Faculty of Medicine

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Alergijska bronhopulmonalna aspergiloza (ABPA) bez istorije bronhijalne astme
(Udruženje bronhologa Srbije, 2022-11)
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Kochovska-Kamchevska, Nade
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Baloski, Marjan
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Bushev, Jane
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Poposki, Bozidar
Plućne bolesti povezane sa aspergilusom su spektar poremećaja kao što su aspergilom, invazivna aspergiloza i alergijska bronhopulmonalna aspergiloza (ABPA). ABPA je imunološka bronhopulmonalna inflamacija (reakcija preosetljivosti disajnih puteva) zbog imunološkog odgovora donjih respiratornih puteva protiv Aspergillus fumigatus. Glavni dijagnostički kriterijumi za ABPA su 1) bronhijalna astma, 2) plućna infiltracija, 3) eozinofilija periferne krvi, 4) pozitivan kožni test na Aspergillus fumigatus, 5) precipitin u serumu na Aspergillus semulino E fumigatus (E6) globulin E6) ), i 7) centralne bronhiektazije. Dijagnozu ABPA treba razmotriti kod astmatičara svih uzrasta. Evolucija bolesti obuhvata pet faza od akutnog do fibroznog stadijuma uključujući plućnu fibrozu i respiratornu insuficijenciju.
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Hemoptiza kao prva klinička prezentacija metastatskog seminoma kod 24-godišnjeg pacijenta
(Udruženje bronhologa Srbije, 2022-11)
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Kochovska-Kamchevska, Nade
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Baloski, Marjan
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Bushev, Jane
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Poposki, Bozhidar
Rak testisa je najčešći malignitet kod muškaraca od 15 do 35 godina. On čini oko 1% svih karcinoma. Prevalencija raka testisa kod belaca je 4,5 puta veća kod crnaca. Seminomi su osetljiviji na terapiju zračenjem i lakše se leče od neseminoma. To je vrsta raka koja počinje u zametnim ćelijama kod muškaraca. Seminomi se najčešće javljaju u testisu, ali se mogu javiti iu drugim delovima tela, kao što su mozak, grudni koš ili stomak.
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METABOLIC SYNDROME (METS) AS ONE OF THE MAJOR COMORBIDITIES OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
(Association of pulmologists from Republika Srpska, 2023-05)
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Baloski, Marjan
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Bushev, Jane
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Mickovski, Ivana
Aim: We aimed to investigate the association between COPD and MetS, the relation to the severity of airflow limitation. Methods: This is a cross-sectional study including 220 patients with initially diagnosed COPD (IG), aged 40 to 75 years and 58 non-COPD subjects matched by age, smoking status, body mass index, as controls (CG). All study participants underwent anthropometric measurements, fasting blood sugar (FBS), lipid profile, pulmonary evaluation (dyspnea severity assessment, baseline and postbronchodilator spirometry, gas analyses, chest X-ray). Results: Results presented statistically significant difference in presence of MetS in COPD patients compared to controls (32.27% vs 10.34%; P=0.0009). According to the GOLD classification, the frequencies of MetS in COPD patients were categorized in stages I, II, III, IV (17.54%, 37.10%, 34.62%, 40.82%, respectively). The proportion of patients with increased glycemic values was: a) GOLD1 - 18 (31.58%); b) GOLD 2 - 32 (51.61%); c) GOLD3 - 29 (55.77%); and d) GOLD4 - 31 (63.27%). There was no significant difference between IG and CG patients regarding HDL level. According to arterial hypertension the highest proportion was observed in GOLD3 - 22 (42.31%) followed by GOLD4 - 20 (40.82%), and GOLD3 - 22 (35.48 %), smallest in GOLD1 - 17 (29.82%). Conclusion: We found higher prevalence of MetS in patients with COPD even in early COPD stages compared to non-COPD. Our findings suggest an urgent need to develop comprehensive strategies for prevention, screening and start of treatment in early stage.
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Case report: Primary hyperparathyroidism due to mediastinal parathyroid adenoma
(Nizameddin KOCA, 2022-10-17)
Milosheska, Radmila
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Mickovski, Ivana
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Crcareva, Biljana
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<jats:p xml:lang="en">Primary hyperparathyroidism is defined by elevated parathyroid hormone and calcium levels, most usually caused by a parathyroid adenoma. Parathyroid adenomas are most commonly detected in the neck or an ectopic site, seldom in the mediastinum. The parathyroid adenoma can occur in ectopic locations such as the mediastinum, thymus, or retro oesophagal area in 6-16% of cases. We presented the example of a 73-year-old woman who was found to have hypercalcemia during a regular test. The patient’s serum calcium (3.11 mmol/L), alkaline phosphatase (162 U/L), parathyroid hormone (PTH: 379 pg/mL) and creatinine (111.6 umol/L) levels were higher than the reference values. A chest computerized tomography scan revealed an anterior mediastinal mass, and nuclear scintigraphy revealed functioning parathyroid tissue in the mediastinum. The mediastinal parathyroid adenoma was effectively removed surgically, and the PTH level began to fall. Any hypercalcemia and high PTH levels in the absence of a parathyroid adenoma in the neck should prompt clinicians to look for ectopic sites using a mix of imaging modalities.</jats:p>
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PREVALENCE OF BRONCHIECTASIS IN COPD PATIENTS
(2023-01)
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Mickovski, Ivana
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Neshovska, Radmila
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Buklioska, Adriana
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Trajkova, Vesna
Introduction - There is increasing recognition that radiological bronchiectasis is present in many patients with COPD. Computed tomography scan images have been used to identify different radiological COPD phenotypes based on the presence and severity of emphysema, bronchial wall thickening, and bronchiectasis. Bronchiectasis is defined as an abnormal dilation of the bronchi, usually as a result of chronic airway inflammation and/or infection. The prevalence of bronchiectasis in patients with COPD is high, especially in advanced stages, estimated prevalence varies from 4% to 50%. Methods - COPD patients underwent chest CT as part of their clinical assessment. Patients were included if COPD was diagnosed based on spirometry and clinical assessment and excluded if there was clinical bronchiectasis. Scoring was by a simplified system based on Smith (Thorax, 1996) and returned a score of 0 (no bronchiectasis), 1 (0–50% of bronchi involved), or 2 (50–100% of bronchi involved) for each lobe, with a total score of 12 including the lingula; emphysema, interstitial lung disease (ILD), or other pathology was noted. A total of 220 COPD patients (77.2% ex- or current smokers, 79.5% male) were consecutively enrolled. Results - Bronchiectasis was present in 54.5% of patients (score ≥2/12) and there was significant inter-observer correlation in the scoring (r=0.63, p<0.0001). Scores were highest in the lower lobes and lowest in the middle lobes (1.66 vs 0.86, p<0.000). Patients with widespread bronchiectasis (score ≥6/12) had a trend towards reduced bronchodilator reversibility (4% vs 9%, p=0.08) than those with limited bronchiectasis. Emphysema was present in 77.2% and ILD in 11.36%. The overall prevalence of emphysema was not different between patients with and without previous pulmonary tuberculosis (PTB) n=30 (13.63%), but in those with previous PTB, a higher number of subjects with middle (p=0.002) and lower (p=0.017) lobe emphysema, higher severity score (p=0.029), higher prevalence of panlobular emphysema (p=0.015), and more extensive centrilobular emphysema (p=0.036) were observed. Conclusions - In this study, we found a higher prevalence of bronchiectasis than previously reported which may reflect the heterogeneity of COPD patients in a general respiratory clinic. Radiological features of bronchial wall thickening and mild bronchiectasis were commonly seen and when widespread this may result in reduced bronchodilator reversibility; however, the presence of radiological bronchiectasis was not related to disease severity. COPD patients with previous PTB had unique features of bronchiectasis and emphysema on HRCT, which were associated with significant dyspnea and higher frequency of severe exacerbations.
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Primary hyperparathyroidism due to mediastinal parathyroid adenoma
(Turkish Journal of Internal Medicine, 2023-10-29)
Miloshevska, Radmila
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Mickovski, Ivana
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Crcareva, Biljana
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Muratovska, Liljana
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Primary hyperparathyroidism is defined by elevated parathyroid hormone and calcium levels, most usually caused by a parathyroid adenoma. Parathyroid adenomas are most commonly detected in the neck or an ectopic site, seldom in the mediastinum. The parathyroid adenoma can occur in ectopic locations such as the mediastinum, thymus, or retro oesophagal area in 6-16% of cases. We presented the example of a 73-year-old woman who was found to have hypercalcemia during a regular test. The patient’s serum calcium (3.11 mmol/L), alkaline phosphatase (162 U/L), parathyroid hormone (PTH: 379 pg/mL) and creatinine (111.6 umol/L) levels were higher than the reference values. A chest computerized tomography scan revealed an anterior mediastinal mass, and nuclear scintigraphy revealed functioning parathyroid tissue in the mediastinum. The mediastinal parathyroid adenoma was effectively removed surgically, and the PTH level began to fall. Any hypercalcemia and high PTH levels in the absence of a parathyroid adenoma in the neck should prompt clinicians to look for ectopic sites using a mix of imaging modalities.
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Clinical Features of a young Patient with COVID-19 presented with ARDS and severe thrombocytopenia
(Via Medica, 2022-07-22)
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Mickovski, Ivana
Case report of a 33-year-old male SARS-CoV-2 positive patient admitted to hospital because of hemopty sis, dyspnea, fever, oxygen saturation of 60%, hypoxemia, elevated C-reactive protein (CRP). The patient was not vaccinated and it was his first infection with the virus. The symptoms started 10 days before with headache, fever, and cough. Chest radiography on hospital admission detected diffuse interstitial pneu monia in both lungs. Initial CT (Computed Tomography) presented extensive lung involvement with bilateral wide areas of consolidation with air bronchogram, the non-consolidated area showing patchy ground glass infiltration. The patient was hospitalized in ICU (Intensive Care Unit), oxygen support was started immediately with non-invasive ventilation (NIV), CPAP (Continuous Positive Airway Pressure) mode, FiO2 (Fraction of inspired Oxygen) 100%, PEEP (Positive end-expiratory pressure) 8, and the saturation started to increase. Therapy consisted of parenteral antibiotic, low-molecular weight heparin (LMWH) in prophylactic doses, pulsed dose of corticosteroid (methylprednisolone), Remdesivir, tocilizumab (Actemra), albumin, protein-pump inhibitor, antipyretics, fluids, physical therapy. Microbiology results from sputum detected MRSA (methicillin-resistant Staphylococcus aureus) and therapy with Vancomycin was started according to recommendations. After three days of vancomycin therapy, the patient manifested profuse epistaxis and tamponade was necessary. Hemostasis result was normal, but severe thrombocytopenia was noticed in the blood count. Platelets and plasma were administered and the bleeding stopped. Vancomycin was replaced with Linezolid. In the next days of follow up, the platelets increased, and the corticosteroid dose was slowly reduced. During the treatment as the health status of the patient improved, the CPAP therapy was replaced with routine oxygen support, gradually lowering the oxygen flow until saturation of 94% was achieved at ambient air. The COVID-19 pandemic is still evolving and the medical fraternity is posed with a huge challenge. COVID-19 is primary a respiratory viral infection, but the virus can affect many organs and systems, presenting various signs, symptoms and outcomes.
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Is Semaglutide superior than Liraglutide in patients with type 2 diabetes on insulin therapy? - case presentation
(Bioscientifica, 2022-05-07)
Mickovski, Ivana
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Milosheska, Radmila
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Hasan, Taner
Introduction Type 2 diabetes (T2DM) is a chronic and progressive disease associated with microvascular and macrovascular complications leading to increased morbidity and mortality. Insulin remains the cornerstone therapy for longer-duration T2DM and b-cell failure. T2DM is a complex disorder that requires individualized treatment strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of multifactorial T2DM medications that have been shown to improve numerous risk factors for diabetes-related complications, including glycemic control, reduction in body weight and a low risk of hypoglycaemia. Case Presentation A 65-year old obese male presented to the outpatient clinic of Endocrinology, 8th September City General Hospital, Skopje for a regular checkup. He has T2DM for a long time and the last 10-15 years was switch on insulin therapy – at the moment was on premix insulin – Insulin Aspart and OAD. He was complaining of variation of glycaemia (5.0-16.5 mmol/l), felling a little bit thirsty, hungry and without energy. He has arterial hypertension and dyslipidemia (medications was prescribe from cardiologist) but could not tolerated any statins. He is a nonsmoker, with two children and retired. Investigations Initial investigation showed HgA1c 55.2 mmol/mol, FPG 9.1 mmol/l, elevated cholesterol (cho -6.8 mmol/l), low density (LDL – 2.8 mmol/l) triglyceride ( Tg - 2.7 mmol/l). His renal and liver functional test were within normal limits. The tests for thyroid functional were also normal. He was 180centimetar tall, 149kg weight and his body mass index (BMI) was 46.0. Echotomography showed steatotic liver, echocardiography and ophthalmic tests were in normal range for his age. Treatment The patient was overweight, hasn’t achieved the optimal glycemic control even though he was on insulin therapy and one of his biggest concerns was his weight , so the medical team decided to add Liraglutide on his diabetes therapy with gradual titration of the dose ( Liraglutide - was started at 0.6mg daily subcutaneously for 1 week and then increased from 1.2 mg to 1.8mg daily). Also he was educated about titration of the dose of the insulin therapy together with additional lifestyle modifications Because of the positive effect from the therapy with once daily GLP-1 RA, and because we wanted to continue with weight loss, but at the same time reduce the everyday subcutaneous therapy we decide to change Sol Liraglutide 1.8mg per day with Sol Semaglutide starting with 0.25mg once a week for 1 month and then titrating the doses till 1mg per week, together with reducing the insulin therapy, metformin 2000mg daily, balance food and physical activity (Table 1). Discussion The objective of this case report was to demonstrate the efficacy and safety of onceweekly semaglutide vs once daily GLP-1 RAs in patient with T2DM inadequately controlled on insulin therapy (± OADs). In our case report, we observed that once-weekly semaglutide 1 mg was dominant compared with once-daily liraglutide 1.8 mg. In this case report, once-weekly semaglutide 1.0 mg was the most clinically effective GLP-1 RA for achieving glycemic targets and reducing HbA1c, FPG, and body weight in patient who is receiving insulin therapy. In patients with T2DM inadequately controlled with insulin therapy, semaglutide provided superior improvements in mean HbA1c, FPG, and superior weight loss compared with liraglutide. Conclusion Semaglutide, administered subcutaneously once weekly, provided superior glycemic control and body weight reductions compared with other GLP-1 RA in patient with T2DM receiving insulin therapy. Therefore, it is likely that once-weekly semaglutide will not increase the risk of hypoglycemia when added to insulin therapy. The reasons for switching to semaglutide from liraglutide included a need to reduce HbA1c or weight further, decreased frequency of administration and cardiovascular protection. In addition, significant weight loss was observed with both doses of semaglutide vs liraglutide.
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Comorbidities of patients with chronic obstructive pulmonary disease (COPD): thyroid abnormalities in stable COPD
(VM Media SP. zo.o VM Group SK, 2021-09-30)
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Mickovski, Ivana
Objective: The aim of the study is to evaluate the prevalence of thyroid abnormalities in patients with stable chronic obstructive pulmonary disease (COPD) and the relationship between thyroid disorder and ventilatory function tests and arterial blood gas analyses. Material and methods: This cross-sectional study was conducted with 60 patients with stable COPD without diagnosed thyroid disorder before the study (37 males and 23 females aged 40-75) as the Investigated Group (IG) and 30 subjects from the general population without COPD as the Control Group (CG). They were matched by age, gender and body mass index with the IG. All patients underwent laboratory tests, thyroid hormones-free thyroxin (fT4), thyroid-stimulating hormone (TSH), and free triiodothyronine (fT3), pulmonary function tests (FEV 1 , FVC%, FEV 1 /FVC, FEF25-75%), and ABG parameters (PH, PaCO 2 , PaO 2 , HCO 3 , O 2 saturation). The severity level in patients with COPD was determined according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria and classified into four stages GOLD I, II, III, and IV. Results: Our results presented a statistically significant difference between prevalence of thyroid hormones abnormalities in stable COPD compared to controls 18 (30.0%) vs 3 (10.0%), p = 0.0355; p < 0.05). Thyroid dysfunction among COPD patients was more common in females than males. Serum level of TSH was lower than the normal range in 18 patients (30.0%) from the IG and in 3 (10.0%) from the CG, with a statistically significant difference, p = 0.0355; p < 0.05. Thyrotoxicosis with low serum TSH and a higher serum level of fT3, according to the referent range, was present in 8 patients (13.3%), and in no patients from the CG 0 (0.0%), p = 0.0375; p < 0.05. The prevalence of subclinical hyperthyroidism with low serum TSH and normal serum level of fT3 was higher in the IG-10 patients (16.7%) compared with 3 (10.0%) of the CG, but the difference was not statistically significant p = 0.3970. Acute exacerbation frequency of IG was significantly higher than in the CG (1.6 ± 0.42 and 0.82 ± 0.79 respectively; p < 0.0001). A positive significant relationship between acute exacerbation frequency and TSH values was found (p < 0.0001; r = 0.82). The mean values of fT3 in the IG were significantly increasing with the increased severity of COPD. The degree of airflow limitation in COPD (FEV 1 as a percentage of the predicted value, FEV 1 %pred) was significantly negatively correlated to fT3, Pearson correlation, (R =-0.525; p = 0.000; p < 0.01). FEV 1 %pred was positively correlated with TSH (R = 0.358; p = 0.005; p < 0.01). Significant negative correlations were present between fT3 levels and both PaO 2 and SO 2 in the IG, and elevation of fT3 was associated with higher PaCO2. Conclusion: The present study confirms that both clinical and subclinical hyperthyroidism was higher in patients with COPD compared to the non-COPD group. TSH and fT3 are related to lung function. A better understanding of the correlation between thyroid gland disorders and COPD may contribute to better care of patients.
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Graft-versus-host disease in patients treated with allogenic hematopoetic cell transplantation: experience from North Macedonia
(VM Media SP. zo.o VM Group SK, 2021-10-28)
Mickovski, Ivana
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Hasan, Taner
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Nedeska Minova, Natasha
Introduction: Graft-versus-host disease (GvHD) is the major complication arising after allogeneic hematopoietic cell transplantation (allo-HCT). It can be presented as acute and/or chronic GvHD. The purpose of this study was describe the incidence of acute and chronic GvHD in patients treated with allo-HCT. Materials and methods: This study was designed as a retrospective study, which included 65 patients treated with allogeneic transplantation from human leukocyte antigen identical donor at University Clinic of Hematology in Skopje, North Macedonia. Results: Acute GvHD (aGvHD) was observed in 28 patients, with the most common localization on the skin (75%). Post-transplant phase had significant effect on the frequency of skin aGvHD (p =0.038). Also statistically significant difference was confirmed between patients with and without acute skin GvHD in terms of conditioning regimen (p =0.034). Chronic GvHD (cGvHD) was diagnosed in 10 patients, mostly progressing from the previous acute GvHD (9.23%). Post-transplant phase had also significant effect on the frequency of skin cGvHD (p =0.018). Patients with higher European Society for Blood and Marrow Transplantation risk score had significantly more frequent skin cGvHD than the others. Conclusions: Acute and chronic GvHD were one of the main causes of morbidity and mortality of patients after aloo-HCT. GvHD remains a major risk for patients with allo-HCT regardless of diagnosis and type of transplantation.

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