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Kenana Ljuca

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Jasminka Mujkanović, Kenana Ljuca, Amir Tursunović, Nadina Ljuca, Dževad Džananović, Farid Ljuca

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. Results Using 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 6 or 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-term mortality comparing to MELD and Child-Pugh score.

Adnan Fojnica, Kenana Ljuca, Saghir Akhtar, Z. Gatalica, S. Vranić

Simple Summary Merkel cell carcinoma (MCC) is a rare and highly aggressive type of skin neuroendocrine cancer that frequently recurs and metastasizes within a relatively short period. Despite rapid growth and characteristic skin color, MCC often goes undiagnosed in its early stage. Therefore, therapy is often initiated at the advanced stage, and selecting appropriate therapeutic interventions is critical. The emergence of novel immunotherapeutic agents, such as immune checkpoint inhibitors (ICI), presents a promising treatment option for advanced MCC. Several biomarkers, such as PD-L1 expression, tumor mutational burden (TMB), and microsatellite instability (MSI), showed significant potential as predictive biomarkers for treatment with ICI. Despite their predictive value, each has demonstrated limited value in MCC over recent years. Abstract Merkel cell carcinoma (MCC) is primarily a disease of the elderly Caucasian, with most cases occurring in individuals over 50. Immune checkpoint inhibitors (ICI) treatment has shown promising results in MCC patients. Although ~34% of MCC patients are expected to exhibit at least one of the predictive biomarkers (PD-L1, high tumor mutational burden/TMB-H/, and microsatellite instability), their clinical significance in MCC is not fully understood. PD-L1 expression has been variably described in MCC, but its predictive value has not been established yet. Our literature survey indicates conflicting results regarding the predictive value of TMB in ICI therapy for MCC. Avelumab therapy has shown promising results in Merkel cell polyomavirus (MCPyV)-negative MCC patients with TMB-H, while pembrolizumab therapy has shown better response in patients with low TMB. A study evaluating neoadjuvant nivolumab therapy found no significant difference in treatment response between the tumor etiologies and TMB levels. In addition to ICI therapy, other treatments that induce apoptosis, such as milademetan, have demonstrated positive responses in MCPyV-positive MCC, with few somatic mutations and wild-type TP53. This review summarizes current knowledge and discusses emerging and potentially predictive biomarkers for MCC therapy with ICI.

E. Bećirović, Kenana Ljuca, Minela Bećirović, Nadina Ljuca, Mugdim Bajrić, Ammar Brkić, Farid Ljuca

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.

F. Ljuca, Amir Tursunović, Kenana Ljuca, Z. Rifatbegović, Mirha Agić

The association between urine amylase levels and the development of post-operative complications after Whipple resection is still unknown. The aim of this study was to determine the prognostic value of urine amylase levels for post-operative complications in patients who underwent Whipple resection. In this retrospective-prospective cohort study we analyzed amylase levels in urine, serum, and drains in 52 patients who underwent Whipple resection preoperatively and on Post-operative Day 1 (POD1) after the intervention. Patients were followed up for 3 months to assess their predictive value for post-operative 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 (p<0.001, 95% Confidence interval [CI]: 0.894-0.942). Patients with urine amylase levels ≥140.00 U/L had significantly higher risks of post-operative 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 post-operative complications after Whipple resection and might be used as an additional predictive risk factor.

Gastrointest Endoscopy, A. Kurtcehajic, E. Zerem, T. Bokun, E. Alibegović, Suad Kunosić, A. Hujdurović, Amir Tursunović, Kenana Ljuca

observation of the gastric body mucosa shows dominant patterns in relation to the regular arrangement of collecting venules, subepithelial capillary network

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