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Pediatric stroke is significantly less common than stroke in adults, but represents a major challenge to public health authorities. The aim of this retrospective study was to identify the total and annual number of children younger than 18 years with arterial ischaemic stroke and transient ischaemic attack referred to the Children's Hospital Zagreb, which is a major national centre specialised for the treatment and prevention of stroke in children. We reviewed the medical records of the Department of Neuropediatrics database at the Children's Hospital Zagreb between 1998–2005 in order to provide demographic and clinical characteristics and neuroimaging findings in children with arterial ischaemic stroke. In the 7-year period, we identified a total of 124 children from different geographic areas of Croatia with a confirmed diagnosis of transient ischaemic attack ( N=77), and arterial ischaemic stroke ( N=47). Perinatal and childhood arterial ischaemic stroke were equally represented (23 and 24 children, respectively). The average number of new cases identified each year was 18 cases (range: 12–21), seven arterial ischaemic stroke and 11 transient ischaemic attack cases. Male predominance was found in children with arterial ischaemic stroke with a male : female ratio of 1·76 : 1, and was slightly higher in childhood arterial ischaemic stroke compared with perinatal arterial ischaemic stroke (2 : 1 and 1·56 : 1, respectively). In contrast, transient ischaemic attack was more frequently found in girls, and more likely identified in older children compared with younger children with arterial ischaemic stroke. Obtained data will contribute to better understanding of paediatric stroke in Croatia and will provide a base for the establishment of the national referral center and national pediatric stroke registry. [ABSTRACT FROM AUTHOR]

Aim: To identify the von Willebrand factor (VWF) gene variant status in Croatian adult patients diagnosed with von Willebrand disease (VWD), provide differential diagnosis of VWD subtypes, and identify patients with mild hemophilia A (HA) who were earlier misdiagnosed as VWD., Methods: Coagulation testing included determination of VWF gain-of-function mutant glycoprotein Ib binding activity (VWF:GPIbM), VWF antigen, VWF collagen-binding activity, and multimeric analysis. Genetic analysis of VWF and FVIII genes was performed with next-generation sequencing (NGS)., Results: The study enrolled 50 patients (72% women; median age 37 years, range 18-75) from 44 unrelated families. Fourteen patients were heterozygous for VWF gene variants compatible with type-1 VWD. Twelve had variants associated with type 2, of whom seven were classified as type 2A, four as type 2B, and one as type 2N. Six type-3 VWD patients were either homozygotes for null variants or combined heterozygotes. Eleven variants within the VWF gene were novel. Three female patients had variants within the FVIII gene, and were re-classified as mild-HA carriers, of whom one had causative novel variants both within VWF and FVIII genes. Fifteen patients remained without a defined genetic cause of their disorder, of whom five had VWF:GPIbM levels below 50%., Conclusion: Croatian adult patients with VWD have considerable genetic heterogeneity. NGS of both VWF and FVIII genes provided accurate differential diagnosis of VWD subtypes and distinction of VWD from mild HA.

Aim: To explore the clinical presentation and epidemiological history of the subjects who underwent SARS-CoV-2 antigen testing. Methods: We included 1,000 consecutive subjects who presented themselves at the diagnostic clinic in Croatia and analyzed their symptoms and epidemiological history. All subjects were classified into three groups, according to their reason of arrival; symptomatic, contacts of confirmed patients, and those who were tested due to administrative reasons. Results: On average, there were 24% of positive antigen results; the positivity rate was 51% among symptomatic, 16% in contacts, and 5% of administrative patients. The commonest symptoms of the disease included febrility and anosmia. We developed a clinical score to predict SARS-CoV-2 positivity, which had an area under the curve of 79.3 [95% confidence intervals (CI) 75.8-82.8]. Contact with the isolated person [odds ratio 0.54 (95% CI 0.31-0.94)] and international travel had a protective effect [0.20 (0.09-0.43)], suggesting that risk perception and mandatory pretravel measures had a key role in the determination of the infection risk. Conclusions: A combination of clinical symptoms can have reasonable predictive power for an antigen-positive test result. Risk perception seems to have a role in the epidemic spread, probably via stricter adherence to personal preventative measures., Competing Interests: DP, GL, and OP are scientific advisors to the Government of the Republic of Croatia for COVID-19 response, which had no influence in the decision to prepare the manuscript, its preparation or the selection of the journal where the manuscript would be submitted. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Primorac, Perić, Matišić, Molnar, Zadro, Vince, Lauc and Polašek.)

Background: Recent studies demonstrated that the expression pattern of bone morphogenetic protein-7 (BMP-7) is altered in different tumors. We determined expression of BMP-7 in human clear cell renal carcinoma (CCRC)., Methods: Samples from cancer and corresponding healthy tissue were obtained from 20 patients who underwent nephrectomy for CCRC. Expression of BMP-7 mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression was analyzed by immunohistochemistry., Results: RT-PCR showed strong down-regulation of BMP-7 mRNA in cancer tissue. Immunohistochemistry revealed expression of BMP-7 in normal renal tissue, with almost complete loss of BMP-7 expression in malignant cells of 6 patients (30%). After 3 years of follow-up, 5 out of 6 patients with high BMP-7 mRNA expression were alive and disease-free, compared with 9 out of 14 patients with low BMP-7 mRNA expression., Conclusions: BMP-7 mRNA and protein expression were down-regulated in CCRC. Further prospective studies are needed to characterize the role of BMP-7 in human CCRC.

The human platelet antigens (HPA) are genetically defined polymorphisms expressed on platelet membrane glycoproteins. As platelet antigens are very important in several clinical situations and in population genetics, we used the polymerase chain reaction with sequence-specific primers (PCR-SSP) to investigate HPA-1, -2, -3 and -5 allele frequencies in the Croatian population. The HPA frequencies obtained in 219 Croatians were: 1a-0.854, 1b-0.146, 2a-0.890, 2b-0.110, 3a-0.575, 3b-0.425, 5a-0.895 and 5b-0.105. These data are similar to the frequencies reported in most European studies with some significant differences in HPA-2 when compared with the Dutch and German population, in HPA-3 when compared with the Swiss population and in HPA-5 when compared with the Finnish population. The three most common condensed HPA genotypes in the Croatian population were: HPA-1a/a, -2a/a, -3a/b, -5-a/a (0.283), HPA-1a/a, -2a/a, -3a/a, -5-a/a (0.137) and HPA-1a/b, -2a/a, -3a/b, -5-a/a (0.087). Data obtained in this study can be used for better understanding and treatment of immune-mediated platelet disorders in our population.

Arterial thrombosis is the major reason for severe complications of coronary artery disease (CAD). Recently it has been suggested that the FXIII-A Val34Leu polymorphism, affecting clot stability, provides protection against thrombosis. Results published up to date implicate that there is a significant correlation between geographical area and the Leu34 allele prevalence and that its contribution to arterial thrombosis is different in different populations. The purpose of this study was to determine frequency of Leu34 allele in Croatian subjects as well as to estimate its association with a CAD. FXIII-A Val34Leu genotyping was carried out by real-time PCR method on the LightCycler using melting curve analysis with forward 5'-AACTTCCAGGACCGGCTTT-3' and reverse 5'-ACCCAGAGTGGTGGGGAA-3' primers. The Leu34 allele frequency in studied Croatian subjects was 24.3%. No significant differences were found in the prevalence of FXIII-A Val34Leu genotype or Leu34 allele distribution between studied subjects (P > 0.05). Carriage of the Leu34 allele was not significantly associated with CAD or MI risk reduction (P > 0.05). This is the first report that studies the prevalence of the Leu34 allele frequency in Croatian subjects and our results suggest that possession of the Leu 34 alele does not provide protection against MI.

Aim: To determine the prevalences of factor V Leiden and the G20210A mutation in the prothrombin gene (PT20210A) and the frequency of their association in healthy subjects and in patients with venous thromboembolism (VTE)., Method: We studied 160 Croatian patients with at least one episode of VTE and 155 healthy subjects as a control group. Genomic DNA was extracted according to standard procedures and the presence of factor V Leiden and PT20210A were determined by polymerase chain reaction-restriction fragment length polymorphism method., Results: The prevalences of factor V Leiden and PT20210A were in VTE patients 21% and 8% respectively, and 4% in controls for both mutations. Additionally, 4 patients were affected by double heterozygous defects, corresponding to a frequency of 3%, whereas none of the controls were double heterozygotes. The coexistence of the PT20210A in heterozygous carriers of factor V Leiden was 15% in VTE group. The results obtained for different subgroups of VTE patients showed that the carriers of analyzed mutations were identified only in subgroups of patients with deep venous thrombosis of lower extremities (in 30 patients with factor V Leiden and in 13 patients with PT20210A) and superficial venous thrombosis (in 3 patients with factor V Leiden)., Conclusion: The prevalences of factor V Leiden and PT20210A in analyzed population of VTE patients are higher than in the group of healthy subjects. High frequency of association between both mutations supports the need to perform simultaneous genetic analyses of factor V Leiden and PT20210A in all VTE patients.