Faculty of Medicine

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    Beyond Sodium: Inflammation as the Strongest Predictor of Mortality Among Non-Diabetic Hemodialysis Patients
    (Macedonian Academy of Sciences and Arts, 2026-06-01)
    Eftimovska-otovikj Natasha
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    Poposka, Elizabeta
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    Popovska, Bojana
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    : Standard dialysate sodium concentration (sDNa) may not adequately reflect individual sodium requirements in each hemodialysis patient, potentially contributing to interdialytic weight gain (IDWG), hypertension and inflammation. The aim of this study was to compare clinical and biochemical outcomes between individualized and standard dialysate sodium prescriptions and to assess factors associated with mortality. : This was a prospective interventional study conducted in two phases. In the first phase, patients were treated with standard hemodialysis (HD) using a fixed dialysate sodium concentration of 138 mmol/L. In the second phase, dialysate sodium was individualized based on each patient's pre-dialysis serum sodium concentration. Each patient served as their own control. Outcomes included IDWG, blood pressure, thirst score, dialysis adequacy (Kt/V, URR), nutritional markers, C-reactive protein (CRP), electrolytes, and mortality. : Individualized dialysate sodium prescription was associated with a significant reduction in IDWG (1.93 ± 0.64 vs 2.17 ± 0.79 kg; p = 0.001) and improved dialysis adequacy (Kt/V: 1.50 ± 0.24 vs 1.36 ± 0.22; p < 0.001). Survivors had higher serum albumin levels and lower CRP values compared to non-survivors. Serum and dialysate sodium concentrations were not independently associated with mortality. In logistic regression analysis, CRP >10 mg/L showed the strongest observed association with mortality (OR 10.278; 95% CI 1.709-61.826; p = 0.011). : Individualized dialysate sodium prescription may improve fluid control and dialysis adequacy in selected patients. Inflammation was significantly associated with mortality in this cohort; however, results should be interpreted with caution due to the limited number of events.
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    NGAL and HPV Subtypes in Cervical Carcinoma: Implications for Cancer Progression and Treatment Response
    (MDPI AG, 2026-02-23)
    Raci, Behar
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    Hodolli, Gezim
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    Background/Objectives: Cervical cancer is a prominent source of morbidity and mortality among women, particularly in low- and middle-income nations. Neutrophil Gelatinase-Associated Lipocalin (NGAL), a glycoprotein involved in cancer-related activities, has been proposed as a biomarker; however, its involvement in cervical cancer remains unknown. The study aim is to evaluate the prognostic significance of serum NGAL levels in cervical cancer patients in relation to International Federation of Gynecology and Obstetrics (FIGO) stage, operability, and HPV subtype distribution before and after treatment. Methods: The study involved 130 women, 100 with histologically proven cervical cancer and 30 healthy controls. The serum NGAL levels were determined before and after treatment using an ELISA test. HPV genotyping was carried out using real-time PCR on 21 high- and low-risk subtypes. Results: NGAL levels increased marginally during therapy (from 134 to 144 ng/mL; p = 0.28), but the rise was significant in inoperable patients (p = 0.02) and increased with advanced FIGO stage, although this did not reach statistical significance (p = 0.07). HPV 16 was the most common subtype (26.0%), while women aged 51–60 had the highest overall HPV positive rate (72.7%). There was no significant association between NGAL levels and HPV subtypes (p = 0.17). Conclusion: NGAL does not appear to be an accurate short-term indicator of therapy response. However, increased levels in advanced-stage and inoperable instances indicate prognostic significance. NGAL most likely represents tumor-associated inflammation rather than HPV subtype. These findings support its possible inclusion in future biomarker panels, subject to validation in bigger investigations. Persistent HPV infection in midlife women highlights the significance of ongoing screening.</jats:p>
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    Linking inflammation and cardiovascular disease: the emerging role of lipoprotein-associated phosphoplipase A2
    (Ltd Chetverta Кhvylia, 2025-12)
    Kostovska, Irena
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    Over the past decades, inflammation has been recognized as a key contributor to the development of atherosclerosis, prompting extensive research. Numerous inflammatory markers have demonstrated predictive value for both initial and recurrent coronary events in individuals with or without established coronary vascular disease (CVD). Among these, lipo protein associated phospholipase A2 (Lp PLA2) has garnered significant attention. Lp PLA2 may be involved in the athero sclerotic process and contribute to plaque destabilization through its inflammatory activity within atherosclerotic lesions. Lipoprotein associated phospholipase A2 (Lp PLA2), a recently identified cardiovascular specific inflammatory mediator, is closely associated with the onset and progression of cardiovascular events. This review explores the potential of Lp PLA2 as both a risk marker and a therapeutic target in CVD. Elevated levels of Lp PLA2 mass and activity have been linked to an increased risk of CVD in both the general population and patients with pre existing disease. However, it remains uncer tain whether incorporating Lp PLA2 measurements into risk prediction models significantly enhances risk stratification beyond traditional cardiovascular risk factors. Additionally, the failure of darapladib, a potent and selective Lp PLA2 inhibitor, to reduce CVD events in major randomized, placebo controlled trials suggests the importance of ongoing research to fully understand its functions and develop effective strategies for CVD prevention and treatment.
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    BIOMARKERS IN OBESITY-RELATED METABOLIC SYNDROME: FROM PATHOPHYSIOLOGY TO CLINICAL APPLICATION
    (Macedonian Association of Anatomists and Morphologists, 2025-11-25)
    Kostovska, Irena
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    Obesity-related metabolic syndrome (MetS) represents a complex, multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, hypertension, and chronic low-grade inflammation. Its rising global prevalence underscores the urgent need for comprehensive understanding and early detection strategies. While traditional clinical and biochemical parameters provide insight into overt metabolic dysfunction, they often fail to capture upstream molecular disturbances. Recent research has identified a spectrum of novel biomarkers that reflect the pathophysiological mechanisms underlying MetS, including inflammatory mediators (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1), adipokines and hormonal regulators (adiponectin, leptin, resistin, visfatin, ghrelin, glucagonlike peptide-1), oxidative stress and endothelial dysfunction markers (malondialdehyde, 8-isoprostane, oxidized LDL, asymmetric dimethylarginine, paraoxonase-1), thyroid function indicators (TSH, free thyroxine, anti-thyroid peroxidase antibodies), vitamin D, and genetic/epigenetic modulators (microRNAs and DNA methylation patterns). This review summarizes current evidence on these biomarkers, highlighting their roles in elucidating disease mechanisms, enabling early risk assessment, guiding therapeutic interventions, and supporting precision medicine approaches. Future research directions are proposed to standardize assays, validate findings across diverse populations, and develop integrated multi-marker panels to optimize the management of obesity-related MetS.