Frane Paić

Background/Objectives: Liver cirrhosis (LC), irrespective of its etiology, is associated with increased mortality from cardiovascular causes. In this study, we aimed to reveal the relationship between fatty LC (nonalcoholic and alcohol related liver diseases) and other causes of LC with aortic valve and mitral annular calcifica-tion. Methods: One hundred and twenty-three LC patients and an equal number of age- and sex-matched cardiovascular patients without cirrhosis or indications for heart valve surgery were included in the study. The two groups were compared in terms of demographic, clinical, and echocardiographic characteristics. In total, 70 fe-male and 176 male patients, with a median age of 64.0 years (range, 58.0-70.0 years), were included in the analysis. Results: Binary logistic regression analyses revealed a significant association between fatty LC and aortic valve calcification, whereas LC, regardless of its cause, was associated with mitral annular calcification. Previous car-diac surgery due to atherosclerosis-related ischemic heart disease and mitral annular calcification were also associated with aortic valve calcification. In contrast, BMI, aor-tic valve calcification, aortic root calcification, and mitral valve calcification were re-lated to the occurrence of mitral annular calcification. The findings also revealed a stark contrast in the burden of atherosclerotic cardiovascular disease risk factors be-tween the two groups. Conclusions: The incidence of heart valve calcification should be considered in the management of cirrhosis patients as potential liver transplant re-cipients for more comprehensive preoperative risk stratification and postoperative follow-ups to identify patients that may benefit from either percutaneous or surgical valvular therapy.

Left ventricular assist devices (LVAD) have been widely adopted for the treatment of both pediatric and adult patients with end-stage heart failure. By unloading the failing ventricle, maintaining sufficient end-organ perfusion, and improving the heart's functional capacity, they are increasingly used as bridges to recovery, cardiac transplantation, or destination therapy, thus improving patients' overall survival rate and life quality. However, beyond their life-sustaining functions, these devices pumping total cardiac output may have a range of short and long-term harmful effects initiated by interactions of blood cells with artificial surfaces at the LVAD/Host interface or by non-physiological flow conditions generated by these devices. One of the major challenges in LVAD therapy is the lack of satisfactory sensitivity and specificity of the currently available biomarkers, making it difficult to differentiate the patients who will benefit from LVAD placement from those at high risk for adverse events and poor outcomes. To this end, myocardial miRNAs have emerged as promising targets for investigating heart failure-related molecular pathways. In addition, extracellular circulatory miRNAs whose concentrations change with pathological state and disease progression may also mediate intercellular signaling pathways that are important in the functional and structural changes associated with the development and progression of HF. Herein, we provide a comprehensive overview of the currently known cardiac miRNAs involved in LVAD-induced myocardial reverse remodeling, remission, and recovery, and circulatory cell-free and platelet-enriched miRNAs that may serve as potential non-invasive biomarkers for pre-LVAD decision-making or monitoring and predicting patient response to LVAD therapy.

Objective: Smaller body surface area (BSA) frequently precludes patients from left ventricular assist device (LVAD) therapy. We sought to investigate the clinical outcomes in patients with small BSA undergoing less invasive LVAD implantation. Methods: We conducted a retrospective review of 216 patients implanted with HeartMate 3 LVAD (Abbott, Chicago, IL) via less invasive surgery at our institution. Patients were dichotomized based on their preimplant BSA for comparison between small BSA (≤1.8 m ² ) and normal/large BSA (>1.8 m ² ). We analyzed patient perioperative characteristics and outcomes. Results: In our study, small BSA was found in 32 patients (14.8%), while 184 patients (85.2%) had normal/large BSA. Women were more prevalent in the small BSA group (50.0% vs 13.0%, P < 0.001). Preoperative and intraoperative data showed comparable results. Major complications and hospital length of stay did not differ by BSA group. Patients with smaller BSA had significantly decreased pump parameters at discharge, including LVAD flow (4.11 ± 0.49 vs 4.60 ± 0.54 L/min, P < 0.001) and pump speed (5,200 vs 5,400 rpm, P < 0.001). Survival to discharge and within 6 months after implantation were similar between the groups. Conclusions: Our study results suggest that less invasive HeartMate 3 implantation can be safely performed and demonstrates equivalent outcomes in patients with smaller body habitus. Randomized trials are required to confirm our data.

Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are part of the spectrum of kidney disorders caused by pathogenic variants in α3, α4, or α5 chains of the collagen type IV, the major structural component of the glomerular basement membrane (GBM). Using targeted next-generation sequencing (NGS), 34 AS/TBMN patients (58.8% male) from 12 unrelated families were found positive for heterozygous c.2881+1G>A variant of the COL4A3gene, that is considered disease-causing. All patients were from the continental or island part of Croatia. Clinical, laboratory, and histopathological data collected from the medical records were analyzed and compared to understand the clinical course and prognosis of the affected patients. At the time of biopsy or first clinical evaluation, the mean age was 31 years (median: 35 years; range: 1 – 72 years). Hematuria was present in 33 patients (97.1%) and 19 (55.9%) patients had proteinuria. There were 6 (17.6%) patients with hearing loss, 4 (11.8%) with ocular lesions, and 11 (32.4%) with hypertension. Twenty-three (67.6%) patients had proteinuria at follow-up, and 5 (14.7%) patients with the median age of 48 years (range: 27-55) progressed to kidney failure, started dialysis, or underwent kidney transplantation. Of the 13 patients who underwent kidney biopsy, 4 (30.8%) developed focal segmental glomerulosclerosis (FSGS), and 8 (66.7%) showed lamellation of the GBM, including all patients with FSGS. It is essential to conduct a detailed analysis of each collagen type IV genetic variant to optimize the prognosis and therapeutic approach for affected patients.

This study aimed to explore the role of preoperative and postoperative C-reactive protein (CRP) levels in mediating the association between the preoperative depression symptoms and postoperative length of stay in patients undergoing coronary artery bypass grafting (CABG). Preoperative depression symptoms of 212 elective CABG patients were measured using the Beck Depression Inventory (BDI-II). The patient’s demographic and clinical parameters were collected from medical records prior to surgery. Patients were followed up during their in-hospital stay to measure early (1–3 days post-surgery) and persistent (4–6 days post-surgery) CRP response to CABG surgery. The higher persistent CRP response was significantly (p < 0.001) associated with a longer postoperative hospital stay. The binary logistic regression analysis confirmed the association of persistent CRP change with prolonged hospital stay (OR = 1.017, 95% CI = 1.005–1.029, p = 0.009). However, when the gender subgroups were analyzed separately, that remained significant (OR = 1.016, 95% CI = 1.004–1.028, p = 0.005) only for the male subgroup. There was no significant association between elevated BDI-II depression scores and longer postoperative hospital stay. Additionally, no significant influence of BDI-II scores on preoperative or postoperative CRP levels, or vice versa, was detected. Further work is needed to explore the extent and pathways through which depression might influence the postoperative recovery of CABG patients.

To determine the predictive value of phosphorylated human epidermal growth factor receptor 2 (pHER2[Y1248] ) status in breast cancer (BC) patients undergoing trastuzumab-based adjuvant therapy.Immunohistochemical status of pHER2[Y1248] , EGFR/HER1, HER3, ...

Diffuse gastric carcinoma (DGC) is characterized by poorly cohesive cells, highly invasive growth patterns, poor prognosis and resistance to the majority of available systemic therapeutic strategies. It has been previously reported that the Wnt/β‑catenin signaling pathway serves a prominent role in the tumorigenesis of gastric carcinoma. However, the mechanism underlying the dysregulation of this pathway in DGC has not been fully elucidated. Therefore, the present study aimed to investigate the expression profiles of Wnt antagonists, secreted frizzled‑related protein 1 (SFRP1) and secreted frizzled‑related protein 3 (SFRP3), and dishevelled protein family members, dishevelled segment polarity protein 2 (DVL2) and dishevelled segment polarity protein 3 (DVL3), in DGC tissues. The association between the expression levels of these factors and the clinicopathological parameters of the patients was determined. Protein and mRNA expression levels in 62 DGC tumor tissues and 62 normal gastric mucosal tissues obtained from patients with non‑malignant disease were measured using immunohistochemical and reverse transcription‑quantitative PCR (RT‑qPCR) analysis. Significantly lower protein expression levels of SFRP1 (PSFRP1, SFRP3, DVL2 and DVL3 may be aberrantly expressed in DGC tissues, implicating their possible role in the development of this malignant disease. The present data also revealed a positive relationship between SFRP3 protein expression and the clinical and T stage of DGC.

Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic mediators involved in canonical and non-canonical Wnt signaling that are important in embryonic development. The role of DVL proteins in the placental tissue remains mostly unknown. In the current study, we explored the role of Dishevelled proteins in naturally invasive tissue, trophoblast. Formalin-fixed paraffin-embedded samples of 15 term placentas from physiologic term pregnancies and 15 term placentas from pregnancies complicated with intrauterine growth restrictions (IUGR) were used for the study. Expression levels of mRNA for DVL1, DVL2, and DVL3 in placentas were analyzed by quantitative real-time PCR (qRT-PCR). DVL1, DVL2, and DVL3 protein expression were semi-quantitatively analyzed using immunohistochemistry. The expression of DVL2 and DVL3 proteins was significantly higher in trophoblasts in placental villi from IUGR pregnancies compared with the control group of term placentas. In contrast, DVL3 protein expression was significantly higher in endothelial cells in placental villi from IUGR pregnancies compared with normal term placentas. The observed differences at protein levels between normal and IUGR placentas were not confirmed at the mRNA levels of DVL genes. Our data indicate the active involvement of DVL proteins in IUGR-related placentas. No significant changes were observed in DVL mRNA levels between the two groups of placentas. Further studies are required to explore the clinical relevance of these observations.