1. Role of endoscopic ultrasound-guided fine needle aspiration biopsies in diagnosing pancreatic neoplasms in the paediatric population : experience from a tertiary center and review of the literatureMaja Kebe Radulović, Jernej Brecelj, Andrej Gruden, Margareta Strojan Fležar, 2024, review article Abstract: Background: Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS FNAB) is a well established diagnostic method in adult patients, but is rarely used in the paediatric population. The Clinical Department of Gastroenterology at the University Clinical Centre Ljubljana and the Department of Cytopathology at the Institute of Pathology, Faculty of Medicine, University of Ljubljana, Slovenia, have been closely collaborating on EUS FNAB since the introduction in 2010. The aim of the study was to review the cases of EUS FNAB of pancreatic neoplasms in children. Patients and methods: In the digital archive of the Institute of Pathology (IP), Faculty of Medicine (FM), University of Ljubljana (UL), we found 6 cases of EUS FNAB in children, 3 had EUS FNAB of the pancreas, 2 of whom had a cytopathologic diagnosis of a tumour. In the first case, the lesion was ultrasonographically solid, and the cell sample contained branching papillary structures surrounded by aggregates of small cells with nuclear grooves. In the second case, the lesion was ultrasonographically cystic, and predominantly necrosis was seen, with only single preserved cells. Positive nuclear reaction for β-catenin was found in both cases by immunohistochemical staining. Results: In both cases, the cytopathological diagnosis of solid pseudopapillary neoplasm of the pancreas was made, the cases represent the totality of paediatric cases of pancreatic neoplasms from the Children's Hospital Ljubljana since 2010. There were no adverse events during and after EUS FNAB. A histopathological examination of the tumour resection specimens confirmed the cytopathological diagnosis. Conclusions: Our experience indicates that EUS FNAB is a safe and effective method for diagnosing pancreatic neoplasms in the pediatric population, as supported by the findings in the literature.
Keywords: fine needle aspiration biopsy, endoscopic ultrasound, pancreatic neoplasm, paediatric pathology
Published in DiRROS: 26.06.2026; Views: 111; Downloads: 82
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2. Cerebrospinal fluid p-tau181, 217, and 231 in definite Creutzfeldt-Jakob disease with and without concomitant pathologiesAndreja Emeršič, Nicholas J. Ashton, Agathe Vrillon, Juan Lantero-Rodriguez, Jernej Mlakar, Milica Gregorič Kramberger, Fernando Gonzalez-Ortiz, Przemyslaw R. Kac, Maciej Dulewicz, Jörg Hanrieder, Uroš Rot, Saša Čučnik, 2024, original scientific article Abstract: Introduction: The established cerebrospinal fluid (CSF) phosphorylated tau181 (p-tau181) may not reliably reflect concomitant Alzheimer's disease (AD) and primary age-related tauopathy (PART) found in Creutzfeldt-Jakob disease (CJD) at autopsy. Methods: We investigated CSF N-terminal p-tau181, p-tau217, and p-tau231 with in-house Simoa assays in definite CJD (n = 29), AD dementia (n = 75), mild cognitive impairment (MCI) due to AD (n = 65), and subjective cognitive decline (SCD, n = 28). Post-mortem examination performed in patients with CJD 1.3 (0.3-14.3) months after CSF collection revealed no co-pathology in 10, concomitant AD in 8, PART in 8, and other co-pathologies in 3 patients. Results: N-terminal p-tau was increased in CJD versus SCD (p < 0.0001) and correlated with total tau (t-tau) in the presence of AD and PART co-pathology (rho = 0.758-0.952, p ≤ 001). Concentrations in CJD+AD were indistinguishable from AD dementia, with the largest fold-change in p-tau217 (11.6), followed by p-tau231 and p-tau181 (3.2-4.5). Discussion: Variable fold-changes and correlation with t-tau suggest that p-tau closely associates with neurodegeneration and concomitant AD in CJD. Highlights: N-terminal phosphorylated tau (p-tau) biomarkers are increased in Creutzfeldt-Jakob disease (CJD) with and without concomitant AD. P-tau217, p-tau231, and p-tau181 correlate with total tau (t-tau) and increase in the presence of amyloid beta (Aβ) co-pathology. N-terminal p-tau181 and p-tau231 in Aβ-negative CJD show variation among PRNP genotypes. Compared to mid-region-targeting p-tau181, cerebrospinal fluid (CSF) N-terminal p-tau has greater potential to reflect post-mortem neuropathology in the CJD brain.
Keywords: Alzheimer's disease, Creutzfeldt–Jakob disease, cerebrospinal fluid, concomitant pathology, neuropathology, phosphorylated tau, p-tau181, p-tau217, p-tau231
Published in DiRROS: 03.06.2026; Views: 191; Downloads: 154
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3. Spectrum of genetic variants and yield of genetic testing in Slovenian probands with suspected cardiomyopathies surviving sudden cardiac arrestNina Vodnjov, Aleš Maver, Borut Peterlin, Karin Writzl, 2025, original scientific article Abstract: Abstract Background Cardiomyopathies (CMs) present phenotypically on a spectrum and in a proportion of patients the initial presentation is sudden cardiac arrest (SCA). Studies performing genetic screening of SCA survivors have identifed (likely) pathogenic (LP/P) variants in 2–50% of probands, with mean cohort ages ranging from 28 to 64 years. Due to inconsistent data in the literature, our study aimed to genetically characterise Slovenian SCA survivors with clinically confrmed/suspected cardiomyopathy (CM). The present study included 29 probands (17 women, 59%) with clinically confrmed/suspected CM who survived SCA and were referred to the Clinical Institute of Genomic Medicine for genetic testing between January 2010 and July 2024. The majority of probands (23; 79%) underwent whole exome sequencing, and the remainder either clinical exome (5; 17%) or panel sequencing (1; 4%). Genetic data were analysed following ACMG/AMP guidelines and ACGS recommendations. Results Probands survived SCA at a mean age of 49±17 years (range 15–71), and 12 (41%) were<50 years old. The majority had clinically confrmed/suspected arrhythmogenic (10; 34.5%) or dilated (9; 31.0%) CM, while the remainder had clinically undefned (5; 17.2%), hypertrophic (4; 13.8%), or non-compaction (1; 3.4%) CM. Seven LP/P variants in CM-related genes were identifed in eight (28.6%) probands. In addition, 16 variants of uncertain signifcance (VUS) were identifed in 12 (41.3%) probands. Probands’ age at SCA did not signifcantly afect the yield, as LP/P variants were identifed in four probands<50 years at SCA and in four>50 years (p=0.56), nor did the positive family history of heart disease (p=0.55) or sudden cardiac death (p=0.43). There were also no signifcant diferences in probands’ age and test outcome, as the mean age of patients with LP/P variants was 46±21 years, those with the VUS(s) were 45±15 years, and those without candidate variant(s) were 55±12 years (p=0.41). Conclusions LP/P variants were identifed in almost one-third of Slovenian SCA survivors with clinically confrmed/ suspected CM. Genetic testing of SCA survivors with structural clinical fndings provides additional confrmation of the clinical diagnosis and a basis for identifying relatives at risk of heart disease, allowing for better management.
Keywords: sudden cardiac arrest, genetic testing, molecular pathology, (likely) pathogenic variants, hereditary cardiomyopathy
Published in DiRROS: 10.04.2026; Views: 289; Downloads: 174
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4. Contemporary valvular mechanisms of aortic regurgitation in tricuspid aortic valves : importance in repair versus replacement strategySaifalislam Almaghrabi, Hector I. Michelena, Matija Jelenc, Karen B. Abeln, Tristan Ehrlich, Hans Joachim Schäfers, 2024, original scientific article Abstract: Background: This study was performed to determine cusp causes of aortic regurgitation in patients with tricuspid aortic valves without significant aortic dilatation and define cusp pathologies amenable to surgical repair (aortic valve repair [AVr]) versus aortic valve replacement. Methods and Results: We retrospectively reviewed surgical reports of consecutive adults with tricuspid aortic valves undergoing surgery for clinically significant aortic regurgitation within a prospective registry from January 2005 to September 2019. Valvular mechanisms were determined by systematic in vivo intraoperative quantification methods. Of 516 patients, 287 (56%) underwent repair (AVr; mean +/- SD age, 59.9 +/- 12.4 years; 81% men) and 229 (44%) underwent replacement (aortic valve replacement; mean +/- SD age, 62.8 +/- 13.8 years [P=0.01 compared to AVr]; 67% men). A single valvular mechanism was present in 454 patients (88%), with cusp prolapse (46%), retraction (24%), and perforation (18%) being the most common. Prolapse involved the right cusp in 86% of cases and was more frequent in men (P<0.001). Two-dimensional transesophageal echocardiography accuracy for predicting mechanisms was 73% to 82% for the right cusp, 55% to 61% for the noncoronary cusp, and 0% for the left-coronary cusp. Cusp prolapse, younger age, and larger patient size were associated with successful AVr (all P<0.03), whereas retraction, perforation, older age, and concomitant mitral repair were associated with aortic valve replacement (all P<0.03). Conclusions: Right cusp prolapse is the most frequent single valvular mechanism in patients with tricuspid aortic valve aortic regurgitation, followed by cusp retraction and perforation. The accuracy of 2-dimensional transesophageal echocardiography is limited for left and noncoronary cusp mechanistic assessment. Prolapse is associated with successful AVr, whereas retraction and perforation are associated with aortic valve replacement. With systematic intraoperative quantification methods and current surgical techniques, more than half of tricuspid aortic valve aortic regurgitation cases may be successfully repaired.
Keywords: aortic regurgitation, tricuspid aortic valve, valvular pathology
Published in DiRROS: 10.03.2026; Views: 349; Downloads: 263
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5. Climate change impacts on plant diseases and crop protectionOctave Lacroix, Sebastjan Radišek, 2025, review article Abstract: Climate change is considered one of the greatest threats to agriculture, resulting in significant yield losses and the loss of arable land due to various factors, ranging from unfavorable climate conditions to soil fertility issues. One significant aspect of climate change affecting crops is the development of diseases. The main factors of climate change affecting agriculture are the increase in temperature and CO2 levels, as well as the alteration of precipitation regimes, which can lead to extreme weather events such as droughts and floods. These factors considerably affect pathogens' expression of disease in hosts, as well as their spatial and temporal distribution and life cycle limiting factors, which are now changing. Early studies show an increase in the severity and occurrence of diseases caused by pathogens in crops, a reduction in plant defense mechanisms, the emergence of new, adapted, and more aggressive pathogen strains, and a wider and faster expansion of pathogens. However, the efficacy of plant protection products is also reduced. However, each pathosystem is affected differently by climate change, and mitigating effects must be studied independently.
Keywords: global warming, food security, plant pathogens, plant pathology
Published in DiRROS: 26.02.2026; Views: 392; Downloads: 336
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6. Unraveling the complexity of skeletal dysplasias in the national health systemDorra Najjar, Aleš Maver, Ana Marija Peterlin, Helena Jaklič, Borut Peterlin, 2025, original scientific article Abstract: Introduction: Skeletal dysplasia (SD) is a large and heterogeneous group of rare genetic disorders that affects bone and cartilage growth. These disorders are diagnosed based on radiographic, clinical, and molecular criteria. However, the diagnostics is challenging due to clinical and genetic heterogeneity. We present the experience of systematic use of comprehensive genetic testing in the national health system and the molecular epidemiology of SD in Slovenia. Methods: We retrospectively reviewed 470 patients with clinical features of SD, including prenatal, childhood, and adult patients referred for diagnostic genetic evaluation to the national genetic reference center over ten years. In 262 patients, whole exome or whole genome sequencing was performed, while direct gene sequencing was performed in 208 patients with a specific clinical diagnosis. Results: A definitive genetic diagnosis using NGS was achieved in 50% (n=131) of patients. Among the positive cases, 49.61% initially presented with a nonspecific diagnosis of SD, and genetic testing contributed to establishing the diagnosis. Moreover, we demonstrated high genetic heterogeneity in our SD cohort with 66 distinct causative genes, resulting in different types of SD. In detail, we detected 132 causative variants, of which 29 were novel, which expanded the mutational spectrum of SD. Furthermore, pathogenic copy number variants (CNVs) were identified in 4.55% of the total number of variants, highlighting the importance of CNV analysis in expanding the yield of molecular diagnosis of SD. Conclusion: With the systematic use of WES and WGS, we have significantly improved the diagnostic yield of SD in the national health system and access to genetic testing. Moreover, we found significant genetic heterogeneity, and we report the genetic epidemiology of SD in the Slovenian population.
Keywords: CNV, copy number variants, NGS, next-generation sequencing, diagnostic yield, molecular pathology, prenatal diagnosis, rare genetic diseases, skeletal dysplasia
Published in DiRROS: 10.11.2025; Views: 675; Downloads: 321
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7. Crayfish pet trade as a pathway for the introduction of known and novel virusesKatarina Bačnik, Luka Kranjc, Leticia Botella, Ivana Maguire, Dora Pavić, Jiří Patoka, Paula Dragičević, Martin Blaha, Ana Bielen, Antonín Kouba, Denis Kutnjak, Sandra Hudina, 2025, original scientific article Abstract: Expanding international pet trade has emerged as one of the main introduction pathways of aquatic invasive species, with ornamental crayfish species commonly available on the EU and global markets. Besides most frequently studied crayfish pathogens, such as Aphanomyces astaci and white spot syndrome virus (WSSV), ornamental crayfish carry associated microbial communities, which may potentially lead to the emergence of known or even novel diseases following intentional or unintentional release of animals into the wild. This is especially problematic in the case of viruses, which represent an important, yet considerably understudied, group of crayfish pathogens. Here we analyzed viromes of hepatopancreas tissue of four crayfish species acquired in the international pet trade in Europe (Procambarus clarkii, Procambarus alleni, Cherax holthuisi, and Cherax quadricarinatus) using a high throughput sequencing based metagenomic approach. Seven different known viruses were identified, which were previously either directly associated with crayfish (WSSV, Cherax quadricarinatus reovirus, chequa iflavirus, athtab bunya-like virus) or with hosts from subphylum Crustacea or invertebrates associated with freshwater environment (Shahe ispoda virus 5, Dicistroviridae sp.). Additional sequences represented 8 potential novel and divergent RNA viruses, most similar to sequences belonging to members of Picornavirales, Elliovirales, Reovirales, Hepelivirales, Tolivirales and Ghabrivirales orders. We discuss our findings in relation to their phylogenetic relationships, geographical origins, and putative pathogenicity implications. The results highlight the need for further research into the risks related to disease emergence associated with the pet trade.
Keywords: virome, RNA viruses, ornamental crayfish, pet-trade, high throughput sequencing, ecology, molecular biology, pathology, virology, environmental risk assessment
Published in DiRROS: 23.05.2025; Views: 1176; Downloads: 888
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8. Solitary ovarian cancer cells in the peritoneum : what happens below the surface?Laura M.C. Vos, Willemien J. van Driel, Gabe S. Sonke, Juliette O. A. M. van Baal, Koen K. van de Vijver, Cornelis J. F. van Noorden, Christianne A. R. Lok, 2022, original scientific article Abstract: Background
In advanced epithelial ovarian cancer (EOC), the peritoneum is the primary site of disease recurrence which occurs in >75% of patients despite complete cytoreductive surgery (CRS) and chemotherapy. Macroscopically undetectable remaining cancer cells are deemed to be a source for recurrent disease. We investigated characteristics of occult disease in biopsies of macroscopically normal peritoneum during CRS.
Materials and methods
We included 14 patients with advanced stage high grade serous ovarian cancer (HGSOC). Eleven patients had received neoadjuvant chemotherapy (NACT) and three patients were chemotherapy naïve. Each patient underwent three study-related peritoneal biopsies: 1) of a metastasis, 2) adjacent to a metastasis and 3) at distance from metastases. Cryostat sections were immunohistochemically stained for PAX8 and PanCK as markers of EOC cells and for CD31 as a marker for vascular and lymphatic endothelium. The sections were analyzed semi-quantitatively.
Results
Macroscopically normal peritoneum showed solitary PAX8-positive cells adjacent to and at distance from metastases in all patients. Thirteen percent of these PAX8-positive cells were found to be attached to the mesothelium and are presumably spread through intra-abdominal fluid. Eighty-seven percent of the solitary PAX8-positive cells were found in the stroma underneath the mesothelium, of which 59% were firmly attached to endothelium and 33% were found in the stroma. In most cases, no sign of proliferation of the solitary cells was observed. Only a few clusters of PAX8-positive cells were found. Chemotherapy did not affect these results.
Conclusions
Solitary PAX8-positive cells are present in the macroscopically healthy-looking peritoneum of all EOC patients investigated, irrespective of the distance to macroscopically-visible metastases and of previous treatment. The majority of these solitary cancer cells were attached to endothelium of capillaries, venules or lymphatic vessels. Their solitary character and lack of proliferation suggests a dormant state, which could explain why these cells are unaffected by neo-adjuvant chemotherapy.
Keywords: ovarian cancer, peritoneal metastasis, translational medical research, human pathology, PAX8, cancer recurrence
Published in DiRROS: 26.02.2025; Views: 1015; Downloads: 648
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9. Statistical modeling of long-term grapevine response to "Candidatus Phytoplasma solani" infection in the fieldAna Rotter, Petra Nikolić, Neža Turnšek, Polona Kogovšek, Andrej Blejec, Kristina Gruden, Marina Dermastia, 2018, original scientific article Abstract: Bois noir (BN) is the most widespread European grapevine yellows disease caused by ‘Candidatus Phytoplasma solani’. Although our knowledge of the mechanisms of interactions of this pathogenic bacteria with host is largely unknown, the plant-pathogen system of BN is commonly used as a model system for studying grapevine yellows diseases. We applied here a conceptual model of general plant pathology – a disease triangle for describing interactions among the host plant, the pathogen and the environment. We generated a proof-of-concept statistical model for disease triangle using original experimental data and different statistical and data mining approaches for a selected system of ‘Ca. P. solani’ infection of cv. ‘Chardonnay’ grapevine plants. We monitored individual plants from a single vineyard over a period of six years. Phytoplasma content, the expression of 21 selected grapevine genes and environmental conditions were recorded and related to disease severity. Our model predicts that in described conditions BN is a function of the expression of grapevine gene VvDMR6, summer rainfall and abundance of ‘Ca. P. solani’. The greatest impact among elements of the disease triangle is attributed to the pathogen, and is independent of the pathogen titer. We showed that this first de facto representation of the disease triangle is useful for showing disease dynamics over several years and could be applied to other plant-pathogen systems. The overall results of this study will contribute to understanding of ‘Ca. P. solani’ biology and its interactions with grapevine host.
Keywords: plant diseases, plant pathology
Published in DiRROS: 24.07.2024; Views: 1501; Downloads: 936
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10. Locoregional disease control after external beam radiotherapy in 91 patients with differentiated thyroid carcinoma and pT4 tumor stage : a single institution experienceNikola Bešić, Marta Dremelj, Gašper Pilko, 2018, original scientific article Abstract: Locoregional recurrence is common in patients with locally advanced differentiated thyroid carcinoma (DTC). Our aim was to find out the rate of locoregional control of the disease after external beam radiotherapy (EBRT) of the neck and mediastinum in patients with DTC and pT4 tumor. Patients and methods Altogether 91 patients (47 males, 44 females, median age 61 years) with DTC had EBRT of the neck and mediastinum as part of the multimodal treatment of pT4 tumor (63 cases pT4a, 28 cases pT4b) from the year 1973 to 2015. Data on clinical factors, histopathology and recurrence were collected. Disease-free, disease-specific and overall survival was calculated. Results Median tumor size was 5 cm (range 1%30 cm). Out of 91 patients, 23 had distant and 38 regional metastases. A total or near-total thyroidectomy, lobectomy, subtotal thyroidectomy and lymph node dissection was performed in 70%, 14%, 2% and 30% of cases, respectively. Thirteen percent of patients were not treated with surgery. All patients had EBRT and 39 had chemotherapy. Radioiodine (RAI) ablation of thyroid remnant and RAI therapy was applied in 90% and 40% of cases, respectively. Recurrence was diagnosed in 29/64 patients without a persistent disease: locoregional and distant in 16 and 13 cases, respectively. Five-year and ten-year disease-free survival rate was 64% and 48%, respectively. Conclusions The majority of patients with DTC and pT4 tumors who were treated with EBRT of the neck and mediastinum region as part of multimodal treatment have long-lasting locoregional control of the disease.
Keywords: thyroid carcinoma, radiotherapy, survival, pathology
Published in DiRROS: 11.06.2024; Views: 1340; Downloads: 422
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