Faculty of Medicine

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The role of pre-existing renal dysfunction on in-hospital morbidity and mortality in patients with acute coronary syndrome
(Oxford University Press (OUP), 2024-04)
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Bogevska, I
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Dobjani, A
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Shehu, E
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Taravari, H
Introduction The baseline renal function is an important predictor for the prognosis of patients with acute coronary syndrome (ACS). The aim of our study was to analyse the impact of pre-existing renal failure (RF) and the risk profile of patients with ACS on the development of in-hospital morbidity and mortality. Materials and methods This was a single-center cross-sectional cohort study on 2702 patients with ACS. The main exclusion criterion was pre-existing left ventricular (LV) dysfunction. Demographical and clinical characteristics, biochemical parameters, the anatomical distribution of coronary artery disease, and the final outcomes were analysed according to presence of RF at the moment of the index event. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease Study Group Equation (MDRD), where patients with eGFR<60 ml/min/1.73 m2 had moderate to severe renal dysfunction. Results 777 (22.3%) out of 2702 patients had eGFR <60 ml/min at the moment of the index event. These patients were predominantly female, 34.1% (333) vs.17.7% (444), p=0.0004,OR 1.921(95%CI 1.701-2.168);older (70.0±9.7vs.60.5±10.7;p <0.000). They had significantly higher values of cardiac troponin (p=0.007), stress glycemia (p=0.000019), glycated hemoglobin (p=0.000012), and WBC (p=0.00001), meaning the extent of myocardial injury was bigger, with a more activated neuro-hormonal and inflammatory response in the conditions of the notably widespread anatomical distribution of CAD. However, patients with significantly reduced eGFR were less likely to be offered coronary angiography and PCI treatment, OR 0.524 (95%CI 0.434–0.632),p <0.000. As expected, anemia predominated in these patients (RBC 4.88±0.75 vs 4.53±0.58, p=0.000001; OR 1.27 (95% CI 1.09-1.48), and Hgb 143.81±16.69 vs 132.03±21.34, p=0.00001). They had a significantly lower level of sodium (p=0.008) and a higher level of potassium (p=0.00003). Interestingly, patients with eGFR <60 ml/min had lower lipoprotein levels. In-hospital mortality rate was 4.2%, however, significantly higher in reduced eGFR group (12% vs 1.9%, OR 6.9 (95% CI 4.9–9.8), p <0.00004). These patients were more likely to develop acute kidney injury [25.7% vs. 1.3%, OR 1.6 (95% CI 1.3-1.9, p = 0.000021)], pulmonary oedema [8% vs. 1.8%, OR 1.12 (95% CI 1.02-1.23, p = 0.000021), and cardiogenic shock [19.5% vs. 2.6%, OR 1.22 (95% CI 1.2-1.4), p = 0.00023]. Independent variables associated with RF were: advanced age, female gender, extracardiac ASCVD, previous CVI, previous RAAS treatment, stress glycemia, triglyceride, cholesterol, LDL-C, Hgb, WBC, and potassium level. Conclusion Patients with reduced eGFR (<60 ml/min) have a very specific risk profile, as identified in our study, and reduced eGFR is a major contributor to the prognosis of ACS, highly responsible for in-hospital morbidity and mortality.
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Left ventricular systolic function in patients with acute coronary syndrome-risk profile
(Oxford University Press (OUP), 2024-04)
Dobjani, A
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Bogevska Naumovska, I
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Shehu, E
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Taravari, H
Introductions and objectives Left ventricular (LV) systolic dysfunction is one of the most important determinants of long-term outcome in acute coronary syndrome (ACS). Aim To determine the impact of the patient’s risk profile on the LV systolic function. Methods A single-center cross-sectional cohort study that included 3093 patients with ACS without pre-existing LV dysfunction. The comparison was performed between patients who did or did not develop a reduction in LV systolic function during the index event (<50%/≥50%), analyzing patients’ demographic, clinical, biochemical data, LV functional data, and anatomical distribution of the coronary artery disease (CAD). Result 1369 patients out of 3093 developed LV systolic dysfunction (44.3%). They were predominantly males 75.1% (1028), p=0.002; older (63.39±11.04 vs 61.21±11.12, p<0.00000); had higher level of cardiac troponin (p=0.00002), higher stress glycemia (9.2±5.3; p=0.0000001), HbA1c (6.9±1.8, p=0.000003), WBC (11.7±4.1, p=0.00001), blood urea nitrogen (BUN) (6.8±3.7, p=0.000003), and creatinine (93.2±45.1 p=0.000167), and had anemia (OR 0.35 (CI 0.29–41, p=0.000012). They had more severe CAD (SINTAX score 16.8±8.4 p=0.000012). Patients with preserved LV systolic function were predominantly females (29.7%, OR 1.1 95% CI 1.0-1.2), p = 0.002), younger (p<0.00000), and severely metabolically burdened (hypothyreosis (2.7%, OR 1.28 95% CI 0.93-1.76, p=0.052), higher levels of triglycerides (2.2±1.7 vs 1.9±1.5, p = 0.001), cholesterol (5.3±1.4 vs 5.2±1.4, p = 0.002), non-HDL-C (4.1±1.5 vs 3.9±1.3, p=0.006), however less likely to have pre-existing DM (OR 0.8 (CI 0.78–0.92), p=0.000094). They were more often NSTEMI [851 (49.4%), p = 0.000012]. Independent variables associated with a reduction in LV function were: advanced age, male gender, previous DM and anemia, stress glycemia, WBC, creatinine, and BUN. Conclusion Patients who developed reduced LV function had a very specific risk profile with bigger neuro-hormonal activation and inflammation, higher degree of myocardial damage, and worse renal function, whereas those with preserved LV systolic function after ACS were younger, predominantly females, more severely metabolically burdened, more often with NSTEMI and without LAD involvement.
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Acute kidney injury in patients with acute coronary syndrome - risk profile
(Oxford University Press (OUP), 2024-04)
Bogevska-Naumovska, I
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Dobjani, A
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Shehu, E
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Taravari, H
Introduction Acute kidney injury (AKI) is a strong predictor of in-hospital adverse outcomes, which is a common complication of acute coronary syndrome (ACS). Aim To analyse the risk profile of patients treated for acute coronary syndrome who develop acute kidney injury. Material and methods This is a single-centre cross-sectional cohort study on 3507 patients with ACS. The main exclusion criteria was left ventricular dysfunction. Demographical and clinical characteristics, biochemical parameters, the anatomical distribution of coronary artery disease (CAD) and the final outcomes were analysed according to RF at the moment of the indexed event. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease Study Group Equation (MDRD), where patients with eGFR<60ml/min 1.73 m2 had moderate to severe renal dysfunction. Results 74 (2.1%) out of 3507 patients developed acute kidney injury (AKI). Those were predominantly males [62.2% (46), OR 1.55 (95% CI 0.98-2.47), p=0.044], significantly older (68.95±9.9. vs 62.5±11.2; p <0.000001), more often with preexisting HBI (OR 4.72 (95% CI 2.20-10.30, p=0.000070), HTA(OR 1.89 95%CI 1.11-3.23, p=0.020), diabetes(OR 1.88 95%CI 1.18-3.00, p=0.008), cancer(OR 2.92 95%CI 1.15-7.44, p=0.024), anaemia (beta -.104, p=0.000032), while less often were smokers (OR 0.51, 95% CI 0.31-0.83, p=0.006). They had statistically significantly higher values of cardiac troponin (beta .075, p=0.000011), stress glycemia (beta .104, p=0. 0.000019), and WBC (beta .074, p=0.000013), higher BUN (beta .325, p=0.000011), creatinine (beta .268, p=0.000016), and lower eGFR at admission (beta -.211, p=0.000032), lower sodium (beta -.101, p=0.000012), and higher potassium levels (beta .087, p=0.0008). Vice versa, total cholesterol, LDL-C and non-HDL-C (beta -.051, p=0.002, -.049, p=0.003, and -.047, p=0.005 respectively), were lower, the same for Hgb (beta -.107, p=0.000021). It is worth mentioning that 18(11.5%), of AKI patients were not PCI treated. Independent variables associated with AKI were: preexisting renal failure, cancer, and WBC. Outcomes: AKI carried a significantly higher in-hospital mortality rate (4.2% in general population, and 21.1% of all deaths were AKI patients, OR 23.01 (95% CI 14.04-47.03, p=0.00002)]. It was significantly associated with the development of pulmonary oedema (OR 17.94, 95% CI 9.67-33.26, p=0.000012), cardiogenic shock (OR 21.59, 95% CI 12.79-36.47, p=0.00006), any type of dysrhythmia (OR 1.83, 95%CI 1.53-2.18, p=0.0001), and any type of bleeding complications (OR 1.61, 95%CI 1.14-2.27, p=0.007). Conclusion AKI is a relatively rare complication in ACS patients, however, it is associated with significant in-hospital morbidity and mortality. Patients with pre-existing renal failure, and cancer, as well as patients who developed more pronounced inflammatory reactions, were more prone to AKI.
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TYPE 2 MYOCARDIAL INFARCTION
(MIT University Skopje, 2023)
Mitevski Goran
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Nikolovski Robert
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Furnadjiski Atanas
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Myocardial injury is when there is elevated cardiac troponin values at least one value above the upper reference limit (URL). Causes of elevated troponin can be sustained bradyarrhythmia, hypotension, shock, respiratory failure, anemia, tachyarrhythmia, hypertension, heart failure, defibrillator shocks, sepsis, chronic kidney disease, stroke, subarachnoid hemorrhage, pulmonary embolism, pulmonary hypertension, infiltrative disease (amyloidosis, sarcoidosis..), chemotherapeutic agents, critically ill patients, strenuous exercise, cardiac ablation, cardiomyopathy, coronary spasm, microvascular dysfunction, atherosclerotic plaque disruption with thrombosis, etc. When it is associated with myocardial ischemia it is designated as myocardial infarction (MI). Type 2 myocardial infarction occurs due to disturbed oxygen supply and/or unbalanced demand. There are no conditions that are characteristic for type 1 MI such as plaque, rupture and thrombosis
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Association of CURB-65 (Confusion, Urea, Respiratory Rate, Blood Pressure) with Mortality of Patients with Severe Community-Acquired Pneumonia
(Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 2009)
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Background. Severe community-acquired pneumonia (sCAP) is serious, life-thretening condition, with high mortality rate. Scoring systems for disease severity are used for predicting mortality in patients with pneumonia. Objective of this study was to identify the parameters of CURB-65 score that have higher association with mortality in patients with severe CAP. Material and methods. One hundred and two patients with community-acquired pneumonia were enrolled in the study. The study was conducted at the Intensive Care Department of the Clinic for Infectious Diseases and Febrile Conditions-Skopje. Demographic, clinical and biochemical parameters were analyzed and CURB-65 was calculated in each patient at admission. Predictors were identified using logistic regression analysis. Receiver Operating Characteristic Curve (ROC) was constructed for assessing discriminative power of analyzed parameters. Results. CURB-65 identified severe CAP in 32 (31,4%) patients, with overall mortality rate of 62,5%. Confusion, respiratory rate > 30/min and urea > 7mmol/L had significant association with the mortality. Conclusion. CURB-65 is a simple tool that can identify patients with severe CAP and can be used for early prediction of patients mortality.
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Evaluation of severity scoring systems in patients with severe community acquired pneumonia
("N Gh Lupu" Foundation of Internal Medicine and Romanian Academy, 2021-12)
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Background. The aim of this study was to evaluate the ability of severity scoring systems to predict 30-day mortality in patients with severe community-acquired pneumonia. Methods. The study included 98 patients aged ≥18 years with community acquired pneumonia hospitalized at the Intensive Care Unit of the University Clinic for Infectious Diseases in Skopje, Republic of North Macedonia, during a 3-year period. We recorded demographic, clinical and common biochemical parameters. Five severity scores were calculated at admission: CURB 65 (Confusion, Urea, Respiratory Rate, Blood pressure, Age ≥65 years), SCAP (Severe Community Acquired Pneumonia score), SAPS II (Simplified Acute Physiology Score), SOFA (Sequential Organ Failure Assessment Score) and MPM (Mortality Prediction Model). Primary outcome variable was 30-day in-hospital mortality. Results. The mean age of the patients was 59.08 ± 15.76 years, predominantly males (68%). The overall 30-day mortality was 52%. Charlson Comorbidity index was increased in non-survivors (3.72 ± 2.33) and was associated with the outcome. All severity indexes had higher values in patients who died, that showed statistical significance between the analysed groups. The areas under curve (AUC) values of the five scores for 30-day mortality were 0.670, 0.732, 0,726, 0.785 and 0.777, respectively. Conclusion. Widely used severity scores accurately detected patients with pneumonia that had increased risk for poor outcome, but none of them individually demonstrated any advantage over the others.
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Hypertension in athletes
(MIT University, 2023-03)
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Furnadjiski, Atanas
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Mitevski, Goran
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Nikolovski, Robert
Hypertension is the most common cardiovascular disease in athletes. Prompt diagnosis and management is crucial for ensuring safe sport participation and prevention of long term complications in athletes. Many diagnostic tools are involved in the management algorithm of the hypertension starting from good anamnesis especially the family history, as well as other simple and sophisticated paramedical imaging techniques, as ECG, Echocardiography, 24 Hours ambulatory ECG monitoring, cardiac MRI and many others. Distinguishing an athlete heart from pathological heart muscle hypertrophy is the key step for the differential diagnosis. Conclusion: Proper pharmacological and non pharmacological measures will facilitate satisfying long term prognosis for the athletes.
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Tumour budding – an additional prognostic facto r in colorectal cancer survival
(Termedia, 2023-03)
Gülçİn Harman Kamall
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Cemal Ulusoy
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Sedat Kamall
Tumour budding (TB) in cancer is a phenomenon of tumour cells forming clusters, and it is associated with an epithelial-mesenchymal transition into the extracellular matrix of the tumour. It has been shown that the presence of TB in colorectal cancer (CRC) is associated with worse overall survival, higher possibility for vessel invasion, lymph node involvement, and distant metastases appearance. In this retrospective study TB presence in operated patients for CRC is analysed. In the data from 81 patients, 26 presented with TB. Analysis revealed high statistical significance of the effect of TB presence on the number of metastatic lymph nodes, and the lymphovascular and perineural invasion. A statistically meaningful correlation was found between the presence of TB and CRC survival (p = 0.016). Patients with right-sided colon cancer presented with worse overall survival (p = 0.011). The patients who presented lymph node metastases and TB presence had worse overall survival (p = 0.026 and p = 0.021, respectively). Tumour budding, tumour location, and age over 64 years are found to be the independent prognostic factors in CRC patients. Tumour budding is an important prognostic factor in CRC patients that will contribute to treatment. Pathological examination must consider TB in detail.
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Incremental Value of Cardiac Biomarkers in Mid-term Prognosis of Patients with Acute Coronary Syndrome
(Scientific Foundation SPIROSKI, 2022-02-14)
Serafimov, A
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Donevski, D
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Karakolevska Ilova, M
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Joveva, E
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Todosieva Serafimova, K
Background: Given the number of prognostic studies, both short- and long-termed, in patients with myocardial infarction (MI), the data on predicting major adverse cardiac events (MACE) following discharge still remains limited. Aim: to identify early predictors of MACE in MI patients, that underwent Primary Percutaneous Coronary Intervention (pPCI), with special emphasis on multiple cardiac biomarkers. Materials and methods: we analysed clinical, LV functional, angiographic variables, as well cardiac troponin, a marker of myocardial necrosis, natriuretic peptide (NT-proBNP), a marker of myocardial stress, and white blood cells (WBC), as a marker of inflammation. The study population were 150 consecutive patients treated for acute myocardial infarction. Results: The average follow-up period was 31 months. In total, 26 patients suffered from at least one MACE. Multivariate logistic regression analysis identified several independent predictors: NT-proBNP (p=0,07), number of diseased vessels (p=0,027), and need for loop diuretic therapy (p=0,050). ROC curve demonstrated excellent discriminatory function for MACE of NT-proBNP and WBC (area under the curve .640, and .658, p=0.025 and 0.011 respectively). Conclusion: The combination of biomarkers for myocardial stress and inflammation improves the prediction of major adverse cardiac events in MI survivors.
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Prognostic significance of the HPV status in early stage cervical carcinoma
(Macedonian Academy of Sciences and Arts, 2006-09)
Kubelka-Sabit, Katerina
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Prodanova, Irina
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Yashar, Genghis
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Zografski, George
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Aims: In order to evaluate their prognostic significance, the parameters of the human papilloma virus (HPV) status were correlated to the lympho-nodal and tumor status, maximal diameter, minimal thickness of uninvolved stroma, histologic type, grade of differentiation, lympho-vascular space invasion, degree of lymphocytic inflammatory stromal reaction at the invasion front, age and the disease-free survival (DFS) of the patients with early stage invasive cervical carcinomas. Material and methods: 77 cases of cervical carcinomas, limited to the uterus, surgically treated and postoperatively irradiated, were selected for this retrospective study. HPV DNA status (presence and HPV type, type of hybridization signal and number of positive cells per sample) was evaluated using sensitive in situ hybridization detection kit with catalyzed signal amplification with biotinylated probes for types 6/11, 16/18 and 31/33 or 31/33/51. Results: The presence of HPV DNA was detected in 45 (58.4%) cases. Thirty-two (71.1%) showed positivity for HPV type 16/18, 8 (17.8%) for 31/33, whereas multiple infection was detected in (8.9%) 4 cases. Dot hybridization signal was found in 31 (68.9%), diffuse in 2 (4.4%) and mixed in 12 (26.7%) cases. More than five positive nuclei per sample were found in 37 (82.2%) of the cases. Only the presence of HPV was associated with absence of regional lymph node involvement, presence of moderate/abundant lymphocytic infiltration and longer 5 and 10-year DFS. Conclusions: According to our results, more extensive studies are needed to assess the real prognostic influence of the other parameters of HPV status in early stage cervical carcinomas.

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