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Copyright of Medicus (1330-013X) is the property of Pliva Hrvatska d.o.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Numerous studies have described genes and loci associated with severe COVID-19 disease such as those for angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease type 2 (TMPRSS2), tyrosine kinase 2 (TYK2), dipeptidyl peptidase 9 (DPP9), the ABO blood group system, certain alleles and the genes of HLA system encoding immune system receptors. However, it should be noted that a variant in genes encoding molecules important for the biological effect of class I and III interferons, such as the TLR gene, is associated with the highest estimated risk of developing severe critical disease COVID-19, especially in men. The importance of male biological sex as a risk factor for the development of severe COVID-19 disease has been proven by several national and global studies. Recent research has also shown an association between the gene for two enzymes from the uridine diphosphate (UDP) -glucuronosyltransferase family (UGT2A1 and UGT2A2) and the smell and/or taste loss during COVID-19 disease. The aim of this paper is to list out genetic markers for which scientific research has proven biological and clinical significance in SARS-CoV-2 infections, especially in terms of host susceptibility to infection and assessment of disease severity and outcome. [ABSTRACT FROM AUTHOR]

Copyright of Croatian Journal of Infection / Infektoloski Glasnik is the property of Croatian Society for Infectious Diseases and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Croatian Journal of Infection / Infektoloski Glasnik is the property of Croatian Society for Infectious Diseases and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Hepatitis C virus (HCV) genotyping is an important part of pre-treatment diagnostic algorithms as it guides the choice of therapeutic regimens. The aim of this study was to analyse the distribution of HCV genotypes in patients with chronic hepatitis C from Croatia in the period 2008-2015.Methods: The study enrolled 3,655 anti-HCV positive patients with available results of HCV genotyping from the three largest national HCV genotyping laboratories.Results: The majority of HCV-infected individuals enrolled in the study were male (70.7%). Analysis of age distribution in a subset of 2,164 individuals showed a mean age of 40.9 years (SD 11.77 years). Croatian patients were mostly infected with HCV genotype 1 (56.6%), followed by genotype 3 (37.3%), genotype 4 (4.2%) and genotype 2 (1.8%). Genotype 1 subtyping in a subset of 1,488 patients showed 54% (803/1,488) of 1b infections and 46% (685/1,488) of 1a infections. Percentages of genotype 1 were the highest in Central/Northwestern and Eastern Croatia and the lowest in the Central/Southern Adriatic Region. Genotype 3 was most frequently found in the Central/Southern Adriatic Region (49.1%) but represented only 17.5% of infections in Eastern Croatia (p < 0.001).Conclusions: The results of this nine-year retrospective analysis on the distribution of HCV genotypes and subtypes in 3,655 HCV-infected individuals from Croatia showed that the majority of infections can be attributed to genotypes 1 and 3 with absence of major changes in the molecular epidemiology of the two most frequent HCV genotypes infection in Croatia in the past 20 years. [ABSTRACT FROM AUTHOR]

State-of-the-art molecular diagnostics of infectious diseases includes the use of a variety of molecular methods due to their superior sensitivity, specificity, standardization, automation as well as speed. Molecular assays are most frequently used for the determination of infectious diseases etiology, monitoring of disease course and treatment outcome in individual patients as well as determination of antimicrobial resistance. The most frequently used molecular methods in clinical practice include real-time polymerase chain reaction, nucleic acid hybridization and population-based sequencing. [ABSTRACT FROM AUTHOR]

We report an HIV-infected person who was treated for lymphogranuloma venereum cervical lymphadenopathy and proctitis in Croatia in 2014. Infection with a variant L2b genovar of Chlamydia trachomatis was detected in a cervical lymph node aspirate. A prolonged course of doxycycline was required to cure the infection. [ABSTRACT FROM AUTHOR]

We report an HIV-infected person who was treated for lymphogranuloma venereum cervical lymphadenopathy and proctitis in Croatia in 2014. Infection with a variant L2b genovar of Chlamydia trachomatis was detected in a cervical lymph node aspirate. A prolonged course of doxycycline was required to cure the infection. [ABSTRACT FROM AUTHOR]

Aim To examine the risk factors, comorbidity, severity of liver disease, treatment course, and outcome in Croatian war veterans with chronic hepatitis C, especially those suffering from posttraumatic stress disorder (PTSD). Methods We collected medical records of 170 adult men diagnosed with chronic hepatitis C who started treatment with a combination of pegylated interferon-alpha and ribavirin between January 2003 and June 2009 at the Croatian Reference Centre for Viral Hepatitis. Results Participants' mean age was 43±9 years. Among 170 participants, there were 37 war veterans (22%). The main risk factor in veteran patients were operative procedures with transfusions (46% vs 5% in non-veterans; P<0.001) and in non-veteran patients intravenous drug use (42.1% vs 13%; P<0.001).The average duration of infection was longer in war veterans (14.5±3.4 vs 12.2±7.2 years; P=0.020). The percentage of PTSD comorbidity in the whole group was 11% (18/170) and in the war veterans group 49% (18/37). The prevalence of sustained virological response in patients with PTSD was 50% and in patients without PTSD 56%. Treatment reduction in patients with PTSD (33%) was higher than in patients without PTSD (12%; P=0.030). Conclusion Croatian war veterans are a group with high risk of chronic hepatitis C infection because many of them were wounded during the Croatian War 1991-1 995. Considerations about PTSD as a contraindication for interferon treatment are unjustified. If treated, patients with PTSD have an equal chance of achieving sustained virological response as patients without PTSD. [ABSTRACT FROM AUTHOR]

We investigated the distribution of memory (CD45RO+) and naive (CD45RA+CD62L+) CD4+ T-cells as well as CD8+ T-cells and total T-cells in the CSF of children with aseptic meningitis following measles-mumps-rubella (MMW) vaccination and those with enteroviral meningitis. Flow cytometric analysis of CSF cells was performed in 12 children with MMR vaccine-associated meningitis and 11 children with enteroviral meningitis. Percentages of total T-cells, CD4+ and CD8+ T-cells and monocytes in CSF of patients from the two groups were not significantly different. The majority of CD4+ T-cells in the CSF of both patient groups were of memory phenotype. Percentages of CSF naive CD4+ T-cells were increased in children with aseptic meningitis following MMR vaccination. Further studies focused on the more detailed immunophenotyping of CSF cells are needed to fully establish the usefulness of flow cytometry in the diagnostic workup of inflammatory CNS diseases in children. [ABSTRACT FROM AUTHOR]

We compared the number/percentages of naive and memory CD4+ T-cells, CD38+CD8+ T-cells, and CD28+CD4+ and CD28+CD8+ T-cells in patients with advanced HIV disease (baseline CD4+ count<100) with those with less advanced (baseline CD4+ cell count>100) HIV disease during 4 years of suppressive highly active antiretroviral therapy. This prospective, longitudinal study included 30 treatment-naive patients and 32 controls. Advanced HIV-infected patients ( n=13) gained more CD4+ T-cells than less advanced patients ( n=11) at 1 month (median: 60 vs. 36μL−1), 3 months (86 vs. 14), 6 months (111 vs. 23), 12 months (174 vs. 47), 24 months (162 vs. 72) and 48 months (257 vs. 123) ( P=0.15, P<0.001, P=0.026, P=0.021, P=0.1 and P=0.06, respectively). Advanced patients gained more naive CD4+ T-cells at 48 months compared to less advanced patients (27.3 vs. 11.4%, P=0.05). The relative gain in memory CD4+ T-cells was greater in advanced vs. less advanced patients at 1 month (median: 6.4 vs. 1.4%), 3 months (4.3 vs. 2.0), 6 months (6.7 vs. 1.6), 12 months (6.9 vs. 2.4), 24 months (7.5 vs. 3.1) and 48 months (11.3 vs. 6.8) ( P=0.002, P=0.013, P<0.001, P=0.004, P=0.001 and P=0.015, respectively). At 48 months, CD38+CD8+ T-cells and naive CD4+ T-cells reached normal values (9.2%, P=0.869 vs. controls and 47.5%, P=0.699, respectively) in less advanced patients, as did CD38+CD8+ T-cells in advanced patients (4.7%, P=0.309 vs. controls). The kinetics of naive and memory CD4+ T-cell reconstitution is different in less advanced compared to advanced HIV patients. [ABSTRACT FROM AUTHOR]

Resistance of Human Immunodeficiency Virus (HIV) to antiretroviral drugs is an important limitation in achieving complete suppression of viral replication and therefore represents an important clinical issue. It refers especially to therapy-naive individuals infected with resistant HIV strains, e.g. individuals with transmitted drug resistance (TDR). Transmitted drug resistance mutations (TDRMs) are clinically relevant and may reduce the efficacy of antiretroviral therapy. In this paper, we report the first case of HIV-1 transmitted triple-class drug resistance in Croatia. The aim of this study was to characterize drug resistance patterns and TDRMs in the newly diagnosed, treatment-naive HIV-1 patient with such a complex resistance pattern. Sanger sequencing (SS) of the sample showed four reverse transcriptase inhibitor (RTI) resistance mutations (E44D, T215E, K103N, L100I) affecting two drug classes and two protease inhibitor resistance mutations (V32I, I47V). To characterize HIV-1 minority drug resistance variants below the detection limit of SS, deep sequencing (DS) analysis was performed. DS analysis identified the same triple class resistance pattern that was identified by SS with addition of several other RTI mutations. The patient described in this report is the first patient with HIV-1 triple-class resistance in Croatia and further studies will be directed toward analysing possible local onward transmission of this resistant virus. [ABSTRACT FROM AUTHOR]

Aim To assess the frequency of human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and high-risk types of human papillomavirus (HPV16 and HPV18) infections in lung adenocarcinoma samples. Methods Lung adenocarcinoma cytological smears and their DNA isolates were obtained from patients hospitalized at the Department for Lung Diseases Jordanovac, Zagreb, in 2016 and 2017. Overall, 67 lung adenocarcinoma samples were examined: 34 with epidermal growth factor receptor gene (EGFR) mutations and 33 without EGFR mutations. The EGFR mutation status and virus presence were assessed with a polymerase chain reaction, and random samples were additionally tested for EBV with Sanger sequencing. HCMV, EBV, HPV16, and HPV18 infections were evaluated in relation to EGFR mutation, smoking status, and sex. A meta-analysis of available data about HPV infection in non-small cell lung cancer was performed. Results More frequent HCMV, EBV, HPV16, and HPV18 infections were observed in lung adenocarcinoma samples with EGFR mutations than in samples without these mutations. Coinfection of the investigated viruses was observed only in lung adenocarcinoma samples with mutated EGFR. In the group with EGFR mutations, smoking was significantly associated with HPV16 infection. The meta-analysis showed that non-small cell lung cancer patients with EGFR mutations had a higher odds of HPV infection. Conclusion HCMV, EBV, and high-risk HPV infections are more frequent in EGFR-mutated lung adenocarcinomas, which indicates a possible viral impact on the etiology of this lung cancer subtype. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the effect of hepatitis C virus eradication using direct-acting antivirals (DAA) on the serum cytokine and growth factor profiles of chronic hepatitis C patients (CHC). Serum concentrations of 12 cytokines and 13 growth factors were measured in 56 patients with CHC before, during the DAA treatment and after sustained virological response using bead-based flow cytometry. Cytokine and growth factor levels were also measured in 15 healthy individuals. The majority of the selected cytokines and growth factors exhibited similar concentrations before, during and after successful DAA treatment, the exceptions being IL-10, EGF, HGF and VEGF. Significantly lower concentrations of IL-10, IL-13, IL-4, IL-4, IL-9, TNF- α and higher levels of Ang-2, HGF and SCF were observed in patients with CHC before and after DAA treatment compared with healthy individuals. Patients with severe fibrosis stages exhibited higher levels of Ang-2 and lower levels of EGF, PDGF-AA and VEGF. Furthermore, IL-4, IL-5 and SCF were characterized as potential biomarkers of DAA treatment using random forest. Additionally, logistic regression characterized EGF as a potential biomarker of severe CHC. Our results suggest inhibition of pro-inflammatory processes and promotion of liver regeneration in CHC patients during DAA treatment.

Research and publication expenses were supported in part by the Croatian Science Foundation and PLIVA Croatia Ltd. (project no. 04/30 'Research on the aetiology, epidemiology, diagnostics, and treatment of patients with prostatitis syndrome').