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Copyright of Medicina Fluminensis is the property of Croatian Medical Association, Rijeka Branch & Faculty of Medicine, University of Rijeka and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The aim of this study was to analyze the efficiency of CytoSorb adsorber in patients presenting with cardiogenic shock and treated with venoarterial extracorporeal membrane oxygenation (VA‐ECMO). Methods: Sixteen patients put on VA ECMO due to cardiogenic shock were included, stratified according to the use of Cytosorb adsorber in the first 24 h and compared across different clinical outcomes. Results: Significantly lower vasopressor doses were required among patients treated with Cytosorb at the initiation and before weaning from ECMO. Furthermore, these patients showed significantly higher urine output before weaning and lower lactate levels during the extracorporeal support. Finally, the mortality rate was lower among the Cytosorb therapy group (22.2% vs 57.1%). Conclusion: While a decrease in vasopressor doses was already associated with CytoSorb use, this is the first study showing an increase in urinary output and a trend towards better survival among patients on VA ECMO treated with CytoSorb. [ABSTRACT FROM AUTHOR]

Copyright of Medicina Fluminensis is the property of Croatian Medical Association, Rijeka Branch & Faculty of Medicine, University of Rijeka and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Pregnancy in heart transplant (HT) recipients with episodes of rejection or positive donor specific antibodies (DSA) is discouraged by all recommendations due to higher risk of complications. Although there is paucity of data for DSA trend during pregnancy in HT recipients, there is evidence of improvement of symptoms during pregnancy in some autoimmune diseases1-3. Case report: 23-year-old female who underwent HT due to post-myocarditis cardiomyopathy in June 2014, reported unplanned pregnancy in June 2022. She had a history of acute cellular (3R/3B) and humoral rejection (DSA major histocompatibility complex (HLA) class I, specificity A11, A30, B13, B35 and HLA class II, specificity DR3, DR15, DR51, DR52, DQ2, mean fluorescent intensity (MFI) 1000-13 300) in August 2017 which required mechanical circulatory support due to severe heart failure with multiorgan damage. She underwent pulse corticosteroid treatment, and 12 cycles of plasmapheresis with administration of rituximab, intravenous immunoglobulins, and thymoglobulin. After that she had persistent positive DSA, predominantly DQ2 (MFI up to 12200), and because of that was on quadruple immunosuppression (tacrolimus, mycophenolate (MMF), everolimus, prednisone) from October 2019 to July 2020 when MMF was discontinued due to gastrointestinal side effects. She had one more cellular rejection episode (2R/3A) in March 2022 which was treated with pulse corticosteroids. During pregnancy she was on tacrolimus, everolimus, and prednisone combination with closely monitoring of immunosuppressants concentrations. Echocardiography controls showed normal left ventricle function and mildly reduced right ventricle function, NT-proBNP was slightly elevated (493-823 ng/L) and DSA were in a downward trend which is shown in Figure 1. At 32+3 weeks of pregnancy, she was hospitalized due to early labor. The following day male baby was delivered by Caesarean section due to pathological cardiotocography (Apgar score 8/9). After delivery DSA remained weakly positive. Conclusion: Although pregnancy in HT recipients with history of rejection and positive DSA is discouraged, positive outcome is possible with close monitoring of multidisciplinary team. Furthermore, we described a rare case of downward trend of positive DSA during pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Immune mediated vascular damage is a major risk for cardiac allograft vasculopathy (CAV). Anti-thymocyte globulin (rATG) provides intense immunosuppression early after HTx. The role of rATG on CAV prevention still remains controversial.1,2 While lymphopenia reflects the therapeutic effect of rATG, a decrease in platelet count is deemed as an adverse effect. We hypothesize that lower lymphocyte and platelet counts following rATG induction may be associated with less risk for the development of CAV. Patients and Methods: We performed a retrospective single-centre study in patients transplanted between 2010 and 2017. All pts received rATG induction therapy for 5 days. Absolute lymphocyte count (ALC) and platelet count were assessed on days 0, 7, 14, and 21 following HTx. The primary outcome was the diagnosis of CAV grade ≥1, during 3 years of follow-up. Results: A total of 133 pts were transplanted in this period. During first three years after HTx 18.8% of pts developed CAV≥1. Those pts had sig nificantly older donors (47 (IQR 40-49) vs 37 (IQR 28-49), p=0.02), higher median platelet count on day 7 (140 x 109 /L (IQR 103-156 X 109 /L) vs 105 x 109 /L (IQR 68-147 x 109 /L), p=0.04), higher median lymphocyte count on day 14 (335 x 109 /L (IQR 184-314 x 109 /L vs 215 x 109 /L (IQR 105-401 x 109 /L), p=0.02), higher median leukocyte count on day 21 (810 x 10³ /µL (IQR 600-960 x 10³ /µL) vs 660 x 10³ /µL (IQR 500-794 x 10³ /µL), p=0.03), and higher median platelet count on day 21 post HTx (237 x 109 /L (IQR 195-278 x 109 /L) vs 193 x 109 /L (IQR 148-226 x 109 /L), p=0.03) than the pts without CAV. Univariate binary logistic regression showed that CAV was associated with older donor age, lymphocyte count ≥200 x 109 /L on day 7, higher platelet count on day 7 and 21, and higher leukocyte count on day 21. In multivariable binary logistic regression, the adjusted risk of CAV was significantly higher for pts with older donors (p=0.027), and higher platelet count on day 21 (p=0.04). Conclusion: Lower platelet count after induction with rATG was associated with lower incidence of CAV. Association with lower lymphocyte count in univariate logistic regression did not reach significance in multivariable analysis. The controversial reports on clinical benefit from rATG induction on CAV prevention could be explained by variable platelet response of the recipients to the therapy. [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]

Introduction: Positive end-expiratory pressure (PEEP) is a positive pressure that remains in the airway at the end of expiration, decreasing atelectasis and improving ventilation-perfusion (VQ) mismatch. Ideal PEEP value is one that enables the preponderance of potential benefits over potential complications. Use of non-invasive ventilation (NIV) in COVID-19 patients with acute respiratory distress syndrome (ARDS), although still debatable, is associated with decreased mortality. Recent studies suggest that high PEEP ventilation decreases atelectrauma, pulmonary oedema, reduces the risk of patient self-inflicted lung injury and helps patients to breathe easier. Aim: Assessment of respiratory response to high PEEP NIV in COVID-19 patients. Materials & Methods: A retrospective cohort study was conducted in the COVID-19 intensive care unit (ICU) of University Hospital Centre Zagreb. Study included 93 patients treated with NIV from October 2021 to February 2022. PEEP values and respiratory frequencies (RF) were observed and HACOR score was calculated on 1st, 3rd and 7th day of hospitalization. The definite outcome was objective and subjective assessment of work of breathing. Results: Out of 93 patients treated with NIV, 40 (43.0%) patients required a switch to invasive mechanical ventilation. For 53 (57.0%) patients, NIV was the only ventilation method for their entire stay in ICU. There was a statistically significant difference between 1st and 3rd (p=0.005), and 1st and 7th day (p=0.010) in RF. A statistically significant difference was found for HACOR scores (p<0.001) between 1st and 3rd day of hospitalization. Patients requiring intubation had higher HACOR scores. Additionally, it was found that for each point of the 7th-day HACOR score, the risk of NIV failure was 66% higher (p=0.003). Conclusion: Treatment of COVID-19 ARDS with high PEEP NIV reduces the work of breathing, improves oxygenation, and helps patients feel comfortable and breathe easier. [ABSTRACT FROM AUTHOR]

Introduction. Ceftazidime/avibactam, a novel beta-lactam antibiotic, demonstrates time-dependent bacterial killing; thus, new reports advocate its administration as a continuous infusion, as opposed to bolus or prolonged infusion application. Methods. Critically ill COVID-19 patients (n=10) superinfected with OXA-48-producing Klebsiella pneumoniae susceptible to ceftazidime/avibactam were treated with ceftazidime/avibactam as a continuous infusion for an average of 10 days. The treatment regimen included an initial loading dose, followed by a continuous infusion of ceftazidime/avibactam. These patients were immunocompromised because of severe COVID-19, treatment with corticosteroids, and some solid organ transplant recipients (n=2), all with high disease severity scores. Discussion. Considering the published literature to this date, this is the one of first reports describing the real-life results of using a continuous infusion of ceftazidime/avibactam in the treatment of OXA-48-producing K. pneumoniae superinfection in critically ill COVID-19 patients. Microbiological effectiveness of treatment, evidenced by negativization of microbiological samples, was achieved in eight cases (80%) overall, but in patients with sepsis and urinary tract infection, the cure rate was 100%. Conclusion. The reasons for the low treatment success rates in pneumonia caused by OXA-48-producing K. pneumoniae could be explained by the concurrent severe COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]