Prikaz primera prvega uspešnega genskega zdravljenja slovenskega bolnika z mukopolisaharidozo tipa I v tujini

Mukopolisaharidoze so skupina lizosomskih bolezni kopičenja. Njihova skupna značilnost je pomanjkanje delovanja encimov, ki razgrajujejo glikozaminoglikane, polisaharide, ki se povezujejo s proteoglikani in tvorijo zunajcelični matriks. Ker ni encimov, ki bi glikozaminoglikane razgrajevali, se ti kopičijo v lizosomih in povzročijo njihovo okvaro in zato se okvarijo drugi celični organeli, celice in končno organi. Klinična slika je široka, od nevro-kognitivnega upada, skeletno-mišičnih deformacij in tipičnih obraznih sprememb. Ključno je zgodnje prepoznavanje bolezni, čeprav s trenutno dostopnimi načini zdravljenja bolezni ne moremo ozdraviti, lahko pa le upočasnimo njen potek, kar je najbolj učinkovito v fazi bolezni še pred pojavom simptomov. Obetavni način zdravljenja je gensko zdravljenje, ki nakazuje možnost ozdravitve bolezni. Predstavljamo primer dečka, pri katerem je bil prepoznan zgodnji kognitivni upad in za bolezen tipične spremembe. Napoten je bil v terciarno ustanovo, kjer je bila diagnoza potrjena. Deček je bil julija 2018 zdravljen z eksperimentalnim genskim zdravljenjem v tujini (bolnišnica San Raffaele, Milano, Italija). V opisanem primeru gre po našem vedenju za prvo uspešno izpeljano gensko zdravljenje pri slovenskih bolnikih ter za enega prvih primerov genskega zdravljenja mukopolisaharidoze tipa I v svetovnem merilu. Gensko zdravljenje s tem postaja del nove klinične stvarnosti, kar predstavlja pomemben mejnik za naš prostor. Zaradi naprednih zdravljenj bi bilo v prihodnosti smiselno uvesti presejalno testiranje novorojenčkov za MPS tipa I, ki se pri nas ali v Evropi doslej še ne izvaja. Do tedaj pa ostaja najpomembnejši predpogoj za uspešno zdravljenje zgodnja klinična prepoznava bolezni in napotitev v terciarno zdravstveno ustanovo

The time is now: Achieving FH paediatric screening across Europe – The Prague Declaration

ReviewFamilial Hypercholesterolaemia (FH) is severely under-recognized, under-diagnosed and under-treated in Europe, leading to a significantly higher risk of premature cardiovascular diseases in those affected. FH stands for inherited, very high cholesterol and affects 1:300 individuals regardless of their age, race, sex, and lifestyle, making it the most common inherited metabolic disorder and a non-modifiable cardiovascular disease risk factor in the world..info:eu-repo/semantics/publishedVersio

Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia A Global Call to Action

Q1Q1Artículo completoE1-E13IMPORTANCE Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH. OBSERVATIONS In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created. CONCLUSIONS AND RELEVANCE By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well

ETHICS OF VACCINATION IN CHILDHOOD

In countries with well-established immunisation programmes, vaccination is the ‘victim of its own success’, because the low incidence of diseases prevented by vaccines has diminished the experience of their historical burdens and hence the obvious benefit of vaccination. The increasing number of parents who reject vaccination of their children already threatens or even effectively disables herd immunity level of the population and results in outbreaks of previously already controlled infectious diseases. We aimed to design a framework for ethical analysis of vaccination in childhood based on the four principles of biomedical ethics (respect for autonomy, non-maleficence, beneficence and justice) to provide a comprehensive and applicable model for addressing the ethical aspects of vaccination at both the individual and societal levels. The principle-based framework can be especially useful to paediatricians in primary care when looking for the best approach to the treatment of children of vaccine-hesitant parents. We suggest finding an ‘ethical equilibrium’, which means that the degree of respect for parents’ autonomy is not constant, but variable; it depends on the level of established herd immunity and it is specific for every society. When the moral obligation of individuals to contribute to herd immunity is not fulfilled, mandatory vaccination policies are ethically justified, because states bear the responsibility to protect herd immunity as a common good

ETIČNI VIDIKI CEPLJENJA V OTROŠTVU

V državah z dobro vzpostavljenimi cepilnimi programi je cepljenje “žrtev lastnega uspeha”, saj je nizka pojavnost bolezni, ki jih preprečujemo s cepljenjem, zmanjšala izkušnjo njihovega bremena in s tem očitnost koristi cepljenja. Povečevanje števila staršev, ki zavračajo cepljenje svojih otrok, je že ogrozilo t. i. skupnostno imunost oz. jo zmanjšalo celo do mere, da so se ponovno začeli pojavljati izbruhi prej obvladanih nalezljivih bolezni. V prispevku predstavljamo sistematični pristop k etičnim vprašanjem glede cepljenja otrok skozi štiri principe biomedicinske etike (tj. spoštovanje posameznikove avtonomije, neškodovanje, dobrodelnost in pravičnost), ki je razumljiv model za razmislek o tovrstnih vprašanjih. Pediatrom na primarni ravni, ki se najpogosteje srečujejo z dilemami glede obravnave otrok, katerih starši zavračajo cepljenje, je lahko sistematičnost opisanega pristopa v pomoč pri etičnem razmisleku, odločanju in iskanju lastne vloge v tovrstnih situacijah. Utemeljujemo iskanje “etičnega ravnovesja”, kar pomeni, da stopnja spoštovanja avtonomije staršev ni stalna, ampak odvisna od ravni vzpostavljene skupnostne imunosti. če moralna dolžnost posameznikov, da prispevajo k imunosti populacije, ni izpolnjena, je upravičeno s strani države pred-pisano obvezno cepljenje. Država je namreč odgovorna za varovanje skupnostne imunosti, ki jo moramo razumeti kot javno dobro in zato potrebuje posebno državno zaščito

Sex-related differences in cardiovascular disease risk profile in children and adolescents with type 1 diabetes

Cardiovascular disease (CVD) is the primary cause of higher and earlier morbidity and mortality in people with type 1 diabetes (T1D) compared to people without diabetes. In addition, women with T1D are at an even higher relative risk for CVD than men. However, the underlying pathophysiology is not well understood. Atherosclerotic changes are known to progress early in life among people with T1D, yet it is less clear when excess CVD risk begins in females with T1D. This review explores the prevalence of classical CVD risk factors (such as glycemic control, hypertension, dyslipidemia, obesity, albuminuria, smoking, diet, physical inactivity), as well as of novel biomarkers (such as chronic inflammation), in children and adolescents with T1D with particular regard to sex-related differences in risk profile. We also summarize gaps where further research and clearer clinical guidance are needed to better address this issue. Considering that girls with T1D might have a more adverse CVD risk profile than boys, the early identification of and sex-specific intervention in T1D would have the potential to reduce later CVD morbidity and excess mortality in females with T1D. To conclude, based on an extensive review of the existing literature, we found a clear difference between boys and girls with T1D in the presence of individual CVD risk factors as well as in overall CVD risk profilesthe girls were on the whole more impacted

High-sensitivity C-reactive protein and carotid intima media thickness as markers of subclinical inflammation and atherosclerosis in pediatric patients with hypercholesterolemia

Hypercholesterolemia is a major cause of atherosclerosis development and premature cardiovascular disease (CVD). It leads to inflammation, which further accelerates atherosclerosis progression. Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevated serum LDL-c from birth, due to a disease-causing variant in one of the causative genes (LDLR, APOB, PCSK9). In polygenic hypercholesterolemia (PH), the disease-causing genetic variant is absentit is likely the cumulative result of multiple single nucleotide polymorphisms in LDL metabolism-related genes and other factors, such as lifestyle and environment. In high risk groups, such as patients with FH, an effective primary prevention of CVD must begin in childhood. High-sensitivity C-reactive protein (hsCRP) and carotid intima media thickness (cIMT) are two potential minimally invasive correlates of inflammation and subclinical atherosclerosis progression. hsCRP and cIMT have been shown to be significantly increased in patients with FH and PH relative to healthy controls, with some studies yielding conflicting results. In this review, we aim to summarize current knowledge and recent findings regarding the applicability of hsCRP and cIMT as markers of low-grade inflammation and subclinical atherosclerosis, focusing especially on children and adolescents with hypercholesterolemia

Towards a comprehensive strategy for the management of rare diseases in Slovenia

Rare diseases (RDs), with distinctive and complex features, pose a serious public health concern and represent a considerable challenge for the Slovenian healthcare system. One of the potential approaches to tackling this problem and treating patients with RDs in a quality and effective manner is to form an RD ecosystem. This represents a functional environment that integrates all stakeholders, procedures, and relationships required for the coordinated and effective treatment of patients. This paper explores the current situation in the field of RDs, especially in light of the proposed ecosystemic arrangement, and provides an outline for the design of an RD ecosystem in Slovenia. The research applies a case-study design, where focus groups are used to collect evidence from the field, assess the state of affairs, and generate ideas. Structured focus group discussions were conducted with preeminent experts affiliated with the leading institutions in the field of RDs in Slovenia. Analyses and interpretations of the obtained data were carried out by means of conventional content analysis. Setting up an RD ecosystem in Slovenia would lead to significant benefits for patients, as it could promote the coordination of healthcare treatment and facilitate extensive monitoring of the treatment parameters and outcomes. A well-organized RD ecosystem could garner considerable systemic benefits for evidence-informed policymaking, a better utilization of resources, and technological innovation. Delivering quality healthcare in this complex field is largely reliant on the effective integration and collaboration of all entities within the RD ecosystem, the alignment of related systemic factors, and the direction of healthcare services to support the needs and well-being of patients with RDs

The first nationwide study on facing and solving ethical dilemmas among healthcare professionals in Slovenia

Background Healthcare professionals (HCPs), patients and families are often faced with ethical dilemmas. The role of healthcare ethics committees (HECs) is to offer support in these situations. Aim The primary objective was to study how often HCPs encounter ethical dilemmas. The secondary objective was to identify the main types of ethical dilemmas encountered and how HCPs solve them. Subjects and methods We conducted a cross-sectional, survey-based study among HCPs in 14 Slovenian hospitals. A questionnaire was designed and validated by HCPs who were selected by proportional stratified sampling. Data collection took place between April 2015 and April 2016. Results The final sample size was n = 485 (385 or 79.4%, female). The response rates for HCPs working in secondary and tertiary level institutions were 45% and 51%, respectively. Three hundred and forty (70.4%) of 485 HCPs (very) frequently encountered ethical dilemmas. Frequent ethical dilemmas were waiting periods for diagnostics or treatment, suboptimal working conditions due to poor interpersonal relations on the ward, preserving patients’ dignity, and relations between HCPs and patients. Physicians and nurses working in secondary level institutions, compared to their colleagues working in tertiary level institutions, more frequently encountered ethical dilemmas with respect to preserving patients’ dignity, protecting patients’ information, and relations between HCPs and patients. In terms of solutions, all HCPs most frequently discussed ethical dilemmas with co-workers (colleagues), and with the head of the department. According to HCPs, the most important role of HECs is staff education, followed by improving communication, and reviewing difficult ethical cases. Conclusions Waiting periods for diagnostics and treatment and suboptimal working conditions due to poor interpersonal relations are considered to be among the most important ethical issues by HCPs in Slovenian hospitals. The most important role of HECs is staff education, improving communication, and reviewing difficult ethical cases

Data highlighting effects of ketogenic diet on cardiomyopathy and hepatopathy in glycogen storage disease type IIIa

Datasets highlighting effects of ketogenic diet (KD) in a glycogen storage disease type IIIa patient is presented with the longest patient follow up report to date. Now a 15-year old girl with GSD type IIIa, diagnosed at 1 year of age, had initially introduced treatment with diet high carbohydrates, according to the recommendations. Progressively she developed left ventricular obstructive hypertrophy, hepatomegaly and skeletal myopathy. At the age of 11 years, she was introduced KD and continuous ketosis has been maintained for over 4 years providing longest reported follow up to date. KD introduction lead to a normalization of left ventricular parameters and ventricular mass and to an improvement in hepatic injury markers and decrease in liver size. We provided a table with biochemical parameters, a table providing detailed diet composition, tables with cardiac and hepatic measures and figures depicting cardiac NMR imagesall the tables/figures are provided referring to the KD introduction (values prior/after). Interpretation of this data can be found in a case report article titled “Normalization of obstructive cardiomyopathy and improvement of hepatopathy on ketogenic diet in patient with glycogen storage disease (GSD) type IIIa”