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Aim To analyze clinical and functional effects of intra-articular injection of autologous micro-fragmented lipoaspirate (MLA) in patients with late stage knee osteoarthritis (KOA). Secondary aims included classifying cell types contributing to the treatment effect, performing detailed MRI-based classification of KOA, and elucidating the predictors for functional outcomes. Methods This prospective, non-randomized study was conducted from June 2016 to February 2018 and enrolled 20 patients with late stage symptomatic KOA (Kellgren Lawrence grade III, n = 4; and IV, n = 16) who received an intra-articular injection of autologous MLA in the index knee joint. At baseline radiological KOA grade and MRI were assessed in order to classify the morphology of KOA changes. Stromal vascular fraction cells obtained from MLA samples were stained with antibodies specific for cell surface markers. Patients were evaluated at baseline and 12-months after treatment with visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS). Results Three patients (15%) received a total knee replacement and were not followed up completely. Seventeen patients (85%) showed a substantial pattern of KOOS and WOMAC improvement, significant in all accounts. KOOS score improved from 46 to 176% when compared with baseline, WOMAC decreased from 40 to 45%, while VAS rating decreased from 54% to 82% (all P values were

Aim To determine the use of evidence-based medicine (EBM) information and the level of awareness and knowledge of EBM among patients in Croatia. Methods A cross-sectional study was conducted among 987 patients in 10 family medicine practices in Croatia. Patients from both urban (n = 496) and rural (n = 482) areas were surveyed. A 27-item questionnaire was used to collect data about sources that patients searched for medical information, patient awareness and use of Cochrane systematic reviews and other EBM resources, and their demographic characteristics. Results Half of the patients searched for medical information from sources other than physician. Internet was the most common place they searched for information. Very few patients indicated using EBM sources for medical information; one fifth of patients heard of EBM and 4% of the patients heard of the Cochrane Collaboration. Patients considered physician’s opinion as the most reliable source of medical information. A logistic regression model showed that educational level and urban vs rural residence were the predictors of awareness about EBM and systematic reviews (P < 0.001 for both). Conclusion Our finding that patients consider a physician’s opinion to be the most reliable source of healthrelated information could be used for promotion of highquality health information among patients. More effort should be devoted to the education of patients in rural areas and those with less formal education. New avenues for knowledge translation and dissemination of high-quality health information among patients are necessary.

AIM: To compare the distribution of cardiovascular disease (CVD) factors between continental and Mediterranean areas and urban and rural areas of Croatia, as well as to investigate the differences in achieving treatment goals by the general practitioners (GP) in different settings. ----- METHODS: A multicenter prospective study was performed on 2467 participants of both sexes ≥40 years old, who visited for any reason 59 general practices covering the whole area of Croatia (May-July 2008). The study was a part of the Cardiovascular Risk and Intervention Study in Croatia-family medicine (CRISIC-fm) study. Patients were interviewed using a 140-item questionnaire on socio-demographics and CVD risk factors. We measured body mass index (BMI) and waist circumference and determined biochemical variables including blood pressure, total, high-density lipoprotein-, and low-density lipoprotein-cholesterol, triglycerides, glycemia, and uric acid. ----- RESULTS: Participants from continental rural areas had significantly higher systolic and diastolic blood pressure (P

Aim To investigate the population genetics of 17 short tandem repeat (STR) loci on the Y chromosome in the population of eastern Croatia. Methods We carried out a statistical analysis of the data from previously performed genetic analysis collected during routine forensic work by the Forensic Science Centre “Ivan Vucetic”. A total of 220 unrelated healthy men from eastern Croatia were selected for the purpose of this study. Genomic DNA was extracted by Chelex from FTA® cards. Y-chromosomal STRs were determined using the AmpFISTR Yfiler PCR amplification kit. The haplotype frequencies were determined by direct counting and analyzed using Arlequin 3.1 and analysis of molecular variance calculated with the Y-chromosome haplotype reference database online analysis tool. Results A total of 207 haplotypes were recorded, 197 of which were unique (90%). Haplotype diversity was 0.9993, with the most frequent haplotype found in 4 of 220 men (1.8%). Average locus diversity was 0.600, and it ranged from 0.256 for DYS392 to 0.780 for DYS458. Our results were compared with the pattern of Y-chromosome variability in publicly available population samples based on a minimal European haplotype set of 9 STRs and the greatest resemblance was found with samples from the Croatian capital of Zagreb, from Bosnia and Herzegovina, and from Serbia. Conclusion This is the first description of Y chromosome haplotyping of the population of eastern Croatia, which may serve as a basis for genetic epidemiology and forensic studies. Further studies are needed for characterization of the genetic structure of the Y-chromosome in the modern Croatian population.

Cancer is one of the leading causes of morbidity and mortality in the world, and the global burden of cancer is predicted to grow rapidly in the coming decade. While cancer affects all communities indiscriminately, there are striking differences in the incidence and mortality among different populations. These large differences reflect a combination of differences in the prevalence of risk factors, differences in genetic susceptibility, and/or variations in cancer detection, reporting, classification systems, treatment, and follow-up. Unfortunately, developing nations or nations in the so called economical transition are those with the fastest growing cancer problem. The International Agency for Research on Cancer estimated that over a half of newly diagnosed cases and two-thirds of cancer deaths occur in low and medium-income countries (1). Priority setting for cancer control and cancer services in any region needs to be based on knowledge of the cancer burden and of the local mix of predominant cancer types (2).

Aim To collect cancer epidemiology data in South Eastern European countries as a basis for potential comparison of their performance in cancer care. Methods The South Eastern European Research Oncology Group (SEEROG) collected and analyzed epidemiological data on incidence and mortality that reflect cancer management in 8 countries – Croatia, Czech Republic, Hungary, Romania, Poland, Slovakia, and Serbia and Montenegro in the last 20-40 years. Results The most common cancer type in men in all countries was lung cancer, followed by colorectal and prostate cancer, with the exception of the Czech Republic, where prostate cancer and colorectal cancer were more common. The most frequent cancer in women was breast cancer followed by colorectal cancer, with the exceptions of Romania and Central Serbia where cervical cancer was the second most common. Cancer mortality data from the last 20-40 years revealed two different patterns in men. In Romania and in Serbia and Montenegro, there was a trend toward an increase, while in the other countries mortality was declining, after increasing for a number of years. In women, a steady decline was observed over many years in the Czech Republic, Hungary, and Slovakia, while in the other countries it remained unchanged. Conclusions There are striking variations in the risk of different cancers by geographic area. Most of the international variation is due to exposure to known or suspected risk factors which provides a clear challenge to prevention. There are some differences in incidence and mortality that cannot be explained by exposure to known risk factors or treatment availabilities.

Aim: To assess secular trends in birth weights of liveborn infants in Croatia from 1983 to 2003. Methods: Of a total of 959 591 liveborn infants in the study period, 384 367 were born in the prewar (1983-1989), 226226 during the war (1991-1995), and 348 998 in the postwar (1996-2003) period. The birth weight of liveborn infants was assessed by 500 g (g) weight groups on the basis of data provided by the Croatian National Institute of Public Health. Results: The gradual and significant increase in the share of infants with birth weight ≥3500 g (P

We describe the response to a new chemotherapy agent, topoisomerase I inhibitor edotecarin in an 18-year-old woman with recurring glioblastoma. The therapy was administered for 17 months. The radiological partial response and clinical improvement have been achieved, with minor toxicity. Median survival of patients with glioblastoma is 10 months. With edotecarin we have achieved promising result, which should encourage further investigations to develop more efficient therapy for such a deadly disease.

To evaluate the effect of vitamin D3 receptor (VDR) gene BsmI/ApaI/TaqI restriction fragment length polymorphisms on Graves' disease susceptibility in a subset of patients from Eastern Croatia.Graves' disease patients (n=110) and ethnically matched euthyroid controls (n=99) with no clinical evidence or family history of thyroid or autoimmune diseases were genotyped for VDR gene polymorphisms by BsmI/ApaI/TaqI endonuclease digestion after polymerase chain reaction amplification with sequence-specific primers. Data were analyzed by chi-square-test, and crude odds ratios (OR) with 95% confidence interval (95% CI) were calculated.The ApaI "AA" (14.5% vs 30.3%, patients vs controls, respectively, OR=0.39, 95% CI [0.2-0.77], P=0.01) and BsmI "BB" (7.3% vs 23.2%, OR=0.26 [0.11-0.61], P=0.002) genotypes were significantly underrepresented in patients, whereas ApaI "aa" (28.2% vs 9.1%, OR=3.92 [1.76-8.74], P=0.001) and TaqI "TT" (51.8% vs 31.3%, OR=2.36 [1.34-4.16], P=0.004) genotypes were significantly more frequent in patients than controls. The genotype combination, which conferred the strongest protection against Graves' disease, was "BBAAtt" (2.7% vs 17.2%, OR=0.14 [0.04-0.48], P=0.001).These findings suggest that VDR gene BsmI/ApaI/TaqI polymorphisms are associated with Graves' disease susceptibility in a subset of patients from Eastern Croatia. The ApaI and BsmI "AA" and "BB" genotypes, respectively, as well as combined "BBAAtt" genotype, appeared to confer protection against Graves' disease, whereas ApaI "aa" and TaqI "TT" genotypes were associated with an increased risk for Graves' disease. However, the true mechanisms of association remain to be elucidated.

To explore the economic justification for introducing ultrasound screening for developmental dysplasia of the hip in Croatia.The analysis was based on the two formulas: that cost-benefit equals benefit/cost, and that net benefit equals benefit minus cost. Screening costs were expressed as a sum of training costs and fee for ultrasound screening of neonates. The neonatologists' working hours and utilization of ultrasound instruments were expressed by multiplying the number of infants born per year in Croatia (N = 47,792) with the standard time needed for one examination and then dividing the product by the number of employed neonatologists (N = 54) and number of ultrasound instruments (N = 58). The benefit was expressed as a late case treatment costs and screening costs ratio. Savings, which would have resulted from the reduction in expected treatment costs of patients with hip problems at later age, represent the indirect benefit.Total hip screening costs would have amounted to US$329,537.80, including the training costs of US$31,035.90. On the average, a neonatologist would spend 71.4 hours screening per year, whereas the instrument utilization would be 64.7 hours. An ultrasound-screening program would save annually US$195,336.50, compared with the existing diagnostic approach. The treatment costs without ultrasound screening were 1.6 times higher than the screening costs. Hospital treatment costs for 165 patients needing endoprosthesis would cover the total screening program in the whole country.It is economically justified to introduce ultrasound screening for developmental dysplasia of the hip in neonates in Croatia, a country with transitional and developing economy.

Analysis of developmental role of fibronectin during differentiation of the human spinal cord, nerves, and ganglia.Seven normal human embryos and fetuses between the 7th and 9th developmental week and a 9-week fetus with cervical spina bifida were histologically examined on hematoxylin and eosin stained serial paraffin sections of thoracic axial segments. Monoclonal antibody to the human cell fibronectin fragment was used for immunohistochemical detection of fibronectin.In the 7th and 8th week of development, fibronectin was weakly expressed in the ventricular and intermediate zones of the spinal cord. Intense fibrillar expression was found in the marginal zone of the spinal cord - first over the ventral gray horns and later over the lateral and dorsal gray horns, and along the pathways of ventral and dorsal roots of the spinal nerves and in the spinal ganglia. At 9th week, fibronectin expression disappeared in the ventricular and intermediate zones a nd became weak and granular in the marginal zone of the spinal cord. In the spinal cord of a 9-week malformed fetus with cervical spina bifida, fibronectin expression was completely absent. Fibronectin was expressed in the nerves and ganglia throughout the investigated period, both in normal and malformed human conceptuses.Transient expression of fibronectin in the human spinal cord coincided with the most intense neuronal differentiation. Temporal and spatial expression of fibronectin during normal development, and its absence in a malformed human fetus suggests developmental role of fibronectin for the normal formation of the spinal cord.