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Background/Aim. Inflammation is the main cause of the onset, progression, and outcome of chronic kidney disease (CKD). The aim of the study was to examine the predictive value of inflammatory biomarkers in patients with CKD stages I–V and their association with parameters characteristic of CKD. Methods. A cross-sectional study analyzed 117 adult patients with CKD who were divided into two groups according to the glomerular filtration rate (GFR): Group 1, with normal to mild impairment of renal function (GFR ≥ 60 mL/min/1.73 m2), stages I and II, and Group 2 with moderate and severe impairment of renal function (GFR < 60 mL/min/1.73 m2), stages III, IV, and V, who have not started dialysis treatment. In addition to standard laboratory analyses, we determined derived parameters in patients, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and system inflammation response index (SIRI), as markers of inflammation. Results. A statistically significant difference between Groups 1 and 2 was observed for body mass index (p < 0.003), for platelets, hemoglobin, creatinine, urea, acidum uricum, iron, phosphorus, parathyroid hormone, and proteinuria 24 hrs (p < 0.001), for calcium (p < 0.031) and leukocytes (p < 0.030). By analyzing the values of NLR, PLR, SII, and SIRI in patients with CKD, a statistically significant difference (p < 0.001) was observed between the groups; the values were elevated in Group 2. NLR, PLR, and SII showed statistical significance for essential parameters in CKD (C-reactive protein, creatinine, GFR, hemoglobin, calcium, phosphorus, parathyroid hormone) and SIRI showed statistical significance for phosphorus in Group 2. The most sensitive was NLR at 87.7%, and PLR had the highest specificity, at 81.7%, with cut-off values for PLR – 151.75, NLR – 2.06, SII – 493.57, and SIRI – 0.739. Conclusion. Our results indicate that the detection of biomarkers NLR, PLR, SII, and SIRI could have a significant role in predicting inflammation in patients with CKD and would contribute to the timely recognition of patients at risk of developing complications.

Introduction. Intravascular papillary endothelial hyperplasia is an unusual reactive proliferation of endothelial cells around an organized thrombus, which occurs either in a dilated blood vessel, hematoma, or preexisting vascular lesion. These tumors rarely affect the central nervous system. Symptoms depend on the localization of the process itself. Localization in the central nervous system is limited to the intracranial space. Localization in the spinal canal is extremely rare, and only a few clinical cases have been described so far in the literature. Case report. A 67- year-old female patient was examined neurologically initially due to bilateral weakness of the lower extremities, accompanied by a feeling of pain and muscle tension, dominantly in the upper legs, more to the right. The complaints were present a year ago, and before that period, the patient was in a stable state of health. Due to a severe neurological deficit and the need for detailed exploration, the patient was hospitalized. A diagnosis was performed, which showed the localization of the pathological process in the thoracic 5–6 region of the spinal column. Decompression surgery was performed, and with the ex tempore findings metastasis was ruled out. Definitive pathohistological findings proved Masson’s tumor. After the operation, the neurological weakness recovered. Conclusion. Masson’s tumor, although rarely localized in spinal canal, is curable if it is correctly diagnosed and if an adequate therapeutic approach is applied. The initially presented symptoms may resemble numerous neurological or systemic diseases, which requires the clinician to be continuously aware of such rare pathological processes.

Background/Aim. Lupus nephritis (LN), as an immuno-inflammatory kidney lesion and the most severe manifestation of systemic lupus erythematosus (SLE), is accompanied by a disorder of nutritional status of patients. The aim of our study was to determine the importance of parameters of nutritional status [nutritional risk index (NRI), prognostic nutritional index (PNI), and Controlling Nutritional Status (CONUT)] and their association with standard parameters of LN activity. Methods. The clinical study included a group of 92 participants: 67 patients with LN (34 patients had LN active disease – the LNa group, and 33 patients were in LN remission – the LNr group) and 25 healthy subjects in the control group. In addition to standard laboratory parameters and LN activity parameters, derived parameters were also determined: PNI = 10 × serum albumin value (g/dL) + 0.005 × total lymphocyte count/mm3; N RI = 1 .519 × serum albumin value (g/dL) + 41.7 × present weight (kg)/usual body weight (defined as stable body weight for last six months) (kg); CONUT score = serum albumin value (g/dL) + total lymphocyte count/mm3 + total cholesterol level (mmol/L). Results. A statistically significant difference between all three groups was observed for the PNI (p = 0.001) and the CONUT score (p = 0.000), while there was no significant difference for NRI. In the LNa group, a statistically significant correlation was found for PNI in relation to albumin, complement C 3 and C 4, and a statistically significant negative correlation with the level of anti-double stranded (ds) DNA antibodies (Abs). NRI had a statistically significant correlation only with proteinuria in the LNa group. CONUT showed significant correlations with most of the parameters of disease activity: negative correlation with albumin and complement C3 (p = 0.000), and positive correlation with anti-dsDNA Abs (p = 0.002), Systemic Lupus Erythematosus Disease Activity Index/renal (SLEDAI/r), and proteinuria g/24 hrs (p = 0.000). Conclusion. A statistically significant difference was observed between the groups for the nutrition score CONUT and the PNI. Their correlation with standard parameters of active disease was significant for most parameters in the group of patients with LNa.

Background/Aim. Diclofenac, a non-selective inhibitor of cyclooxygenase with analgesic, anti-inflammatory, and antipyretic effects, is one of the most prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to analyze the prescription patterns of diclofenac systemic formulations at primary health care (PHC) level in Montenegro, in patients with cardiovascular (CV) diseases (CVD) and patients with risk factors for CVD, from 2016 to 2020. Methods. A retrospective national drug utilization study was conducted and it included patients with CVD, to whom prescribing diclofenac was contraindicated, and patients with risk factors for CVD, to whom diclofenac could be prescribed but with increased precaution. PHC information system has been used as a source of medical data for these patients. Results. Within the observed period, prescribing diclofenac systemic formulations, dominantly oral formulations in 75 mg dose, increased by 36.9% [from 4.6 of defined daily doses (DDD) /1,000 inhabitants/day in 2016 to 6.3 DDD/1,000 inhabitants/day in 2020]. A rising trend in prescribing diclofenac was also recorded in patients with CVD or those with risk factors for CVD, to whom diclofenac prescribing is contraindicated. Out of the overall number of patients who were prescribed diclofenac in 2016, 2017, 2018, 2019, and 2020, 16%, 18%, 24%, 15%, and 20% of them, respectively, already had a CVD or some risk factor for CVD. Most CV patients (39.7%), for whom the use of diclofenac was contraindicated, had ischemic heart disease and were prescribed 40.7% of the total amount of diclofenac prescribed for this group of patients (expressed in DDD/1,000 inhabitants/day for the given medicine). The majority (77.4%) of CV patients to whom the drug could be prescribed, but with increased precautions, had hypertension, and they were prescribed 77.2% of the total amount of diclofenac prescribed for this group of patients (expressed in DDD/1,000 inhabitants/day for the given medicine). Conclusion. Despite the undertaken regulatory measures aimed at a safer prescription of diclofenac to patients with CVD or at high risk of developing CVD, this medicine is still widely prescribed at the level of PHC in Montenegro, even in cases that represent a contraindication for its use. This article has been corrected. Link to the correction 10.2298/VSP2310892E

Background/Aim. The best treatment for the occlusion of the largest artery in the thigh is a femorodistal (FD) bypass. Ankle-brachial index (ABI) and multidetector computed tomographic (MDCT) angiography are the gold standards for diagnosing peripheral arterial occlusive disease. The finite element analysis (FEA) method can help measure the quantity of blood flow and arterial pressure in the arteries in the leg. The aim of this study was to examine the possibility of using the FEA method in predicting the outcome of FD bypass surgery. Methods. The study involved 45 patients indicated for FD arterial reconstruction from December 1, 2021, to March 31, 2023. Each patient underwent pre- and postoperative MDCT angiography of the arteries of the lower extremities, on the basis of which, with the use of FEA, models were made for measuring ABI. All patients had their ABI measured pre-operatively and postoperatively using the Doppler ultrasound and sphygmomanometer. Based on the findings of the preoperative MDCT angiography, postoperative virtual surgical models were created using the FEA method, on which ABI were also measured. The values of ABI were divided into five groups: ABI measured preoperatively (ABI pre-op), ABI measured postoperatively (ABI post-op), ABI measured on FEA models based on the MDCT findings [ABI (sim) pre-op], ABI sim post-op, and ABI measured on virtual surgery model [ABI sim post-op (virtual)]. The ABI of the models were statistically compared with preoperative and postoperative measurements done on patients. Results. The values based on the virtual ABI model did not show significant differences compared to the values obtained on patients and values obtained with the FEA method using MDCT angiography (p < 0.001). A strong statistically significant correlation was shown between the virtual ABI and the values obtained by the other two methods, measured on the postoperative MDCT angiography model and virtual postoperative model (p < 0.001). Conclusion. Virtual simulation based on the MDCT angiography parameters of peripheral blood vessels can be successfully used to predict the immediate outcome of the FD bypass surgery.

Introduction. Portal vein (PV) thrombosis (PVT) is a partial or complete obstruction of blood f low as a result of a thrombus mass in the lumen of PV. In the acute phase, the symptoms such as right upper quadrant pain, nausea, and fever are unspecific. A diversity of subacute and chronic symptoms is associated with complications related to PVT and portal hypertension. Case report. A 50-year-old female was admitted to the hospital due to acute abdominal cramping pain. The pain lasted for 15 to 20 min and was followed by defecation of normal stool and hematochezia on three occasions. The abdominal pain recurred after several hours, again followed by hematochezia and tenesmus every 10 min. After admission, a colonoscopy was performed, and it revealed vulnerable, erythematous mucosa of the colon with contact bleeding from the lienal flexure to the rectosigmoid junction. During the colonoscopy, a biopsy was performed. A computed tomography (CT) scan revealed partial PVT of intrahepatic branches of PV, and thrombosis of the inferior mesenteric vein. After conservative treatment with low molecular weight heparin (LMWH) and other supportive measures, the digestive bleeding ceased, and defecation became normal. During the one-month follow-up, the patient had no complications, and the control CT scan revealed normal PV flow without thrombosis. Conclusion. Although rare, a non-malignant and non-cirrhotic PVT should not be neglected in the differential diagnosis because timely and vigilant therapy with LMWH can lead to complete resolution without serious complications.

Background/Aim. Measuring the quality of life (QoL) is vital in daily clinical practice because it shows significant in-formation in addition to symptoms. There are a large number of scales for assessing the QoL. The Brunnsviken Brief Quality of Life scale (BBQ) measures importance-adjusted satisfaction across six life areas. A validation study of the BBQ scale showed good questionnaire features (high con-current and convergent validity, internal and test-retest reliability, and sensitivity to change). Therefore, the BBQ scale is excellent for use in psychiatric patients to measure outcomes, as well as for everyday screening. Methods. This prospective cross-sectional study was performed among the final-year students in five high schools in Kragujevac, Serbia. Students completed the BBQ questionnaire. Statistical analysis was performed using a standard statistical method for scale validation and standardization. Results. Our study showed that the BBQ scale had high internal consistency (Cronbach’s alpha = 0.687). That result showed that the scale had good reliability in our study. The average BBQ score was 69.63 ± 16.70 (male: 69.66 ± 18.46; female: 69.83 ± 15.78, p = 0.944). Conclusion. The Serbian version of BBQ satisfies all the criteria of successful validation. There-fore, this scale can be helpful in assessing the QoL in the healthy youth population in Serbia.

Background/Aim. Unilateral optic neuritis (ON), and its pathological substrate, retrobulbar neuritis (RBN), is a common presentation of multiple sclerosis (MS). The aim of the study was to determine the diagnostic and prognostic value of structural and functional examination using novel ‘swept-source’ optical coherence tomography (SS-OCT) and OCT angiography (OCTA) techniques in patients with MS who experienced RBN. Methods. For examining retinal structural and functional changes in both the affected and nonaffected eye of patients with MS, novel techniques, OCT and O CTA, w ere u sed. The obtained results w ere compared with the results of the same examination on the left and right eye of the healthy controls. Results. Using OCT, significant differences in the structural integrity and thickness of retinal layers between the eye in which RBN had been detected and the contralateral, nonaffected eye were found (83.73 ± 18.36 vs. 98.67 ± 11.84; p = 0.013). On the other hand, the functional examination of the macular vascular plexus did not show significant differences between the affected and the nonaffected eye in these patients (41.86 ± 1.52 vs. 42.52 ± 1.40; p = 0.228). Interestingly, comparing the nonaffected eye of patients with RBN and healthy controls, a significant difference in the thickness of the retinal layers between the contralateral eye of the patient and both healthy eyes of healthy subjects was found. OCT examination showed particularly significant thinning of the macular ganglion cell-inner plexiform layer (mGCIPL) (61.07 ± 5.04 vs. 67.53 ± 4.57; p < 0.001). Conclusion. Overall, our research showed that OCT and OCTA offer an unprecedented opportunity for a safe, reliable, and repetitive assessment of structural and functional retinal changes as invaluable diagnostic and prognostic tools, paving the way for a better understanding of pathogenic mechanisms underlying inflammatory demyelinating and neurodegenerative diseases. In addition, mGCIPL may be a particularly sensitive and reliable biomarker of pathological changes in MS and perhaps in other neurodegenerative diseases.

Background/Aim. The incidence of nodular thyroid dis-ease increases significantly with age as well as the incidence and aggressiveness of thyroid cancers. The aim of the study was to determine whether thyroid surgery for geriatric patients is safe in a short hospital stay surgery set-ting. Methods. In this retrospective study, medical histories of all operated geriatric patients (65 years and older), in whom a total thyroidectomy (TT) or hemithyroidectomy (HT) was performed from January 2012 to December 2018, were analyzed. A total of 976 patients were operated on for thyroid diseases in the mentioned period, out of which 247 geriatric patients fulfilled the inclusion criteria. Patients with thyroid reoperations and simultaneous neck lymph node dissections were excluded from the study. The geriatric patients were divided into two groups: the HT group (33 patients) and the TT group (214 patients). Each of these two geriatric groups, HT and TT, had two additional paired control groups. Control group I consisted of younger subjects from 20–44 years, and control group II included middle-aged subjects from 45–64 years. Results. All three TT groups – geriatric, control I, and control II, had 214 patients each, and all three HT groups had 33 patients each. In all three HT groups, the average hospital stay was 24 hrs, while in the TT geriatric group, 150 (70.1%) of 214 patients spent 24 hrs at the hospital. In the geriatric population, the incidence of neck swelling and in-creased drainage output were higher compared to both control groups, and thus the need for longer hospitalizations. When the age was compared, it was shown that sub-jects with each subsequent year of intervention had a 22% lower chance of developing complications, and regarding the pathohistological finding, benign thyroid hyperplasia was less likely to develop complications compared to malignant hyperplasia. Conclusion. According to the study, TT can be safely performed within the concept of a short hospital stay in patients under 65 years, while in the elder-ly, hospitalization days may be extended due to more frequent surgical and nonsurgical complications. Speaking of HT, the short hospital stay is safe for all age groups.

Background/Aim. Prostate carcinoma (PCa) is second occurring carcinoma that affects the male population. Although PCa incidence rates are high, most cases have a favorable prognosis, with comfortable long-term life quality. The aim of the study was to compare long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) plasma levels between healthy individuals and patients with PCa, and also between PCa patients with different prognostic scores. Methods. The present study included a total of 40 patients with PCa and a control group of 20 healthy individuals. PCa patients were divided into two subgroups (20 patients each) based on the prognostic criteria of the American Joint Committee on Cancer. The patient data were collected and analyzed; lncRNA GAS5 levels were quantified using the re-al-time polymerase chain reaction method. Statistical analysis was conducted using the IBM SPSS Statistics 26.0 computer program (IBM, USA, 2019). Results. The relative quantification of lncRNA GAS5 expression levels showed down-regulation in PCa patients compared to healthy individuals; however, the difference was marginally statistically significant (p = 0.056). With further analysis of the given results, we concluded that the expression level of lncRNA GAS5 was not significantly different in the first patient subgroup and the healthy individuals (p = 0.268). Patients from the second subgroup had significantly lower plasma levels of lncRNA GAS5 than healthy individuals (p = 0.033). The difference in the level of lncRNA GAS5 expression between patients with favorable prognoses (Group 1) and the ones with worse prognostic scores (Group 2) did not indicate statistical significance (p = 0.275). In both Group 1 (p = 0.805) and Group 2 (p = 0.454), the plasma levels of lncRNA GAS5 were not significantly different in comparison to the age (≤ 65 vs. > 65 years). Conclusion. One of the main objectives of PCa research is identifying novel and more efficient biomarkers. Conducted research provides strong evidence about the significance of lncRNAs GAS5 in PCa, as well as the correlation between decreased expression of lncRNA GAS5 and poor prognosis in various tumors.

Background/Aim. Patients in developing countries do not always receive adequate pain-relieving treatment. Monitoring analgesics consumption is of great importance since this can help assess the quality of painful condition management. The aim of this paper was to present a five-year consumption and costs of drugs with analgesic effects in developing countries, exemplified by Serbia and Montenegro, and indicate the main reasons for their (in)adequate prescribing. Methods. The observational, retrospective, cross-sectional study was conducted in order to analyze the consumption of all analgesics, both opioid and non-opioid, in Serbia and Montenegro, as developing countries. The data concerning analgesic consumption and drug prices were obtained from annual editions of the publications of the Medicines and Medical Devices Agency of Serbia and Montenegro. The World Health Organization methodology with defined daily dose (DDD) as a unit of measure (defined by the number of DDD per 1000 inhabitants per day) was used in these publications. Results. Over the course of five years (from 2015 to 2019) in Serbia, the total allocations for analgesic therapy had a rising trend, from about 43.6 million to 63.3 million euros, while in Montenegro, expenditures showed annual variations with the highest value in 2018. Most of the money in both countries was invested in the M01A group of drugs, for which the highest consumption was also recorded. Significantly higher consumption of opioid analgesics in Montenegro compared with Serbia was observed in the same period, and it predominantly reflected the difference in fentanyl (N02AB03, transdermal patch) prescribing. In Montenegro, consumption of the M01AB group of drugs was prominently higher in comparison to the M01AE drugs group during the whole five-year period, like in Serbia, in which this was not the case just in 2018. Conclusion. Taking into account the importance of analgesics for everyday medical practice, more rational prescribing of these drugs is necessary both in Serbia and Montenegro in the future.

Background/Aim. Chronic pancreatitis (CP) causes inflammatory changes in the tissue of the pancreas, resulting in irreversible tissue damage. Pain, endocrine, and exocrine pancreatic insufficiency develop, thereby reducing the quality of life (QoL) of patients. The aim of the study was to determine the significance of surgical treatment in improving the QoL of patients with CP. Methods. QoL assessment of 50 patients diagnosed with CP was per-formed using a certified Euro Quality of Life-5 Dimension-5 Level (EuroQol-5D-5L) Questionnaire translated into Serbian. According to the method of treatment, patients completed the questionnaire. Patients were divided into two groups (conservatively treated – CT and surgically treated – ST), and all comparisons were made between groups. Results. Patients in stage B of CP were divided into two groups of 25 patients. The mean age in the ST group was 48.56 ± 11.91, and in the CT group was 51.08 ± 11.61 (p = 0.452). The male/female ratio in the ST group was 18/7, and in the CT group was 22/3 (p = 0.289). Pain in the ST group was present in 23 patients, and in the CT group was present in 18 patients (p = 0.141). Loss of appetite in the ST group was present in 7 patients and in the CT group in 10 patients (p = 0.256). Weight loss in both groups was equal (p = 1.000). Based on the EuroQol-5D-5L Questionnaire, significant differences were found (p < 0.001) between groups in Mobility and Pain/Discomfort, in Anxiety/Depression (p = 0.003), in Self-care (p = 0.004), and in Usual activities (p = 0.008). Conclusion. CP significantly reduces the QoL of patients treated either conservatively or by surgical approach. This study showed that surgical treatment is more beneficial for the QoL of patients with CP than the conservative approach.

Background/Aim. Monitoring the renal function following donor nephrectomy (DN) or radical nephrectomy (RN) due to kidney tumors is considered essential. The aim of this study was to compare pre-operative and post-operative renal function in patients who underwent DN in relation to patients who underwent RN due to renal malignancy. Methods. A retrospective case-control study was performed, which included 199 patients divided into two groups: group 1 (105 patients) were patients who underwent DN due to living-related/unrelated kidney transplantation, while group 2 (94 patients) was a control group, and included patients who underwent RN due to clear cell renal cell carcinoma in the T1bNoM0 clinical stage, where this surgical procedure was the final form of treatment. Results. Preoperative estimated glomerular filtration rate (eGFR) according to the Chronic Kidney Disease−Epidemiology Collaboration (EPI) equation (eGFR EPI) in the DN group was 94.95 mL/min/1.73 m2, while in the RN group, it was 71.00 mL/min/1.73 m2. Patients who underwent RN tended to have eGFR EPI below 60 mL/min/1.73 m2 after ten years of follow-up compared with patients who underwent DN. In the DN group, the average eGFR EPI was 80.40 mL/min/1.73 m2, and in the RN group, it was 56.00 mL/min/1.73 m2. A higher incidence of diabetes mellitus (DM) and arterial hypertension (AH) was also observed in the DN group of patients compared to the RN group (AH: 44.3% vs. 21.3%; DM: 22.6% vs. 9.6%, respectively). Conclusion. Comparative monitoring of these two groups showed that in both groups, the recovery of the renal reserve was achieved one year after nephrectomy due to the known adaptive mechanisms. Even though the initial renal reserve in a kidney donor is reduced after living kidney transplantation (nephrectomy, permanent loss of renal mass), kidney donors recover kidney function within the first year after surgery due to the adaptive mechanisms.

Background/Aim. Health indicators provide comparable in-formation relevant to defining health goals. The aim of this study was to perform a forecasting analysis of the selected indicators, which could help anticipate the future necessities in the health economy and prevent the problems that would predictively grow in the future. Methods. Health indicators are collected from publicly available databases of the World Health Organization and Eurostat. We used the quantitative forecasting technique, commonly used for historical data, to predict several years in the future concerning selected health- and economy-related indicators. Results. Total health expenditures as a percentage of gross domestic product (GDP) by 2025 will increase in most of the 17 surveyed countries. The percentage of direct household budget payments (out-of-pocket) for health services will decrease in half of the countries, while values of GDP expressed in US$ will increase significantly com-pared to the last surveyed year (2017), except in Greece. The infant mortality indicator shows that the numbers will decrease in each surveyed country, while the urban population percent-age will rise almost in each country except Estonia. Life expectancy will increase in each surveyed country. Conclusion. Health- and economy-related indicators must be monitored over time, as they provide significant information concerning the relevant issues in the health care system. Moreover, they may indicate changes that should be made in order to accomplish progress in each individual country.

Background/Aim. In renal cell carcinoma (RCC), the choice of surgical technique, radical (RN) or partial nephrectomy (PN), is still center-dependent because there are still no absolute recommendations for this approach. The aim of this study was to analyze the oncological aspects, time until recurrent disease appears, and cancer-specific survival in patients with RCC in T1bN0М0 stadium depending on the type of surgical procedure, PN or RN technique. Methods. In a clinical observational study, data of 154 patients operated at the Clinic for Urology, Military Medical Academy, Belgrade, Serbia with a mean follow-up period of no less than five years were analyzed. Patients were divided into two groups; a group of patients with RN and a group of patients with PN. The inclusion criteria were: renal tumors 4–7 cm, histopathological confirmation of RCC, absence of metastasis, and normal serum creatinine. Exclusion criteria included: the presence of other malignancies, solitary functional kidney or comorbidities that can compromise renal function, bilateral tumors, or unilateral multiple tumors. Results. The study analyzed data from 154 patients, 97 (63%) RNs, and 57 (37%) patients that underwent PN. Analyzing cancer-specific survival in four patients with RN, there was a disease advancement that led to a lethal outcome, and one PN patient died as a result of local relapse and distant metastasis. Conclusion. Based on our results, PN is a good and safe treatment option for patients with RCC in T1b stadium. PN offers a similar tumor control and better cancer specific survival.

Background/Aim. Approximately one-third of individuals with only one cardiovascular (CV) risk factor or without any, as well as 40% of individuals with a concentration of cholesterol less than average, die from CV diseases (CVD). Recent studies underlined the significant role of inflammation in atherosclerosis and its complications. The aim of this study was to analyze the association of high-sensitivity C-reactive protein (hs-CRP) with traditional risk factors for coronary heart disease. This is the first such study in Serbia. Methods. This is an observational cross-sectional study, which included active-duty military personnel of similar socio-epidemiological and economic characteristics. Plasma hs-CRP and traditional CV risk factors were evaluated. The relative CV risk was staged as low (hs-CRP < 1 mg/L), intermediate (hs-CRP between 1 and 3 mg/L), and high (hs-CRP > 3 mg/L). The Systematic Coronary Risk Evaluation (SCORE) system was used for absolute CV risk assessment and total risk (fatal and non-fatal events). Results. The study included 205 participants, aver-age age of 39 (35–43) years, with median and interquartile range values of hs-CRP 0.80 mg/L (0.43–1.75 mg/L), with average hs-CRP values of 0.71 mg/L in participants younger than 40 years of age and 1.2 mg/L in the older than 40 years. The difference in hs-CRP values between these two groups was statistically significant (p = 0.006). There was a significant positive correlation between hs-CRP and age (r = 0.266, p < 0.001), weight (r = 0.223, p = 0.001), body mass index (BMI) (r = 0.344, p < 0.001), diastolic hypertension (r = 0.190, p = 0.007), LDL cholesterol (r = 0.152, p = 0.032), triglycerides (r = 0.144, p = 0.039), number of risk factors (r = 0.210, p < 0.003), as well as negative correlation with HDL cholesterol concentration (r = -0.148, p < 0.035). There was no significant correlation between hs- CRP concentration and total cholesterol (r = 0.131, p = 0.062). According to hs-CRP values, high CVD risk was found in 17.7% of participants older than 40 years of age, and based on SCORE system staging, 90% of participants have intermediate CVD risk. The results of stepwise multiple regression analyses showed that BMI was independently associated with an hs-CRP concentration in the group younger than 40 years of age. Among the older participants, age was found to be associated with concentration of fibrinogen. Conclusion. In the population of active military personnel in the Republic of Serbia, hs-CRP is correlated with some of the risk factors for CVD, and only BMI is in-dependently correlated with hs-CRP in those under 40 years of age. Levels of plasma hs-CRP are increased with aging, implying that hs-CRP measurement may provide a more ac-curate assessment of the individual overall risk profile for CVD in the Serbian military personnel population.

Background/Aim. Renal transplantation is the best and preferred way of treating patients with end-stage renal disease, as it offers improved survival and better quality of life compared to dialysis. The aim of this study was to present single-center (Military Medical Academy in Belgrade, Serbia) results of the kidney allograft and patient survival from 1996 to 2017. Methods. A retrospective 22-year co-hort study was conducted. Variables of interest were graft and patient survival in kidney transplanted patients. Age, gender, serum creatinine levels, and induction therapy after transplantation were analyzed in this group of patients as well. Results. Among 386 transplanted patients, 316 had a living donor and 70 patients had a deceased donor. Pre-emptive renal transplantation was done in 29 (7.5%) patients and AB0-incompatible kidney transplantation in 21 (5.4%) patients. One-year, 5-year, 10-year, and 20-year overall patient survival after kidney transplantation in the observed group was 97.7%, 95.3%, 93.8%, and 91.7%, respectively. One-year, 5-year, 10-year, and 20-year graft survival in our patients were 93.8%, 85.5%, 78.5%, and 73.3%, respectively. Conclusion. The outcome of graft and patient survival in the Belgrade Military Medical Academy kidney transplantation program is good and in line with the leading world medical centers.

Introduction. Kidney failure in multiple myeloma is some-times initial symptomatology and a very serious complication with an unfavorable effect on the course and prognosis of the disease. Multiple myeloma is a disease characterized by the proliferation of plasmocytes in the bone marrow, and in rare cases, it can be extramedullary in various organs and systems. Pulmonary plasmacytoma localization is a rare extramedullary localization, especially when it represents one of the initial manifestations of multiple myeloma. Case report. We present a patient with progressive acute kidney failure who has started hemodialysis treatment. On chest radiography, a homogeneous shadow was observed along the left chest wall, and the multislice computed tomography (MSCT) pointed to the tumor formation in the pulmonary parenchyma in the projection of the left upper pulmonary lobe with signs of pleural infiltration, intercostal muscles, and V rib destruction. Laboratory examination indicated the presence of Bence-Jones proteinuria in the urine sample in addition to anemia syndrome and azotemia with hyperuricemia. After bronchoscopy and needle biopsy, diffuse infiltration of mature plasma cells was demonstrated in the cytological and histopathological findings of the lungs. The histopathological finding of bone marrow biopsy indicated multiple myeloma of Lambda type with infiltration of plasma cells – about 70%. The hematologist determined a diagnosis of multiple myeloma BJ lambda III BCS, with extramedullary lung infiltration and acute kidney failure. Further treatment was continued according to the hematological protocol while performing intermittent hemodialysis. Conclusion. Sometimes, extremely rarely, and in completely asymptomatic patients with massive pulmonary infiltration observed initially, the differential diagnosis may also represent an extramedullary presentation of multiple myeloma, which should be considered.

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Background/Aim. Contrast-induced acute kidney injury (CI-AKI) is a common complication after the percutaneous coronary intervention, associated with a prolonged hospital stay, increased medical costs, and risk of adverse clinical outcomes. The aim of this study was to compare changes in levels of serum creatinine (sCr) and cystatin C (sCyC) 24 h after coronary angiography as an early indicator of CI-AKI. Methods. The study included 45 patients with chronic renal failure grade I–III scheduled for coronary angiography. Levels of sCr and sCyC were measured a day before and 24 h after coronary angiography. CI-AKI was defined as a 25% and 10% increase of sCr and sCyC levels from baseline within 24 h from contrast media exposure, in the absence of alternative causes. Results. Mean sCr and sCyC concentra-tions were 86.4 ± 22.6 μmol/L and 1.18 ± 0.52 mg/dL, respectively before contrast administration, and 90.6 ± 24.1 μmol/L and 1.24 ± 0.65 mg/dL, respectively 24 h after contrast media exposure. sCr-based CI-AKI occurred in 4 patients (8.89%) and sCyC-based CI-AKI was detected in 19 patients (42.22%) after the contrast procedure (p < 0.001). Conclusion. sCyC level measured 24 h after contrast media exposure is a more sensitive indicator of CI-AKI than sCR level.

Background/Aim. The corona virus disease 2019 (COVID-19) primarily affects the respiratory system, so radiological diagnosis has been shown to be necessary. Chest computed tomography (CT) is to be shown the best modality in suspected COVID-19 cases for initial evaluation because CT findings may be present before the onset of symptoms. The aim of this study was to show different CT imaging features or patterns in COVID-19 patients with a different time course and disease severity. Methods. This prospective cohort study analysed 330 patients (the average age was 52.37 ± 15.36) with confirmed COVID-19 via laboratory testing. During hospitalization, all patients included in the study underwent chest CT in order to assess the extent of changes in their lungs. COVID-19 patients, with a different time course and disease severity, were classified into four categories: lung, bronchial, pleural and mediastinal changes. Based on the time interval between the onset of symptoms and performed CT scan, all patients were divided into three groups: group 1 (CT scans done ≤ 1 week after symptom onset); group 2 (from > 1 to 2 weeks after symptom onset); group 3 (from > 2 weeks after symptom onset). In order to monitor the distribution of changes in the lungs more accurately, bilateral lungs were divided into 12 ‘lung’ zones. Each zone was assigned a CT score. Total severity score was calculated by summing the scores for each zone. Results. In 93.6% patients with COVID-19, the CT findings were positive. About 92.1% patients had multiple lesions. The lesions were bilateral in 87.6% of patients, localized both peripheral and centrally in 63.3% of patients, and occurred more frequently in posterior areas (93%), as well as in lower lung zones (91.2%). The average total severity score was 11.00 (7.00–16.00). The most common CT findings in all patients were the ground-glass opacities (97.7%), reticular pattern (91.3%), consolidation (71.5%) and fibrotic streaks (63.8%). In the group 1, changes on CT were found in 80.0%, in the group 2 in 95.0%, and in the group 3 in 99.4% of the patients. Conclusion. CT is proven to be a very important diagnostic method in COVID-19 patients, and together with clinical and laboratory findings, gives a complete picture of the patient's condition and contributes significantly to decision-making for further treatment.

Background/Aim. Paragongliomas are rare hypervascular neoplasms. The aim of this study was to present the experience in the treatment of paragangliomas using preoperative embolization. Methods. This retrospective cross-sectional study included 10 patients (7 women and 3 men; median age 55 years) with paragangliomas that were embolized before surgery. Results. Three patients had tympanicum paragangliomas, two carotid bodies, three jugular and two jugulare-tympanicum paragangliomas. During the operation, only one out of 10 patients had bleeding which required blood transfusion. This patient received 1,130 mL of blood transfusion due to surgical complication. Conclusion. Adequate preoperative selective embolization of paragangliomas is essential in the preoperative preparation of these patients, because this strategy is feasible with low complication rates.

Introduction. Pulmonary arteriovenous malformation (PAVM) is pathological communication between pulmonary artery and pulmonary vein, in way that it shunts normal alveolar capillary membrane resulting in inadequate blood oxygenation in this part of the lung parenchyma Modern therapy of PAVMs includes surgical treatment or endovascular embolization. Case report. A 30-year-old female patient had signs of parestesia and weakness of the extremities on the left side of her body. On physical examination there was only cyanotic discoloration of her lips and clubbing fingers. On the chest x-ray, in the right hemithorax, in the inferior region of the lung, there was relatively homogeneous and well defined shadow, intensity of the soft tissue, which was about 35 mm. A multislice computed tomography pulmonary angiography was performed and showed, in lung parenchyma on both sides, many PAVMs, of which the largest (35 mm) was in inferior right region of the lung on crossing between apical and posterior basal lung segment with 7 mm diameter feeding artery and 9 mm diameter draining vein. The selective pulmonary angiography was per-formed by Seldingers technique. Through sheath, we placed a plug with a diameter of 10 mm. The plug was expanded and a complete occlusion of the final part of the feeding branch of this PAVM was achieved (confirmed by control angiography). In that way, the PAVM was fully shut off from the circulation. In 3 months follow-up, the patient was feeling well, without any recorded complication. Conclusion. Endovascular embolization is recommended as therapy of the first choice for all of PAVMs that have feeding artery greater than 2 mm. Endovascular embolization has high success rate with minimal complications.

Background/Aim. Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors and a leading cause of cancer-related deaths. The aim of this study was to assess the impact of biological markers on the overall survival rate in surgically treated NSCLC patients who received adjuvant chemotherapy and/or radiation therapy. Methods. This retrospective case series study included patients with NSCLC treated in the period between 2008 and 2017 at the Pulmonology Clinic and the Clinic for Chest Surgery, Military Medical Academy, Belgrade, Serbia. The survival analysis performed was based on immunohistological findings, histology type, and tumor, node, metastasis (TNM) stages. Results. The mortality rate was higher in the adenocarcinoma patient group compared to the squamous cell carcinoma group, albeit without statistical significance (58.3% vs. 31.2%, respectively; p = 0.175). Overall survival was shorter in the adenocarcinoma patient group compared to the squamous cell carcinoma group by approximately 750 days. Likewise, overall survival was shorter in the adenocarcinoma patient group compared to the squamous cell carcinoma group for CD31 positive (p = 0.029), p-63 positive (p = 0.049), MMP-9 positive (p = 0.032), and matrix metalloproteinase (MMP)-2 positive patients (p = 0.016). Conclusion. Adenocarcinoma is a more aggressive cancer type compared to squamous cell carcinoma with shorter overall survival. Our research showed a poorer overall survival in the adeno-carcinoma group of patients compared to the squamous cell carcinoma group in CD31, p-63, MMP-9, and MMP-2 positive patients.

Background/Aim. Often asymptomatic, enthesitis can be an integral feature of the wide clinical spectrum in psoriasis as well as an early sign of development of psoriatic arthritis (PsA). It may be difficult to clinically recognize enthesitis in patients with psoriasis or distinguish it from other causes of extraarticular pain. Ultrasound (US) expanding use with the development of accurate assessments through standardized US algorithms as the Glasgow Ultrasound Enthesis Scoring System (GUESS) and the Madrid Sonographic Enthesitis Index Scoring System (MASEI) scores made the US the dominant imaging technique in diagnosing enthesitis. The aims of this study were to establish the prevalence of US signs of en-thesitis, compare it with screening questionnaires results, and estimate possible connections of US verified enthesitis with quality of life (QOL) of patients with psoriasis without PsA diagnosis. Methods. A cross-sectional study was performed on 67 patients with psoriasis who were without systemic therapy. The clinical presence of enthesitis was examined by an experienced rheumatologist, and systemic inflammation was estimated through serum level of C-reactive protein (CRP). The Psoriasis Area Severity Index (PASI) and Body Surface Area- Psoriasis (BSA-PsO) were calculated by a dermatologist. Visual analogue scale (VAS) for pain, screening questionnaires – the Toronto Psoriatic Arthritis Screening (ToPAS), Psoriasis Ep-idemiology Screening Tool (PEST), Psoriatic Arthritis Screening and Evaluation (PASE), Early Psoriatic Arthritis Screening Questionnaire (EARP), and Psoriasis and Arthrosis Screening Questionnaire (PASQ) – were filled by patients. GUESS and MASEI scores were determined by US. The QOL was estimated by the Dermatology Life Quality Index (DLQI). Results. The presence of clinical enthesitis was recorded in 8.7% of patients. According to US signs of enthesitis using GUESS and MASEI scores, only 7% and 2% of patients, respectively, had no sign of enthesitis. Duration of psoriasis and age of subjects were in a significant correlation with GUESS and MASEI scores, while systemic inflammation, V AS v alue, PASI, and BSA-PsO scores were not. GUESS and MASEI scores significantly correlated with scores of all screening questionnaires as well as with DLQI. Conclusion. US can detect subclinical enthesitis better than clinical examination and widely used screening questionnaires, even though the correlations between MASEI and/or GUESS scores and results of screening questionnaires were positive. US examination is important in the multidisciplinary approach in diagnosing and managing psoriasis.

Background/Aim. Overhydration (OH) and shortcomings of clinical assessment of so called „dry weight“ in hemodialysis (HD) patients are well known risk factors for high cardiovascular morbidity and mortality in this population. The purpose of this prospective randomized study was to investigate possible benefits of the active fluid management (AFM) guided by bioimpedance spectroscopy (BIS) on cardiac morphology, mechanics and function in chronic hemodialysis patients. Methods. The study lasted 9 months and 83 BIS naive patients were enrolled. Cardiac structural and functional characteristics were obtained using two dimensional Doppler echocardiography and global strains by speckle tracking modality. In addition, cardiac markers were measured. Results. Seventy three patients completed the study (38 in the active – AFM group and 35 in the control group). At the end of the study, the main structural change in the active group of patients was reduction of left ventricular mass index (from 62.81 ± 19.74 g/m2.7 to 57.74 ± 16.87g/m2..7; p = 0.007), while main functional improvements in this group were better left ventricular ejection fraction (LVEF; from 41.27 ± 9.26% to 43.95 ± 8.84%; p = 0.006) and fractional shortening (FS; 27.86 ± 5.94% to 29.86 ± 5.83%; p = 0.056) in accordance with improvement of radial left ventricular (LV) mechanics detected by higher global radial strain (GRS) (18.56 ± 10.24% to 21.79 ± 12.16%; p = 0.014). The diastolic function of patients in the control group worsened significantly, assessed as ratio of Doppler velocity of early diastolic filling of left ventricle – E, and average velocity of tissue Doppler measured at lateral part of the mitral annulus (e’ lateral; E/e’ lateral ratio 10.59 ± 5.00 to 11.12 ± 4.06; p = 0.036) and consecutively the right ventricular systolic pressure (RVSP) estimated indirectly by echocardiography: from 34.84 ± 10.18 mmHg to 38.76 ± 8.34 mmHg; p = 0.028. These functional changes were in correlation with significantly higher levels of Nterminal prohormone brain natriuretic peptide (NTproBNP) in this group of patients [median and interquartile range (IQR): 5810.0 pg/mL (3339.0–15627.0 pg/mL) to 8024.0 pg/mL (4433.0–17467.0 pg/mL; p = 0.038)]. The improvement in the LV structure and function in the active group correlated with better relative overhydration (ROH) management in this group – the proportion of “critically” overhydrated patients decreased from 45% at the start to 24% at the end of study (p = 0.003). At the end of the study, there were 49% of post-dialysis “critically“ dehydrated patients in the control group. Proportion of anuric patients increased only in the control group (63% to 77%; p = 0.063). Conclusion. Active fluid management, guided by bioimpedance spectroscopy had positive impact on cardiac hemodynamics and mechanics in our study patients and could improve clinical decisions regarding their optimal weight and further clinical course. Further data from well designed studies are needed urgently.

Background/Aim. Acute intoxication by ethanol constitutes a significant part of the acute pathology caused by toxic chemicals, which require medical care in specialized health care institutions. The aim of the study was to determine some principal characteristics of the patients treated after acute ethanol poisoning, such as: participation in the total number of patients treated after acute poisoning by all chemical agents, age, sex, severity of poisoning and capacities for ambulatory or hospital treatment. Methods. A five-year retrospective case study was conducted on 20,891 acute poisoned patients, of which 10,731 were treated after acute ethanol poisoning during the period 2011–2015. All the subjects satisfied the diagnostic criteria of poisoning according to the World Health Organization International Classification of Diseases-10 and standardized Poison Severity Score scale. Results. Monitored parameters were analyzed in 10,731 patients acutely poisoned by ethanol, and their average number during one study year was 2146.2 ± 437.95. The average number of treated patients due to poisoning by ethanol (51.47 ± 2.86%) was statistically significantly higher than that of other causes of acute poisoning (p < 0.001). The majority of poisoned patients were men, aged 19 to 65 years, with mild to moderate symptoms of acute ethanol intoxication. The highest number of patients poisoned by ethanol had Poison Severity Score 1 (70.25 ± 5.04%, p < 0.001). Very few acute poisoned with ethanol required hospital treatment (1.05%). Anticipated number of patients acutely poisoned by ethanol had high percentage of increase for the period 2016–2020 (slightly more than 20%), which is worrying, primarily due to their high absolute number. Conclusion. Acute alcohol poisoning represents a significant part of the pathology in the total number of patients treated due to acute poisoning with various chemical substances. The results of this analysis showed that certain populations are particularly vulnerable to abuse of alcohol to the level requiring health care (male population, age 19˗65 years). Only a small number of patients (1% of all patients treated for acute alcohol poisoning) required clinical treatment. The obtained data provided the basis for a more targeted preventive action in certain population groups, as well as the adequate planning of professional medical staff engagement, material, spatial and other capacities. These data, also, provided the basis for additional detailed social, economic, health and other researches in this area as well as a more detailed registration of this type of poisoning and establishing a monitoring system and database.

Background/Aim. Vitamin D insufficiency/deficiency is often present in patients with type-2 diabetes mellitus (DM) and could present a risk factor for rapid progression of diabetic nephropathy and for higher incidence of cardiovascular events. The aim of this study was to examine the influence of vitamin D supplementation on proteinuria, cholesterol, triglycerides, C-reactive protein (CRP) and hemoglobin A1c in patients with type-2 DM and vitamin D insufficiency/ deficiency. Methods. This prospective, cohort study included 90 patients with type-2 DM and vitamin D insufficiency/ deficiency divided into 3 equal groups: with normal proteinura, with microproteinuria and with macroproteinuria. Therapy included six months of supplementation with cholecalciferol drops: first two months with 20,000 IU twice weekly, than if level of vitamin D was below normal the same dose was given next four months. If the level of vitamin D was normal 5,000 IU was given twice weekly. At the begining and at the end of the study the levels of urea, creatinine, fasting blood glucose, calcium, phosphorus, cholesterol, triglycerides, CRP, hemoglobin A1c, intact parathyroid hormone, 24-hour urine protein and creatinine clearance were determined. Levels of calcium, phosphorus and vitamin D were also checked 2 months after beginning of therapy due to possible correction of cholecalciferol dose. Results. The lowest level of vitamin D before therapy was found in patients with macroproteinuria, while at the end of the study the significantly higher level of vitamin D was found in all three groups. After 6 months of therapy a significant decrease of 24-hour urine protein, cholesterol, triglycerides, hemoglobin A1c in all three groups, and CRP in patients with normal proteinuria and microproteinuria were found. Significantly negative correlation between vitamin D and 24-hour urine protein, cholesterol and CRP was found in patients with macroproteinuria. Also, significantly negative correlation was found between vitamin D and hemoglobin A1c, in patients with normal proteinuria, vitamin D and CRP in patients with microproteinuria. Conclusion. A preventive use of high-dose cholecalciferol supplementation in patients with type-2 DM (with or without proteinuria) decreases cholesterol, triglycerides, proteinuria, CRP and hemoglobin A1c.

Background/Aim. Idiopathic retroperitoneal fibrosis (IRF) is characterized by the fibroinflammatory periaortic tissue that affects the ureters, causing obstructive nephropathy and variable impairment of renal function. The findings strongly suggest an autoimmune etiology. The optimal treatment has not been established. The aim of this study was to analyze a long-term efficacy of combined corticosteroid therapy with mycophenolate mofetil (MMF) in the patients with IRF. Methods. We retrospectively followed 13 patients (8 males and 5 females) with IRF. All patients received corticosteroids and MMF. For the patients with severe renal failure, an initial ureteral decompression was made and prednisone was started orally 0.5 mg/kg with fast tapering. In cases with a mild renal failure corticosteroids were administrated as intravenous methylprednisolone pulses for 3 days, followed by oral prednisone. The dose of MMF was 1000 mg twice a day. MMF was stopped after 18 months and prednisone after 48 months. Results. Systemic symptoms resolved in all patients. Erythrocyte sedimentation (SE) rate declined from the mean of 67.6 to 26.3 mm/h and C-reactive protein (CRP) from the mean of 18.5 to 6.3 mg/L. In 7 out of 8 patients, the ureteral stents were successfully removed 13 weeks on average. Seven patients had 100% of reduction in the periaortic mass, and the average percent reduction was 76.9%. The kidney function improved and remained normal in 6 treated patients. In 4 patients a mild chronic renal failure remained due to afunction of one kidney. Three patients, with a prior chronic renal failure, did not get worse renal function. The disease recurred in 3 patients. There were no treatment side effects noted. Conclusion. Combination of corticosteroids and MMF is a potentially effective treatment in restoring the renal function and reducing the fibrotic tissue in the patients with idiopathic retroperitoneal fibrosis. It could prevent the need for ureteral stenting and surgery. Longer treatment may reduce a possibility of recurrence.

Background/Aim. Lung cancer is one of the most common malignant tumors. About 80% of all lung cancers are non-small cell lung cancer (NSCLC). According to histopathological characteristics, the most common types of NSCLC are squamous cell carcinoma and adenocarcinoma. The aim of this study was to evaluate the overall survival rate in the NSCLC patients initially received surgery according to its histopathological type and T – primary tumor, N –regional lymph nodes, M – distant metastasis (TNM) stages which were treated with surgical treatment, and after that, according to the TNM stage, chemotherapy protocols and/or radiation therapy. Methods. This retrospective case series study included all patients with NSCLC admitted to the Military Medical Academy in Belgrade in the period 2010–2015. A total number of selected patients was 85 (27 females and 58 males). Results. Out of 41 patients with squamous cell carcinoma, 19.5% deceased. On the other hand, in the group of patients with adenocarcinoma, 43.2% out of 44 patients deceased. The average cumulative survival was statistically significantly lower in the adenocarcinoma patients in comparison to the patients with squamous cell carcinoma (1,605.2 vs.1,304.8 days; p = 0.005). On the other hand, the average cumulative survival was statistically significantly lower in our patients in the recurrence group with adenocarcinoma in comparison to the recurrence group with squamous cell carcinoma (1,212.8 vs. 1,835.5 days; p = 0.032). Conclusion. Adenocarcinoma is more aggressive cancer in comparing to squamous cell carcinoma with lower overall survival in comparing to squamous cell carcinoma. Additional studies are needed to identify risk factors for recurrence after surgery, and to additionally explain role of tumor markers and molecular biological techniques in the progression of this kind of cancer.

Background/Aim. Tacrolimus concentration-dose ratio as a potential therapeutic drug monitoring strategy was suggested to be used for the patients subjected to renal transplantation. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio, suggested to be used as a therapeutic drug monitoring strategy and the polymorphisms of genes encoding the most important enzymes, such as CYP3A5 and CYP3A4, as well as the transporter P-glycoprotein, for its metabolism and elimination. Methods. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real- Time PCR System by assessing allelic discrimination based on TaqMan® methodology. Results. Patients (n = 13) who were treated with less than 2 mg of tacrolimus/day (0.024 ± 0.006 mg/kg/day) had the tacrolimus concentration-dose ratio larger than 150 ng/mL/mg/kg. In this group, 84.62% patients had CYP3А5 *3*3 allele. All of these patients had CYP3А4 *1*1/*1*1B allele. Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant, while 69.23% of our patients had CC and CT gene variants. Conclusion. Tacrolimus concentration-dose ratio greater than 150 ng/mL/mg/kg is cut-off value in patients subjected to renal transplantation which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein.

Background/Aim. During the homicidal act, a victim usually tries to defend himself/herself, and due to these attempts he/she could sustain so-called defense injuries, mostly localized on the arms. The aim of this research was to analyze important medicolegal characteristics of defense injuries, particularly regarding their importance in forensic expertise of homicides. Methods. We analyzed autopsies of all homicidal cases with defense injuries in Belgrade during a three-year period. Results. Defensive injuries were registered in 71 victims of murder. The majority (67.61%) of victims with defense injuries were males. About 25% of victims were aged from 21 to 30 years. The majority (60) of victims were not under influence of alcohol. Homicides were mostly (90.14%) performed by mechanical weapons. The highest frequency of defense injuries was noticed in the victims with multiple homicidal injuries localized on the front side of the body. In a half (50.7%) of the cases they were present on both arms of the victim, mostly on the dorsal side of hands and forearms. Bruises were the most frequent form of defense injuries (36.61% out of 71 cases), while incisions, abrasions, gunshot injuries and stab wounds were less common. Conclusion. Determination of defense injuries and their medicolegal characteristics enables collecting of facts that are important for legal estimation of homicide, as well as for adequate sentence at the end of the court procedure. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175014]

Background/Aim. Bronchial asthma is a disease that is characterized by the variability of the clinical picture, physical and functional status and the existence of bronchial hypersensitivity and hyperreactivity with varying degrees. Bronchial responsiveness and sensitivity are tested in patients with clinically suspected existence of asthma and normal spirometry test. The aim of the study was to analyze the patients with atopic asthma and study test results of skin sensitization to inhaled allergens, nonspecific bronchial hyperreactivity and specific hyperreactivity estimated by bronchial provocation tests with inhalant allergens. Methods. The prospective study at the Pulmonology Clinic of the Military Medical Academy in Belgrade Serbia, during 2014, included 70 male subjects aged 18–30 years, who had perennial asthma symptoms. All subjects were nonsmokers, with normal spirometry findings, with normal radiological chest findings and with no symptoms of respiratory infection over the past two months. All respondents were tested with skin prick tests with inhalant allergens and nonspecific bronchial provocation test with histamine. On the basis of histamine test, subjects were divided into two groups: the group I, in which there was a slight degree of hypersensitivity [provocation concentration of histamine causing a 20% fall in forced expiratory volume – PC20 = 6.09 ± 1.1 mg/mL], and the group II with negative histamine test (PC20 = 14.58 ± 6.34 mg/mL). Specific bronchial provocation test was performed in all patients, and the selection of the allergens was carried out based on the results of testing of skin hypersensitivity. Results. Results of skin sensitization show the highest incidence of mites Dermatophagoides pterronissinus (83.3% group I and 85.0% group II) followed by grass pollen (53.3% group I and 52.0% group II), and house dust (33.3% group I and 50.0% group II). There were no statistically significant differences in allergens between groups (p > 0.05). In both groups, spirometry findings were within normal values [forced vital capacity – FVC and forced expiratory volume 1 – FEV1 > 80% predictive value], but statistically significant difference was found in FEV1 between groups (p < 0.05). Specific bronchial provocation tests with solutions of inhaled allergens in both groups caused a significant decline in FEV1 (≥ 20%) in all patients individually. No statistically significant differences were found neither between groups, nor between individual allergens (average decline in FEV1: Group I 32.9 ± 2.4% and group II 31.5 ± 2.2%). Conclusion. There is no relationship between the degree of specific and non-specific bronchial hyperreactivity in patients with allergic asthma.

Background/Aim. Polymorphisms of genes which encode transporter P-glycoprotein and most important enzymes for tacrolimus pharmacokinetics can have significant influence reflecting on blood concentrations of this drug. The aim of this study was to examine the distribution of polymorphisms of CYP3A5, CYP3A4 and ABCB1 genes in patients subjected to renal transplantation, for the first time in our transplantation center. Methods. The research was designed as a prospective cross-sectional study which included 211 patients subjected to renal transplantation in the Centre for Solid Organ Transplantation of the university tertiary health care hospital, Military Medical Academy, Belgrade, Serbia. Patients of both genders, 22−69-year-old, Caucasians, subjected to immunosuppressive regimen, including tacrolimus, were recruited for the study. CYP3A5 6986A>G (the *3 or *1, rs776746), CYP3A4 - 392A>G (the *1 or *1B, rs2740574) and ABCB1 3435C>T (rs1045642) genotypes were determined by TaqMan® SNP genotyping assays. Results. Most of our patients (94.8%) had functional CYP3A4 enzyme, while 87.7% of all the patients had diminished CYP3A5 enzymatic activity. On the other hand, about one third of them, 31.3%, had functional ABCB1 transporter. Conclusion. A total of 84.8% of our patients were found to express both the CYP3А5*3*3 genotype (associated with diminished CYP3А5 enzymatic activity) and CYP3А4*1*1/*1*1B (associated with functional CYP3А4 enzymatic activity), while out of all the patients with diminished CYP3A5 enzymatic activity, 68.7% had diminished activity of ABCB1 transporter. However, further studies are necessary in order to show the influence of these genetic polymorphisms on tacrolimus blood concentrations in patients after renal transplantation.

Background/Aim. A combination of tacrolimus and other drugs such as corticosteroids has been commonly used immunosuppresive regimens. On the other hand, there is a growing body of evidence that male and female may differ in their response to the equal drug treatment. The aim of the study was to estimated the use of tacrolimus concentration/dose (C/D) ratio for the assessment of the influence of gender differences and comedication on tacrolimus exposure in renal transplant recipients. Methods. This prospective case series study included 54 patients, in which the unit of monitoring was outpatient examination (1,872) of the renal transplant patients. The patients were monitored in the period 2010-2014, starting one month after the transplantation. Tacrolimus trough concentrations (TTC) were measured by chemiluminescence microparticles immunoassay. Results. TTC and the tacrolimus C/D ratio were significantly lower in the females comparing with the males. Contrary to the males, in the females a significant increase of the tacrolimus daily dose (TDD) per body weight and TTC, along with the corticosteroid dose increase, was not accompanied by any significant changes in the tacrolimus C/D ratio; in different corticosteroid doses faster elimination of tacrolimus was found with the exception of the doses > 0.25 mg/kg. In the patients treated with proton pump inhibitors, mainly with pantoprazole TDD per body weight and TTC were significantly higher, while the tacrolimus C/D ratio was significantly lower compared to the patients without this treatment. In the patients treated with calcium channel blockers, TDD per body weight was significantly lower (particularly with amlodipine) while the tacrolimus C/D ratio was higher compared to the patients who were not treated by them. Conclusion. A lower tacrolimus exposure was detected in females in comparison to males. When gender differences were considered in the context of different corticosteroid doses, faster elimination of tacrolimus in the females was also seen, with the exception of the doses > 0.25 mg/kg. Tacrolimus exposure in the pantoprazole-treated patients was significantly less expressed, while in patients treated with CCB amplodipine the tacrolimus C/D ratio was significantly higher in comparison with the patients not treated with them. [Projekat Ministarstva nauke Republike Srbije, br. 175014 and 175093]

Background/Aim. Promotion of oral health in military population is not only a significant component of general health, but also of the military readiness and represents the strategic orientation of each country. The basic task of military dentistry is to provide oral health of military personnel and to enable their operational readiness at the optimal level. The aim of the study was to assess the periodontal condition in Serbian military population using the community periodontal index of treatment needs (CPITN), and the influence of general life habits and local risk factors on periodontal health. Methods. This prospective cross-sectional pilot study was conducted on 101 examinees at the mean age of 38.94 ± 11.63 years who had dental check-ups at the Dental Clinic of the Military Medical Academy in Belgrade. All the categories of military personnel aged 20-64 years were divided into five groups. The frequency distribution of general and local factors on periodontal health, oral hygiene index, and the assessment of the mean number of sextants by CPITN compared to age were examined. Results. The examinees at the age of 51-60 years had the best oral hygiene index (0.95 ± 0.65), whereas the oldest population had the worst (1.63 ± 0.42). Only one person (5.6%) at the age group of 51-60 years had a completely healthy periodontium. Observed in relation to the age groups, the mean values of sextants increased linearly, but in general population, the most frequent CPITN categories were in sextant with the periodontal pockets 4-5 mm (score 3). Conclusions. Compared to the results from other countries shown by the World Health Organization, the periodontal condition in our examinees is below the average. The appropriate preventive program preparation and its implementation are needed, including primarily the appropriate training on oral hygiene, as well as education based on periodontal disease prevention and treatment. [Projekat Ministarstva nauke Republike Srbije, br. 175014]

Background/Aim. Cancer, one of the leading causes of mortality in the world, imposes a substantial economic burden on each society, including Serbia. The aim of this study was to evaluate the major cancer cost drivers in Serbia. Methods. A retrospective, indepth, bottom-up analysis of two combined databases was performed in order to quantify relevant costs. End-of-life data were obtained from patients with cancer, who deceased within the first year of the established diagnose, including basic demographics, diagnosis, tumour histology, medical resource use and related costs, time and cause of death. All costs were allocated to one of the three categories of cancer health care services: primary care (included home care), hospital outpatient and hospital inpatient care. Results. Exactly 114 patients were analyzed, out of whom a high percent (48.25%) had distant metastases at the moment of establishing the diagnosis. Malignant neoplasms of respiratory and intrathoracic organs were leading causes of morbidity. The average costs per patient were significantly different according to the diagnosis, with the highest (13,114.10 EUR) and the lowest (4.00 EUR) ones observed in the breast cancer and melanoma, respectively. The greatest impact on total costs was observed concerning pharmaceuticals, with 42% of share (monoclonal antibodies amounted to 34% of all medicines and 14% of total costs), followed by oncology medical care (21%), radiation therapy and interventional radiology (11%), surgery (9%), imaging diagnostics (9%) and laboratory costs (8%). Conclusion. Cancer treatment incurs high costs, especially for end-of-life pharmaceutical expenses, ensued from medical personnel tendency to improve such patients’ quality of life in spite of nearing the end of life. Reimbursement policy on monoclonal antibodies, in particular at end-stage disease, should rely on cost-effectiveness evidence as well as documented clinical efficiency. [Projekat Ministarstva nauke Republike Srbije, br. 175014]

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