Multicolored MIS-C, a single-centre cohort study.

BACKGROUND: The aim of this study was to investigate the clinical and laboratory parameters that can predict the severity of Multisystem Inflammatory Syndrome in Children (MIS-C) at admission. METHODS: We conducted a single-center, partly retrospective, partly prospective, observational cohort study between November 1, 2020 and December 31, 2021, which included patients aged from 1 month to 19 years, meeting the diagnostic criteria of MIS-C. We categorized the patients into three subgroups based on clinical and laboratory markers and assessed the predictive value of these factors in terms of ICU administration and cardiac abnormalities. RESULTS: 53 patients were classified in the following subgroups: Kawasaki-like disease (group 1) (47.2%, n = 25), shock with or without acute cardiac dysfunction (group 2) (32%, n = 17), fever and inflammation (group 3) (20.8%, n = 11). Subgroup analysis revealed that patients with shock and KD at initial presentation had significantly more severe manifestation of MIS-C requiring intensive care unit (ICU) treatment. Of the initial laboratory values, only CRP showed a significant difference between the 3 clinical groups, being lower in group 3. 52.6% of patients were admitted to the ICU. The median length of ICU stay was 3 days (range 3-20). ICU admission was more likely in patients with shortness of breath, renal failure (AKI) and patients with significantly increased concentrations of ferritin, D-dimer, INR and significantly milder increase concentration of fibrinogen. We found that fibrinogen and ferritin levels are independent risk factors for ICU admission. Cardiac abnormalities were found in 56.6% of total (30/53), with the following findings: decreased left ventricular function (32%), coronary abnormality (11.3%), pericardial effusion (17%), arrhythmia (32.1%) and mitral regurgitation (26.6%). Diarrhea and conjunctivitis at the initial presentation with significantly elevated CRP, Pro-BNP and blood pH concentrations were found to be a potential predisposing factor for decreased cardiac function while Pro-BNP and pH were independent risk factors for MIS-C. Regardless of the initial symptoms of MIS-C, the outcome was generally favorable. CONCLUSIONS: Clinical characteristics and baseline laboratory values ​​may help identify patients at increased risk for severe disease outcome, such as need for intensive care, presence of shock and decreased cardiac function. TRIAL REGISTRATION: Participation consent was not reqired and ethical considerations were unnecessary, since we did not perform any extra interventions, only the necessary and usual therapeutic and diagnostic methods were used.

Copy number variants detection by microarray and multiplex ligation-dependent probe amplification in congenital heart diseases.

Congenital heart diseases (CHDs) are the most common birth defects among life births, which could be presented as isolated or syndromic with other congenital malformations. The etiology of CHD largely unknown, genetic and environmental factors contribute to the disease. Recurrent copy number variants (CNVs) have been reported in the pathogenesis of CHD. The aim of this study was to evaluate the clinical utility of multiplex ligation-dependent probe amplification (MLPA) and microarray analyses on isolated and syndromic CHD cases and to explore the relationship between identified CNVs and CHD. Eighteen prenatal samples, 16 isolated and 33 syndromic patients with mild to severe CHD phenotype were tested. Prenatal and isolated CHD cases did not show pathogenic CNVs. Clinically significant CNVs were detected in 7/33 (21%) syndromic CHD patients: del 22q11.2 (n = 2), 8p23.1 duplication (n = 2), deletion 5p (n = 1), deletion 6q21q22 (n = 1), unbalanced translocation causing partial deletion of 4q34.3 and duplication of 6q25.1 (n = 1). These genomic imbalances contain genes that has been associated with human CHD before. The present study demonstrates that using microarray and MLPA analysis increase the detection rate of causal CNVs in individuals with syndromic CHD.

Does the prophylactic and therapeutic use of beta-blockers in preoperative patients with tetralogy of Fallot significantly prevent and treat the occurrence of cyanotic spells?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Does the use of beta-blockers significantly prevent and treat the occurrence of cyanotic spells in preoperative infants with tetralogy of Fallot?' Altogether, 80 papers were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The author, journal, date, country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The participants in the papers reviewed were uncorrected (native or palliated) tetralogy of Fallot patients, all younger than 18 years of age, with some patients younger than 1 year. Each study reviewed included at least 10 patients, and all the studies were case series. Although even the most recent studies found were from 30 years ago, their data remain relevant. Several reviews reported either cases of overdosage or changes in efficacy of treatment after long-term usage. Four of the 6 case reviews demonstrated a decrease in the number of recurring cyanotic spells in at least 66% of the participants, following the introduction of beta-blockers. We can therefore conclude that the use of beta-blockers prevents the occurrence of cyanotic spells in preoperative patients with tetralogy of Fallot. There were insufficient data to establish optimum dosages or duration of treatment.

[Support in diagnostics and therapy]. / Szisztematikus irodalmi áttekintések módszertana és jelentosége. Segítség a diagnosztikus és terápiás döntésekhez.

There is no proven effective treatment for many diseases today that proves to be one of the greatest problems of health care. Therefore, different therapeutic decisions are made in connection with the same disease by hospitals. There is a growing need for reviews which summarize the information collected from professional literature with scientific methods. The aim of the authors was to show the limitations of conventional narrative reviews, and to present the method and importance of systematic reviews to Hungarian professionals. Systematic reviews are transparent studies which are based on a predetermined protocol and collate all empirical evidence to answer a specific research question, and consequently provide more reliable results. They use explicit and systematic methods to minimize bias, and provide evidence for clinicians and policy makers to help them make diagnostic and therapeutic decisions which are essential in several fields of the health care system and health policy, too.

[Deletion 15q26 syndrome]. / 15q26-microdeletio-szindróma.

The association of short stature, microcephaly, congenital cardiac anomaly and intellectual deficit should always raise the suspicion of chromosomal etiology. If G-banded karyotyping fails to detect large chromosomal aberrations, array comparative genomic hybridization (array CGH) should be performed to screen for submicroscopic pathological copy number changes. The authors present a six-year-old girl whose symptoms arose from a 4.1 Mb loss in the 15q26.2-26.3 telomeric region. The syndrome is characterized by a resistance to the insulin-like growth factor 1 - in our case the increased level of the insulin-like growth factor 1 together with the persistent longitudinal growth failure was an important finding and differential diagnostic feature. A brief overview of the literature is provided.

Pediatric myocarditis: A sentinel of non-cardiac chronic diseases?

INTRODUCTION: Although long-term outcome studies in large pediatric myocarditis/cardiomyopathy populations have been reported in literature, none of them focused on comorbidities. METHODS: All children and adolescents (age <18 years) treated with myocarditis at the Department of Pediatrics, University of Debrecen, Hungary were followed. Patients suffering from myocarditis during the period 1996-2011 were enrolled. RESULTS: Over the 16-year period, a diagnosis of myocarditis was established in nine children. Their median age was 1.11 (0.03-8.71) years. Three of the nine patients died. Left ventricular dilatation and ejection fraction normalized within 1-21 months in the survivors. None of the cases progressed to dilated cardiomyopathy. Regarding non-cardiac comorbidities, myocarditis or recurrent peri-myocarditis preceded the manifestation of celiac disease in two patients, while cystic fibrosis was diagnosed after the improvement of cardiac function in another, and Alström syndrome was diagnosed several years after complete recovery from myocarditis in yet another patient. CONCLUSION: These results suggest that manifestations of other chronic pediatric diseases may be more frequent among survivors of pediatric myocarditis. Prolonged follow-up of patients who survive myocarditis is therefore recommended not only to detect possible progression to cardiomyopathy but also to identify non-cardiac comorbidities.

Measuring health-related quality of life in Hungarian children with heart disease: psychometric properties of the Hungarian version of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and the Cardiac Module.

OBJECTIVES: The aim of the study was to investigate the psychometric properties of the Hungarian version of the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales and Cardiac Module. METHODS: The PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Cardiac Module was administered to 254 caregivers of children (aged 2-18 years) and to 195 children (aged 5-18 years) at a pediatric cardiology outpatient unit. A postal survey on a demographically group-matched sample of the general population with 525 caregivers of children (aged 2-18 years) and 373 children (aged 5-18 years) was conducted with the PedsQL 4.0 Generic Core Scale. Responses were described, compared over subgroups of subjects, and were used to assess practical utility, distributional coverage, construct validity, internal consistency, and inter-reporter agreement of the instrument. RESULTS: The moderate scale-level mean percentage of missing item responses (range 1.8-2.3%) supported the feasibility of the Generic Core Scales for general Hungarian children. Minimal to moderate ceiling effects and no floor effects were found on the Generic Core Scales. We observed stronger ceiling than floor effects in the Cardiac Module. Most of the scales showed satisfactory reliability with Cronbach's alpha estimates exceeding 0.70. Generally, moderate to good agreement was found between self- and parent proxy-reports in the patient and in the comparison group (intraclass correlation coefficient range 0.52-0.77), but remarkably low agreement in the perceived physical appearance subscale in the age group 5-7 years (0.18) and for the treatment II scale (problems on taking heart medicine) scale of the Cardiac Module in children aged 8-12 years (0.39). Assessing the construct validity of the questionnaires, statistically significant difference was found between the patient group and the comparison group only in the Physical Functioning Scale scores (p = 0.003) of the child self-report component, and in Physical (p = 0.022), Emotional, (p = 0.017), Psychosocial Summary (p = 0.019) scores and in the total HRQoL (health-related quality of life) scale score (p = 0.034) for parent proxy-report. CONCLUSION: The findings generally support the feasibility, reliability and validity of the Hungarian translation of the PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Cardiac Module in Hungarian children with heart disease.

Measuring health-related quality of life in Hungarian children attending a cardiology clinic with the Pediatric Quality of Life Inventory.

The aim of the study was to evaluate health-related quality of life (HRQoL) of Hungarian children attending a pediatric cardiology outpatient unit with the Pediatric Quality of Life Inventory (PedsQL) questionnaire. The PedsQL Generic Core Scales and Cardiac Module were administered to 254 families including 195 children during a pediatric cardiology outpatient visit, and 525 families including 373 children from the general population were examined by the PedsQL Generic Core Scale by a postal survey. The relationships between PedsQL scores and patient characteristics were analyzed. Hungarian children attending a cardiology outpatient unit as an entire group and patients with severe heart diseases report significantly lower physical functioning than the general population, while more HRQoL dimensions are negatively affected according to the parents' opinion. Children with congenital heart disease of mild and great complexity also report impaired psychosocial functioning. HRQoL impairment is concentrated to the age of 5-7 years. Comparing our results with previous ones on U.S. pediatric cardiologic samples, we found significantly lower scores mainly for the physical functioning and heart symptoms subscales. This HRQoL study with an internationally well-validated instrument on children with heart disease in a Central European country highlights certain aspects of the health-care system and brings the possibility for the assessment of pediatric cardiology outcomes in a more comprehensive way.

[In utero thrombosis of neonates: inherited thrombophilia?]. / Ujszülöttek in utero kialakult thrombosisa: örökletes thrombophilia?

Thromboembolic events are relatively uncommon in childhood. It involves mainly children under one year of age and adolescents, with an incidence is 5.1/10000 live births. Authors present a course of disease of seven cases with neonatal thromboembolic events (2.5/admissions), diagnosed and treated at the Neonatal Division of Department of Pediatrics. In three of seven cases thrombosis proved to be of intrauterine origin. In each of the latter cases, inherited thrombophilia of the mothers was detected. Additional risk factors including infection could be revealed only in one case. Using in vivo and post mortem DNA analysis, mother-like-thrombophilia could not be confirmed in any of the newborns. Based on their experiences, authors suppose that undetected predisposing factors added to maternal thrombophilia can be considered as etiological factor. Authors suggest the intensive follow-up of pregnant women with thrombophilia and also their fetuses.

[Hungarian validation of the cardiac module of the Pediatric Quality of Life Inventory]. / A Pediatric Quality of Life Inventory (PedsQL) gyermekkori életminoség-méro kérdoív kardiológiai moduljának magyarországi validálása.

UNLABELLED: The authors report the validation process of the cardiac module of the Pediatric Quality of Life Inventory (PedsQL ) into Hungarian. BACKGROUND: The PedsQL which is a modular instrument to evaluate health-related quality of life (HRQL ) in children and adolescents of ages 2-18 years, comes up to the current professional requirements at a high level. There is no report on health-related quality of life measure in Hungary which was performed among children with heart disease. OBJECTIVE: To adapt and to test a pediatric quality of life questionnaire for measuring HRQL in children with heart disease. METHODS: Sequential validation process which follows international guidelines. Pilot-study on 105 children with heart disease. RESULTS: According to the results of the pilot-study the psychic domains have a negative influence on general HRQL index in both child and parent-proxy reports in all age groups. On the cardiac module parents of children of all age groups but only children of ages 5-7 years reported marked treatment anxiety. Cognitive and communication problems are mainly important for children of ages 8-18 years. Parent-child concordance is depending on the age of the child, there was expressed difference in the psychosocial domains. We have found no negative effect of heart operation on HRQL by itself but taking medicine may impair it. CONCLUSION: Further methodologic research should evaluate the psychometric properties of the newly validated Hungarian version of the PedsQL cardiac module. The detailed report about the validation process can help in the spreading of patient reported outcome measures in Hungary.

[Quality-of-life measures in pediatric cardiology]. / Eletminôség-mérések a gyermekkardiológiában.

UNLABELLED: The need of outcome measures from the patients' aspect emerges reasonably in the field of rapidly developing pediatric cardiac surgery and pediatric cardiology. The professional standards and the possibilities of applicability of quality of life measures are often unknown for medical doctors. This is particularly true in pediatrics due to the numerous difficulties of pediatric measures and--in consequence--to the lower number of correct investigations. AIM: To summarize the basic professional expectations and results of previous quality of life studies performed in pediatric cardiology from a clinical point of view. METHOD: Survey of the literature of quality of life measures performed on mixed or specified adult and child population with congenital heart disease with a presentation of the main results and the basic characteristics of methodology. CONCLUSION: According to previous results, quality of life measures have a role in pediatric cardiology. Adequate measures can improve the level of care.

[Principles of quality of life measurement and its application in childhood]. / Az életminôség-mérés alapjai és annak gyermekkori alkalmazása.

BACKGROUND: The evaluative and critical analysis of articles on the quality of life which appear in growing number in the medical literature, and the adaptation of the measures to clinical practice can be realised only through knowledge of the professional standards of the measuring methods. OBJECTIVE: To outline the most widely accepted definitions of life- and health-related quality of life, to define the application possibilities as well as the parameters of the measuring methods. To demonstrate the most common problems as well as the possibilities of implementing pediatric measures. To give concrete guidance on evaluating previous measures and designing new ones. METHOD: Through a review of literature on methodology, cultural equivalence and paediatric measures, the authors outline the most frequent problems and give examples of some methods corresponding to the current professional standards. CONCLUSION: The quality of health care can be improved by using patient-reported outcome measures such as health-related quality of life measures. To assess different patient groups, modular approaches with general and disease-specific modules are advisable. The linguistic and cultural equivalence and the international comparability of the results can be achieved by adhering to professional guidelines and by performing psychometric tests to control the parameters of the methodology. In paediatric measures efforts should be made to conduct the simultaneous questioning of children and their parents as early as possible.

[Molecular pathology and clinical manifestations of Fabry disease]. / A Fabry-kór molekuláris patológiája és klinikai megjelenési formái.

Fabry disease is a rare, progressive lysosomal storage disorder caused by mutation in the GAL gene and an impaired function of the alpha-galactosidase A enzyme. The enzymatic defect results in the progressive accumulation of glycosphingolipids in endothelial cells, smooth muscle cells, leucocytes and fibroblasts leading to organ damage in the skin, eye, nervous system, kidney and heart. Major clinical manifestations include acroparesthesis, angiokeratoma, corneal opacities, vascular diseases of the heart, kidney, and the central nervous system. Enzyme replacement therapy has recently become available for the treatment of Fabry patients. In this review the authors describe clinical features of Fabry disease in 31 Hungarian patients. At the time of this analysis the database consisted of 31 cases (15 males, 16 females) of whom 5 have died (4 males, 1 female). The most common disease-specific manifestation was angiokeratoma in males, and eye symptoms in females. 25% of female subjects were symptom free. Genotyping was performed in all cases and disease-causing mutations were found in all families. Three new mutations were identified. Twelve patients (8 males and 4 females) are currently receiving enzyme replacement therapy.

[Critical appraisal of articles about clinical audit]. / Klinikai auditról szóló közlemények kritikus elemzése.

OBJECTIVE: To summarize the most important criteria used in critical appraisal of publications about clinical audit by the review of the relevant English language literature. METHODS: Electronic databases, including Medline, Science Direct, and Ingenta Select, and Internet search were used to find relevant English language publication between 1985 and 2005. Hand search and the reference lists search for publications were also applied. In addition, researchers were also contacted for publications. RESULTS: The literature is surprisingly scarce about the critical appraisal of clinical audit publications. As a result hand search was as important as electronic search. The following three screening criteria can be used in order to critically appraise the scientific literature: (a) whether or not valid and relevant criteria and standards were used to evaluate clinical practice, (b) the criteria were used systematically on a representative sample of patients, and (c) the results are important and applicable (generalizable) in our practice. The publication is useful if it helps to improve the quality of our own clinical practice. CONCLUSION: Critical appraisal criteria can be used to improve the quality of clinical audit, and disseminate the results of audit, as well as find high quality evidence for designing and implementing quality improvement initiatives.

[Practice pattern and geographic variation in test ordering. A literature review]. / Külónbségek a vizsgálatok használatáinak gyakoriságában: irodalmi áttekintés.

OBJECTIVE: To review the available research results in order to identify evidence about geographical variation and practice variation in primary care in the diagnostic test ordering. METHODS: Electronic databases, Medline, Cochrane Library, Science Direct, and Ingenta Select were used to find relevant English language publication between 1989 and 2004. Hand search and the reference lists search for publications were also applied. In addition, researchers were also contacted for publications. Quality of the studies were assessed by using criteria such as sound description of research methodology, detailed and clear presentation of study results. RESULTS: There is a significant (2-4 fold) variation in laboratory test ordering between countries as well as between regions and praxis. There is larger (10-20 fold or more) variation between regions and praxis in the case of diagnostic tests which clinical usefulness is uncertain. The variation between diagnostic test ordering can be larger than variation between medical treatments or invasive interventions. Both geographical and praxis variation could be a result of multiple factors. None of the examined single factor alone was able to explain most of the variations. CONCLUSIONS: Variation in diagnostic test utilisation is significant, and could be caused by multiple factors. Optimisation of diagnostic test ordering and promotion of appropriate utilisation may require multifaceted intervention throughout the health system including changes in regulation, licensing, available capacity, reimbursement/incentive systems and continuous medical education as well as better patient information.

The application of a simplified system of criterions for audit to improve paediatric cardiologic and paediatric cardiac surgical care: evidence from a regional approach in Hungary.

AIMS: To evaluate the quality of cardiac and surgical care provided for children with congenital cardiac malformations in the eastern county of Hungary. METHODS: We used the method of clinical audit based in selection of criterions, developing five such criterions concerning timely diagnosis, access to treatment, and outcome. To examine compliance with these criterions, we analysed retrospectively the routine data relating to children living in Hajdu-Bihar County. The period of observation lasted from January, 1994, until December, 2001, and was divided into two epochs in order to evaluate any changes over time. RESULTS: In the first epoch, 28 infants, representing 0.1% of all newborns, died of congenital cardiac disease, with one of the malformations being recognised post mortem. In the second epoch, 21 infants died, representing 0.09% of newborns. In this group, each malformation was diagnosed before death. In each period, 6 infants died without having undergone cardiac surgery, and having no other non-cardiac disease. The overall postoperative mortality was 9.2% for the first period, and 4.6% for the second. The number of patients waiting for non-urgent repair had reduced significantly by the end of the second epoch. CONCLUSIONS: The results show that the timely diagnosis of congenital cardiac malformations is in line with accepted international standards. Conversely, the access to invasive treatment was limited over the period of observation, albeit that the waiting list was reduced significantly by the end of the second epoch. The postoperative mortality for those suffering congenital cardiac malformations is also comparable with international standards, except for mortality during infancy for treatment of complex anomalies. Our audit highlights the need for surgical repair of the more complex malformations during infancy.

[The role of clinical audit in the quality improvement of health care]. / A klinikai audit szerepe az egészségügyi minoségfejlesztésben.

The aim of clinical audit is continuous improvement of the quality of care through systematic and critical review of current practice against explicit criteria and the implementation of change if necessary. The audit is a regular multidisciplinary activity by which all participants of care including doctors, nurses and other health professionals carry out a systematic review of their own practice. Data collected during the process of audit should be handled with care, and individual data concerning care-givers, patients or health professionals must be treated confidentially. Clinical audit needs realistic timeframe and necessary resources as well as tolerant culture of learning organisations. Furthermore the success of clinical audit depends on the commitment and support of the management of the organisations. Clinical audit could relatively easily be embodied into the current practice of peer-review processes and other quality improvement initiatives in Hungary. Widespread and systemic application of clinical audit may improve the quality of patient care and maintain the trust of the population. However, clinical audit should be effective and cost-effective. The recently published methodological guideline by the Ministry intends to promote good practice in clinical audit.

Phenotypic manifestations of the OCTN2 V295X mutation: sudden infant death and carnitine-responsive cardiomyopathy in Roma families.

In two non-consanguineous Hungarian Roma (Gypsy) children who presented with cardiomyopathy and decreased plasma carnitine levels, we identified homozygous deletion of 17081C of the SLC22A5 gene that results in a frameshift at R282D and leads ultimately to a premature stop codon (V295X) in the OCTN2 carnitine transporter. Carnitine treatment resulted in dramatic improvement of the cardiac symptoms, echocardiographic, and EKG findings in both cases. Family investigations revealed four sudden deaths, two of them corresponded to the classic SIDS phenotype. In postmortem tissue specimens available from three of them we could verify the homozygous mutation. In liver tissue reserved from two patients lipid droplet vacuolization could be observed; the lipid vacuoles were located mainly in the peripherolobular regions of the acini. In the heart tissue signs of generalized hypertrophy and lipid vacuoles were seen predominantly in the subendocardial areas in both cases; some aggregates of smaller lipid vacuoles were separated, apparently by membranes. Review of all OCTN2 deficiency cases reported so far revealed that this is the first presentation of histopathology in classic familial sudden infant death syndrome (SIDS) with an established SLC22A5 mutation. In addition to the two affected homozygous cardiomyopathic children and three homozygous sudden death patients, the genetic analysis in 25 relatives showed 14 carriers. The mutant gene derived from five non-consanguineous grandparents, each of them having 6-14 brothers and sisters. This alone suggests a wide ancestral spread of the mutation in certain Roma subpopulations.