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Background Patients with hematologic malignancy have a higher risk of death from COVID-19 compared to the general population. A blunted immune response from both the underlying disease and applied treatment may contribute to development of more severe forms of COVID-19, absence of seroconversion, prolonged viral shedding, and might also impair humoral vaccine response. Factors influencing efficacy of SARS-CoV-2 vaccines in this patient population are still insufficiently explored. Methods We prospectively enrolled 143 patients with malignant or non-malignant hematologic diseases from University Hospital Centre Zagreb vaccinated between January and June 2021 with either mRNA-1273 (Moderna), BNT162b2 mRNA (Pfizer-BioNTech), or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines. A qualitative assay against SARS-CoV-2 nucleocapsid antigen was used to detect prior infection; these patients (n=23) were excluded from the final analysis. Humoral response following vaccination was monitored using serological immunoassay registered for quantitative measurement of serum anti-SARS-CoV-2 RDB-spike protein antibodies. Both electrochemiluminescent assays performed by Cobas e801 analyzer (Roche Diagnostics, Mannheim, Germany) detect total antibodies (including IgG). Response was recorded after the first and second doses. A positive response was defined as > 0.8 U/mL. Upper and lower limits of quantification were 0,4 U/mL and 250 U/mL respectively. We reviewed patient records for demographics, underlying hematological diseases, current treatment, the total number of lines of therapy received, IgG levels, application of anti-CD20 monoclonal antibodies (mAbs) and corticosteroids in the last 6 months before vaccination, and subsequent SARS-CoV-2 infection. Inter-group comparisons were performed with Mann-Whitney U, χ 2, or Fisher's exact test as appropriate. ROC curve analysis was used to find optimized cut-off values of numerical variables regarding response to the second dose. P values Results We evaluated a total of 120 patients who received at least one dose. Patient characteristics are summarized in Table 1. The majority received the Pfizer-BioNTech vaccine (66.7%), followed by Oxford-AstraZeneca (24.2%) and Moderna (9.2%). Data on humoral response after the first dose was available in 66 patients, among whom 20 (33%) achieved response with median specific IgG levels 6.1 U/mL. Response after the second dose was available in 90 patients; 58 (64.4%) achieved response with median specific IgG levels 250 U/mL. The second dose significantly improved response both in terms of achieved response (P=0.031) and specific IgG levels (P0.05). Lower response rates after the second dose were achieved in patients aged >67 years (P120 mg prednisone equivalent dose) did not influence the response significantly (response in 88.9% vs. 42.1%; P=0.056), and neither did steroid type. Four (3,3%) patients tested positive for SARS-CoV-2 after vaccination, 2 of which had no humoral response, and 2 had received only one dose. Three patients required in-hospital treatment and oxygen supplementation. Conclusions Patients with hematologic diseases have lower serological response rates to SARS-CoV-2 vaccines than those previously reported in clinical trials. Our results also suggest they benefit from receiving both doses with no significant difference between vaccine types. Those in active treatment, no prior HSCT, diagnosed with NHL, and receiving anti-CD20 mAb seem more likely to be seronegative after receiving both doses. However, the present study did not examine potential confounding effects between these factors and these findings should be elaborated further in larger patient cohorts. Figure 1 Figure 1. Disclosures Aurer: Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Swixx/BMS: Honoraria; sanofi genzyme: Consultancy, Honoraria; Teva/Pilva: Honoraria; Abbvie: Consultancy, Honoraria; Eusapharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; takeda: Consultancy, Honoraria. Durakovic: Takeda, Novartis, Genyzme: Honoraria.

Currently, there is no consensus regarding optimal front-line treatment for younger high-risk patients with large B cell lymphoma. American recommendations list only R-CHOP as standard, while European also include R-ACVBP and R-CHOEP14. We have been routinely using the latter regimen at our institution since 2011 and performed this retrospective real-life single-center study to analyze outcomes. Between September 2011 and April 2019, 66 newly diagnosed patients aged 18 to 60 years with B-large cell lymphoma and high-risk age-adjusted International Prognostic Index score were scheduled to receive 6 or 8 cycles of bi-weekly chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, etoposide, steroids, and rituximab (R-CHOEP14). After a median follow-up of 4.7 years, the estimated 3-year progression-free survival was 87% (95% CI 80-96%) and 3-year overall survival 90% (95% CI 83-98%). Grade ≥ 3 hematological side effects occurred in 83% and infectious in 41% of patients; one patient died of toxicity. Grade ≥ 2 cardiac toxicity occurred in 21% of patients, more frequently than previously reported. The cumulative 5-year risk of congestive heart failure with all-cause mortality as the competing risk was 17%. R-CHOEP14 is a very effective and manageable regimen for younger high-risk patients with B-large cell lymphoma, but the risk of cardiotoxicity warrants further investigations.

Previous studies have demonstrated cardiovascular causes to be among the leading causes of death after liver (LT) and kidney transplantation (KT). Although both recipient populations have unique pre-transplant cardiovascular burdens, they share similarities in post-transplant exposure to cardiovascular risk factors. The aim of this study was to compare cardiovascular mortality after LT and KT. We analyzed causes of death in 370 consecutive LT and 207 KT recipients from in-hospital records at a single tertiary transplant center. Cardiovascular causes of death were defined as cardiac arrest, heart failure, pulmonary embolism, or myocardial infarction. After a median follow-up of 36.5 months, infection was the most common cause of death in both cohorts, followed by cardiovascular causes in KT recipients and graft-related causes in LT recipients in whom cardiovascular causes were the third most common. Cumulative incidence curves for cardiovascular mortality computed with death from other causes as the competing risk were not significantly different (P = .36). While 1-year cumulative cardiovascular mortality was similar (1.6% after LT and 1.5% after KT), the estimated 4-year probability was higher post-KT (3.8% vs. 1.6%). Significant pre-transplant risk factors for overall mortality after KT in multivariable analysis were age at transplantation, left ventricular ejection fraction

Atrial fibrillation is the most common cardiac arrhythmia. It increases the risk of death and thromboembolic events. Vitamin K antagonists reduce these risks. Disadvantages of vitamin K antagonist therapy are narrow therapeutic range and interactions with drugs and food. In a single center prospective study, we enrolled 249 patients with atrial fibrillation over a 12-month period. The aim of our study was to evaluate vitamin K antagonist use regarding the indication and adequate dose. Data on 249 consecutive patients with atrial fibrillation were collected before general availability of novel oral anticoagulants. Out of 249 patients, 160 (64.2%) had indication for oral anticoagulant therapy. Only 81 (50.6%) patients had vitamin K antagonist in therapy, 12 (14.8%) of them in adequate dose. We also analyzed 129 patients aged over 75, of which 109 (84.4%) had absolute indication for oral anticoagulant therapy. Only 34 (31.2%) patients aged over 75 had been receiving vitamin K antagonist therapy and 6 (17.6%) had the International Normalized Ratio values within the proposed therapeutic interval. We found a significantly higher rate of anticoagulant therapy introduction in patients under 75 years (p=0.03), but there were no significant differences in the adequacy of anticoagulant therapy (p=0.89) between these two populations. Our results showed clear inadequacies of vitamin K antagonist treatment with a growing need for a wider use of novel oral anticoagulants., Atrijska fibrilacija je najučestalija aritmija koja povećava rizik smrti i tromboembolijskih incidenata. Antagonisti vitamina K smanjuju taj rizik. Problem terapije s antagonistima vitamina K je uska terapijska širina i brojne interakcije s lijekovima i hranom. Cilj ovoga istraživanja bio je utvrditi dostatnost primjene antagonista vitamina K s obzirom na indikaciju i dozu. Prikupljeni su podaci 249 bolesnika s atrijskom fibrilacijom hospitaliziranih u Kliničkoj bolnici “Merkur” u razdoblju od 12 mjeseci i to prije šire dostupnosti novijih oralnih antiokoagulansa. Od svih bolesnika, 160 (64,2%) ih je imalo indikaciju za primjenu oralne antikoagulantne terapije, a tek je njih 81 (50,6%) imalo antagonist vitamina K u terapiji. Samo 12 (14,8%) bolesnika je uzimalo antagonist vitamina K u dostatnoj dozi, a 129 (51,8%) ih je bilo iznad 75 godina starosti. Njih 109 (84,4%) je imalo indikaciju za oralnu antikoagulantnu terapiju, a samo 34 (31,2%) ih je uzimalo antagonist vitamina K, od kojih je 6 (17,6%) imalo INR u terapijskim vrijednostima. Statistička analiza podataka pokazala je da su bolesnici mlađi od 75 godina češće uzimali indiciranu oralnu antikoagulantnu terapiju u odnosu na bolesnike starije od 75 godina (p=0,03), dok nije bilo statistički značajne razlike u dostatnoj primjeni antikoagulantne terapije između ovih dviju populacija (p=0,89). Naši rezultati jasno pokazuju nedostatnosti primjene antagonista vitamina K kao i potrebu bržeg prijelaza prema terapiji novijim oralnim antikoagulansima.

Introduction: Transthoracic echocardiography (TTE) is recommended as the standard of care in evaluation of cardiovascular (CV) disease in liver (LT) and kidney (KT) transplant candidates.1,2 Guidelines for preoperative CV assessment are oriented at the immediate perioperative period and non-ischemic CV processes that would predict poor outcomes after LT and KT are defined less clearly. Aim: to establish whether ≥moderate mitral (MR), tricuspid regurgitation (TR) or ≥mild aortic stenosis (AS) on pretransplant TTE are associated with mortality, graft survival or major CV adverse events (MACE) in the late postoperative period (>30 days). Patients and Methods: Patients were stratified into cohorts based on the presence of ≥moderate MR, TR and ≥mild AS. Exclusion criteria was loss to follow up, incomplete TTE findings and death within 30 days of transplantation. MACE were defined as stroke, myocardial infarction (MI) or heart failure. Patient survival was defined as time from transplantation to death or last follow-up and graft survival as time from transplantation to last follow-up, death, graft dysfunction or re-transplantation. Outcomes of interest were compared between cohorts via logistic or Cox regression. Results: 306 LT (median age 59, IQR 53-64) and 196 KT patients were included (median age 52, IQR 40- 61). Median follow up was 36 months for LT (range 14.3 – 55.9), 40,5 months for KT (range 18-64.9). MACE occurred in 4.25% LT and 4.59% KT recipients. Upon univariate analysis AS was associated with MACE in KT recipients but crossed the significance level after adjusting for common confounders (age, sex, hypertension, diabetes, smoking). 11.76% LT and 9.69% KT recipients died. The most common cause of death was sepsis. MR was found to be associated with LT patient survival, but the association was lost after adjusting for age. In an age adjusted model MR was found to be associated with KT patient survival (HR 2.97, 95% CI 1.06-8.26, P=0.037). Graft survival was not associated with any potential predictors. Conclusion: Associating TTE findings with adverse outcomes after LT and KT might help distinguish patients who would benefit from closer management in the late postoperative period. Moderate or more severe MR was found to be associated with late mortality in KT recipients, however the significance of this is yet to be determined in larger sample studies.