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

Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial.

BACKGROUND: Mycophenolate mofetil has replaced azathioprine in immunosuppression regimens worldwide to prevent graft rejection. However, evidence that its antirejection activity is better than that of azathioprine has been provided only by registration trials with an old formulation of ciclosporin and steroid. We aimed to compare the antirejection activity of these two drugs with a new formulation of ciclosporin. METHODS: The mycophenolate steroids sparing multicentre, prospective, randomised, parallel-group trial compared acute rejections and adverse events in recipients of cadaver-kidney transplants over 6-month treatment with mycophenolate mofetil or azathioprine along with ciclosporin microemulsion (Neoral) and steroids (phase A), and over 15 more months without steroids (phase B). The primary endpoint was occurrence of acute rejection episodes. Analysis was by intention to treat. FINDINGS: 168 patients per group entered phase A. 56 (34%) assigned mycophenolate mofetil and 58 (35%) assigned azathioprine had clinical rejections (risk reduction [RR] on mycophenolate mofetil compared with azathioprine 13.7% [95% CI -25.7% to 40.7%], p=0.44). 88 patients in the mycophenolate mofetil group and 89 in the azathioprine group entered phase B. 14 (16%) taking mycophenolate mofetil and 11 (12%) taking azathioprine had clinical rejections (RR -16.2%, [-157.5% to 47.5%], p=0.71). Average per-patient costs of mycophenolate mofetil treatment greatly exceeded those of azathioprine (phase A 2665 Euros [SD 586] vs Euros 184 [62]; phase B 5095 Euros [2658] vs 322 Euros [170], p<0.0001 for both). INTERPRETATION: In recipients of cadaver kidney-transplants given ciclosporin microemulsion, mycophenolate mofetil offers no advantages over azathioprine in preventing acute rejections and is about 15 times more expensive. Standard immunosuppression regimens for transplantation should perhaps include azathioprine rather than mycophenolate mofetil, at least for kidney graft

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.)

End-group ionisation enables the use of poly(N-(2-methacryloyloxy)ethyl pyrrolidone) as an electrosteric stabiliser block for polymerisation-induced self-assembly in aqueous media

A series of near-monodisperse poly(N-2-(methacryloyloxy)ethyl pyrrolidone) (PNMEP) homopolymers was prepared via reversible addition-fragmentation chain transfer (RAFT) solution polymerisation of NMEP in ethanol at 70 °C using a carboxylic acid-functional RAFT agent. The mean degree of polymerisation (DP) was varied from 19 to 89 and acid titration indicated end-group pK a values of 5.07-5.44. Turbidimetry studies indicated that homopolymer cloud points were significantly higher at pH 7 (anionic carboxylate) than at pH 3 (neutral carboxylic acid). Moreover, this enhanced hydrophilic character enabled PNMEP to be used as a steric stabiliser for aqueous polymerisation-induced self-assembly (PISA) syntheses. Thus, a PNMEP 42 precursor was chain-extended via RAFT aqueous dispersion polymerisation of 2-hydroxypropyl methacrylate (HPMA) at 44 °C. A series of PNMEP 42 -PHPMA x diblock copolymers were synthesised using this protocol, with target PHPMA DPs of 150 to 400. High conversions were achieved and a linear evolution in M n with increasing PHPMA DP was observed. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies confirmed a spherical morphology in all cases. The nanoparticles flocculated either below pH 4.5 (owing to protonation) or on addition of 60 mM KCl (as a result of charge screening). Thus the anionic end-groups on the PNMEP stabiliser chains make an important contribution to the overall colloidal stability. Similarly, a PNMEP 53 macro-CTA was chain-extended via RAFT aqueous emulsion polymerisation of 2-ethoxyethyl methacrylate (EEMA) at 44 °C. Again, a neutral solution pH was critical for the synthesis of colloidally stable nanoparticles. High conversions were achieved as the target PEEMA DP was varied between 100 and 600 and a linear evolution in molecular weight with PEEMA DP was confirmed by chloroform GPC studies. DLS experiments indicated a monotonic increase in nanoparticle diameter with PEEMA DP and TEM studies confirmed a spherical morphology in each case. In summary, PNMEP can be used as a water-soluble steric stabiliser for aqueous PISA syntheses provided that it contains an anionic carboxylate end-group to enhance its hydrophilic character

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

Genetic architecture of common bunt resistance in winter wheat using genome-wide association study

Background: Common bunt (caused by Tilletia caries and T. foetida) has been considered as a major disease in wheat (Triticum aestivum) following rust (Puccinia spp.) in the Near East and is economically important in the Great Plains, USA. Despite the fact that it can be easily controlled using seed treatment with fungicides, fungicides often cannot or may not be used in organic and low-input fields. Planting common bunt resistant genotypes is an alternative. Results: To identify resistance genes for Nebraska common bunt race, the global set of differential lines were inoculated. Nine differential lines carrying nine different genes had 0% infected heads and seemed to be resistant to Nebraska race. To understand the genetic basis of the resistance in Nebraska winter wheat, a set of 330 genotypes were inoculated and evaluated under field conditions in two locations. Out of the 330 genotypes, 62 genotypes had different degrees of resistance. Moreover, plant height, chlorophyll content and days to heading were scored in both locations. Using genome-wide association study, 123 SNPs located on fourteen chromosomes were identified to be associated with the resistance. Different degrees of linkage disequilibrium was found among the significant SNPs and they explained 1.00 to 9.00% of the phenotypic variance, indicating the presence of many minor QTLs controlling the resistance. Conclusion: Based on the chromosomal location of some of the known genes, some SNPs may be associated with Bt1, Bt6, Bt11 and Bt12 resistance loci. The remaining significant SNPs may be novel alleles that were not reported previously. Common bunt resistance seems to be an independent trait as no correlation was found between a number of infected heads and chlorophyll content, days to heading or plant height