Search

Donated human milk is the best substitute for breast milk in the case when the mother cannot feed her baby. Human milk banks provide safe and high quality donated human milk. That was the reason why the Human Milk Bank was established in the Croatian Tissue and Cell Bank at the Zagreb University Hospital Centre in January 2020. The Bank works in accordance with the Law on the Application of Human Tissues and Cells. In this paper, we present the results of the Bank work since from its opening until June 2020. Due to logistic reasons caused by the COVID-19 epidemic and the earthquake in Zagreb, the Human Milk Bank did not collect milk for 43 days. Milk was donated by 31 mothers. Their median age was 31 years and 81% of them had high education level. In 52% of cases, mothers started donating milk three months after giving birth. Most donors donated milk only once (45%). The median period of donation was 46 days. The majority (52%) of donors gave birth for the fi rst time, in the expected term of childbirth (94%), birth weight was >2500 g. Only three of donors' children (9%) were in intensive care. A total of 175.5 L of milk were collected (mean 5.7 L per donor), of which 151.5 L met the requirements of input quality control, and 141 L were pasteurized. A critical number of viable aerobic and facultative bacteria were identified in 32.6% of milk pools prepared for pasteurization, and 8.9% after pasteurization. For clinical use, 78.7 L were dispensed in three neonatal intensive care units. The Human Milk Bank has already shown the importance of its activities during the fi rst months of operation. In order to be able to meet the needs for donated human milk at the national level, it is necessary to constantly inform mothers about the importance of human milk and to promote its donation. [ABSTRACT FROM AUTHOR]

Introduction: Aortic valve pathology carries a high mortality burden. Its incidence is growing in proportion to the continuous ageing of the population. Surgery remains the gold standard in the treatment of severe aortic valve disease. Methods: We performed a retrospective analysis of the University Hospital Center Zagreb’s cardiac surgical database from 2009 to 2020, focusing on surgical aortic valve replacement (SAVR). We dichotomized patients with respect to the date of their surgical procedures into two eras. Group 1 included patients operated from 2009-2014, whereas Group 2 included patients operated on from 2015-2020. Results: A total of 1012 SAVRs were identified during the study period. The procedural volume over the two identical 6-year time periods increased in the latter era from 413 to 598. When comparing groups 1 and 2, we have observed in increase in the number of patients with diabetes (19% vs. 26%, P=0.015) and coronary artery disease (14% vs. 18%, P=0.099). The composite risk assessment score increased significantly from 3.0±2.4 to 3.2±2.7, P=0.023. Despite an increase in the comorbidity burden of the targeted patient population, the periprocedural mortality remained the same (2.1% vs 2.5%, P=0.835). The per-patient averaged volume of transfused packed red blood cells decreased from 839±954 to 614±821 ml, P<0.001. An increase in the proportion of tissue valve implantations in comparison to mechanical prostheses was also noted in the present era (58% vs 68%, P=0.001) Conclusion: Despite an increasingly more complex patient population referred for SAVR in the contemporary era, the results have remained excellent. The introduction of transcatheter methods should measure up to the surgical standard. [ABSTRACT FROM AUTHOR]

Aim To evaluate the impact of minimally invasive aortic valve replacement (mini-AVR) on clinical outcomes in comparison with the gold standard. Methods We retrospectively reviewed the records of all patients who underwent isolated AVR at the University Hospital Center Zagreb from 2010 to 2020. Patients undergoing mini-AVR were compared with patients undergoing conventional AVR (fs-AVR). The primary outcome measure was blood product consumption. Propensity score matching was used to create a balanced covariate distribution across treatment groups. Additionally, we compared the contemporary outcomes with a historical control. Results The final sample consisted of 1088 patients. In the unmatched cohorts, mini-AVR patients were younger (65 ± 12 vs 68 ± 10 years, P < 0.001) and had lower risk profiles (EuroSCORE2 2.8 ± 2.0 vs 3.5 ± 3.1, P = 0.003). After matching, mini-AVR patients required less blood transfusion than fs-AVR patients (270 [0-790] vs 510 [0-970] mL, P = 0.029). The incidences of stroke, dialysis, new AV block, and mortality were comparable. Cross-clamp times were longer in the mini-AVR group (71 [60-87] vs 66 [53-83] minutes, P = 0.013). Outcomes were improved in the contemporary mini-AVR era compared with our early mini-AVR experience across multiple metrics. Blood product consumption was reduced in the latter tercile of experience (0 [0-520] vs 500 [0-1018] mL, P < 0.001), and the operation was performed more expeditiously (cross-clamp times: 63 [54,80] vs 74 [62,88] minutes, P < 0.001) in comparison with earlier periods. Conclusions We showed that mini-AVR was associated with less blood product requirement than conventional surgery. Our data supports wider adoption of minimally invasive techniques in dedicated centers of excellence. [ABSTRACT FROM AUTHOR]

Due to the expansion of cell therapy using not only haematopoietic stem cells (HSC) but also other leukocyte subpopulations, the loss of these cells in cryopreserved apheresis products needs to be evaluated. Various factors that could negatively affect post-thaw recovery, such as leukapheresis product characteristics, storage time and cryopreservation protocols have been identified. The post-thaw recovery of HSCs, lymphocytes, NK cells and monocytes, as well as the factors that could adversely affect it were analysed in autologous and allogeneic leukapheresis products. The lowest post-thaw recovery was observed in autologous and allogeneic CD34+ cells, with the median of 73.7% and 68.1%, respectively. In leukocyte subpopulation, the lowest post-thaw recovery was observed for CD14+ cells, both autologous and allogeneic. The highest post-thaw recovery was observed for CD3+/CD8+ cells in autologous, and for CD19+ cells in allogeneic samples. The statistically significant difference was observed between autologous and allogeneic PBSC products for CD3+ cell recovery (P = 0.031) and CD3+/CD8+ cell recovery (P = 0.009). The evaluation of factors that could adversely affect the post-thaw recovery in autologous samples showed weak negative correlations between platelet concentration and CD3+ recovery, as well as between storage time and CD3+CD8+ recovery. In allogeneic samples, a strong negative correlation was observed only between the percentage of granulocytes and CD3+, CD3+/CD8+ and CD3+/CD4+ cell recoveries. Since various post-thaw recoveries of leukocyte subpopulations were observed, the cell therapy manufacturing centers should evaluate how their cryopreservation method and other factors affect the recovery of cell population of interest in their settings. [ABSTRACT FROM AUTHOR]

Introduction: Human leukocyte antigen (HLA) sensitization is a barrier for successful heart transplantation (HTx), reduces the chance for compatible donors, prolongs waiting time to HTx, and increases the risk of acute rejection and cardiac allograft vasculopathy. Increasing prevalence of HLA sensitization and limitations of current desensitization strategies represent a great challenge in transplantation cardiology1,2. Rather than using pretransplant desensitization, in the last several years we have started peritransplant prophylactic therapy after careful selection of acceptable HLA antigen incompatibility. Therapy includes mechanical removal of antibodies, intravenous immunoglobulins (IVIg), and immunosuppressive drugs targeting antibody production³. We present a series of four HLA sensitized patients who underwent successful HTx at University Hospital Center Zagreb. Case 1: 58-year-old male patient with history of two cardiac surgeries (mitral valve replacement in 1993 and coronary artery bypass graft and mitral valve repair in 2009) underwent HTx in September 2018. Due to positive complement-dependent cytotoxicity (CDC) crossmatch and donor-specific antibodies (DSA, anti-HLA antibodies class I), seven procedures of plasmapheresis followed by intravenous immunoglobulins were conducted, starting on the first postoperative day. Initial endomyocardial biopsy (performed on twenty fourth postoperative day) showed no cellular (CMR) or antibody-mediated (AMR) graft rejection, and DSA showed decline in reaction sensitivity during first 6 post-transplant months. In March 2019 endomyocardial biopsy revealed signs of AMR (without clinical correlate) and three plasmapheresis procedures with intravenous immunoglobulins application were performed. Procedures were suspended due to leukopenia, influenza infection and Cytomegalovirus (CMV) viremia. Follow-up biopsy two months later showed no signs of AMR, with further decline in DSA reaction intensity. Treatment was continued with monthly extracorporeal photopheresis (ECP) procedures (25 cycles over the course of 2,5 years). One year after HTx a coronary angiography with optical coherence tomography imaging was performed and it showed signs of intimal hyperplasia. Due to that finding and continuously positive anti-HLA antibodies, everolimus was introduced as fourth immunosuppressant drug (together with tacrolimus, mycophenolate mofetil and prednisone). Latest patients’ check-up was in September 2022, there were no signs of heart failure, CMR or AMR, and DSA are still positive, but with low Luminex median fluorescence intensity (MFI) reactions. Case 2: 44-year-old female patient with end-stage heart failure due to left ventricular noncompaction cardiomyopathy (LVNC) underwent urgent HTx in December 2019. Due to positive anti-HLA DSA (with negative CDC crossmatch), desensitization protocol was performed (five plasmapheresis procedures, intravenous immunoglobulins and rituximab application). Since initial biopsy, performed one month after HTx, showed CMR (class 1R/2) and AMR, and DSA values showed MFI increase, pulse corticosteroid therapy followed by additional five cycles of plasmapheresis and intravenous immunoglobulins was applied. Control biopsy showed resolution of CMR and AMR. Patient attends regular check-ups (latest in September 2022) in which no signs of CMR or AMR were detected, and DSA are positive, but with low MFI reaction. Case 3: 60-year-old male patient with ischemic cardiomyopathy underwent HTx in February 2020. Due to positive anti-HLA DSA (with negative CDC crossmatch), desensitization protocol was performed (seven plasmapheresis procedures and intravenous immunoglobulins, followed by anti-CMV immunoglobulin application). Early post-transplantation period was marked with prolonged leukopenia, with no other adverse events. Patient attends regular check-ups (latest in September 2022) in which no signs of CMR or AMR were detected, and DSA remain continuously negative. Case 4: 54-year-old female patient underwent HTx in August 2022 due to end-stage heart failure caused by ischemic cardiomyopathy. Due to positive virtual crossmatch (but prospective CDC crossmatch negative) and anti-HLA DSA, desensitization protocol was started immediately, with first procedure of immunoadsorption prior to the transplantation. Another eight cycles of immunoadsorption were performed in initial postoperative days, followed by application of intravenous immunoglobulins, without adverse events. First endomyocardial biopsy, one month after transplantation, showed no signs of CMR or AMR, with no anti-HLA DSA in follow-up. Conclusion: Anti-HLA sensitization among heart transplant candidates is a growing problem with significant risk for posttransplant graft dysfunction and death. Strategy that includes virtual crossmatch and peritransplant desensitization therapies allow us to perform transplantation with good clinical outcome. [ABSTRACT FROM AUTHOR]

Background: Oral anticoagulation therapy for the prevention of thromboembolic complications of atrial fibrillation in patients awaiting heart transplantation (HTx) traditionally includes warfarin, and in the last few years it increasingly includes dabigatran. Anticoagulation must be reversed before the surgery. The possibility of rapid reversal of the anticoagulant effect of dabigatran with idarucizumab seems to represent an advantage¹. A comparison of bleeding complications between these two strategies has not been completely investigated. Patients and Methods: We did a retrospective analysis of bleeding complications during and immediately after HTx performed in University Hospital Center Zagreb in 15 patients divided into 3 groups: patients who were on warfarin prior to HTx, patients who were on dabigatran prior to HTx, and control patients without indication for anticoagulation therapy. Patients were mutually paired to eliminate the influence of other risk factors including age, gender, etiology of heart failure, renal function, as well as whether surgery was primary or after previous sternotomy. For the comparison of bleeding complications we measured the utilization of blood products (red blood cells, platelets, fibrinogen, fresh frozen plasma (FFP), prothrombin complex (PC) and the amount of thoracic drainage within the first 24 hours after the HTx. Results: There was no significant difference in the utilization of blood products as well as the amount of 24h thoracic drainage between these three groups (Table 1). Only 2/5 patients in the warfarin group were within the therapeutic INR range (2 pts below and 1 pts above the range). 24h thoracic drainage, FFP and PC consumption correlated with pretransplant INR (Table 2). Conclusion: Although there was no difference in the consumption of blood products and 24h thoracic drainage between patients who were on warfarin or dabigatran anticoagulation before HTx, it should be noted that the majority of patients on warfarin were not within the therapeutic INR range, and it was precisely the elevated INR that significantly correlated with the consumption of blood products and 24h thoracic drainage. It is necessary to conduct a study on a larger number of patients in order to find out whether the pre-HTx use of warfarin is equally safe and effective as the use of dabigatran, in terms of the perioperative bleeding. [ABSTRACT FROM AUTHOR]