Farid Ljuca

Background/Objectives: Elevated lipoprotein(a) [Lp(a)] is an independent causal risk factor for atherosclerotic cardiovascular disease and may contribute to increased coronary complexity and adverse outcomes after acute myocardial infarction (AMI). Data regarding its prognostic significance in Southeastern Europe remains limited. This study aimed to evaluate the association between elevated Lp(a) levels, coronary artery disease severity, and major adverse cardiovascular events (MACE) at 1 and 6 months after AMI. Methods: This prospective study included 150 consecutive patients with STEMI and NSTEMI enrolled between December 2024 and August 2025. MACE was defined as a composite of overall cardiac death, recurrent myocardial infarction, cerebrovascular insult, heart failure with reduced ejection fraction occurrence, and new revascularization, either PCI or CABG. Results: Patients with elevated Lp(a) had significantly greater coronary disease burden, reflected by higher mean SYNTAX scores (17.3 ± 7.0 vs. 13.8 ± 7.0; p = 0.011) and a greater proportion of intermediate- and high-risk SYNTAX classifications (p = 0.016). Although the number of diseased vessels did not differ significantly, three-vessel disease was more frequent in the elevated Lp(a) group. At 1-month follow-up, overall MACE incidence was numerically higher but not statistically significant between groups. At 6 months, heart failure with reduced ejection fraction was significantly increased in patients with elevated Lp(a) (27.7% vs. 12.2%; p = 0.027). Binary logistic regression demonstrated that elevated Lp(a) independently predicted 6-month MACE (OR 2.768, p = 0.011, 95% CI 1.262–6.072), but not 1-month outcomes. Conclusions: Elevated Lp(a) is associated with increased coronary artery disease severity and higher mid-term MACE risk after AMI.

Background/Objectives: Cardiorenal syndrome type 2 (CRS-2) is characterized by progressive renal dysfunction caused by chronic heart failure (HF) and is associated with increased morbidity and mortality. However, the prognostic value of renal biomarkers in patients with CRS-2 hospitalized for decompensated HF remains unclear. Methods: This prospective observational cohort study included 200 consecutive patients hospitalized for decompensated HF in the Intensive Care Unit of the Clinic for Internal Medicine at the University Clinical Centre Tuzla between April and October 2025. CRS-2 was defined as chronic HF with chronic kidney disease persisting for ≥3 months before admission according to KDIGO criteria. Patients were followed for three months. The primary composite outcome was all-cause mortality or initiation of renal replacement therapy. Results: CRS-2 was identified in 130 patients (65.0%) and was associated with higher in-hospital mortality (32.3% vs. 11.4%, p = 0.002) and three-month mortality (44.6% vs. 21.4%, p = 0.002). Within the CRS-2 subgroup, patients who experienced the primary composite outcome had higher admission levels of cystatin C and urinary albumin-to-creatinine ratio (UACR) and lower estimated glomerular filtration rate (eGFR). ROC analysis demonstrated moderate discriminative ability of cystatin C (AUC 0.739) and UACR (AUC 0.733). In Cox regression analysis, cystatin C (HR 1.534, 95% CI 1.263–1.863, p < 0.001) and UACR (HR 1.003, 95% CI 1.001–1.006, p = 0.001) were significantly associated with the primary composite outcome. Conclusions: Renal dysfunction markers, particularly cystatin C and albuminuria, are associated with early adverse outcomes in CRS-2 patients hospitalized for decompensated HF. Routine assessment of these biomarkers may provide additional prognostic information and support risk assessment in this high-risk population.

Aim To create a predictive score based on functional parameters of the liver and determine its prognostic value in survival of patients with decompensated cirrhosis.Methods Retrospective observational study included 91 consecutive patients with decompensated cirrhosis. Functional parameters (bilirubin, AST – aspartate aminotransferase, ALT – alanine aminotransferase, ALP – alkaline phosphatase, GGT – gammaglutamyltranferase, albumin, prothrombin time, platelet count, haematocrit and creatinine), Child-Pugh (CP) and Model of EndStage Liver Disease (MELD) scores have been measured at first hospitalization and at every exacerbation episode over follow-up period of 24 months.ResultsUsing Cox regression analysis, we found that age (OR=1.206; p=0.03; 95% CI=1.019-1.428), serum bilirubin(OR=1.017; p=0.003; 95% CI=1.006-1.029), INR (International normalized ratio) (OR=6.262; p=0.002; 95% CI=1.924-20.378) and serum creatinine (OR=1.019; p=0.005; 95% CI=1.006- 1.032) had statistically strong association with the incidence of a six-month mortality. Age (OR=1.120; p=0.006; 95% CI=1.033- 1.214), serum bilirubin (OR=1.021; p=0.0001; 95% CI=1.010-1.032), GGT (OR=1.007; p=0.023; 95% CI=1.001-1.014), INR (OR=9.571; p=0.001; 95% CI=2.610-35.098), haematocrit (OR=0.695; p=0.001; 95% CI=0.559-0.864) and serum creatinine (OR=1.023; p=0.0001; 95% CI=1.011-1.035) showed an increased the risk for a 24-month lethal outcome. Predictive score derived from liver functional parameters, CP and MELD scores, each independently has shown a high degree of death prediction after 6or 24 months in patients with end-stage liver disease.Conclusion Predictive score derived from liver functional parameters had a better prognostic value for short-term and long-termmortality comparing to MELD and Child-Pugh score.

The current study aimed to explore whether the level of decrease in platelet distribution width (PDW), platelet-large cell ratio (P-LCR), and mean platelet volume (MPV) has prognostic value for major adverse cardiovascular events (MACEs) in acute myocardial infarction without ST-segment elevation (NSTEMI) treated with clopidogrel. In this prospective observational cohort study, PDW, P-LCR, and MPV were determined on admission at the hospital and 24 h after clopidogrel treatment in 170 non-STEMI patients. MACEs were assessed over a one-year follow-up period. Using the Cox regression test, a decrease in PDW showed a significant association with the incidence of MACEs (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.66–0.99, p = 0.049) and overall survival rate (OR 0.95, 95% CI = 0.91–0.99, p = 0.016). Patients with a decrease in PDW<9.9% had a higher incidence of MACEs (OR 0.42, 95% CI = 0.24–0.72, p = 0.002) and a lower survival rate (OR 0.32, 95% CI = 0.12–0.90, p = 0.03) than patients who had a decrease in PDW < 9.9%. In the Kaplan–Meier analysis using log-rank test, patients who had a decrease in PDW < 9.9% had an increased risk for MACEs (p = 0.002) and lethal outcomes (p = 0.002). However, a decrease in MPV or P-LCR did not have prognostic value. A decrease in PDW < 9.9% measured 24 h after clopidogrel treatment in NSTEMI patients has good prognostic value for determining the short-term risks of MACEs, possibly providing a better risk stratification of those patients.

The association between urine amylase levels and the development of postoperative complications after Whipple resection is still unknown. Aim of this study was to determine the prognostic value of urine amylase levels for postoperative complications in patients who underwent Whipple resection. In this retrospective cohort study, we analyzed amylase levels in urine, serum and drains in 52 patients who underwent Whipple resection preoperatively and on Postoperative Day 1 (POD1) after the intervention. Patients were followed up for 3 months to assess their predictive value for postoperative complications. In patients with complications, urine amylase levels were significantly higher on POD1 than before resection (198.89 ± 28.41 vs. 53.70 ± 7.44, p=0.000). Considering the sensitivity and specificity of the urine amylase level on POD1, an area under the ROC curve of 0.918 was obtained (p³140.00 U/L had significantly higher risks of postoperative pancreatic fistula (POPF) grade C (definition of POPF done according to the ISGP) (RR:20.26; 95% CI: 1.18-347.07; p=0.038), readmission to hospital (RR: 6.61; 95% CI: 1.53-28.58; p=0.011), reoperation (RR: 5.67; 95% CI: 1.27-25.27; p=0.023), and mortality (RR:17.00; 95% CI: 2.33-123.80; p=0.005) than patients with urine amylase levels <140.00 U/L. Urine amylase levels on POD1 displayed strong and significant positive correlations with serum amylase levels (r=0.92, p=0.001) and amylase levels in drains (r=0.86, p=0.002). We can conclude that urine amylase levels on POD1 have good prognostic value for postoperative complications after Whipple resection and might be used as an additional predictive risk factor.

To examine a relationship between protein C (PC) and antithrombin III (AT III) activities with ejection fraction of left ventricle (EFLV), in the early phase of acute ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), and to investigate whether PC and AT III are associated with major adverse cardiovascular events (MACE) within 6 months following from pPCI. The research had a prospective character and included 357 patients who had, following the diagnosis of the STEMI, undergone pPCI at the Clinic of Cardiology and Emergency Internal Medicine, Military Medical Academy, Belgrade, Serbia, from January 2010 until April 2019. The EFLV positively correlated with PC values (rho = 0.229). There was a statistically significant increase in the PC values between patients with MACE compared with those without MACE at 6 months’ follow-up evaluation (p < 0.0001). Also, significant difference in PC values between patients who died in hospital and those who were alive at 6 months’ follow-up (p < 0.01) was observed. PC values were different across different EFLV groups (p < 0.001), increasing from the 1^st to the 4^th EFLV quartiles: the median and the interquartile values for the 1^st, 2^nd, 3^rd and 4^th quartiles were 1.0400IU/l ± 0.15, 1.1400IU/l ± 0.15, 1.1350IU/l ± 0.16 and 1.2200IU/l ± 0.14, respectively. Increased PC activity in the early phase of STEMI is associated with higher EFLV 5 days after the pPCI as well as with MACE at 6 months after the pPCI.

Background: Histone deacetylase 9 (HDAC9) plays an important role in transcriptional regulation, cell cycle progression and developmental events; moreover, it has been investigated as a candidate gene in a number of conditions, including the onset and progression of atherosclerosis. We hypothesized that the rs2107595 HDAC9 gene polymorphism may be associated with advanced carotid artery disease in a Slovenian cohort. We also investigated the effect of this polymorphism on HDAC9 receptor expression in the internal carotid artery (ICA) specimens obtained by endarterectomy. Methods: This case-control study enrolled 619 unrelated Slovenian patients: 311 patients with ICA stenosis > 75% as the study group and 308 patients with ICA stenosis < 50% as the control group. Patient laboratory and clinical data were obtained from the medical records. The rs2107595 polymorphisms were genotyped using TaqMan SNP Genotyping assay. HDAC9 expression was assessed by immunohistochemistry in 30 ICA specimens from patients with ICA atherosclerosis > 75%, and the numerical areal density of HDAC9 positive cells was calculated. Results: The occurrence of advanced ICA atherosclerosis in the Slovenian cohort was 3.81 times higher in the codominant genetic model (OR = 3.81, 95%CI = 1.06–13.77, p = 0.04), and 3.10 times higher in the recessive genetic model (OR = 3.10, 95%CI = 1.16–8.27, p = 0.02). In addition, the A allele of rs2107595 was associated with increased HDAC9 expression in the ICA specimens obtained by endarterectomy. Conclusions: We observed a significant association between the AA genotype of rs2107595 with the advanced carotid artery disease in our Slovenian cohort, indicating that this polymorphism may be a genetic risk factor for ICA atherosclerosis.

Osteoporosis is a chronic progressive bone disease where the bone tissue resorption exceeds its regenerative capacities. Such a process leads to the reduction of bone mineral density (BMD), and distortion of trabecular microarchitectonics, which creates the basis for an increased fracture risk on a "low trauma" for osteoporosis patients. The notion of low trauma implies a stressor that will not cause a fracture in a healthy person under normal circumstances. BMD is a strong predictor of future fractures. However, many fractures occur in persons with BMD values beyond the defined osteoporosis threshold, and BMD measurement only partially identifies the part of the population with increased fracture risk. Also, it is known that risk factors are influencing the bone mass reduction as predictors of future fractures, and their association may lead to an increased fracture risk irrespective of the bone mass and T-score. The 10-year individual risk assessment for osteoporotic fracture and the analysis of impact of individual and multiple osteoporosis risk factors on the degree of osteoporotic fracture risk. The research is a retrospective-prospective study which analyzed 120 patients divided into two groups: 1) asymptomatic patients with known risk factors for osteoporosis in the age group of 40-65 (n=60), 2) asymptomatic patients with known risk factors for osteoporosis in the age group of 65-90 (n=60). FRAX® algorithm was used as a tool for the 10-year hip fracture risk assessment, with prior approval of the Centre for Metabolic Bone Diseases, University of Sheffield from the United Kingdom. Fracture risk assessment was calculated using the online FRAX® calculator. High risk is defined as the hip fracture risk higher than 3% or the risk of a "big" osteoporotic fracture higher than 20%. Results are expressed as mean values with a standard deviation. A comparison between tested patient groups was made applying the student T-test. 32% of patients of average age of 65.8±12.6 years are under high hip fracture risk, 28% of patients are under the hip fracture risk higher than 3%, and the risk for 0.03% patients is higher than 20%. Patients with high fracture risk are of advanced age, female, with lower body weight and height values, lower bone mineral density (BMD) and T score values than patients who are not under a high fracture risk. A positive family anamnesis to osteoporosis and fractures, earlier fractures, smoking, rheumatoid arthritis, and use of glucocorticoids are risk factors that are more represented in patients with high fracture risk and osteoporosis. The impact of the majority of individual risk factors for osteoporosis and fracture is moderate, and their joint effect is significant. The contribution of individual risk factors to the overall 10-year fracture risk depends on the type, number and association of risk factors. This research is a contribution to the resolution of polemics among authors, i.e. a dilemma whether persons with multiple clinical risk factors for osteoporosis with T score values beyond the defined threshold for osteoporosis are candidates for therapy with bisphosphonates, and a dilemma whether persons without any clinical risk factors for osteoporosis with T score values within the defined osteoporosis threshold require therapy with bisphosphonates, or only monitoring is sufficient.