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Povzetek: The introduction of nitisinone (NTBC) and newborn screening for Tyrosinemia type 1 (TT1) enabled preemptive treatment ofpatients, thereby significantly improving outcomes by preventing liver, kidney, and neurological issues. Treatment goals haveshifted from emergency treatment to long-term care. To evaluate the risk of developing complications with aging, due to TT1itself or its treatment, long-term follow-up is essential. In 2014, an overview of TT1 management practices in Europe was pub-lished. Within the Metabolic European Reference Network's subnetwork on amino-and-organic acidurias (MetabERN-AOA),we considered it important to give an update on current TT1 management practices in Europe. An online survey study was per-formed among members of the MetabERN-AOA subnetwork, and participants of a workshop on TT1 at the European MetabolicGroup Meeting of Nutricia. Findings were compared to existing data from the aforementioned publication from 2014 and pre-viously published recommendations. Thirty-two centers (16 European countries) completed the survey. Both consistencies andinconsistencies in TT1 management were seen. Inconsistencies were observed in the frequency and methods of follow-up, dosingof NTBC, and target ranges of biochemical markers. Compared to 2014, key differences included an increased number of patientsdetected by newborn screening, lower NTBC dosing, and a shift from interest in mainly hepatic to hepatic and neurocognitiveoutcomes. These results align with trends seen in TT1 recommendations over the years. In addition to numerous consistencies,many aspects in TT1 management still differ widely across Europe, suggesting the need for uniform guidance in clinical man-agement beyond existing recommendations.
Ključne besede: tyrosinemia type 1, NTBC, nitisinone, management, guidelines
Objavljeno v DiRROS: 22.12.2025; Ogledov: 41; Prenosov: 24
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Povzetek: Background: Hypoplastic left heart syndrome (HLHS) was a fatal congenital heart defect (CHD) until the 1980s. Introduction of the Norwood procedure and subsequent Fontan operation significantly improved survival by creating a single-ventricle circulation. Due to the high mortality associated with the Norwood operation, neonatal orthotopic heart transplantation emerged as an alternative, despite challenges such as lifelong immunosuppressive treatment and uncertain longevity of transplanted hearts. Methods: A narrative review with a systematic literature search was conducted in the PubMed, following PRISMA guidelines and included studies of ethical and medical considerations, decision-making, counseling and treatment planning in children with HLHS. In addition, we manually screened reference lists to identify further relevant literature. We aimed to explore: how do ethical considerations and decision-making processes influence the management and outcomes of fetuses and neonates with HLHS and their families across prenatal, postnatal, and long-term care? Results: Of the 115 studies, 56 met the inclusion criteria. Early diagnosis through prenatal fetal ultrasound has markedly improved survival rates by enabling better parental awareness, counseling, and decision-making. Managing HLHS requires urgent, extensive, and costly medical interventions, with outcomes influenced by the healthcare system's expertise, the experience of cardiologists and surgeons, ethical, legal, and religious considerations of the parents and medical team. The prenatal phase is crucial for optimal management, with advanced fetal ultrasound facilitating early detection. Postnatal care involves a multidisciplinary approach, including stage palliation physiology/surgery tailored to each patient. Despite surgical advancements, HLHS patients face higher morbidity and mortality rates than other patients with CHDs, with long-term survival and quality of life remaining key concerns. Ethical considerations play a significant role in the management of HLHS, encompassing the autonomy of families, the best medical interests of the child, societal, and cultural factors. Decision-making must balance full disclosure with sensitivity to parents' values and beliefs. Conclusions: Management of HLHS involves multidisciplinary approach with complex medical and ethical considerations, but the current literature lacks high-quality studies or consensus guidelines on ethical decision-making. Therefore, the influence of ethical considerations on clinical management and patient care remains unclear, highlighting the need for further research.
Ključne besede: hypoplastic left heart syndrome, congenital heart defect, prenatal diagnosis, neonatal care, palliative surgery, medical ethic, multidisciplinary care, decision making
Objavljeno v DiRROS: 12.12.2025; Ogledov: 151; Prenosov: 54
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Povzetek: Palliative care should be an integral part of follow-up for patients with life-limiting/life-threatening conditions, irrespective of age and diagnosis. Many patients with inherited metabolic disorders (IMD) have palliative care needs due to multi-systemic conditions without curative treatment options. To map the organisation and accessibility of palliative care across European IMD expert centres, and to explore the experiences of IMD physicians with palliative care, the European Reference Network for Hereditary Metabolic Disorders (MetabERN) invited physicians from all 103 member institutions to participate in a survey covering various aspects of palliative care. Ninety-two physicians from 63 institutions in 23 countries participated. A national plan or strategy for palliative care had been established in most countries (87%). Both children (91%) and adults (89%) had access to palliative care services. Most paediatric (86%) and many adult IMD physicians (67%) used advance care planning. A total of 284 referrals to palliative care were reported, mostly IMD patients with lysosomal and mitochondrial disorders, and neurological, respiratory, cognitive and gastrointestinal comorbidities. However, during the past 5 years, the majority of physicians (60%) had referred 20% or fewer of their deceased patients to palliative care. Although palliative care is available in most European IMD expert centres, only a small proportion of deceased IMD patients has been referred. The findings of this study indicate both a misconception and underutilisation of modern palliative care services. Addressing existing barriers is essential, and both IMD physicians and patients may need more information about available palliative care services and up-to-date indications for referral.
Ključne besede: palliative care, quality of life, patients, paediatric palliative care, inherited metabolic diseases, genetic disorders, MetabERN, The European Reference Network for Hereditary Metabolic Disorders
Objavljeno v DiRROS: 11.12.2025; Ogledov: 132; Prenosov: 64
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Povzetek: ewborn screening for Phenylketonuria enables early detection and timely treatment with a phenylalanine-restricted diet to prevent severe neurological impairment. Although effective and in use for 60 years, screening, diagnostic, and treatment practices still vary widely across countries and centers. To evaluate the Phenylketonuria newborn screening practices internationally, we designed a survey with questions focusing on the laboratory aspect of the screening system. We analyzed 24 completed surveys from 23 countries. Most participants used the same sampling age range of 48–72 h; they used tandem mass spectrometry and commercial non-derivatized kits to measure phenylalanine (Phe), and had non-negative cut-off values (COV) set mostly at 120 µmol/L of Phe. Participants mostly used genetic analysis of blood and detailed amino acid analysis from blood plasma as their confirmatory methods and set the COV for the initiation of dietary therapy at 360 µmol/L of Phe. There were striking differences in practice as well. While most participants reported a 48–72 h range for age at sampling, that range was overall quite diverse Screening COV varied as well. Additional screening parameters, e.g., the phenylalanine/tyrosine ratio were used by some participants to determine the screening result. Some participants included testing for tetrahydrobiopterin deficiency, or galactosemia in their diagnostic process. Results together showed that there is room to select a best practice from the many practices applied. Such a best practice of PKU-NBS parameters and post-screening parameters could then serve as a generally applicable guideline.
Ključne besede: phenylketonuria, newborn, neonatal, screening, international, survey, laboratory, methods, cut-off
Objavljeno v DiRROS: 04.12.2025; Ogledov: 144; Prenosov: 66
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Povzetek: Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients’ lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field since 2018, marked by successful gene therapy trials and treatments for various rare diseases. Significant strides have been made in the field of gene therapy in Slovenia, treating patients with spinal muscular atrophy and rare metabolic disorders, including the pioneering work on CTNNB1 syndrome. Additionally, immune gene therapy, exemplified by IL-12 adjuvant therapy for cancer, has been a focus of research in Slovenia. Through patient-centred initiatives and international collaborations, researchers in Slovenia are advancing preclinical research and clinical trials, paving the way for accessible gene therapies. Establishing clinical infrastructure and genomic diagnostics for rare diseases is crucial for gene therapy implementation. Efforts in this regard in Slovenia, including the establishment of a Centre for Rare Diseases, Centre for the Technologies of Gene and Cell Therapy, and rapid genomic diagnostics, demonstrate a commitment to comprehensive patient care. Despite the promises of gene therapy, challenges remain, including cost, distribution, efficacy, and long-term safety. Collaborative efforts are essential to address these challenges and ensure equitable access to innovative therapies for patients with rare diseases.
Ključne besede: gene therapy, rare genetic diseases, Slovenia, CAR-T cells, cancer, immune gene therapy
Objavljeno v DiRROS: 04.12.2025; Ogledov: 160; Prenosov: 124
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