The aim of the present study was to investigate the impact of CCR5 Δ32 and CTLA-4 polymorphisms on the response to IFN-β treatment in our cohort of MS patients from Croatia and Slovenia. Genomic DNA was obtained from 295 MS patients (230 female; 65 male) classified as responders (n = 173) and non-responders (n = 122) based on clinical criteria for treatment efficacy. Genotyping was performed via PCR/PCR-RFLP. No significant differences in the genotype/allele frequencies of CCR5Δ32 and CTLA-4 +49 A/G were detected between male responders and non-responders. A significantly higher prevalence (p = 0.039) of the CTLA-4 +49 AA genotype was found in female responders (42.1%) compared to non-responders (28.9%). Using multiple forward regression analysis, the CTLA-4 +49 AA genotype significantly predicted a positive response to IFN-β therapy in females (p = 0.011) and contributed to 4.5% of response variability. Furthermore, the combined presence of the CCR5Δ32 wtwt/CTLA-4 +49 AA genotype significantly predicted a positive response to treatment in females (p = 0.025). The age at disease onset, pretreatment relapse rate, and baseline EDSS score were not reliable predictors of treatment response in MS patients. Our results indicate that the presence of the CCR5Δ32 polymorphism was not associated with the response to IFN-β treatment, whereas the CTLA-4 +49 polymorphism showed a positive correlation with an optimal response in female patients.

Background: The largest documented outbreak of hemorrhagic fever with renal syndrome occurred in Primorje-Gorski Kotar County, Croatia, in 2021, marking the first-time cases of hantavirus infection recorded outside of the known endemic region in the north of the county. Aim: To identify the factors contributing to the spread of the outbreak and to compare risk factors for acquiring hantavirus infection in the endemic and newly affected regions. Methods and Results: A total of 189 cases were confirmed by positive Puumala IgM/IgG antibodies (93.6%), and 13 probable cases were identified by clinical and epidemiological data (6.4%) using a structured questionnaire. Of the 179 cases with available clinical data, 59 (33.0%) were hospitalized. Three cases received hemodialysis, and no deaths were reported. Among 170 cases with information on exposures, 66 (38.8%) reported occupational risk. Cases in the northern part of county were more likely to have been infected in early spring (OR 27.1, 95% CI 2.93-250.7), to report seeing a rodent (OR 6.5; 95%CI 2.3-18.4), and to know someone with hemorrhagic fever with renal syndrome (HFRS) (OR 3.0; 95%CI 1.2-8.0) than cases from the southern part of the county. Data from Croatian Forests Ltd. suggested that an unusually good production of beech seeds in 2020 may have contributed to an increased rodent population in 2021. However, average temperature, rainfall, and humidity data from 2021 did not illustrate a significant difference from previous years (Kruskal-Wallis p = 0.837, p = 0.999, p = 0.108). Conclusion: The 2021 HFRS outbreak was likely fueled by an abundant rodent population and virus transmission in rodent hosts. Human activity, environmental factors, and the ensuing animal-human interactions have spread hantavirus infection from Croatia\'s mountainous region to a previously nonendemic coastal area with a Mediterranean climate.

The aim of this study was to compare the number of newly diagnosed, histopathologically confirmed cases of urothelial carcinoma before and during the COVID-19 pandemic at the Zagreb University Hospital Center. We retroactively collected and analyzed 300 histopathologically confirmed urothelial carcinoma between January 1, 2019, and December 31, 2020, at the Department of Pathology and Cytology, Zagreb University Hospital Center. Our results showed that during the COVID-19 pandemic, there was a statistically significant decrease (p=0.001; χ2-test) in the number of newly diagnosed, histopathologically confirmed cases of urothelial carcinoma at the Zagreb University Hospital Center. There was a decrease in the absolute number of newly diagnosed urothelial carcinoma by 25.8% in the observed time of the pandemic (March 19, 2020 to December 31, 2020) as compared to the same period of the previous year (March 19, 2019 to December 31, 2019). Our study is the first study of this type based on the number of newly diagnosed urothelial carcinoma in Croatia. Observing the early period of the pandemic, our results provide important foundation for future monitoring and long-term consequences of the pandemic on the morbidity and mortality of urothelial carcinoma.

Increased values of arsenic in potable water in eastern Croatia has been a matter of scientific interest for the past two decades due to numerous health effects, including carcinogenic ones. This study investigated whether prolonged exposure to increased arsenic from water could be detectable through increased arsenic in urine, and whether it influenced the incidence of kidney and bladder cancer in Osijek-Baranja County. Inductively coupled plasma mass spectrometry (ICP-MS) was used for analysis of water samples from available water sources (wells, aqueducts). In addition, examinees from Osijek, Našice, Vladislavci, Čepin and Dalj gave their urine samples for analysis. Data on cancer incidence were obtained from the Institute for Public Health Registry and cumulative incidence of kidney and bladder cancer was calculated for the period between January 1, 2000 and December 31, 2018. Elevated arsenic concentration in drinking water was recorded in Vladislavci, Čepin and Osijek area with values above the allowed maximum according to the EU standards (10 µg L-1) and as a result, arsenic levels in urine of the inhabitants were also elevated. Cumulative incidence for bladder cancer showed correlation between increased arsenic in water and urine in the areas affected by increased arsenic in water. Epidemiologic data suggest a conclusion that elevated arsenic could be considered at least as a cofounding factor for urinary tract cancer.

Benign prostatic hyperplasia is one of the most common diseases in men, with a prevalence rate of 50% in their 50s to 80% in their 80s, and is mostly treated with chronic drug therapy. The aim of this study was to analyze adverse drug reactions (ADR) to drugs used in benign prostate hyperplasia (BPH) treatment reported to HALMED from 2008 to 2021. Data on ADR reports in Croatia were obtained from the VigiFlow national database and on the use of drugs for BPH in Croatia from Drug Utilization Reports from HALMED. In the observed period, the number of reports on each BPH drug, total number of reports, seriousness of reported ADR, patient age and sex, type of reporter, and most reported ADRs were analyzed. Results showed that 438 ADR reports were received, of which 45.95% on tamsulosin as the most frequently used drug for BPH. Of all reports, 84% were non-serious, 96% were reported in men and 82% in patients older than 45 years. The most frequently reported ADRs were consistent with the known safety profile of BPH drugs. Pharmacists were the most common (47%) reporters of ADRs for BPH drugs, while 33% were reported by physicians. Analysis of the reported ADRs showed that most frequently reported ones were in line with the known safety profile of BPH drugs. However, given the prevalence of the disease and the extent of the use of BPH drugs, it could be argued that the number of reports could be higher (i.e., 34 reports/year). Reporting on ADRs is necessary to better understand the safety profile of drugs in the post-authorization period, and more information on the safe use of medicines could be collected by raising awareness of healthcare professionals.

The aim of this study was to compare the number of biopsy and surgical procedures on prostate, as well as the number of newly diagnosed, histologically confirmed cases of prostate cancer during the COVID-19 pandemic at Zagreb University Hospital Center (UHC). We retrospectively collected and processed a total of 1344 histopathologic findings of the prostate at the Zagreb UHC. Our results show that during the COVID-19 pandemic, there was a statistically significant decrease in the absolute number of biopsy and surgical procedures on prostate at Zagreb UHC, and so was the number of newly diagnosed, histologically confirmed cases of prostate cancer. During the observed time of the pandemic (March 19, 2020 to December 31, 2020), there was a 37.5% decrease in the absolute number of newly diagnosed prostate cancer cases compared to the same period of the previous year (March 19, 2019 to December 31, 2019). To our knowledge, this is the first study of this kind that is based on the number of prostate cancer diagnoses in Croatia. By observing the early period of the pandemic, our results provide important guidelines for monitoring and understanding the long-term consequences of the pandemic on the prostate cancer morbidity and mortality.

Kidney cancer is estimated to be responsible for more than 400 000 new cancer cases and 180 000 cancer deaths a year. Its incidence is increasing in the majority of developed countries, due to an increased prevalence of recognized risk factors such as smoking, alcohol use and obesity, as well as incidental findings on unrelated diagnostic imaging procedures. Mortality is decreasing in the majority of European countries, due to improvements in treatment and stage at diagnosis shift with more tumors being diagnosed at an early stage. In this paper, we present kidney cancer incidence and mortality trends in Croatia using joinpoint regression analysis. The incidence was rising throughout the 2001-2019 period, with an annual percent change (APC) of 2.5%; more so in men (APC of 2.5%) than in women (APC of 2.2%). Mortality increased during the 2001-2014 period (APC of 2.4%), but started to decrease in recent years (APC -2.7%, 2014-2020). Unlike sex differences observed in other European countries, with more favorable mortality trends found in women, our study showed a constant increase in mortality in women (APC of 1.2%) and a recent decrease in mortality in men, starting in 2013 (APC of -2.8%), after a period of increase from 2001 (APC of 3.3%).

Sacral neuromodulation (SNM) is a safe, efficacious, and minimally invasive advanced therapy that involves electrical stimulation to sacral nerve root to modulate neural pathway. Indications for SNM include symptoms of overactive bladder (OAB), urinary incontinence, urinary retention, urgency and frequency and, regarding bowel dysfunction, fecal incontinence . In Europe and Canada, indication is also established for chronic constipation. The mechanism of action is still not fully elucidated and complete understanding is yet to be determined. It is proposed that SNM modulates neural circuits in both central and peripheral pathways, thus having an impact on the brain, as well as on the bladder-targeting neuronal activity. Another possible significant effect on irregular bladder activity is through inhibition of the bladder afferent pathways by stimulation of the pudendal nerve. Over the past two decades, with more than 300 000 treated patients, SNM has confirmed its efficacy to relieve refractory OAB symptoms, as well as urinary retention or fecal incontinence. First SNM applications in Croatia were uneventful and we are glad to offer our patients this novel therapy in the future.

The aim of this study was to explore occupational safety in pregnant Croatian healthcare workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic. To this end we composed an anonymous questionnaire that included pregnancy data, risk assessment and mitigation, and workplace intervention and distributed it to HCWs through social media of their groups and associations. The study includes a total of 173 respondents (71.1 % physicians, 19.7 % nurses, 9.2 % other HCWs) diagnosed with pregnancy in 2020 and 2021. Employers were notified about HCWs\' pregnancy at the eighth (IQR 7.0-11.0) week of pregnancy, which delayed workplace risk assessment and mitigation beyond the first trimester. Only 19.6 % of the participants had the risk assessed and mitigated, mostly on their own initiative (76.5 %). After notifying employers about pregnancy, 37.0 % of participants opted for temporary work incapacity (TWI) due to \"pregnancy complications\" despite healthy pregnancy, 16.8 % were granted a pregnant worker\'s paid leave at the expense of the employer, while 5.8 % continued to work at the same workplace. Nurses used the TWI benefit more frequently than physicians (58.8 % vs 30.1 %, P=0.004). Our findings suggest that occupational safety of pregnant HCWs in Croatia lacks clear-cut and transparent strategies to protect pregnant HCWs, forcing them to misuse the healthcare system.
Cilj ovog istraživanja bio je istražiti zaštitu na radu trudnih hrvatskih zdravstvenih radnica (ZR) tijekom pandemije koronovirusne bolesti 2019 (COVID-19). U tu smo svrhu sastavili anonimni upitnik koji je uključivao podatke o trudnoći, procjeni i smanjenju rizika te o intervencijama na radnom mjestu i distribuirali ga ZR putem društvenih medija njihovih grupa i udruženja. Istraživanje je obuhvatilo ukupno 173 sudionice (71,1 % liječnice, 19,7 % medicinske sestre, 9,2 % ostale ZR) kojima je dijagnosticirana trudnoća 2020. i 2021. Poslodavci su o trudnoći ZR obaviješteni u osmom (IQR 7,0–11,0) tjednu trudnoće, što je odgodilo procjenu i smanjenje rizika na radnom mjestu nakon prvog tromjesečja. Postupak procjene i smanjenja rizika proveden je u samo 19,6 % sudionica, uglavnom na njihovu inicijativu (76,5 %). Nakon što su poslodavca obavijestile o trudnoći, 37,0 % sudionica koristilo je privremenu nesposobnost za rad (PNR) zbog „komplikacija u trudnoći” unatoč zdravoj trudnoći, 16,8 % odobren je plaćeni dopust trudne radnice na teret poslodavca, dok je 5,8 % nastavilo raditi na istom radnom mjestu. Medicinske sestre koristile su PNR češće nego liječnice (58,8 % prema 30,1 %, P=0,004). Naši rezultati upućuju na nedostatak jasnih i transparentnih strategija zaštite trudnih ZR u Hrvatskoj, što ih prisiljava na zlouporabu zdravstvenog sustava.

The invasion of Ukraine and military operations around Ukrainian nuclear power plants and other nuclear facilities have prompted us to search for radiocaesium in mosses from the Kopački Rit Nature Park in Croatia, since mosses are known bioindicators of airborne radioactive pollution, and Kopački Rit is a known low radiocaesium background area. Sampling was finished in August 2023, and our analysis found no elevated radiocaesium levels. Kopački Rit therefore remains a suitable place for future detection of anthropogenic radioactive pollutants.
Invazija na Ukrajinu i vojne operacije oko ukrajinskih nuklearnih elektrana i drugih nuklearnih postrojenja potaknule su nas da potražimo radiocezij u mahovinama u Parku prirode Kopački rit, jer su mahovine poznati bioindikatori radioaktivnog onečišćenja zraka, a Kopački je rit poznat po niskoj razini onečišćenja radiocezijem. Uzorkovanje je završeno u kolovozu 2023. Naša analiza nije otkrila povišene razine radiocezija. Kopački rit stoga ostaje pogodno mjesto za buduću detekciju antropogenog radioaktivnog onečišćenja.