Methylenetetrahydrofolate reductase (MTHFR) regulates the flow of folate groups between DNA synthesis and DNA methylation. A common C677T substitution (Ala222Val) in exon 4 of the MTHFR gene has been linked with the risk of colorectal cancer (CRC). To assess this risk in the Macedonian population, we conducted a case-control study of 413 randomly selected CRC patients and 185 controls without a clinical diagnosis of CRC. We found a statistically significant inverse association between the MTHFR T allele (35.35% for the patients and 41.35% for the controls) and the CRC risk [odds ratio (OR) 0.776; 95% confidence interval (95% CI) 0.603-0.997; p = 0.047). The prevalence of the MTHFR T allele is lower in patients with advanced CRC (Duke' s stage C and D) and with microsatellite instable tumors (MSI+), indicating the inverse association with the CRC aggressiveness and MSI status. This effect seems to be independent of gender, age of onset and localization. We concluded that the MTHFR 677T allele is more likely to have a protective effect on CRC development and progression in the Macedonian population.

Cor triatriatum sinister е ретка срцева мана кај која левата преткомора е поделена на два дела со фибромускулна мембрана. Проксималната преткомора ги прима пулмоналните вени заедно со крвта која тие ја носат, а дисталната или (вистинска) преткомора е вообичаено празна и таа е поделена од комората со митралната валвула. Има постојана комуникација помеѓу двата дела на поделената преткомора преку која крвта се пренасочува кон левата комора. Маната е многу ретка, најчесто е изолирана, но може да оди во комбинација со други срцеви мани. Презентираме случаи на две деца на возраст од 8 и 3 години во времето кога е поставена дијагнозата. Кај обете причина за дијагнозата бил замор и чуен срцев шум. За поставување на дијагнозата беа користени анамнезата, клиничките знаци и симптоми, ЕКГ, рендген на срце и бели дробови и златниот стандард - ехокардиографијата. Дефинитивно излекување беше направено со изведување на кардиохируршка ресекција на фибромускулната мембрана со користење на екстракорпорална циркулација. Потребно е регуларно периодично следење на децата со цел откривање на доцни компликации од типот на нарушувања на срцевиот  ритам.

Hereditary factors are assumed to play a role in ~35.0-45.0% of all colorectal cancers (CRCs) with about 5.0-10.0% associated with high penetrant disease-causing mutations in genes correlated to hereditary polyposis (HP) or hereditary non polyposis syndromes (HNPCC). Although inherited germline mutations in mismatch repair (MMR) and the APC genes contribute significantly to CRC, genetic diagnosis cannot yet be obtained in more than 50.0% of familial cases. We present updated data of 107 probands from the Macedonian population with clinically diagnosed HP (n = 41) or HNPCC (n = 66) obtained by next generation sequencing (NGS) with three different gene panels covering the coding, flanking and promoter regions of 114 cancer predisposition genes. Using this approach, we were able to detect deleterious mutations in 65/107 (60.7%) patients, 50.4% of which were in known well-established CRC susceptibility genes and 10.2% in DNA repair genes (DRG). As expected, the highest frequencies of deleterious variants were detected in familial adenomatous polyposis (FAP) and in HNPCC patients with microsatellite instability (MSI) tumors (93.8 and 87.1%, respectively). Variants of unknown significance (VUS) were detected in 24/107 (22.4%) patients, mainly in HNPCC patients with microsatellite stable (MSS) tumors or patients with oligopolyposis. The majority of VUS were also found in DRG genes, indicating the potential role of a doble-strand brake DNA repair pathway deficiency in colorectal cancerogenesis. We could not detect any variant in 18/107 (16.8%) patients, which supports the genetic heterogeneity of hereditary CRC, particularly in HNPCC families with MSS tumors and in families with oligopolyposis.

Juvenile idiopathic arthritis (JIA) is the most common chronic disease in childhood. It manifests a heterogenic group of symptoms of arthritis, lasting at least 6 weeks and it appears before the age of 16. Patients who had no good therapeutic response to conventional therapy with Methotrexate were treated with biological therapy. The aim of this paper was to evaluate 9 patients who were receiving Tocilizumab at the Department of Rheumocardiology, University Clinic of Pediatric Diseases in Skopje. Materials and methods: Our study included 9 patients treated at our Department with biological therapy with Tocilizumab. Prior to initiation of the biological therapy, all patients underwent laboratory investigations, purified protein derivative (PPD) skin test for tuberculosis, X ray of the lungs and heart, and analysis of hepatitis markers. All patients were treated with amp. Actemra (tocilizumab) 8 mg/kg/tt i.v. Two of the patients had a severe form of the disease (one with severe systemic form and one with severe oligoarticular form of JIA). All presented patients had clinical remission of the disease. Conclusion: Therapy with tocilizumab in patients with juvenile idiopathic arthritis is a good therapeutic choice. The results obtained in our study have shown a significant therapeutic effect of tocilizumab even in severe forms of the disease.