The role of echocardiography in the diagnosis of fetal and pediatric cardiac tumors

В исторически план развитието на образните методи на изследване при сърдечните тумори позволи преминаването от аутопсионна към прижизнено поставена диагноза. Ехокардиографията е лесно достъпен, неинвазивен и високо информативен диагностичен метод на първи избор.Представени са възможностите на съвременното комплексно ехокардиографско изследване за ранно, включително и пренатално, откриване на туморите на сърцето, придружаващите сърдечни аномалии и извършването на коректна хемодинамична оценка. Включени са и наши собствени наблюдения на пациенти с различни по вид сърдечни тумори, диагностицирани както фетално, така и след раждането.Ехокардиографското изследване е утвърден, бърз, удобен и информативен метод за пре- и постнатално диагностициране на сърдечните тумори в детската възраст, както и за тяхното пре- и постоперативно проследяване.The development of different imaging techniques allows the diagnosis of cardiac tumors to be made before the death of a person, and not as it used to be made - following a post mortem. Echocardiography is easily available, noninvasive and a highly informative diagnostic method of choice.We`re presenting the possibilities of current echocardiography examination for the early, including prenatal, diagnosis of cardiac tumors, concomitant congenital heart diseases and hemodynamic evaluation. In this report we also include the observations of our own patients with different kinds of cardiac tumors, which were diagnosed prenatally and after birth. Echocardiography is an approved, quick, convenient and informative prenatal, and postnatal, diagnostic method for cardiac tumors in childhood, as well as for their preoperative and postoperative follow-up

Intralobar Pulmonary Sequestration – Clinical Case In A Three-Year-Old Child

Pulmonary sequestration is a rare congenital lung anomaly, which presents with a solid or cystic primitive tissue that has no function. Commonly, this formation does not communicate with the tracheobronchial tree and has an anomalous blood supply, most often from the systemic circulation. There are two types of pulmonary sequestration – intralobar (intrapulmonary) and extralobar (extrapulmonary).We present a 3-year-old boy from normal pregnancy and delivery through Cesarean section with intralobar pulmonary sequestration. The child is with normal physical and neuropsychological development, has had all the necessary vaccinations, and suffers from frequent respiratory infections with recurrent cough. The anomaly was discovered accidentally during another hospitalization due to cough, but without a fever, and with suspected inflammatory changes in the radiography, with a wider mediastinal shadow. The performed chest CT with contrast revealed a cystic formation in the posterior-basal left lung with an anomalous supply from the thoracic aorta. Despite the controversial behavior in sequestration, without or with mild symptoms, the child was referred for consultation with a pediatric surgeon and for possible surgical treatment.Pulmonary sequestration is a rare congenital anomaly with the intralobar type being more frequent. A distinctive feature for the latter is the absence of clinical symptoms, especially in childhood. However, it has to be suspected in cases of a chronic cough and recurrent pneumonias. Non-invasive imaging techniques, such as CT angiography, MRI, echography, including fetal one, are the preferred diagnostic tool

Therapeutic approach to idiopathic hypertrophic cardiomyopathy

Идиопатичната хипертрофична кардиомиопатия е рядко срещана в детска възраст с висок потенциален риск от фатален край. Отличителен белег е миокардната хипертрофия при липса на хемодинамична причина. От първия описан случай на експериментално лечение на кърмаче през 1971 г. бета-блокерите имат водеща роля в медикаментозното лечение с вариации в дозовите режими. По последни литературни данни и клинични проучвания употребата на високи дози бета-блокер неоспоримо показва значим процент на преживяемост в дългосрочен план.Представяме клиничен случай на 11-месечно кърмаче, което постъпва в нашата клиника с данни за сърдечна недостатъчност. От проведените образни изследвания - рентгенография на гръден кош и ехокардиография, се установи изразена симетрична хипертрофична необструктивна кардиомиопатия. Започна се медикаментозно лечение с пропранолол в постепенно покачваща се доза до 5 мг / кг / 24 часа. Няколко седмици по-късно при контролно ехокардиографско изследване се установи значително подобрение в диастолната функция на лява камера с известна регресия в хипертрофията на миокарда. Контролираното прилагане на високи дози бета-блокери би могло съществено да подобри прогнозата и дългосрочната преживяемост при пациентите с идиопатична хипертрофична кардиомиопатия.Idiopathic hypertrophic cardiomyopathy is a rare disease in childhood with a high potential of a lethal outcome. The hallmark of the disorder is myocardial hypertrophy that occurs in the absence of an obvious hemodynamic stimulus. Since the first case of an experimental treatment of an infant described in 1971, beta blockers have become one of the leading medication options with variations of the dose regimens. According to the current literature data and clinical trials the use of beta blockers in high doses is consistent with a high percentage of survival.We`re presenting a clinical case of an 11-month old infant, who was admitted to our clinic with symptoms of congestive cardiac failure. The chest radiography and echocardiography results showed a severe symmetric hypertrophic cardiomyopathy without an obstruction in the left ventricular outflow tract. The treatment was started with Propranolol in a titrating dose until reaching the dose of 5mg/kg/24hours. Several weeks later, echocardiography examination showed a significant improvement in the left ventricle diastolic function with some degree of regression of myocardial hypertrophy.The use of high doses of beta blockers together with the monitoring of the clinical state could improve the prognosis and survival in patients with idiopathic hypertrophic cardiomyopathy

The Impact of Gender on Mid-Career Labour Income: The Case of Bulgaria

The impact assessment of education and gender on mid-career labour income in a transitional economy could provide for better understanding of the influence of the labour market dynamics over individuals with different characteristics. Here, we attempt to find an answer to the question: How education and gender determine mid-career labour income? We estimate the returns to education depending on gender using Mincerian equations and regressions. The data set we use is from the Structure of Earnings Survey conducted by the National Statistical Institute in 2002 and 2006. The analysis covers over 130,000 employees between 35 and 49 years old. The impact assessment allows conclusions about the wage gap between men and women, working in different economic sectors incl. the division of public and private sector, services and industry. The access to managerial position and gender differences in the type of the labour contract have been investigated for their contribution to the persistence of a gender pay gap among the individuals with a tertiary education

A Novel, Low-Volume Method for Organ Culture of Embryonic Kidneys That Allows Development of Cortico-Medullary Anatomical Organization

Here, we present a novel method for culturing kidneys in low volumes of medium that offers more organotypic development compared to conventional methods. Organ culture is a powerful technique for studying renal development. It recapitulates many aspects of early development very well, but the established techniques have some disadvantages: in particular, they require relatively large volumes (1–3 mls) of culture medium, which can make high-throughput screens expensive, they require porous (filter) substrates which are difficult to modify chemically, and the organs produced do not achieve good cortico-medullary zonation. Here, we present a technique of growing kidney rudiments in very low volumes of medium–around 85 microliters–using silicone chambers. In this system, kidneys grow directly on glass, grow larger than in conventional culture and develop a clear anatomical cortico-medullary zonation with extended loops of Henle

A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia

BACKGROUND: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS: A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 μg per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS: The percentage of patients with transfusion-dependent β-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.)

Harmonizing and improving European education in prescribing: An overview of digital educational resources used in clinical pharmacology and therapeutics

Aim: Improvement and harmonization of European clinical pharmacology and therapeutics (CPT) education is urgently required. Because digital educational resources can be easily shared, adapted to local situations and re-used widely across a variety of educational systems, they may be ideally suited for this purpose. Methods: With a cross-sectional survey among principal CPT teachers in 279 out of 304 European medical schools, an overview and classification of digital resources was compiled. Results: Teachers from 95 (34%) medical schools in 26 of 28 EU countries responded, 66 (70%) of whom used digital educational resources in their CPT curriculum. A total of 89 of such resources were described in detail, including e-learning (24%), simulators to teach pharmacokinetics and/or pharmacodynamics (10%), virtual patients (8%), and serious games (5%). Together, these resources covered 235 knowledge-based learning objectives, 88 skills, and 13 attitudes. Only one third (27) of the resources were in-part or totally free and only two were licensed open educational resources (free to use, distribute and adapt). A narrative overview of the largest, free and most novel resources is given. Conclusion: Digital educational resources, ranging from e-learning to virtual patients and games, are widely used for CPT education in EU medical schools. Learning objectives are based largely on knowledge rather than skills or attitudes. This may be improved by including more real-life clinical case scenarios. Moreover, the majority of resources are neither free nor open. Therefore, with a view to harmonizing international CPT education, more needs to be learned about why CPT teachers are not currently sharing their educational materials

EurOP2E – the European Open Platform for Prescribing Education, a consensus study among clinical pharmacology and therapeutics teachers

Purpose Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. Methods CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. Results Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. Conclusion Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Adverse Drug Reactions in Children—A Systematic Review

Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided