31. Modified unipolar return pulsed field ablation in ventricular myocardiumMaria Terricabras Casas, Peter Lombergar, Terenz Escartin, Bor Kos, Philippa R. Krahn, Jennifer Barry, Graham Wright, Tomaž Jarm, Jernej Štublar, Matej Kranjc, Nicolas Coulombe, Lars M. Mattison, Daniel C. Sigg, Damijan Miklavčič, Atul Verma, 2025, original scientific article Abstract: BACKGROUND: Various pulsed field ablation (PFA) parameters have been proposed to improve lesion depth. This study evaluated a modified unipolar return PFA system to create deep lesions in healthy and infarcted ventricular myocardia. METHODS: Numerical modeling was used to compare a modified unipolar return PFA system configuration with a conventional unipolar return (skin patch). We then performed ablation in 14 swine (5 with chronic myocardial infarction and 9 healthy). PFA lesions were created in the left ventricle using a focal catheter (4-mm tip) with a return electrode positioned in the inferior vena cava (biphasic, microsecond pulses of 1300 and 1500 V, 1–16 trains). Electroanatomical mapping guided ablation and lesion localization on magnetic resonance imaging were performed 48 hours post-ablation in the infarcted group and at 1 day, 7 days, and 6 weeks post-ablation in the healthy group. RESULTS: Numerical modeling demonstrated that the modified unipolar return PFA system produced deeper lesions with reduced variability compared with the skin patch. In healthy pigs (n=35 lesions), depths of 6.8±1.8 mm and widths of 11.5±4.7 mm were achieved with 8 pulse trains. Depths of 8.2±2.8 mm and widths of 14.0±4.7 mm were achieved with 16 trains. The maximum lesion depths were 8.8 and 11.6 mm for 8 and 16 trains, respectively. In the infarcted cohort (n=22 lesions), all lesions applied to scar tissue penetrated through fibrotic regions, with epicardial involvement observed in 57% of lesions. CONCLUSIONS: The modified unipolar return PFA system effectively creates large lesions and can achieve transmurality in healthy and infarcted animals. Compared with conventional unipolar, it may offer greater lesion depth, width, and consistency. GRAPHIC ABSTRACT: A graphic abstract is available for this article.
Keywords: atrial fibrillation, catheter ablation, heart ventricles, pulmonary veins, tachycardia ventricular
Published in DiRROS: 11.12.2025; Views: 55; Downloads: 31
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32. Sudden death of a four-day-old newborn due to mitochondrial trifunctional protein/long-chain 3-hydroxyacyl-coa dehydrogenase deficiencies and a systematic literature review of early deaths of neonates with fatty acid oxidation disordersAna Drole Torkar, Ana Klinc, Žiga Iztok Remec, Branislava Ranković, Klara Bartolj, Sara Bertok, Sara Colja, Vanja Čuk, Maruša Debeljak, Eva Kozjek, Barbka Repič-Lampret, Matej Mlinarič, Tinka Mohar Hajnšek, Daša Perko, Katarina Štajer, Tine Tesovnik, Domen Trampuž, Blanka Ulaga, Jernej Kovač, Tadej Battelino, Mojca Žerjav-Tanšek, Urh Grošelj, 2025, review article Abstract: Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies have been a part of the Slovenian newborn screening (NBS) program since 2018. We describe a case of early lethal presentation of MTPD/LCHADD in a term newborn. The girl was born after an uneventful pregnancy and delivery, and she was discharged home at the age of 3 days, appearing well. At the age of 4 days, she was found without signs of life. Resuscitation was not successful. The NBS test performed using tandem mass spectrometry (MS/MS) showed a positive screen for MTPD/LCHADD. Genetic analysis performed on a dried blood spot (DBS) sample identified two heterozygous variants in the HADHA gene: a nucleotide duplication introducing a premature termination codon (p.Arg205Ter) and a nucleotide substitution (p.Glu510Gln). Post-mortem studies showed massive macro-vesicular fat accumulation in the liver and, to a smaller extent, in the heart, consistent with MTPD/LCHADD. A neonatal acute cardiac presentation resulting in demise was suspected. We conducted a systematic literature review of early neonatal deaths within 14 days postpartum attributed to confirmed fatty acid oxidation disorders (FAODs), which are estimated to account for 5% of sudden infant deaths. We discuss the pitfalls of the NBS for MTPD/LCHADD.
Keywords: FAOD, LCHAD deficiency, LCHADD, MTP deficiency, MTPD, NBS, fatty acid oxidation disorder, newborn, newborn screening, sudden infant death
Published in DiRROS: 11.12.2025; Views: 43; Downloads: 28
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34. Subjective well-being and its predictors in Parkinson's disease and dystonia : a comparative studySuzette Shahmoon, Dejan Georgiev, Paul Jarman, Kailash P. Bhatia, Patricia Limousin, Marjan Jahanshahi, 2025, original scientific article Abstract: Background: Quality of life (QoL) is a commonly used outcome measure in people with chronicneurological diseases (CND). As valuable as QoL is, it does not take into account aspects of subjective well-being (SWB) such as subjective happiness, meaning in life, life satisfaction and hope; all constructs that areconsidered central to well-being.ObjectivesObjectives: The goal was to assess how the different aspects of SWB are altered in Parkinson’s disease(PD) and dystonia relative to healthy controls (HCs) and to identify the most important predictors of differentdimensions of SWB in PD and dystonia.MethodsMethods: Eighty-two people with PD, 63 with dystonia, and 50 HCs were surveyed using various measuresof SWB.ResultsResults: People with PD and dystonia had significantly lower satisfaction with life than HCs, with self-esteemand loneliness being significant covariates. Although people with PD and dystonia had significantly lessmeaning in life, they still sought meaning in life as much as HCs. Self-esteem, resilience and neuroticism weresignificant covariates for the presence of “meaning in life.” There were no significant group differences insubjective happiness or hope. In people with PD, mood (depression and anxiety), personality traits (extraversionand self-esteem), disease duration, and pain/discomfort were significant predictors of various measures ofSWB. The main significant predictor of SWB in dystonia was depression, which predicted 49% of the variance insubjective happiness.ConclusionsConclusions: These results emphasize the importance of SWB as a field of investigation and clinical care in themanagement of people with PD and dystonia
Keywords: dystonia, Parkinson's disease, positive psychology, self-esteem, subjective well-being
Published in DiRROS: 10.12.2025; Views: 67; Downloads: 28
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37. Uncovering early predictors of cerebral palsy through the application of machine learning : a case–control studySara Rapuc, Blaž Stres, Ivan Verdenik, Miha Lučovnik, Damjan Osredkar, 2024, original scientific article Abstract: Objective Cerebral palsy (CP) is a group of neurological disorders with profound implications for children’s development. The identification of perinatal risk factors for CP may lead to improved preventive and therapeutic strategies. This study aimed to identify the early predictors of CP using machine learning (ML). Design This is a retrospective case–control study, using data from the two population-based databases, the Slovenian National Perinatal Information System and the Slovenian Registry of Cerebral Palsy. Multiple ML algorithms were evaluated to identify the best model for predicting CP. Setting This is a population-based study of CP and control subjects born into one of Slovenia’s 14 maternity wards. Participants A total of 382CP cases, born between 2002 and 2017, were identified. Controls were selected at a control-to-case ratio of 3:1, with matched gestational age and birth multiplicity. CP cases with congenital anomalies (n=44) were excluded from the analysis. A total of 338CP cases and 1014 controls were included in the study. Exposure 135 variables relating to perinatal and maternal factors. Main outcome measures Receiver operating characteristic (ROC), sensitivity and specificity. Results The stochastic gradient boosting ML model (271 cases and 812 controls) demonstrated the highest mean ROC value of 0.81 (mean sensitivity=0.46 and mean specificity=0.95). Using this model with the validation dataset (67 cases and 202 controls) resulted in an area under the ROC curve of 0.77 (mean sensitivity=0.27 and mean specificity=0.94). Conclusions Our final ML model using early perinatal factors could not reliably predict CP in our cohort. Future studies should evaluate models with additional factors, such as genetic and neuroimaging data
Keywords: early predictors, cerebral palsy
Published in DiRROS: 10.12.2025; Views: 84; Downloads: 37
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38. Systemic auto-inflammatory manifestations in patients with spondyloarthritisCarla Gaggiano, Mojca Zajc Avramovič, Antonio Vitale, Nina Emeršič, Jurgen Sota, Nataša Toplak, Stefano Gentileschi, Valeria Caggiano, Maria Tarsia, Gašper Markelj, Tina Vesel, Anja Koren Jeverica, Tadej Avčin, 2024, original scientific article Abstract: Objectives. – (1) characterizing a group of spondyloarthritis (SpA) patients with systemic autoinflammatory symptoms (S-SpA); (2) comparing SpA features with and without auto-inflammatory symptoms; (3) comparing the auto-inflammatory features of S-SpA and Still’s disease (SD). Methods. – Retrospective observational study. Clinical data of adult and pediatric patients with S-SpA, SD or SpA were collected retrospectively and analyzed. Results. – Forty-one subjects with S-SpA, 39 with SD and 42 with SpA were enrolled. The median latency between systemic and articular manifestations in S-SpA was 4.4 (IQR: 7.2) years. S-SpA and SpA had similar frequency of peripheral arthritis and enthesitis (N.S.), while tenosynovitis was more frequent(P = 0.01) and uveitis less frequent (P < 0.01) in S-SpA. MRI showed signs of sacroiliac inflammation and damage in both S-SpA and SpA equally (N.S.). S-SpA patients had less corner inflammatory lesions (P < 0.05) and inflammation at the facet joints (P < 0.01), more interspinous enthesitis (P = 0.01) and inter-apophyseal capsulitis (P < 0.01). Compared to SD, S-SpA patients had lower-grade fever (P < 0.01), less rash (P < 0.01) and weight loss (P < 0.05), but more pharyngitis (P < 0.01), gastrointestinal symptoms (P < 0.01) and chest pain (P < 0.05). ESR, CRP, WBC, ANC, LDH tested higher in SD (P < 0.01). Resolution of systemic symptoms was less frequent in S-SpA than SD on corticosteroid (P < 0.01) and methotrexate (P < 0.05) treatment. When considering all SD patients, a complete response to corticosteroids in the systemic phase significantly reduced the likelihood of developing SpA (OR = 0.06, coefficient −2.87 [CI: −5.0 to −0.8]). Conclusions. – SpA should be actively investigated in patients with auto-inflammatory manifestations, including undifferentiated auto-inflammatory disease and SD
Keywords: spondyloarthritis, febrile spondyloarthritis, Still’s disease, systemic juvenile idiopathic arthritis, adult-onset Still’s disease, auto-inflammatory diseases
Published in DiRROS: 10.12.2025; Views: 60; Downloads: 27
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39. Relation of JAK2 V617F allele burden and coronary calcium score in patients with essential thrombocythemiaAjda Anžič Drofenik, Aleš Blinc, Mojca Božič Mijovski, Tadej Pajič, Matjaž Vrtovec, Matjaž Sever, 2024, original scientific article Abstract: JAK2 V617F (JAK2) mutation is associated with clonal hemopoiesis in myeloproliferative neoplasms as well as with faster progression of cardiovascular diseases. Little is known about the relationship between allele burden and the degree of atherosclerotic alteration of coronary vasculature. We previously reported that carotid artery stiffness progressed faster in patients with JAK2 positive essential thromocythemia (ET) patients. After a four-year follow-up we investigated whether mutation burden of a JAK2 allele correlates with a higher coronary calcium score. Patients and methods. Thirty-six patients with JAK2 positive ET and 38 healthy matched control subjects were examined twice within four years. At each visit clinical baseline characteristics and laboratory testing were performed, JAK2 mutation burden was determined, and coronary calcium was measured. Results. JAK2 allele burden decreased in 19 patients, did not change in 5 patients, and increased in 4 patients. The coronary calcium Agatston score increased slightly in both groups. Overall, there was no correlation between JAK2 allele burden and calcium burden of coronary arteries. However, in patients with the JAK2 mutation burden increase, the coronary calcium score increased as well. Conclusions. The average JAK2 allele burden decreased in our patients with high-risk ET during the four-year period. However, in the small subgroup whose JAK2 mutation burden increased the Agatston coronary calcium score increased as well. This finding, which should be interpreted with caution and validated in a larger group, is in line with emerging evidence that JAK2 mutation accelerates atherosclerosis and can be regarded as a non-classical risk factor for cardiovascular disease.
Keywords: essential thrombocythemia, JAK2 V617F mutation, JAK2 V617F allele burden
Published in DiRROS: 10.12.2025; Views: 82; Downloads: 41
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40. Genetic variability of HIF1A and response to treatment with cisplatin in combination with pemetrexed or gemcitabine in patients with malignant mesotheliomaMatic Šetina, Eva Šetina, Žiga Doljak, Katja Goričar, Vita Dolžan, Viljem Kovač, 2025, original scientific article Abstract: Background. Treatment of malignant mesothelioma (MM) still relies on chemotherapy with cisplatin in combination with pemetrexed or other drugs. Studies indicate that hypoxic conditions within tumour tissue may reduce responsiveness to cisplatin-based chemotherapy. Hypoxia-inducible factors (HIF) play an important role in regulation of cellular adaptation to hypoxia. The aim of our study was to investigate single nucleotide polymorphisms (SNPs) in the HIF1A gene coding for the regulatory alpha subunit (HIF-1A) and their role in the response to chemotherapy in patients with MM. Patients and methods. Our retrospective genetic association study included 234 patients with MM, who were treated with a combination of cisplatin/pemetrexed or cisplatin/gemcitabine at the Institute of Oncology Ljubljana between January 2001 and September 2018. Selected HIF1A SNPs (rs1154965, rs11549467, and rs2057482) were genotyped using the competitive allele-specific polymerase chain reaction (KASP). Additionally, we used a TaqMan assay for independent confirmation of rs11549465 genotyping results. The impact of the SNPs on response to chemotherapy was analysed using logistic regression. For survival analysis, we used the Kaplan-Meier method and Cox regression. Results. In heterozygotes with the HIF1A rs11549465 CT genotype, response to chemotherapy was significantly worse compared to homozygotes with the CC genotype, but only after adjustment for weight loss and CRP (ROadj = 0.37; 95% CI = 0.14–0.97; Padj = 0.044). HIF1A rs11549467 and rs2057482 were not associated with response to chemotherapy (all P > 0.05). None of the investigated SNPs were associated with progression-free survival or overall survival (all P > 0.05). Conclusions. Among the investigated HIF1A SNPs, only rs11549465 has showed association with a worse response to chemotherapy after the adjustment for clinical parameters. The findings of this study have improved our understanding of the role of HIF1A polymorphisms in MM and may offer valuable insights into their impact on other cancers as well.
Keywords: malignant mesothelioma, chemotherapy, polymorphism
Published in DiRROS: 10.12.2025; Views: 61; Downloads: 15
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