Jovan Kosutic

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 (FEV1 < 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 PaO2 during maximum cardiopulmonary exercise testing. All children with cystic fibrosis who exhibit static hyperinflation and ventilatory limitation may require SaO2 monitoring during progressive exercise.

Echocardiographic analysis of the subtypes of right ventricular restrictive physiology in surgically treated patients with tetralogy of Fallot.

BACKGROUND Our study focuses on echocardiographic assessment of the right ventricular diastolic function and adaptive right ventricular response to volume overload resulting from pulmonary and tricuspid regurgitation in surgically treated patients with tetralogy of Fallot. METHOD AND RESULTS We included 60 patients subsequent to surgical correction of tetralogy of Fallot, dividing them into two groups - a group of 18 patients with restrictive physiology, having antegrade flow to the pulmonary arteries greater than 30 centimetres per second in late diastole in five consecutive beats, and a group of 42 patients with non-restrictive physiology. Based on the cardiothoracic ratio, being more or equal to, or less than 0.55, we further divided those with restrictive physiology into a group of 14 patients deemed to have primary restriction, and the other 4 patients considered to have secondary or acquired restriction. Those with non-restrictive physiology were divided into groups of 16 patients with a small heart, and 26 patients with a large heart. A fraction of the venous retrograde diastolic flow in the hepatic vein greater or equal to 30 centimetres is important for distinguishing between the subgroup with primary restriction and the other subgroups. In the four patients with secondary restriction, anterograde diastolic flow in the pulmonary artery greater than 30 centimetres per second was recorded after the average period of follow-up of 2.4 years. The mean value of the pulmonary regurgitant jet pressure half-time was higher in the subgroup with the secondary restriction in comparison to the nonrestrictive subgroup with large hearts at 152 milliseconds with standard deviation of 36 milliseconds versus 85 milliseconds with standard deviation of 11 milliseconds, p less than 0.05. This was significantly lower in comparison to those with primary restriction, where the value was 238 milliseconds, with standard deviation of 42 milliseconds, p less than 0.02. CONCLUSION Echocardiographic analysis offers great possibilities for assessment of right ventricular diastolic function, identifying in particular those with restrictive physiology, its interrelation with pulmonary and tricuspid regurgitation, as well as timing and selection of patients for re-intervention.

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.

Bilateral Giant Coronary Aneurysms in Kawasaki Disease How Difficult Can It Be

We report on a 4-year-old boy admitted to our Institute because of fever (39°C) persisting for 8 days. Physical examination showed bilateral conjunctivitis, strawberry tongue, lip fissures, enlarged cervical lymph nodes, and polymorphous rash, followed by finger and toe desquamation (see Figure I in the online-only Data Supplement). Diagnosis of Kawasaki disease was made. According to the Kobayashi risk score, our patient had 8 points, predicting treatment unresponsiveness of 71.4%.1 Over the next 2 weeks, the symptoms of acute phase persisted despite treatment with intravenous immunoglobulin, as well as retreatment with intravenous immunoglobulin and methyl-prednisolone boluses. In week 4 of the disease, he was given infliximab in a single dose of 5 mg/kg. He became afebrile, and his inflammatory parameters normalized after treatment with infliximab. An initial echocardiography examination performed immediately after the admission showed no specific changes. The second echocardiographic …

Low-bandwidth teleconsultations for patients with complex congenital heart diseases.

We have reviewed our experience with a low-bandwidth paediatric telecardiology link (using ISDN at 128 kbit/s) between a tertiary centre in Belgrade and a tertiary centre in London. Over a two-year period, 12 videoconferences were held, during which 40 case histories of 38 patients were presented from Belgrade. The patients were aged 7 days to 20 years, and most of them had complex congenital heart defects. Changes in diagnosis and/or therapy occurred in 21 cases. Clinically relevant changes in diagnosis occurred in 2/40 cases (5%). In 12 cases, there were slight differences in opinion which resulted in minor changes in therapy for 9 of the patients. In another 9 patients, major changes in therapy occurred. There were no major problems with the quality of image and sound in any of the videoconferences. Our experience suggests that when there are experienced paediatric cardiologists at both ends of the connection, transmission via a single ISDN line is safe and accurate.

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-D-aspartate (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, pH-adjusted (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.

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.

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

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.

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.

Experience with developing antibiotic stewardship programmes 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 childrens hospitals. METHODS Retrospective observational analysis of antimicrobial utilization and resistance patterns over 5 years in a tertiary care childrens 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.