Main features and disease outcome of congenital myotonic dystrophy - experience from a single tertiary center.

Congenital myotonic dystrophy type 1 (CDM1) is a rare neuromuscular disease. The aim of our study was to evaluate clinical variability of CDM1 and factors that may influence survival in CDM1. Research included 24 pediatric patients with CDM1. Most of our patients had some form of hypoxic ischemic encephalopathy (HIE) (74 %), from mild to severe. Prolonged and complicated deliveries (75 %), high percentage of children resuscitated at birth (57 %) and respiratory insufficiency (46 %) with consequent hypoxia were the main reasons that could explain high percentage of HIE. Therapeutic hypothermia was applied in three children with poor outcome. Median survival of all CDM1 was 14.2 ± 1.5 years. Six patients had a fatal outcome (25 %). Their mean age of death was 3.0 ± 2.8 years. Poor prognostic factors for the survival of our CDM1 patients were: preterm delivery, resuscitation at birth, severe HIE, hypothermia treatment and permanent mechanical ventilation. Respiratory insufficiency was the main life-threatening factor. Our data clearly indicates the need to develop natural history studies in CDM1 in order to enhance the standards of care and to develop clinical trials investigating causative therapies in pediatric patients with CDM1.

Analysis of cardiac manifestation and treatment of multisystem inflammatory syndrome in children related to SARS-CoV-2.

Cardiovascular manifestations are common (35-100%) in the multisystem inflammatory syndrome in children. Our study aimed to analyze treatment impact and cardiovascular involvement in patients with multisystem inflammatory syndrome in children. The retrospective cohort included 81 patients treated between April 2020 and December 2021 (9.3±4.6 years). Elevated cardiac troponin I and pro-B-type natriuretic peptide were observed in 34.2% and 88.5% of patients, respectively. Myocardial dysfunction was observed in 50.6%. Children older than 10 years had a 4-fold increased risk of myocardial dysfunction (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.4-8.9; p=0.006). A moderate negative correlation was proved between left ventricle ejection fraction and C-reactive protein (rr = - 0.48; p < 0.001). More than one-fifth of the patients presented with shock. Coronary artery dilatation was observed in 6.2% of patients. Mild pericardial effusion was detected in 27.1% of children. On standard electrocardiogram, 52.6% of children had negative T waves in the inferior and/or precordial leads; transient QTc prolongation was registered in 43% of patients. Treatment failure was observed in 19 patients. Patients initially treated with intravenous immunoglobulins had 10-fold higher chances for treatment failure than patients treated with corticosteroids (OR 10.6, 95% CI 3,18 - 35.35; p < 0.001). Cardiovascular manifestations were observed in more than half of the patients, with acute myocardial dysfunction being the most common, especially in children older than 10 years. We established a negative association between the degree of elevation of inflammatory markers and left ventricular ejection fraction. Patients treated with intravenous immunoglobulins who had cardiovascular manifestations had treatment failures more frequently than patients treated with corticosteroids.

Recent Experience: Corticosteroids as a First-line Therapy in Children With Multisystem Inflammatory Syndrome and COVID-19-related Myocardial Damage.

BACKGROUND: Cardiovascular complications with myocarditis in multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 infection have been reported, but the optimal therapeutic strategy remains unknown. METHODS: A retrospective cohort study included 19 patients with acute left ventricular systolic dysfunction associated with MIS-C, average years of age 13.2 ± 3.8, treated from April 2020 to April 2021. RESULTS: Treatment failure (TF) was observed in 8 patients (in the intravenous immunoglobulin [IVIG] group 7/10; in the corticosteroid [CS] group 1/9). The independent risk factor for TF was IVIG treatment (odds ratio [OR] 18.6, 95% confidence interval [CI] 1.6-222.93, P = 0.02). Patients initially treated with CS became afebrile during in-hospital day 1 (1.5, interquartile range [IQR] 1-2), while IVIG-treated patients became afebrile on in-hospital day 4 (IQR 2-4.25), after CS was added. The C-reactive protein (CRP) significantly declined in CS-treated patients on day 2 (P = 0.01), while in the IVIG group, CRP decreased significantly on the fourth day (P = 0.04). Sodium and albumin levels were higher on third in-hospital day in the CS group than in the IVIG group (P = 0.015, P = 0.03). A significant improvement and normalization of ejection fraction (EF) during the first 3 days was observed only in the CS group (P = 0.005). ICU stays were shorter in the CS group (4, IQR 2-5.5) than in the IVIG group (IVIG group 7, IQR 6-8.5) (P = 0.002). CONCLUSIONS: Among children with MIS-C with cardiovascular involvement, treatment with CS was associated with faster normalization of LV EF, fever, laboratory analysis, and shorter ICU than IVIG-treated patients.

Myocardial damage in multisystem inflammatory syndrome associated with COVID-19 in children and adolescents.

BACKGROUND: In multisystem inflammatory syndrome in children (MIS-C) temporarily associated with coronavirus disease-19 (COVID-19), myocardial damage has been reported. MATERIALS AND METHODS: A retrospective observational cohort study included children under 18 who had a myocardial injury related to COVID-19 treated in mother and child health institute from April 2020 to August 2020. Myocardial injury related to COVID-19 was manifested by elevated serum cardiac troponin and NT-proBNP with LV dysfunction, arrhythmias, and coronary arteries (CAs) dilatation or aneurysms. During the short-term follow-up, cardiac testing (electrocardiography, laboratory analysis, echocardiography, 24-h Holter monitoring, exercise stress test, and cardiac magnetic resonance) was performed. RESULTS: Six male adolescents (14.7 ± 2.4 years) were included in the analysis (2/6 had MIS-C shock syndrome). All patients had elevated acute-phase reactants and NT-proBNP, whereas troponins were elevated in 5/6 patients. Echocardiography revealed left ventricular (LV) systolic dysfunction (EF 45.2 ± 6.9%); 2/6 had dilated CAs. IVIG was prescribed to all patients with MIS-C. Four patients required inotropic drug support. During hospitalization, a significant reduction of CRP, LDH, NT-proBNP, and D-dimer (P < 0.05) was registered. LV systolic function recovery was registered 3 days after applied therapy (P < 0.001). None of the patients developed dilated cardiomyopathy or CA aneurysms. CONCLUSIONS: With early recognition and adequate MIS-C therapy, children recovered entirely, maintained in the short-term follow-up period.

Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a double blind, phase III randomized clinical trial in healthy Serbian adults.

This study was a phase III, multicenter, double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a seasonal trivalent split, inactivated influenza vaccine (TIV) in healthy Serbian adults between the ages of 18 and 65 years. This egg-based vaccine was manufactured by the Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia. A total of 480 participants were assigned randomly in a ratio of 2:1 to receive a single intramuscular dose (0.5 ml) of the vaccine (15 µg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Participants were monitored for safety, including solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). No SAEs related to vaccination were reported. Injection site pain (51.3%), injection site tenderness (40.4%), tiredness (17.0%), and headache (15.1%) were the most commonly reported solicited events in the vaccine group. Incidence of related unsolicited AEs was low (1.3%) among vaccinees. Hemagglutinin inhibition (HAI) titers were measured before and 21 days after vaccination in 151 participants. Overall, HAI seroconversion rates to H1 and H3 were observed in 90.1% and 76.2% of vaccinees, respectively. For B antigen, it was 51.5%, likely due to high pre-vaccination titers. Post-vaccination seroprotection rates were in the range of 78.2-95.0% for the three antigens. Post-vaccination geometric mean titers (GMT) were at least 3.8 times higher than baseline levels for all the three strains among vaccinees. Overall, the study showed that the vaccine was safe and well tolerated, and induced a robust immune response against all three vaccine strains. ClinicalTrials.gov identifier: NCT02935192, October 17, 2016.

[The effect of parental attitudes on habilitation of hearing impaired children]. / Uticaj stavova roditelja na habilitaciju dece sa ostecenim sluhom.

BACKGROUND/AIM: Habilitation of children with hearing loss is a very complex process and requires a team work. Habilitation period length, as well as the effects themselves are individual and depend on many factors. The goal of any habilitation process is to improve the quality of life of each individual to the maximal extent possible, regardless of whether embedded cochlear implant, or other forms of am plification applied. A long-standing practice has shown that the influence of parents and their attitudes in the habilita tion process is great. The aim of this study was to examine the extent of this influence in order to educate the parents so to help their children maximize their potential. METHODS: The instruments used in this study were: semi-structured interview, the Parental Attitudes Scale (PAD), Package Nottingham Early Estimates (NEAP). The participants in this study were the parents with children aged 4-15 years. The extent of hearing loss in the children was recorded at the beginning and during the habilitation process and all were actively involved at least three months. For statistical analysis of this study the descriptive and inferential statisti cal techniques were applied. RESULTS: The results of our study show significant differences in certain parental atti tudes. A close cooperation of the parents and quality ex perts interactions with the parents are a prerequisite for a successful habilitation. CONCLUSION: The result of this re search show that the process of habilitation of children with hearing and speech disorders is significantly affected by the parent attitudes. Parental attitudes were proved to be espe cially important for children with greater hearing loss. It was also noted that in our society mainly mothers are concerned with hearing-damaged children, which indicates that the educational process should be extend to both parents.

[Use of mechanical ventilation in pediatric patients].

BACKGROUND/AIM: Major aims of mechanical ventilation (MV) in pediatrics mean the contribution to complete recovery of acute disorder or to establishing stability of previously long-term changed health condition. MV is used today in 16-46% of patients treated in pediatric intensive care units. The aim of this paper was to get insight into the presence of the disease and pathologic conditions and outcome of MV regarding previous health condition of pediatric patients. METHODS: This retrospective study included 476 pediatric patients (beyond neonatal age) who underwent mechanical ventilation (MV). On the basis of previous health status the patients were classified in two groups: the group A consisted of 157 children with no previous chronic disease leading to MV and the group H comprised of 319 children who received MV due to worsening ofprevious chronic disease. RESULTS: In both groups of pediatric patients there was significant predominance of younger age patients. Acute and chronic neurological disorders were the most frequent conditions requiring use of MV. Out of a total number (476) of the patients, 178 patients (37.40%) died. In the group A 17 patients (10.9%) died, while in the group H mortality rate was significantly higher (161 or 50.5% patients died; p < 0.01; RR 4.85; CI 3.1-7.6). Total duration time of MV in all the patients was 7 525 days, with 1 345 days (15%) accounted for the group A and 4 567 days (85%) for the group H. Mean MV duration was 7.48 (+/- 9.23) days for the patients in the group A which is significantly shorter in comparison to mean 21.8 (+/- 57.96) days for the group H patients (p < 0.001). CONCLUSION: These results point out significant contribution of MV to better outcome in pediatric patients with different acute disorders. Clear dominance of chronically ill children requiring mechanical ventilation due to acute worsening of their condition implies new complexity of problems regarding organization of pediatric intensive care and treatment.

[Prevalence of asthma in college student population].

INTRODUCTION: Bronchial asthma is common chronic disease among young people and prevalence of this condition has been constantly growing over past two decades throughout the world. OBJECTIVE: To establish the prevalence of asthma in student population of Belgrade University and to determine the frequency distribution in regard to their permanent residence. METHOD: Data obtained from annual physical examinations of 118 342 students (age 19-23 years) treated at the Student's Health Care Institute between 1996-2001 were analyzed. Affirmative answer to the question: "Are you currently treated", or "Have you ever been treated for asthma" indicated diagnosis of asthma. Data on student's age, gender, permanent residence, and smoking habits were collected. RESULTS: The prevalence of asthma was 3680/100.000 and mildly growing trend was noted over the last several years (from 2.96% to 4.05%) (F = 42.427; df=4; p < 0.01). Asthma was more prevalent in females (57%) than among males (43%) (chi2 = 91.189; df=1; p < 0.01). Several regions with increased asthma incidence were identified and the causes of such findings still need to be clarified. Cigarette smoking was common in students (chi2 = 236.781; df=1; p < 0.01), but also among asthmatics [one out of three students was a smoker (chi2= 8.141; df=1; p < 0.01)]. CONCLUSION: The prevalence of asthma in student population is 3.68% with mildly growing trend over the last years. The disease is more prevalent in females. Cigarette smoking is common in students as well as among asthmatics. To our knowledge, this is the first study on prevalence of asthma in young adult population in our country.