1. Challenges in establishing optimal pediatric palliative care at the university hospital in SloveniaJakob Meglič, Ajda Lisec, Dušanka Lepej, Tanja Loboda, Sara Bertok, Petra Lešnik Musek, Ivana Kreft, Majda Oštir, Tehvida Ponjević, Anamarija Meglič, 2023, izvirni znanstveni članek Povzetek: The integration of pediatric palliative care (PPC) should become a standard of care for all children with life-limiting and life-threatening illnesses. There are many barriers and misperceptions in pediatrics which hinder the early implementation of PPC. The aim of the study was to design starting points for the establishment of accessible PPC with early involvement of patients in a tertiary-level children’s hospital. An intervention, presentation, and discussion on PPC were ofered by the hospital PPC team to all employees in the hospital. A total of 237 participants (physicians 30.4%, nurses 49.4%, psychologists 8.4%, and others) completed a questionnaire before and after the intervention. The personnel’s knowledge, self-assessment of their ability to perform PPC, attitude to participate in PPC, and their awareness and understanding of the need for PPC were evaluated. The results were analyzed using Pandas and SciPy libraries in Python. The knowledge, awareness, and attitude of the physicians, nurses, and other professionals improved signifcantly after the intervention. However, the self-assessment of their ability to perform PPC did not increase. Previous experience with the death of a patient has proven to be a stimulus for self-initiative in acquiring knowledge in PPC and was linked with a better attitude and higher awareness of the need for PPC. Conclusions: More education and practical work tailored to the diferent professional profles are needed, with adjustments for specifc subspecialist areas, especially where patients could be included in early PPC. Although additional studies are needed, we identifed the main directions for the further implementation of PPC in clinical practice in our setting.
Ključne besede: pediatric palliative care, implementation, life-limiting disease, life-threatening condition, quality of children’s life
Objavljeno v DiRROS: 31.08.2026; Ogledov: 149; Prenosov: 79
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2. Kidney transcriptome sequencing improves molecular diagnosis and reveals splicing complexity across the Alport spectrumJerica Pleško, Špela Kert, Sara Petrin, Špela Borštnar, Željka Večerić-Haler, Anamarija Meglič, Nejc Piko, Alenka Matjašič, Nika Kojc, Andrej Zupan, 2026, izvirni znanstveni članek Povzetek: Introduction: Hereditary glomerular basement membrane (GBM) disorders caused by pathogenic variants in COL4A3/A4/A5 are increasingly recognized as Alport spectrum. Disease severity varies widely and is influenced by variant type, allelic dosage, sex, and genetic modifiers. DNA-based testing incompletely captures this heterogeneity, particularly splice-altering and regulatory variants, limiting precise molecular diagnosis and prognostic stratification. Methods: We performed whole-transcriptome sequencing on 93 kidney biopsies from 93 patients (90 families) with ultrastructural GBM abnormalities. RNA-derived variant detection, splicing analysis, and gene expression profiling were integrated with histopathology, electron microscopy, and clinical data. Aberrant splicing events were quantified, and differential gene expression and microRNA (miRNA) motif enrichment analyses assessed molecular changes associated with kidney function decline. Results: Transcriptome sequencing identified 64 pathogenic or likely pathogenic variants, including 14 splice-altering variants (22%), often involving noncanonical events, whose functional consequences are not readily resolved by routine DNA sequencing alone. Pathogenic or likely pathogenic variants were detected in 52 of 93 patients (56%), including novel missense and splice-altering variants in COL4A3, COL4A4, COL4A5, and CLCN5. Quantitative splicing revealed heterogeneous exon 27 skipping in COL4A4, indicating regulated exon usage. Gene expression profiling showed progressive estimated glomerular filtration rate (eGFR)-associated remodeling with activation of inflammatory and profibrotic pathways and suppression of renal transporter genes. miRNA enrichment implicated miR-335-5p, miR-325-3p, and miR-874-3p as potential regulators. Conclusion: Kidney transcriptome sequencing improves molecular diagnosis across the Alport spectrum, enables interpretation of splice-altering variants, and captures signatures linked to progression. Integrating RNA-based analysis may refine classification, enhance prognostic assessment, and support precision medicine in hereditary nephropathies.
Ključne besede: Alport spectrum, kidney transcriptomics, splicing variants, COL4A4 exon 27 skipping
Objavljeno v DiRROS: 19.08.2026; Ogledov: 244; Prenosov: 436
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3. A 15-year experience highlighting the spectrum of Alport kidney disease in the pediatric population and novel genetic variants in COL4A3-5Nastja Andrejašič, Anja Blejc Novak, Mirjam Močnik, Nataša Marčun-Varda, Špela Stangler Herodež, Danijela Krgović, Andrej Zupan, Anamarija Meglič, 2025, izvirni znanstveni članek Ključne besede: Alport kidney disease, COL4A3-5
Objavljeno v DiRROS: 17.04.2026; Ogledov: 365; Prenosov: 325
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4. Paediatric palliative care in clinical practice : ethical issues in advance care planning and end-of-life decisionsAnamarija Meglič, Ajda Lisec, 2025, izvirni znanstveni članek Povzetek: Rationale This study examines ethical challenges faced by a paediatric palliative care (PPC) team when making end-of-life (EOL) decisions for children with life-limiting conditions. Aim To assess the team's attitudes towards ethical issues and propose innovative solutions. Methods The data was collected in 2022 at the University Children's Hospital Ljubljana. A researcher-made questionnaire was developed based on team experience. Ten PPC team members participated anonymously, evaluating ethical concerns in communication, decision-making, and patient characteristics. Mann–Whitney U test was used to analyze the data. Results Ethical issues emerge when coordinating treatment opinions becomes challenging, resulting in excluding a child from PPC. Situations involving communication, differing healthcare opinions, and patient characteristics were seen as ethical issues, highlighting the importance of communication and shared decision-making. Conclusions Ethical complexities in paediatric EOL care require adept communication and interdisciplinary teamwork. Poor communication may be associated with excluding children from PPC. Innovative strategies and ongoing training are vital to address these challenges effectively, ensuring optimal care for children and their families.
Ključne besede: end-of-life decision, ethics, children, palliative care, advance care planning
Objavljeno v DiRROS: 27.02.2026; Ogledov: 581; Prenosov: 479
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5. Severe clinical phenotype in Alport syndrome due to two COL4A4 exon skipping eventsJerica Pleško, Nika Kojc, Špela Kert, Sara Petrin, Alenka Matjašič, Anamarija Meglič, Andrej Zupan, 2025, drugi znanstveni članki Povzetek: Alport syndrome (AS) is a genetically heterogeneous disorder caused by mutations in COL4A3, COL4A4, or COL4A5, leading to progressive renal dysfunction. While genetic screening has advanced, many cases remain undiagnosed due to deep intronic splice site variants. We report a male patient diagnosed with autosomal recessive AS, characterized by hematuria, proteinuria, and chronic kidney disease progression. Initial kidney biopsy at age 10 revealed glomerular basement membrane thinning and focal sclerosis, while targeted DNA sequencing failed to detect pathogenic variants. Over 15 years, renal function declined, and a second biopsy showed severe GBM abnormalities with multilamellated structures. Whole-transcriptome sequencing revealed two events of exon skipping, specifically at exons 27 and 38 of the COL4A4 gene, which were verified by exon-specific PCR and Sanger sequencing. Intronic regions analysis revealed two heterozygous variants positioned 78 bp downstream of exon 27 and 8 bp upstream of exon 38, though their role in aberrant splicing remains uncertain. Immunofluorescence analysis confirmed disrupted α3α4α5(IV) heterotrimer assembly. This is the first documented case of dual exon-skipping events in COL4A4, highlighting their contribution to disease severity. Our findings emphasize the need for RNA-based diagnostics and raise questions about potential benefit of exon-skipping therapy in autosomal recessive AS.
Ključne besede: Alport syndrome, exon skipping, whole transcriptome sequencing, kidney, COL4A4
Objavljeno v DiRROS: 24.11.2025; Ogledov: 1028; Prenosov: 431
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6. Temeljni pojmi in predlagano izrazoslovje v paliativni oskrbiMaja Ebert Moltara, Marjana Bernot, Jernej Benedik, Andrej Žist, Nena Golob, Stanislav Malačič, Maja Kolšek-Šušteršič, Maja Ivanetič Pantar, Blaž Koritnik, Anamarija Meglič, Nevenka Krčevski-Škvarč, 2020, strokovna monografija Povzetek: Paliativna oskrba je v slovenskem prostoru mlada stroka. Z njenim razvojem so se začeli uporabljati številni izrazi, ki so včasih nejasno in nenatančno opredeljeni. Posledica tega je, tako med strokovnjaki kot na splošno v družbi, njeno neustrezno razumevanje. občasno zato prihaja do nesporazumov in posledično tudi do strokovnih napak. Namen izvajanja paliativne oskrbe je zagotoviti čim boljšo kakovost življenja bolnikom z napredujočimi neozdravljivimi boleznimi ter nuditi podporo njihovim bližnjim, v času bolnikove bolezni in po smrti. V paliativni oskrbi zdravstveno osebje veliko bolj kot sicer posveča pozornost celostni obravnavi posameznega človeka, kot osebo z individualnimi telesnimi, psihološkimi, socialnimi in duhovnimi potrebami. To je dinamičen proces, saj se moramo ves čas prilagajati trenutnim potrebam bolnika in njegovih bližnjih ter z aktivnim načrtovanjem učinkovito preprečevati nove in nepotrebne zaplete. Zgodnja paliativna oskrba se v začetku obravnave bolnika z neozdravljivo boleznijo prepleta s specifičnim zdravljenjem. Kasneje, z napredovanjem bolezni, obravnava prehaja v obdobje pozne paliativne oskrbe in obdobje oskrbe umirajočega. Po sodobnih smernicah se paliativna oskrba izvaja celostno, neprekinjeno in integrirano v ostale zdravstvene stroke. Cilj paliativne oskrbe je sledenje vrednotam posameznika in ohranjanje dostojanstva življenja. V prispevku smo zbrali najpogosteje uporabljene izraze s področja paliativne oskrbe. Na podlagi mednarodnih priporočil, lokalnih značilnosti in nacionalnih izkušenj smo jih skušali čim bolj jasno opredeliti za naš prostor. Natančno opredeljeni pojmi paliativne oskrbe in njihova dosledna uporaba bodo vodili k boljšemu medsebojnemu razumevanju strokovnjakov in uporabnikov paliativne oskrbe ter k njenemu kakovostnejšemu izvajanju.
Ključne besede: paliativna oskrba, zdravljenje, mesebojno sporazumevanje
Objavljeno v DiRROS: 04.01.2021; Ogledov: 4436; Prenosov: 1122
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