical congenital aortic valve stenosis.

Percutaneous balloon aortic valvoplasty (BAV) and surgical aortic valvotomy (SAV) are palliative procedures in patients with non-critical congenital valve stenosis. The aim of the study was to evaluate long-term BAV and SAV results after up to 24 years of follow-up. From 1987 to 2013, 74 consecutive interventions were performed in patients with aortic stenosis, and 62 were included in the study (39 BAVs and 23 SAVs). Age of BAV patients was 1.3 months to 17 years, and of SAV patients 1.2 months to 15 years. Although BAV patients were older, there was no difference between groups according to sex, valve function/morphology, and early/late follow-up results, with exception to hospitalization period. Significant pressure gradient reduction and aortic regurgitation increment were registered after procedures. Three patients did not survive early period after surgery. Follow-up period was 7.0 ± 5.4 and 9.0 ± 8.0 years after BAV and SAV, respectively (p = 0.242). Follow-up pressure gradient rose only in the BAV group, and was emphasized after 10-year-follow-up (p = 0.020). Significant aortic insufficiency progression was registered after 15 years of follow-up in both groups (p = 0.007 and p = 0.009, respectively). Mean reintervention-free survival was 12.0 years in the BAV and 14.5 years in the SAV group (p = 0.733), and mean survival without aortic valve replacement was 15.2 and 17.4 years, respectively (p = 0.877). BAV and SAV in patients with congenital aortic stenosis are very comparable in both early and late follow-up results.

Predictive value of biochemical, echocardiographic and electrocardiographic markers in non-surviving and surviving asphyxiated full-term newborns.

Severe perinatal asphyxia can cause multiple organ dysfunction and early neonatal mortality. This prospective study was conducted at the Regional University Hospital Neonatology Center in Serbia. The aim of this study was to compare fullterm asphyxiated newborn infants (n=55) with (n=13) and without (n=42) mortality outcome and healthy full-term newborns (n=36) regarding biochemical (cardiac troponin I, creatine kinase (total and MB fraction) and C-reactive protein), echocardiographic (ejection fraction, fractional shortening, mitral regurgitation, significant tricuspid regurgitation, and patent ductus arteriosus) and electrocardiographic (ST segment elevation/depression, T wave inversion and corrected QT interval) markers of myocardial damage in order to assess their predictive value in the clinical outcome. Statistically significant differences in the majority of the tested markers of ischemic myocardial lesion were found between perinatal asphyxia survivors and the control group. However, among the biochemical indicators, only the level of cardiac troponin I was significantly higher in the group of neonates who died compared to the group of asphyxiated neonates who survived (p: 0.000), with an area under the receiver operating characteristic curve of 0.821 and cutoff value for lethal outcome of 0.135 µg/L (sensitivity 0.85; specificity 0.69). In addition, differences in ejection fraction, fractional shortening and significant tricuspid regurgitation (≥2+) were also found between the two subgroups of asphyxiated newborns. Cardiac troponin I is the most sensitive ischemic myocardial lesion biochemical marker in the prediction of early mortality in perinatal asphyxia patients.

Beta-Blockers (Carvedilol) in Children with Systemic Ventricle Systolic Dysfunction - Systematic Review and Meta-Analysis.

BACKGROUND: Numerous prospective randomized clinical trials demonstrated favorable effect of beta-blockers in adults with chronic heart failure. However, effectiveness of beta blockers in pediatric patients with systemic ventricle systolic dysfunction was not recognized sufficiently. Limited number of pediatric patients might be the course of unrecognized carvediolol treatment benefit. Currently, no meta-analysis has examined the impact of carvedilol and conventional therapy on the clinical outcome in children with chronic heart failure due to impaired systemic ventricle systolic function. MATERIALS AND METHODS: We have systematically searched the Medline/PubMed and Cochrane Library for the controlled clinical trials that examine carvedilol and standard treatment efficacy in pediatric patients with systemic ventricle systolic dysfunction. Mean differences for continuous variables, odds ratios for dichotomous outcomes, heterogeneity between studies and publication bias were calculated using Cochrane Review Manager (Rev Man 5.2). RESULTS: Total of 8 prospective/observational studies met established criteria. Odds ratio for chronic heart failure related mortality/heart transplantation secondary to carvedilol was 0.52 (95% CI: 0.28-0.97, I(2) = 0%). Our analysis showed that carvedilol could prevent 1 death/ heart transplantation by treating 14 pediatric patients with impaired systemic ventricle systolic function. CONCLUSION: Meta-analysis demonstrated clinical outcome benefit of carvedilol in children with chronic heart failure.

Modified Chrispin-Norman score: correlation with peak exercise capacity and efficiency of ventilation in children with cystic fibrosis.

The modified Chrispin-Norman radiography score (CNS) is used in evaluation of radiographic changes in children with cystic fibrosis (CF). We evaluated the correlation of modified CNS with peak exercise capacity (Wpeak) and ventilatory efficiency (reflected by breathing reserve index-BRI) during progressive cardiopulmonary exercise testing (CPET). Thirty-six children aged 8-17 years were stratified according to their CNS into 3 groups: mild (<10), moderate (10-15), and severe (>15). CPET was performed on a cycle ergometer. Lung function tests included spirometry and whole-body plethysmography. Patients with higher CNS had lower FEV1 (p < .001), Wpeak predicted (%; p = .01) and lower mean peak oxygen consumption (VO2peak/kg; p = .014). The BRI at the anaerobic threshold and at Wpeak was elevated in patients with the highest CNS values (p < .001). The modified CNS correlates moderately with Wpeak (R = -0.443; p = .007) and BRI (R = -0.419; p = .011). Stepwise multiple linear regression showed that RV/TLC was the best predictor of Wpeak/pred (%; B = -0.165;  = -0.494; R2 = .244; p = .002). Children with CF who have high modified CNS exhibit decreased exercise tolerance and ventilatory inefficacy during progressive effort.

The role of biochemical markers as early indicators of cardiac damage and prognostic parameters of perinatal asphyxia.

BACKGROUND/AIM: In recent years, the focus of interest of the scientific community is the application of heart markers as early indicators and prognostic parameters of perinatal asphyxia (PA). The aim of this study was to evaluate the significance of clinical application of heart markers in term newborns with perinatal asphyxia. METHODS: During a 3-year period we analyzed 91 full-term newborns (55 with and 36 without perinatal asphyxia). In all the subjects within the first 24-48 h after birth, we simultaneously determined serum concentrations of cardiac troponin I, brain natriuretic peptide, MB fraction of creatine kinase (CK-MB) and C-reactive protein. RESULTS: In the group of full-term neonates with PA significantly higher levels of cardiac tropon-inI (p = 0.000), CK-MB fraction (p = 0.000), brain natriuretic peptide (p = 0.003) and C-reactive protein (p = 0.017) were found, compared to the group of healthy full-term newborns. In merged group (n = 91) cardiac troponin I level correlated with the fifth minute Apgar score (r = -0.637, p = 0.000) and the serum lactate concentration in the first 12h after birth (r = 0.529, p = 0.000). Early increase in cardiac troponin I > 0.135 microg/L predicted the risk of death with the sensitivity of 84.6% and specificity of 85.9%, while the increase in CK-MB fraction, brain natriuretic peptide and C-reactive protein did not have a predictive value with respect to a mortality outcome. CONCLUSION: Among the tested cardiac markers, cardiac troponin I is the most sensitive and the only reliable early predictor of mortality in full-term neonates with perinatal asphyxia.

N-terminal pro-brain natriuretic peptide in the assessment of respiratory distress in term neonates.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) is used as a biomarker to differentiate congestive heart failure from lung disease in adults and children. The clinical significance of its use in term neonates has not yet been extensively studied. METHODS: NT-proBNP level was measured in 62 term neonates admitted for respiratory distress (RD): 38 with congenital heart disease (CHD) and 24 with pulmonary disease. The control group consisted of 28 healthy neonates. Findings of auscultation, chest radiography, Silverman-Anderson score and echocardiography were recorded for each patient. Blood samples for measuring NT-proBNP were collected on admission, when blood sampling was indicated for the clinical management of the newborn. RESULTS: In the control group NT-proBNP was significantly higher during the first week of life compared to the rest of the neonatal period (P < 0.001). The RD group, regardless of etiology, had significantly higher NT-proBNP than the control group (P < 0.001). Neonates with more severe RD had significantly higher NT-proBNP (P = 0.002). No significant difference was found between the RD group with CHD and those with pulmonary disease. Neonates with CHD and myocardial hypocontractility had significantly higher NT-proBNP than those with normal contractility (P = 0.022). CONCLUSION: Term neonates with RD have significantly higher NT-proBNP than healthy neonates. A single measurement of NT-proBNP level cannot be used as the sole biomarker for distinguishing between cardiac and pulmonary cause of RD in term neonates.

Risk factors for thrombosis in Serbian children.

Venous and arterial thromboses are increasingly encountered in the pediatric population. We present results of a case-control study of inherited and acquired risk factors for thrombosis in 129 pediatric patients from the first day of life to 18 years. The aims of study were to determine the importance of thrombophilic risk factors and comorbidity as a cause of thrombosis in children. Single thrombophilic risk factor was found in 24.4% (n = 21), whereas combined thrombophilic factors were found in 15.1% (n = 13) patients. A total of 87.2% of the children had recognized thrombophilic risk factors for thrombosis and/or additional comorbid risk factors. The single independent risk factors for thrombosis were mutation of factor V Leiden (P = 0.021), lupus anticoagulant antibodies (P = 0.028), and comorbidity (P = 0.000). Mutation of factor V Leiden [odds ratio (OR), 6.2 (95% confidence interval, CI 1.1-38.1, P = 0.048] was found to be a risk factor for venous thrombosis. Lupus anticoagulant antibodies were related to both venous (P = 0.008) and arterial thrombosis (P = 0.016). The frequency of inherited thrombophilic factors were the same in neonates and adolescents (23%). The prothrombotic gene mutations were present in 18.6% (n = 8) of asymptomatic children. Our study confirms that thrombosis in children is a multifactorial disorder, and associated most with the underlying medical disease (comorbidity) for vein thrombosis [OR, 18.6 (95% CI 3.7-93.4), P = 0.000] and for arterial thrombosis [OR, 10.5 (95% CI 2.2-49.9) P = 0.003]. Inherited thrombophilic disorders contributed to the development of thrombosis in children.

Static hyperinflation is associated with decreased peak exercise performance in children with cystic fibrosis.

BACKGROUND: We evaluated the exercise capacity of children with cystic fibrosis to determine whether ventilatory limitation associated with static hyperinflation is related with decreased exercise capacity, thus predisposing these children to arterial hypoxemia during progressive exercise. METHODS: Thirty-seven children, ages 8-17 years, underwent spirometry, body plethysmography, and cardiopulmonary exercise testing after arterial catheter placement. According to the ratio of residual volume to total lung capacity (RV/TLC), the subjects were categorized as either with (RV/TLC > 30%) or without static hyperinflation (RV/TLC < 30%). RESULTS: Children with static hyperinflation showed lower values of maximum load per kilogram (% predicted) (P = .01), which was aggravated by ventilatory limitation (FEV(1) < 80% of predicted, peak oxygen consumption [% predicted] < 85%, and breathing reserve index > 0.7). Subjects with ventilatory limitation had significantly lower oxygen saturation (P = .04) and hypoxemia (P = .03) than did subjects without ventilatory limitation. CONCLUSIONS: In children with cystic fibrosis, static hyperinflation and ventilatory limitation are associated with decrease in exercise performance, oxygen saturation, and P(aO(2)) during maximum cardiopulmonary exercise testing. All children with cystic fibrosis who exhibit static hyperinflation and ventilatory limitation may require S(aO(2)) monitoring during progressive exercise.

Severe transient left ventricular pseudohypertrophy during treatment of hemophagocytic lymphohistiocytosis: a case report.

BACKGROUND: An association between hemophagocytic lymphohistiocytosis (HLH) and severe transient left ventricular (LV) hypertrophy has not been described to date. Possible explanations, including etoposide toxicity, are discussed. OBSERVATION: A 2-month-old male infant with HLH was treated according to the HLH-2004 protocol. Initial cardiac evaluation was within normal limits. During the second month of therapy, a heart murmur was discovered; electrocardiogram demonstrated signs of LV hypertrophy, and echocardiogram confirmed the presence of thickness of LV walls. This complication was transient: clinical findings, echocardiogram, and electrocardiogram recorded 6 months afterward were all within normal limits. CONCLUSIONS: The case suggests the need for close echocardiographic monitoring during HLH treatment.