Miroslav Misovic

According to the World Health Organization, malocclusion type III is third, most important oral health problem. It may be the least prevalent malocclusion, but it is the most noticeable and challenging for orthodontic therapy. With this narrative review, we wanted to give a summation of the most current knowledge about diagnostics, different therapy options, limitations, and additional factors that can influence the therapy of class III malocclusion to help clinicians and researchers focus on the specific approaches. Therapy options were divided into the following groups: orthopedic, orthodontic, and surgical. The SNA, SNB, and ANB angles (cephalometric values) are the best ones to examine improvements in different skeletal improvements, while dentoalveolar improvements were also described, emphasizing the limitation of orthopedic therapy to change the skeletal discrepancy. Eruption-guided appliances and chin cups are more effective in early childhood, mixed dentition, during permanent teeth eruption, with no significant skeletal discrepancy. If a discrepancy exists, a face mask is the first therapy choice. The therapy of an underdeveloped maxilla can be solved with different palate expanders. Bulkiness, lack of long-term results, and duration of therapy make fixed orthodontic appliances with braces and elastic traction favorable nowadays. If the skeletal discrepancy is major, a surgical approach should be considered. One of the main limitations in articles is the combination of different therapy approaches, ages, and dentition preferred for device application, duration of therapy, and lack of information about long-term outcomes. On the other hand, the lack of original articles is noticeable, so further research should be done.

Introduction/Objective. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection manifests with an unpredictable clinical course that could rapidly progress, leading to serious and often fatal complications. The identification of effective laboratory biomarkers that could stratify patients at risk of developing severe forms of the disease is imperative to ensure they receive prompt medical treatment. The aim of our study was to compare baricitinib and tocilizumab regarding clinical outcomes in hospitalized patients with severe COVID-19. Methods. A retrospective study included analysis of data from 82 patients of both sexes who were treated with biological immunosuppressive therapy at the Military COVID Hospital, Karaburma. All patients who met the criteria for use according to the guidelines of the national protocol for the treatment of COVID-19, version XIII, had a consultative decision made for the application of biological immunosuppressive therapy. Half were treated with tocilizumab, and the other half with baricitinib. Results. The results of our study show that the mortality rate is lower in the group treated with tocilizumab compared with the group treated with baricitinib: 17.1% vs. 26.8%, but without statistical significance (p = 0.286). Additionally, the use of tocilizumab reduces the need for mechanical ventilation compared with baricitinib: 53.6% vs. 68.3%, without statistical significance (p = 0.454). Conclusion. The results obtained in our study indicate that both drugs are equally clinically effective.

Introduction: Antiphospholipid syndrome (APS) is an autoimmune disease characterised by arterious and venous thrombosis, miscarriage, and the presence of antiphospholipid antibodies (aPL) in the blood. As we know, APS is also characterised by accelerated atherosclerotic degeneration with an increased risk of thrombosis in all blood vessels, including the carotid arteries. Carotid artery stenosis can manifest in many different ways. The aim of this study is to present the results of our multidetector computerised tomography angiography (MDCTA) analysis of the carotid arteries in patients with primary and secondary APS compared with a control group. Materials and Methods: This study examined 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients with secondary antiphospholipid syndrome (SAPS). The results were compared with a control group also comprising 50 patients. The groups were analysed with respect to age, sex and the presence of well-established risk factors for vascular disease. The study was conducted using MDCTA, where we analysed the quantitative and qualitative (morphologic) characteristics of carotid artery lesions. Results: Patients from the control group had significantly elevated levels of cholesterol and triglycerides in comparison with patients with PAPS and SAPS (p < 0.001 and p < 0.05). The results show that carotid artery lesions were significantly more common in patients with APS (PAPS, n = 40, CI95: 0.50–0.75, p = 0.0322 and SAFS, n = 54, CI95: 0.59–0.80, p = 0.0004) than within the control group (n = 23). There was a statistically significant difference between patients with APS and the control group with respect to lesions in the distal segments (n = 27, CI95: 0.67–0.95, p = 0.0001), bulbi and proximal segments (n = 21, CI95: 0.84–1.00, p = 0.000005). The number of patients with one lesion (L) (n = 27) was significantly greater than the number of those with three (n = 10, CI95: 0.56–0.86, p = 0.0051) or four (n = 3, CI95: 0.73–0.98, p = 0.00001) lesions. There were also more patients with two lesions (n = 24) than those with four (n = 3) (CI95: 0.71–0.97, p = 0.00005). Carotid artery stenosis was shown as a percentage of the carotid artery lumen diameter (%DS). Stenosis of up to 30%, was more common in patients in the PAPS group (n = 12) than in the control group (n = 3) (CI95: 0.52–0.96, p = 0.0201), while the SAPS group (n = 17) had an even larger disparity (CI95: 0.62–0.97, p = 0.0017). We observed a highly significant difference in the frequency of stenoses between 30% and 50% DS between the PAPS group (n = 24) and the control group (n = 7) (CI95: 0.59–0.90, p = 0.0023), as well as the SAPS group (n = 30) (CI95: 0.65–0.92, p = 0.0002). A qualitative analysis of plaque morphology revealed that patients with PAPS had significantly more soft tissue lesions (n = 23) compared with calcified lesions (n = 2) (CI95: 0.74–0.99, p = 0.00003), as well as more mixed plaques (n = 9) and calcified plaques (n = 2) (CI95: 0.48–0.98, p = 0.0348). Patients within the SAPS group had significantly more soft tissue (n = 35) than calcified lesions (n = 3) (CI95: 0.79–0.98, p = 0.00000021), as well as more mixed lesions (n = 21) compared with calcified (n = 3) (CI95: 0.68–0.97, p = 0.0002). Conclusions: Our study shows that subclinical manifestations of carotid artery lesions were more common in patients with APS. We came to the conclusion that MDCTA is an accurate diagnostic method because it is a safe method that provides us with a great quantity of accurate information about the characteristics of atheromatous plaques, which aids us in the further planning of treatment for patients with APS.

Background/Aim. Since 2014 and the publication of the results of the first study on the accumulation of gadolinium contrast, we have witnessed a growing body of evidence on the deposition and retention of gadolinium in the brain after the use of gadolinium-based contrast agents (GBCAs). However, there is still no strong clinical evidence of the adverse effects of GBCAs on the brain parenchyma. The aim of the study was to determine the existence of gadolinium deposits in the brain of patients with relapsing-remitting multiple sclerosis after a ten-year follow-up period. During this period, the patients have regularly, each year, undergone magnetic resonance imaging (MRI) with the administration of gadolinium contrast (gadopentetate dimeglumine ? Magnevist?) in order to follow the course of the disease. Methods. A cohort of 20 patients was formed for the purpose of this study. The ratio of the values of the signal intensity (SI) of different regions of the brain-to-cerebrospinal fluid (CSF) was com-pared for each patient on the initial MRI examination and the MRI examination ten years later. Results. Frontal cortex-to-CSF (p < 0.01), occipital cortex-to-CSF (p < 0.01), the white matter of the corona radiata-to-CSF (p < 0.01), parietal cortex-to-CSF (p < 0.05), thalamus-to-CSF (p = 0.051), putamen-to-CSF (p = 0.06), and anterior and posterior limb of the capsula interna-to-CSF (p = 0.062) SI ratios increased after multiple gadopentetate administrations. An increase in the absolute values of the T1- weighted (T1W) signal in three-quarters of patients was registered in the frontal and occipital cortex and cerebellar hemispheres. A slightly smaller increase in SI, but still greater than 55?65%, was registered in structures of the parietal cortex, putamen, cornu anterior and posterior of the capsula interna, corpus callosum (CC) splenium, pons, thalamus, nucleus caudatus, substantia nigra, CC genu, and temporal cortex. Conclusion. In the cohort of 20 patients, there was a statistically significant increase in SI in the pre-contrast T1W sequence in the following structures: frontal, parietal, and occipital cortex, as well as supratentorial white matter. This result speaks in favor of the existence of chronic accumulation of gadolinium contrast agent gadopentetate dimeglumine in brain structures.

Background/Aim. Prostate cancer (PCa) is second occurring carcinoma that affect males population. Although PCa incidence rates are high, most cases has favorable prognosis, with comfortable long term life quality. This study was aimed to assess distinction of lncRNA 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 American Joint Committee on Cancer. The patient data were collected and analysed. GAS5 levels were quantified using Real-time PCR metod. Statistical analysis was conducted using the IBM SPSS Statistics 26.0 computer program (IBM, USA, 2019). Results. The relative quantification of GAS5 expression levels shows downregulation in PCa patients compared to healthy individuals, however the difference was marginaly statistically significant (p = 0.056). With further analysis of the given results, we have concluded that the expression level of GAS5 was not significantly different in the first patient subgroup and the healthy individuals (p = 0.268). Patients from second subgroup had significantly lower plasma levels of GAS5 than healthy individuals (p = 0.033). Levels of GAS5 expression between patients with favorable prognosis (Group 1) than in the patients with worse prognostic score (Group 2), did not indicate the statistical significance (p = 0.275). In both Group 1 (p = 0.805) and Group 2 (p = 0.454), the plasma levels of GAS5 were not significantly different in comparing to the age (≤ 65 vs > 65 years). Conclusion. One of the main objective in PCa researching is identifying novel and more efficient biomarkers. Conducted research provides strong evidence about the significance of lncRNAs in PCa, as well as the correlation of decreased expression of GAS5 and poor prognosis in various tumours.

Objective Gadolinium-enhanced T1-weighted lesions are a well-established marker of areas with acute inflammatory activity. A majority of these gadolinium-enhanced T1 lesions are isointense relative to the surrounding white matter, but 20–40% of such active lesions will evolve during one year into areas of low signal ("black hole"). This study sought to characterize evolution of "black hole" lesions in patients with relapsing–remitting multiple sclerosis (MS) using the magnetic resonance imaging (MRI), which measures active lesions via the count of new or enlarged T2 and gadolinium-enhanced T1-weighted lesions. Materials and methods This was a prospective, observational case-series study which utilized pre- and post-gadolinium contrast T1-weighted and Proton density MRI scans. Twenty-nine patients (8 males and 21 females) with average age of 38.86 ± 6.58 years and disease duration of 5.75 ± 7.00 years were used to analyze 196 acute demyelinating plaques detected on MRI images during the 24-month follow-up of post-gadolinium signal intensity enhancement of MS plaques. Results Significant difference in black hole development was found between the shapes of acute and chronic "black holes". Ring-shaped and patchy plaques were 4.09 (1.87–8.91) times more likely and 1.49 (0.71–3.12) times less likely to develop an acute "black holes" than homogeneous plaques, respectively. Acute plaques with higher lesion-to-CSF SI ratio and larger surface area showed a greater tendency to develop into acute and chronic "black holes". Conclusions The value of lesion-to-CSF SI ratio and surface area were found as the predictors of the "black hole" formation.

The long non-coding RNA (lncRNA) GAS5 can be a marker for early diagnosis and postoperative follow-up in the patients with prostate cancer, whereby lower levels of GAS5 correlate with tumorigenesis and unfavourable clinical course. Expression of the GAS5 can be affected by rs145204276 polymorphism, a 5 base pairs insertion-deletion polymorphism shown as ?AGGCA/-?. The aim of this study was to analyse the association between rs145204276 and prostate cancer susceptibility and prognosis. This study was included 121 healthy subjects and 70 patients with prostate cancer. Diagnosis of prostate cancer was established by histopathology after the surgery. Genotyping was performed by allelic discrimination method using the TaqMan? assay. In the healthy subjects, the obtained frequencies of GAS5 rs145204276 genotypes were 80.2% of ins/ins, 16.5% of ins/del and 3.3% of del/del. The allele frequencies were 88.5% of ins and 11.5% of del, respectively. In the patient group, the frequencies of ins/ins, ins/del and del/del genotypes were 70%, 20% and 10%, respectively; the frequency of ins allele was 80% and the frequency of del allele was 20%. Observed frequencies of GAS5 rs145204276 genotypes were not significantly different between healthy subjects and patients with prostate cancer, and also between prognostic groups of prostate cancer. This study demonstrate no significant association between GAS5 rs145204276 and sussceptibility/prognosis of prostate cancer.

Background/Aim. About 1.8 million new lung cancer cases are diagnosed worldwide every year, and about 1.6 million cases have a fatal outcome. Despite improvements in treatment in the previous decades, the survival of patients with lung cancer is still poor. The five-year survival rate is about 50% for patients with localized disease, 20% for patients with regionally advanced disease, 2% for patients with metastatic disease, and about 14% for all stages. The median survival of patients with untreated non-small cell lung carcinoma (NSCLC) in the advanced stage is four to five months, and the annual survival rate is only 10%. The aim of the study was to determine the results of treatment with concomitant chemoradiotherapy (CHRT) in terms of efficacy and toxicity in selected patients with advanced inoperable NSCLC. Methods. The study included data analysis of 31 patients of both sexes who were diagnosed and histopathologically verified with NSCLC in inoperable stage III and were referred by the Council for Malignant Lung Diseases to the Radiotherapy Department of the Military Medical Academy in Belgrade, Serbia for concomitant CHRT treatment. Upon expiry of the three months from the performed radiation treatment (RT), the tumor resonance was assessed based on multislice computed tomography (MSCT) examination of the chest and upper abdomen according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. According to the same criteria, progression-free survival (PFS), as well as overall survival (OS), was assessed every three months during the first two years, then every 6 months or until the onset of disease symptoms. Results. The median PFS was 13 months, and the median OS was 20 months. During and immediately after RT, 9 (29%) patients had a grade 2 or higher adverse events. Conclusion. The use of concomitant CHRT in patients in the third stage of locally advanced inoperable NSCLC provides a good opportunity for a favorable therapeutic outcome with an acceptable degree of acute and late toxicity and represents the standard therapeutic approach for selected patients in this stage of the disease.

Background/Aim. The COronaVIrus 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 purpose of this study is to show different CT imaging features or patterns in COVID-19 patients with a different time course and disease severity. Methods. This is a prospective cohort study that 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. Because chest CT images could show different imaging features or patterns in COVID-19 patients with a different time course and disease severity, we classified them into four categories: lung, bronchial, pleural and mediastinal changes. Based on the time interval between the onset of symptoms and the CT scan, all patients were divided into three groups: group 1 (CT scans done ≤1 week after symptom onset); group 2 (CT scans done >1 to 2 weeks after symptom onset); group 3 (CT scans done >2 weeks after symptom onset). In order to more accurately monitor the distribution of changes in the lungs, 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, had both peripheral and centrally localised lesions 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 are the ground- glass opacities (97.7%), reticular pattern (91.3%), consolidation (71.5%) and fibrotic streaks (63.8%). When the time interval is monitored between onset of symptoms and the CT scan, it is noticed that in group 1 changes on CT were found in 80.0% of patients, in group 2 in 95.0%, and in group 3 in 99.4%. Conclusion. CT has 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 significantly contributes to decision- making for further treatment.

Introduction/Aim: Lipomas are frequent benign tumors; however, they are rarely localized in bone tissue. Osseous lipomas are categorized according to their location into parosteal, intraosseous, and intracortical. The incidence of intraosseous lipomas is 0.1% of all bone tumors. The most frequent location is in the long tubular bones and calcaneus. This case report aims to present the radiological diagnostics of intraosseous lipoma. Case report: 43-year-old patient with Achilles tendon rupture was admitted to the orthopedic clinic. Radiography of left ankle joint detected a radiolucent, well-circumscribed lesion in the anterior aspect of the calcaneus with a sclerotic board. Magnetic resonance imaging (MRI) revealed bone lesion dimension anteroposterior, craniocaudal, and laterolateral 38 x 22 x 37 mm, composed of peripheral adipose tissue and central calcified nidus, which indicate intraosseous lipoma. Based on histopathological findings, necrotic and viable bone tissue with components of mature and necrotic fatty tissue confirmed the diagnose of intraosseous lipoma. Conclusion: Standard radiographs of bone structures, as the first diagnostic procedure, can make suspects of intraosseous lipoma. MRI and multidimensional computerized tomography can further verify and with more details completely characterize, while histopathological verification is the final step in the diagnose of intraosseous lipoma.