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Povzetek: Aim: Metamizole is an analgesic drug with moderate cytochrome P450 (CYP) inductive properties. The antifungal triazoles aremetabolized by several CYP enzymes, but the interaction with metamizole remains poorly described. We investigated the influ-ence of metamizole on the exposure of voriconazole, isavuconazole, and posaconazole.Methods: Patients from UZ Leuven (Belgium) and Ljubljana University Medical Centre (Slovenia) receiving voriconazole, is-avuconazole, or posaconazole concomitantly with metamizole were included in the study. Routine therapeutic drug monitoring(TDM) measurements collected between January 2019 and December 2024 were retrieved retrospectively. TDM concentrationsoutside of concomitant therapy were collected as controls. The influence of metamizole and other clinically relevant covariateswas analysed using generalized estimating equations (GEE).Results: A total of 126 distinct treatments with a triazole from 115 patients, accounting for 392 measurements, were includedin the study. GEE analysis revealed a significant negative association between the 7-day cumulative metamizole dose and lowervoriconazole and posaconazole concentrations. Additionally, C-reactive protein had a positive association with voriconazole con-centrations. Only ICU admission and patient characteristics, that is, sex and weight, had a significant influence on isavuconazoleconcentrations.Conclusion: Concomitant therapy with metamizole led to lower voriconazole and posaconazole concentrations, presumablythrough induction of CYP enzymes and possibly UDP-glucuronyltransferase. We recommend avoiding concomitant use of meta-mizole with the antifungal triazoles to prevent underexposure and treatment failure or frequent TDM if the combination cannotbe avoided. Further studies are needed to confirm our findings and investigate the influence of metamizole on other triazoles
Ključne besede: drug interactions, metamizole, mould-active triazoles
Objavljeno v DiRROS: 23.07.2026; Ogledov: 239; Prenosov: 227
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Povzetek: Background: Vertigo and dizziness in children represent diagnostically challenging conditions with heterogeneous etiologies. At initial presentation, a substantial proportion of pediatric patients remain without a definitive etiological diagnosis. Evidence on the impact of longitudinal follow-up on etiological classification in pediatric vertigo is limited. Methods: This observational cohort study uses prospectively collected clinical data. Children aged 1-17 years who presented to a tertiary ENT clinic with vertigo and/or dizziness between 2015 and 2020 were systematically enrolled and followed. The present study represents a retrospective revision of a previously published cohort of 257 children. In 2025, extended follow-up data were reviewed to reassess etiological classification using the same diagnostic categories as in the original analysis. Descriptive statistics were applied to compare etiological distributions at initial evaluation and after follow-up revision. Results: After data revision, the proportion of children with unclassified etiology decreased from 44% to 10%. Central etiologies accounted for 35% of cases, peripheral vestibular disorders for 18%, hemodynamic causes for 16%, psychogenic etiologies for 10%, and other specific causes for 7%. Follow-up duration ranged from 0 to 132 months (mean 17.6 months; median 4.5 months). Diagnostic investigations were frequently performed; however, the etiological yield of certain tests, particularly cranial computed tomography, was low. Conclusions: Extended follow-up significantly improves etiological classification in children with vertigo and dizziness, demonstrating that diagnostic uncertainty at initial presentation often reflects evolving clinical phenotypes rather than the absence of an underlying disorder. A longitudinal, clinically guided, and multidisciplinary approach is essential to enhance diagnostic accuracy and optimize the use of diagnostic investigations in pediatric vertigo.
Ključne besede: dizziness, etiology, follow-up, migraine, pediatric vertigo, vestibular disorders
Objavljeno v DiRROS: 15.05.2026; Ogledov: 232; Prenosov: 187
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Povzetek: Background: Skull base tumours frequently manifest as severe physical morbidity and quality of life (QoL) impairment. The disease-related QoL measurement can be performed with disease specific questionnaires, e.g. Skull base inventory (SBI). Patients and methods: The study consisted of two parts: (1) cross-cultural adaptation and psychometric testing of the Slovenian SBI (SBI-SLO) and (2) QoL assessment in skull base tumours. Two groups completed the SBI-SLO: 1.) adult patients without prior treatment of anterior, anterolateral and/or central skull base and 2.) healthy controls. Patients with skull-base tumours were further analysed for difference in SBI-SLO total score and domain scores between 1.) benign and malignant tumours and 2.) pituitary macroadenomas and other benign tumours. Results: 59 patients (46% male, 54% female, median age 57.7 years) and 47 subjects from control group (49% male, 51% female, median age 42,2 years) completed SBI-SLO, which demonstrated an excellent level of internal consistency (Cronbach's alpha = 0.924) and excellent test-retest reliability (intraclass correlation coefficient [ICCA] = 0.952). The discriminant validity was confirmed (p = 0.000). SBI-SLO total score, emotional, other and family domain scores were lower in malignant than in benign tumours (p = 0.031, p = 0.038, p = 0.008, and p = 0.046, respectively). Macroadenoma and other benign tumours differed only in neurological domain score (p < 0.05). Conclusions: A skull base tumour, especially malignant, can exert a substantial detrimental effect on a patient's quality of life. The SBI is a key tool for assessing QoL, also available in Slovenian.
Ključne besede: quality of life, skull base, neoplasms, meningioma, carcinoma
Objavljeno v DiRROS: 24.04.2026; Ogledov: 365; Prenosov: 340
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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: 798; Prenosov: 495
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Povzetek: Background. The aim of the study was to identify the value of extensive resection and reconstruction with flaps in the treatment of locoregionally advanced lateral skull-base cancer.Patients and methods. The retrospective case review of patients with lateral skull-base cancer treated surgically with curative intent between 2011 and 2019 at a tertiary otorhinolaryngology referral centre was made. Results. Twelve patients with locoregionally advanced cancer were analysed. Lateral temporal bone resection was performed in nine (75.0%), partial parotidectomy in six (50.0%), total parotidectomy in one (8.3%), ipsilateral selective neck dissection in eight (66.7%) and ipsilateral modified radical neck dissection in one patient (8.3%). The defect was reconstructed with anterolateral thigh free flap, radial forearm free flap or pectoralis major myocutaneous flap in two patients (17.0%) each. Mean overall survival was 3.1 years (SD = 2.5) and cancer-free survival rate 100%. At the data collection cut-off, 83% of analysed patients and 100% of patients with flap reconstruction were alive. Conclusions. Favourable local control in lateral skull-base cancer, which mainly involves temporal bone is achieved with an extensive locoregional resection followed by free or regional flap reconstruction. Universal cancer registry should be considered in centres treating this rare disease to alleviate analysis and multicentric research.
Ključne besede: temporal bone, microsurgery, parotid region, free tissue flaps, neoplasm staging, ear
Objavljeno v DiRROS: 22.07.2024; Ogledov: 1472; Prenosov: 604
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