Normative Data of Handgrip Strength in Macedonian Children and Adolescents According to Chronological and Biological Age / Datos Normativos de la Fuerza de Prensión Manual en Niños y Adolescentes Macedonios Según la Edad Cronológica y Biológica

SUMMARY: The handgrip strength is used as a means of individual's health prediction during life. It is used as an indicator of the nutrition status, bone fragility, presence of sarcopenia and it correlates with certain diseases and clinical complications. The research goal was to analyze the results of the hand dynamometry test, based on the chronological and biological age, and to offer normative and referent standards about children and adolescents from the Republic of North Macedonia. The study was conducted on a sample of 4031 respondents of both sexes at the age 6-14 years. In order to achieve the research goals, the measured characteristics were of the weight, height, sitting height and handgrip strength. The body mass index and biological maturity values (APHV) were obtained by using formulas. On the basis of the obtained results, it can be concluded that statistically significant differences in handgrip strength are established between the boys and girls of all age categories. Also, statistically significant differences between boys and girls are established in the hand dynamometry test of all APHV levels. In general, the use of the APHV allows a better categorization of the performance of the studied children and adolescents. With boys, the correlation between the chronological age and test was 68 %, and with girls - 77 %. The normative referent standards of the hand dynamometry test are presented in percentiles for both sexes. Thye hand dynamometry test's results during childhood and adolescence should be analyzed and interpret on the basis of biological age, and not on the chronological age. These tools can help specialists who work with children and adolescents in ethnic and epidemiological context.

La fuerza de prensión se utiliza como medio para predecir la salud del individuo durante la vida. Se utiliza como indicador del estado nutricional, fragilidad ósea, presencia de sarcopenia y se correlaciona con determinadas enfermedades y complicaciones clínicas. El objetivo de la investigación fue analizar los resultados de la prueba de dinamometría manual, con base en la edad cronológica y biológica, y ofrecer estándares normativos y referentes sobre niños y adolescentes de la República de Macedonia del Norte. El estudio se realizó en una muestra de 4031 encuestados de ambos sexos con edades comprendidas entre 6 y 14 años. Para lograr los objetivos de la investigación, las características medidas fueron el peso, la altura, la altura al sentarse y la fuerza de prensión. El índice de masa corporal y los valores de madurez biológica (APHV) se obtuvieron mediante fórmulas. Sobre la base de los resultados obtenidos, se puede concluir que se establecen diferencias estadísticamente significativas en la fuerza de prensión manual entre niños y niñas de todas las categorías de edad. Asimismo, se establecen diferencias estadísticamente significativas entre niños y niñas en la prueba de dinamometría manual de todos los niveles APHV. En general, el uso del APHV permite una mejor categorización del desempeño de los niños y adolescentes estudiados. En los niños, la correlación entre la edad cronológica y la prueba fue del 68 %, y en las niñas, del 77 %. Los estándares normativos referentes de la prueba de dinamometría manual se presentan en percentiles para ambos sexos. Los resultados de la prueba de dinamometría manual durante la infancia y la adolescencia deben analizarse e interpretarse en función de la edad biológica y no de la edad cronológica. Estas herramientas pueden ayudar a los especialistas que trabajan con niños y adolescentes en un contexto étnico y epidemiológico.

Cardio-Physiological and Anthropometric Profile of Elite International Handball Players from Top Ranking Macedonian Teams / Perfil Cardiofisiológico y Antropométrico de Jugadores Internacionales de Balonmano de Élite de Equipos Macedonios de Primer Nivel

SUMMARY: Monitoring of body composition and cardiophysiological parameters are main part of the general health status of handball players and significant indicators of their physical fitness. The assessment of body components, especially skeletal muscle mass and body fat mass are important because of their influence on sport performance. The aim of this study is to determine the body composition and cardiophysiological characteristics of elite handball players from Republic of North Macedonia. 27 male HB players from two top ranking teams from RNM were tested ergometrically with Bruce protocol for determination of maximal oxygen consumption; body analysis was made with bioelectrical impedance analyzer, InBody 720. Anthropometric parameters were as follows: mean height was 190.4±7.8 cm and weight 96.3±15.5 kg, skeletal muscle mass (SMM)=47.11±6.69 kg; BMI=26.38±3.1; BF%=15.04±6.01 and WHR=0.9±1.8. The result of ergometrical test produce mean VO2 max=43.92 ml/kg/min which is 100.46 % of reference value. The body composition of elite international handball players from the top handball teams in Republic of North Macedonia showed similar body components as other European handball players. The obesity diagnose parameters were negatively associated with exercise time and maximal oxygen consumption.

El seguimiento de la composición corporal y los parámetros cardiofisiológicos son una parte principal del estado de salud general de los jugadores de balonmano y son indicadores importantes de su condición física. La evaluación de los componentes corporales, especialmente la masa muscular esquelética y la masa grasa corporal, son importantes debido a su influencia en el rendimiento deportivo. El objetivo de este estudio fue determinar la composición corporal y las características cardiofisiológicas de jugadores de balonmano de élite de la República de Macedonia del Norte. Se evaluaron 27 jugadores masculinos de HB de dos equipos de primer nivel de RNM ergométricamente con el protocolo de Bruce para determinar el consumo máximo de oxígeno; el análisis corporal se realizó con el analizador de impedancia bioeléctrica InBody 720. Los parámetros antropométricos fueron los siguientes: talla media 190,4±7,8 cm y peso 96,3±15,5 kg, masa músculo esquelética (SMM)=47,11±6,69 kg; IMC=26,38±3,1; %GC=15,04±6,01 y RCC=0,9±1,8. El resultado de la prueba ergométrica produce un VO2 máximo medio = 43,92 ml/kg/ min, que es el 100,46 % del valor de referencia. La composición corporal de los jugadores de balonmano internacionales de élite de los mejores equipos de balonmano de la República de Macedonia del Norte mostró componentes corporales similares a los de otros jugadores de balonmano europeos. Los parámetros diagnósticos de obesidad se asociaron negativamente con el tiempo de ejercicio y el consumo máximo de oxígeno.

Unveiling The Neuropathology Tumour Landscape: 10-Year Statistical Analysis With Global Comparison - Single Centre Experience.

Introduction: Central nervous system (CNS) tumours represent a significant public health issue worldwide, and their incidence and distribution vary across different populations. Although studies on CNS tumours have been conducted in various countries, there is a lack of information regarding their patterns in Macedonia. Therefore, this study is aimed at investigating the distribution, histopathological types and subtypes and demographic features of CNS tumours in our country. Materials and Methods: A cross sectional study was conducted using the electronic database of the Institute of Pathology - Medical Faculty, University "Ss. Cyril and Methodius" in Skopje which contains data from 3286 received and analysed surgical specimens, mainly from the University Clinic of Neurosurgery in Skopje, and a smaller number of surgical specimens from the University Surgical Centre "St. Naum Ohridski" in Skopje between 2012 and 2022. The collected and analysed data includes patient age, sex and histopathological types and subtypes of the tumours. Results: The majority of CNS tumours were diagnosed in adults aged between 50-70, with a male to female ratio of 1.5:1. The most common location of the tumours was the cerebrum, followed by the pituitary gland and cerebellum. The most frequent histological groups were gliomas, with glioblastoma as the most common diagnosis, followed by meningiomas. Conclusion: Following a detailed and thorough review of the CNS tumours in our study, we can conclude that the R. of Macedonia follows global statistics and trends regarding brain tumours.

Once-weekly semaglutide use in glucagon-like peptide-1 receptor agonist naïve patients with type 2 diabetes in North Macedonia: Real-world data from the MIRAGE study.

AIMS: The MIRAGE study aimed to evaluate the real-world use of once weekly (OW) subcutaneous semaglutide in glucagon-like peptide-1 receptor agonist naïve type 2 diabetes patients in routine clinical practice in North Macedonia. METHODS: MIRAGE was a multicentre, single-arm, retrospective and 30-weeks study, conducted in North Macedonia. Primary [change in glycated haemoglobin (HbA1c)] and secondary endpoints [change in body weight, fasting plasma glucose (FPG), lipid parameters, blood pressure, waist circumference, glycaemic and weight-loss target achievement] were evaluated between baseline and end of study (EOS). RESULTS: Baseline characteristics of 314 patients enrolled in the study were, mean age: 55.5 years, HbA1c: 9.0 %, diabetes duration: 7.8 years, body weight: 105.2 kg and waist circumference: 114 cm. Patients at EOS experienced statistically significant estimated mean change in HbA1c: -2.2 % points, body weight: -9.0 kg, and FPG: -4.1 mmol/L (all p < 0.0001). At EOS, 62.1 % patients achieved HbA1c < 7 %, and 79.3 % had ≥ 1 % HbA1c reduction. A weight reduction of ≥ 3 % and ≥ 5 % was noted in 88.3 % and 73.3 % patients, respectively. No new safety concern has emerged. CONCLUSIONS: Findings from MIRAGE study demonstrated glycaemic and weight-loss benefits of semaglutide, with improvements in other cardiometabolic parameters. The study supports real-world OW subcutaneous semaglutide use in North Macedonia.

Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group.

INTRODUCTION: In 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care. METHODS: We conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the "ACT" component of VBA. Participants were aged ≥ 35 years, smoked ≥ 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation. RESULTS: There was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses. CONCLUSION: Overall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists. TRIAL REGISTRATION: The trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.

Laparoscopic Donor Nephrectomy in the Republic of North Macedonia.

Introduction: Hand-assisted laparoscopic living donor nephrectomy has become the technique of choice for living donor kidney donations. Since 2018, 30 procedures have been performed at our clinic using this technique. The goal of this comparative analysis was to determine how surgical technique, specifically, hand-assisted laparoscopic living donor nephrectomy with hand assistance may affect early graft function when compared to open classical nephrectomy. Material and methods: Retrospective analyses were performed, comparing the two techniques of kidney donation. Kidney transplantation was performed with the open standard technique in both groups. The primary outcome was early graft function, and levels of urine output, and plasma creatinine were analyzed at three time points. A secondary outcome was the quality of the operative technique, which was determined by the time of warm ischemia, blood loss, and duration of surgery. Additionally, we noted all complications, length of hospital stay, and patient satisfaction. Results: In terms of warm ischemia time, there was no statistically significant difference between donors in both groups. It is important to note that in 2 recipients from Group II we did not observe diuresis at the conclusion of the operation. The recipients' diuresis was 515 ml ± 321SD in group I and 444 ml ± 271SD in group II. At 3, 12, and 36 hours postoperatively, there were statistically significant differences in the average serum creatinine values (p 0.05) in favor of group I. Similar results were observed in the second time measurement at 12 h and the third time measurement at 36 h for serum urea levels in recipients. The difference in serum urea values between the recipients in the groups at the first measurement (3h) following surgery was not statistically significant. Conclusion: Hand-assisted laparoscopic donor nephrectomy is recognized as a safe and effective treatment. Donors in this situation have a different profile from other surgical patients; hence, they do not undergo surgery due to their own medical condition but for an altruistic reason, and with hand-assisted living donor nephrectomy. Such patients receive all the advantages of minimally invasive surgery. The two main objectives of a donor nephrectomy are to give the recipient the best possible kidney and to ensure the donor's complete safety.

Biologic Therapy in Inflammatory Bowel Disease - Results from a Single Tertiary Care Center in North Macedonia.

Medical therapies used for Inflammatory Bowel Disease (IBD) include conventional (e.g. 5-aminosalicylates, steroids, immunomodulators) and biologic (e.g. inhibitors of tumor necrosis factor - alpha, integrin inhibitors, interleukin inhibitors) medications. Biologics, due to their high cost, were unfortunately not covered by the public health insurance system in North Macedonia until 2019 and, therefore, not widely utilized for our IBD patients. In 2019, the University Clinic of Gastroenterology and Hepatology in Skopje developed a biologic therapy supply, provided by the National Health Insurance Fund, making this therapy available for a larger number of patients. This report presents the initial results of our prospective, single tertiary-care center study on the effects of biologic therapy in patients with IBD in North Macedonia. The study is focused on the evaluation of clinical outcomes after anti-tumor necrosis factor alpha (anti TNF-alpha) therapy in IBD patients with prior inadequate response to conventional medications.

Incidence and Prevalence of Vaginal Infections in Women of Reproductive Age in North Macedonia.

In the available literature on this subject there are many studies which describe the effects of sexually transmitted infections on pregnancy and fertility of women. Because of the frequency of the infections with the atypical bacteria of the Ureaplasma Spp., Mycoplasma Spp., Chlamydia Trachomatis, as well as HPV infections in women of reproductive age, it is easy to underestimate their importance when establishing the basis of the genital health of women of reproductive age. In this prospective analysis, conducted from 2014 to 2018 in the laboratory for HPV and Molecular diagnostics at the University Clinic of Gynaecology and Obstetrics in Skopje, North Macedonia, we analysed the results of 10,387 patients of all ages, of which 973 patients were of reproductive age. A Panel analysis was also conducted (including the above-mentioned pathogens). An HPV analysis was also conducted on 643 patients in this group. Within the group of 643 patients, there was a positive result for HPV in 26.7% of them, while in 40.9% there was a positive result for one or more pathogens on the Panel analysis of bacterial pathogens. The statistical analysis of the results showed that the most frequent of all bacterial pathogens within the Macedonian population of women of reproductive age is Ureaplasma Spp, with an incidence of 33%, followed by Mycoplasma Spp., with 7.8%, while Chlamydia Trachomatis was present in 6.4% of the cases. We should highlight that a co-infection with HPV was present in 18.5% of all the patients where there was analysis of both diagnostic procedures. The analysis of the results in the patients co-infected with HPV and at least one bacterial pathogen on the Panel Analysis, showed a very high statistical correlation (p<001).

Mutational Spectrum and Genotype-phenotype Correlations in Neurofibromatosis Type 1 Patients from North Macedonia: Identification of Ten Novel NF1 Pathogenic Variants

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, characterized by multiple café-au-lait macules, axillary and inguinal freckling, tumors of the nervous system, and iris hamartomas. More than 3,100 different pathogenic variants have been reported in the NF1 gene, including missense, nonsense, frameshift, in-frame, splicing, and large deletions. Aims: To determine the NF1 mutational spectrum in patients with NF1 from the Republic of North Macedonia. Study Design: A cohort study. Methods: Molecular analyses included reverse transcription and cDNA sequencing of the NF1 gene and next-generation sequencing using the TruSight Cancer panel, along with the multiple ligation probe amplification method to detect single nucleotide variants and copy number variations. Direct DNA sequencing was also used for the family member analysis. Results: Our 9-year study of patients suspected of having NF1 in the Republic of North Macedonia encompassed molecular characterization of 30 cases of the disease. We identified 28 unique pathogenic NF1 variants (NM_001042492.3), of which ten were novel: c.208delA; c.341_364del; c.1480_1481delTT; c.2325+1G>C; c.2495_2496dupAC; c.2533_2541del; c.4517delC; c.5844C>G; c.6971delA; c.7605_7606delGAinsAT. In addition to the variant spectrum analysis, our research revealed two positive genotype-phenotype correlations. One between the clinical manifestation of cognitive impairment and gross deletions in the NF1 gene, and the other between cognitive impairment and truncating variants located in the RAS-GAP functional domain. Conclusion: This is the first study of NF1 patients in the Republic of North Macedonia, and it contributes ten novel variants to the global spectrum of pathogenic NF1 variants. It also corroborates the crucial importance of NF1 genetic testing for a prompt and precise diagnosis, particularly in younger patients.

Prevalence of keratoconus in refractive surgery practice population in North Macedonia.

PURPOSE: To determine the prevalence of keratoconus (KC) in relation to ethnicity in a group of people who consulted an ophthalmological care institution seeking for refractive surgery in N. Macedonia. METHODS: This was a cross-sectional, interventional retrospective study. Chart reviews were performed for all new patients attending between January 2016 and January 2020 at the Sistina Ophthalmology Hospital in Skopje. All patients were screened; KC diagnosis and classification were based on the corneal topography. Ethnicity and gender classifications were according to patients' self-opinions. RESULTS: A total of 2812 patients charts reviewed. The mean age was 31.71 years (SD ± 9.73), and 1209 (43%) were male. A total of 2050 (72.9%) declared themselves as Macedonians, 649 (23.1%) Albanians, 76 (2.7%) Turks and 37 (1.3%) in other ethnicities. Differences in age between the ethnic groups were statistically significant (x2 = 90.225, p < 0.001). KC was diagnosed in 343 patients (12.2%), while 9 (0.7%) were KC suspects and 6(0.21%) presented pellucid marginal degeneration. KC was more frequent in males (n = 246, 71.7% of total) and skewed toward younger patients. Increasing patients' age decreased the odds of KC diagnosis by 3.7% (95% CI 1.8%-4.4%) per annum. Males were four times more likely to be diagnosed with KC (AOR = 4.01; 95% CI 3.12-5.16). In comparison with Macedonian patients, Turks were more likely to be diagnosed with KC (AOR = 4.09; 95% CI 2.47-6.78). There was no difference between Macedonians and Albanians (p = 0.08). CONCLUSION: The prevalence of KC at a refractive surgery practice in N. Macedonia is much higher compared with general population (6.8/100,000) and similar to the prevalence in Middle East Asia. Nationwide screening programs are needed to diagnose the disease earlier.

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia / Função tireoidiana de mulheres grávidas e resultados perinatais na Macedônia do Norte

Abstract Objective Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). Methods Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). Results Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypo thyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). Conclusion Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

Resumo Objetivo As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). Métodos Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). Resultados Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). Conclusão Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

Epidemiology of Thyroid Carcinomas in North Macedonia (1999-2015).

OBJECTIVE: We have set as objective to analyze epidemiological data of diagnosed thyroid carcinoma (TC) cases, incidence and prevalence rate by gender, age, histopathological type, and statistical regions in R. of N. Macedonia during the period 1999 to 2015. MATERIAL AND METHODS: Retrospective analysis of medical data collected from the 2 state thyroid departments. Inclusion criteria included newly diagnosed cases of TC in appropriate years for the period 1999 to 2015. We have evaluated: yearly incidence rate, incidence and prevalence by gender, age, the distribution in 8 statistical state regions and histopathological types and subtypes representation. RESULTS: A total number of 422 TC patients were detected, average incidence rate of 1.22/105, with most prevalent papillary TCs79.5%, followed by follicular 10.9%, medullar 4.1%, anaplastic 3.1%, and other rare types with 2.3%. The highest incidence rate was detected in Skopje region, while the lowest in Southeast and the Polog region. The total prevalence rate for the female gender was 32.61/104 and for male 9.27/104 (f/m ratio = 3.52:1), with lowest female/male difference found in the elderly > 65 years (f/m = 2.21/1). CONCLUSION: Compared with regional epidemiological data we can conclude that Republic of N. Macedonia has very low incidence and prevalence rate, while female/male ratio was similar to that described in the literature. Our low incidence and prevalence rate may be due to 2 possible reasons, 1 would be insufficient diagnosis of only small portion of the real cases in the population, or the second reason may be a real low incidence resulting of specific etiopathogenetic circumstances.

Sacrectomy with Ilio-Lumbar Stabilization Due to Low-Grade Chondrosarcoma of Sacrum and Iliac Wing. Case Report of the First Surgery Performed in the Republic of North Macedonia.

Low - grade chondrosarcomas are primary malignant bone tumors that are resistant to chemo- and radiotherapy and are treated surgically. Sacral localization makes surgical resection technically difficult due to position, anatomic structures involved, and large tumor size at detection. The risk of complications is high. We present the introduction of a novel surgical technique in our country, sacrectomy with ilio-lumbar stabilization. This was performed on a 67-year-old man with low-grade chondrosarcoma of the sacrum with sacroiliac joint involvement. The procedure was performed via an antero-posterior approach in two stages. Ilio-lumbar fixation with a mesh cage bridge was used to obtain spinopelvic continuity and stability. Sacrectomy is a technically demanding procedure that requires careful preoperative planning and a multidisciplinary approach, as well as high level of surgical experience.

Clinical Characteristics and Treatment Results of Childhood Acute Lymphoblastic Leukemia in North Macedonia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. This study was designed to determine the clinical, biological features and outcomes among children with ALL treated at the only pediatric hematology-oncology center in North Macedonia. PATIENTS AND METHODS: Seventy four consecutive children age 1 to 14 years, diagnosed with ALL between January 1, 2010 and October 31, 2017 and treated according to ALL IC BFM 2002 protocol were retrospectively evaluated. RESULTS: The median age at diagnosis was 5 years and males were predominant (60.8%). Precursor B-cell ALL was diagnosed in 81.1% of patients, while 18.9% had T cell ALL. CNS involvement at the time of diagnoses was present in 6.8% of patients. Complete remission was achieved in 93.2% of patients. The induction death rate was 5.4%. The rate of death during first complete remission was 4.1%. Relapse occurred in 13.5% of patients. After a median observation time of 44 months, the 5-year overall survival (OS) and event-free survival (EFS) rates (± standard error) were 79.4% ± 5.2% and 74% ± 5.7%, respectively. The 5-year EFS rate for patients categorized as standard risk by NCI criteria was significantly higher than for high risk patients (83.3% versus 46.7%; P<0.001). Patients with precursor B-cell ALL and negative minimal residual disease (MRD) status at the end of induction had the best prognoses. CONCLUSION: Our study demonstrated that the treatment results of childhood ALL in North Macedonia are comparable to those obtained in the ALL IC BFM 2002 trial.

Waist circumference, waist-to-hip ratio, and waist-to-height ratio reference percentiles for abdominal obesity among Macedonian adolescents.

INTRODUCTION: Background: the goal of this study was to define waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHRt) smoothed reference percentiles for assessing abdominal obesity in Macedonian adolescents aged 11 to 18 years in order to investigate possible obesity cut-offs of WHR and WHtR, and to compare WC percentiles with those of other adolescents. Methods: the research was conducted on a sample of 2,490 adolescents of the Republic of Macedonia aged 11 to 18 years: 1,288 males and 1,202 females. Weight, height, body mass index (BMI), WC, hip circumference (HC), WHR and WHtR were measured and percentiles were calculated using Cole's Lambda, Mu and Sigma (LMS) method. The relation between WHR, WHtR and general obesity, as defined by the International Obesity Task Force, was investigated with a receiver operating characteristic (ROC) analysis. Results: the boys had statistically significant higher values in all anthropometric measures except in HC, where statistically significant gender differences were not found. BMI, WC, and HC showed an increasing trend with age. The WHtR variable is a better indicator for assessing general obesity in both boys and girls (AUC, 95 % CI: 0.905-0.928) than WHR, which showed lower AUC values (95 % CI: 0.697-0.734) in predicting IOTF obesity; the WHtR cut-off of 0.5 had a sensitivity of 74 % and a specificity of 92 % for both genders and all age groups. Conclusions: the obtained reference percentile curves can be used temporarily for early detection of abdominal obesity among Macedonian adolescents aged 11 to 18 years; a WHtR of 0.5 may also be used as an obesity threshold in these age groups.

INTRODUCCIÓN: Antecedentes: el objetivo de este estudio fue definir los percentiles de referencia suavizados perímetro abdominal (WC), relación cintura-cadera (WHR) y relacion cintura-talla (WHtR) para evaluar la obesidad abdominal en adolescentes macedonios de 11 a 18 años, con el fin de investigar posibles valores de corte de WHR y WHtR para la obesidad, y comparar los percentiles de WC con los de otros adolescentes. Métodos: la investigación se realizó en una muestra de 2490 adolescentes de la República de Macedonia de 11 a 18 años de edad; 1288 varones y 1202 mujeres. Se midieron peso, altura, índice de masa corporal (IMC), WC, circunferencia de cadera (HC), WHR y WHtR, y se calcularon los percentiles utilizando el método LMS. La relación entre WHR, WHtR y la obesidad general, según lo definido por la International Obesity Task Force, se investigó con el análisis de las características operativas del receptor (ROC). Resultados: los varones tuvieron valores estadísticamente más altos en todas las medidas antropométricas excepto en HC, donde no se encontraron diferencias estadísticamente significativas entre ambos sexos. IMC, WC y HC mostraron una tendencia creciente con la edad. La variable WHtR es un indicador para evaluar la obesidad general en niños y niñas (AUC, IC 95 %: 0,905-0,928) mejor que WHR, que mostró valores de AUC más bajos (IC 95 %: 0,697-0,734) para predecir la obesidad IOTF. El valor de corte de WHtR, de 0,5, tuvo una sensibilidad del 74 % y una especificidad del 92 % para ambos sexos y para todos los grupos de edad. Conclusiones: las curvas de percentiles de referencia obtenidas pueden usarse temporalmente para la detección temprana de la obesidad abdominal entre los adolescentes macedonios de 11 a 18 años; una WHtR de 0,5 también puede utilizarse como un umbral de obesidad en estos grupos de edad.

Association of TNF-a (rs361525 and rs1800629) with susceptibility to cervical intraepithelial lesion and cervical carcinoma in women from Republic of North Macedonia.

Cervical cancer (CCa) is one of the most common malign diseases in women associated with human papillomavirus (HPV). The virus is an initiating factor, but not sufficient for the development of cervical intraepithelial lesions (CIN) and CCa. The disease might be a result of the influence of host's genetic factors and polymorphisms in inflammatory-related genes that modify the immune response to HPV and attribute to cancer susceptibility. We carried out a study to determine the association between TNF-a-238G/A and TNF-a-308 G/T polymorphisms with HPV-positive CIN and CCa in women living in the Republic of North Macedonia. Using multiplex SNaPshot analysis for single nucleotide polymorphisms (SNPs), we analysed the genotype and allele distributions of TNF-a-238G/A and TNF-a-308 G/T in 134 cases (HPV-positive and histologically confirmed CIN and CCa) and in 113 controls (cytological and HPV-negative women). For further analysis, the case group was stratified in three subgroups (all cases: CINs+ CCa- group; CIN2+ -group and CIN1- group). Data analysed using the odds ratio (OR) and chi-square test showed the frequency of AA genotypes and A alleles are not significantly higher in cases compared to the controls for both SNPs: AA of TNF-a-238 (0.7% versus 0%) and TNF-a-308 (1.5% versus 0.9%) as well as A allelic frequency (3.0% versus 1.7%) and (13.1% versus 10.6), respectively. The comparison of the case's subgroups with the control group did not show a statistically significant difference. Compared to controls, TNF-a-238G/A and TNF-a-308 G/T are not associated with the risk of HPV associated CIN or CCa in the studied women.

Outcomes with Ventricular Assist Device Therapy for Advanced Heart Failure in North Macedonia: First Annual Report

INTRODUCTION: Mechanical circulatory support by a continuous-flow ventricular assist device (VAD) improves survival and quality of life in selected patients with advanced heart failure. Developing countries have been struggling to construct a contemporary and effective health care system to manage advanced heart failure. This observation represents the first annual report on clinical outcomes with VAD for patients with advanced heart failure in the Republic of North Macedonia. METHODS: Data from all patients with VAD implantations between November 2018 and December 2019 were collected. The etiology of the heart failure was dilated cardiomyopathy in 4 patients (57%), ischemic cardiomyopathy in 2 (28%), and hypertrophic cardiomyopathy in 1 (14%). The primary outcome was survival; secondary outcomes included adverse events defined according to the Interagency Registry for Mechanically Assisted Circulatory Support. RESULTS: A total of 7 patients (85% males, median age 56 years) received a VAD; 5 of them received left VAD, and the remaining 2 received biventricular VAD. There were no deaths. Observed morbidity during a mean follow-up of 216 days included 3 bleeding events in 1 patient, 2 patients with superficial driveline infection, and 1 minor stroke and a pump thrombosis, which were treated with VAD exchange. Significant improvement in quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire and the Functional Independence Measure™ instrument, was seen with all patients. CONCLUSIONS: Our results demonstrate a successful initiation of the VAD program in the Republic of North Macedonia. Proper training of a dedicated HF team supports the reproducibility of this treatment in developing countries.

Safety and Efficacy of Methoxy Polyethylene Glycol-epoetin Beta in Anemia Treatment in Patients on Hemodialysis: a Macedonian Experience.

INTRODUCTION: Anemia in patients with chronic kidney disease (CKD) is present in about 50% in pre-dialysis and over 90% of patients on hemodialysis. Erythropoiesis-stimulating agent (ESA) is a standard therapy for renal anemia, but management of anemia in CKD still remains a challenge from the treatment point of view. AIM: To evaluate safety and efficacy of methoxy polyethylene glycol-epoetin beta as continuous erythropoietin receptor activator (C.E.R.A.) in maintenance of haemoglobin (Hb) concentrations in patients with chronic renal anemia in the routine clinical practice. METHODS: National, multicenter, observational, prospective study in patients with CKD on hemodialysis for maintenance of Hb levels with once-monthly therapy with C.E.R.A. In 8 dialysis centers 184 adult patients were observed and followed up every month during one year. Total number of enrolled patients was 185 from whom 184 patients were observed and 147 patients were followed for 12 months as 37 dropped out from the study earlier. RESULTS: Overall mean dose of C.E.R.A. was 115.2 µg with average 4.99 dose modifications per patient. Among 184 patients observed, total number of 121 adverse events (AEs) were identified in 49 of the patients. The most of the AEs were of mild or moderate severity. A few serious AEs were assessed and reported as not related to the drug administration. Mean Hb levels during the study varied but were maintained stable in the range of 100-120 g/l. CONCLUSION: Safety and tolerability of C.E.R.A. was as expected as the frequency and type of AEs was similar to the known pattern from the studies done in other countries and relevant literature. Hb levels as the primary efficacy parameter of C.E.R.A. treatment were maintained stable within the target range during the study.

The effect of different pollutants exposure on the pigment content of pigmented macrophage aggregates in the spleen of Vardar chub (Squalius vardarensis Karaman, 1928).

Pigmented macrophage aggregates (MAs) are known to change under influence of various factors, such as aging, season, starvation, and/or pollution. In this study, changes in the pigment content of the MAs in the spleen of Vardar chub (Squalius vardarensis, Karaman) (n = 129) collected in spring and autumn, from three rivers with different pollution impact was examined: Zletovska River (metals), Kriva River (metals and municipal wastewater), and Bregalnica River (municipal wastewater). Collected data revealed increased relative volume and number of MAs containing hemosiderin under the influence of metals, significant in autumn (p < .05). In chub exposed to metals combined with municipal wastewater, significant increase of lipochrome accumulation in MAs in autumn, melanin in MAs in fish captured in the spring season, and number of splenic MAs containing combination of melanin and lipochrome was noted. Volumes and number of MAs containing combination of hemosiderin and lipochrome increased in spleen of fish captured in autumn from both Zletovska River and Kriva River, most likely due to the contribution of hemosiderin and lipochrome, respectively. Values measured for the various pigments in splenic MAs in fish captured from Bregalnica River, were overall closer to the values measured for fish captured from Kriva River. Notably, melanin and lipochrome are more likely to be found in fish from waters influenced by municipal wastewater (organic pollution) and hemosiderin in fish spleen from water influenced by mining activity (heavy metals pollution).

Non-Opioid Substances Acute Poisonings with Suicidal Intent in Patients with Opioid Use Disorder.

INTRODUCTION: Several epidemiological studies have evaluated the role of illicit drug use in suicide behaviour. AIM: To assess patients with opioid use disorder and suicidal intent related to behavior, severity of acute poisoning and the most commonly used non-opioid substances. MATERIALS AND METHODS: This cross sectional study included 67 patients diagnosed with opioid use disorder. The study was conducted at the University Clinic of Toxicology in Skopje over a 5-year period (2013-2017). The following variables were examined: gender, age, duration and route of opioid administration, duration of hospitalization, and types of substances used in acute poisoning. Assessment of patients' behavior and severity of poisoning was made by using the Suicide Behaviours Questionnaire-Revised and the Poison severity score. RESULTS: The majority of patients were male (88.1%). The mean age of patients was 30±6.1 years. The average duration of opioid use disorder was 8.5±3.9. A single poisoning was found in 62.7%, double poisoning in 25.4%, and triple poisoning in 11.9% of participants. Benzodiazepines were most commonly used by the patients (55.2%). The largest number of patients (32.8%) had minor Poison severity score (PSS), and only 17.9% had severe PSS. None of the patients had a fatal suicide attempt. 86.6% of patients had a score of ≥7 indicating a high risk of repeat suicide attempts. CONCLUSION: Benzodiazepines were most commonly used as a single or combined substance in patients with opioid use disorder. PSS indicated that most of the participants were with minor PSS and with high risk of a repeat suicide attempt.