Browsing by Author "Bukumiric, Zoran (36600111200)"

Objectives: Recent front-line clinical trials used the International Prognostic Index (IPI) to identify trial-eligible patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, many IPI-like variants with improved accuracy have been developed over the years for rituximab-treated patients. Methods: We assessed the impact of International Prognostic Indices on patient enrolment in clinical trials, aiming to exclude low-risk IPI patients based on POLARIX/EPCORE DLBCL-2 trial criteria. Results: We identified 2877 patients in the Danish Lymphoma Registry who would have been eligible for the POLARIX trial if patients with IPI 0–1 scores were included. IPI and NCCN-IPI assigned 33.3% and 11.9% of patients to the low-risk group, respectively. Shorter 5-year overall survival (91.4% vs. 97.5%), higher relapse rate (9.9% vs. 4.4%), and more deaths (16.1% vs. 4.4%) occurred in the low-risk IPI group compared with low-risk NCCN-IPI group. Analyzed models failed to identify true high-risk patients with poor prognosis. Similar results were found in the confirmatory cohort developed based on EPCORE DLBCL-2 trial eligibility criteria. Conclusion: True low-risk patients are more optimal identified by NCCN-IPI and should be excluded from front-line clinical trials due to their excellent prognosis. However, additional high-risk factors besides clinical prognostic models need to be considered when selecting trial-eligible patients. © 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.

Patients with acute leukemia (AL) have a high mortality rate from coronavirus disease 2019 (COVID-19). However, studies including patients with AL and COVID-19 are few. Fifty-one patients with AL and COVID-19 were included in our study. The mortality rate was 17/51 (29.4%). In all cases, death was associated with COVID-19 pneumonia. The major driver of outcome was the disease status (worse outcome was observed in newly diagnosed (OR, 6.00; 95% CI, 1.133–15.188) and patients with bone marrow aplasia (OR 4.148 [95% CI 1.133–15.188])). Higher mortality rate was associated with lower platelet count, prolonged PT, higher ISTH DIC score, CRP and LDH. Moreover, careful risk-benefit assessment regarding the continuation of anticancer therapy is required in patients receiving nonintensive and supportive therapy. Considering the high frequency of intrahospital viral transmission (50.98%), isolation of AL patients in single rooms, and permanent symptom monitoring and testing should be prioritized. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Patients with acute leukemia (AL) have a high mortality rate from coronavirus disease 2019 (COVID-19). However, studies including patients with AL and COVID-19 are few. Fifty-one patients with AL and COVID-19 were included in our study. The mortality rate was 17/51 (29.4%). In all cases, death was associated with COVID-19 pneumonia. The major driver of outcome was the disease status (worse outcome was observed in newly diagnosed (OR, 6.00; 95% CI, 1.133–15.188) and patients with bone marrow aplasia (OR 4.148 [95% CI 1.133–15.188])). Higher mortality rate was associated with lower platelet count, prolonged PT, higher ISTH DIC score, CRP and LDH. Moreover, careful risk-benefit assessment regarding the continuation of anticancer therapy is required in patients receiving nonintensive and supportive therapy. Considering the high frequency of intrahospital viral transmission (50.98%), isolation of AL patients in single rooms, and permanent symptom monitoring and testing should be prioritized. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Objective: The initiation of extracorporeal membrane oxygenation (ECMO) triggers complex coagulation processes necessitating systemic anticoagulation. Therefore, anticoagulation monitoring is crucial to avoid adverse events such as thrombosis and hemorrhage. The main aim of this work was to analyze the association between anti-Xa levels and thrombosis occurrence during ECMO support. Design: Systematic literature review and meta-analysis (Scopus and PubMed, up to July 29, 2023). Setting: All retrospective and prospective studies. Participants: Patients receiving ECMO support. Intervention: Anticoagulation monitoring during ECMO support. Measurements and Main Results: A total of 16 articles with 1,968 patients were included in the review and 7 studies in the meta-analysis (n = 374). Patients with thrombosis had significantly lower mean anti-Xa values (standardized mean difference -0.36, 95% confidence interval [CI] -0.62 to -0.11, p < 0.01). Furthermore, a positive correlation was observed between unfractionated heparin infusion and anti-Xa levels (pooled estimate of correlation coefficients 0.31, 95% CI 0.19 to 0.43, p < 0.001). The most common adverse events were major bleeding (42%) and any kind of hemorrhage (36%), followed by thromboembolic events (30%) and circuit or oxygenator membrane thrombosis (19%). More than half of the patients did not survive to discharge (52%). Conclusions: This work revealed significantly lower levels of anti-Xa in patients experiencing thromboembolic events and a positive correlation between anti-Xa and unfractionated heparin infusion. Considering the contemplative limitations of conventional monitoring tools, further research on the role of anti-Xa is warranted. New trials should be encouraged to confirm these findings and determine the most suitable monitoring strategy for patients receiving ECMO support. © 2024 The Author(s)

Objective: Extracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to maintain the circuit patency. However, the use of anticoagulation carries a risk of severe hemorrhage, necessitating rigorous monitoring. Activated clotting time (ACT) is a widely used monitoring tool; however, the evidence of its correlation with unfractionated heparin (UFH) infusion dose is limited. Here we aimed to analyze the correlation between ACT and UFH infusion during ECMO. Design: Systematic literature review and meta-analysis of correlation coefficients (Scopus and PubMed, up to July 13, 2024). PROSPERO: CRD42023448888 Setting: All retrospective and prospective studies Participants: Patients receiving ECMO support Intervention: Anticoagulation monitoring during ECMO support Measurements and Main Results: Nineteen studies were included in the analysis, and the meta-analysis encompassed 16 studies. The vast majority of studies (n = 15) found a weak correlation, and no study reported a strong correlation between ACT and UFH infusion dose. The meta-analysis (n = 12,625 samples) identified a weak correlation, with a pooled estimate of correlation coefficients of 0.132 (95% confidence interval 0.03-0.23). The most common adverse events were hemorrhage (pooled incidence, 45%) and thrombosis (30%), and 47% of the patients died during their hospital stay. Conclusions: Even though ACT is a widely used UFH monitoring tool in ECMO patients, our meta-analysis found a weak correlation between ACT and UFH infusion dose. New trials are needed to investigate the role of emerging tools and to clarify the most appropriate monitoring strategy for patients receiving ECMO support. © 2024 The Author(s)

Introduction: Hemorrhagic early death (HED) remains a major cause of treatment failure among patients with acute promyelocytic leukemia (APL). We aimed to investigate the prognostic potential of rotational thromboelastometry (ROTEM) for bleeding in patients with APL. Materials and Methods: 31 newly-diagnosed APL patients (median age of 40 years; 14 female/17 male) that underwent treatment at the Clinic of Hematology UCCS from 2016-2020 with all-trans retinoic acid and anthracyclines were recruited. CBCs (complete blood count), conventional coagulation tests (CCTs), and ROTEM parameters obtained before treatment initiation were evaluated. Results: All patients demonstrated at least one ROTEM parameter out of the reference range. ROTEM parameters associated with significant hemorrhage were EXTEM clotting time (CT) (P = 0.041) and INTEM amplitude 10 (A10) (P = 0.039), however, only EXTEM CT (P = 0.036) was associated with HED. Among CBCs and CCTs, only platelets were associated with significant bleeding (P = 0.015), while D-dimer was associated with both bleeding and HED (P = 0.001 and P = 0.002, respectively). Conclusion: Our results indicate that ROTEM parameters may reveal hypocoagulability in APL patients and have the potential to improve current hemorrhage prognostic methods. Additionally, these results suggest the combination of ROTEM and CCTs might be useful in identifying patients at risk for HED. © The Author(s) 2022.

Introduction: The initiation of the extracorporeal membrane oxygenation (ECMO) is associated with complex coagulatory and inflammatory processes and consequently needed anticoagulation. Systemic anticoagulation bears an additional risk of serious bleeding, and its monitoring is of immense importance. Therefore, our work aims to analyze the association of anticoagulation monitoring with bleeding during ECMO support. Material and methods: Systematic literature review and meta-analysis, complying with the PRISMA guidelines (PROSPERO-CRD42022359465). Results: Seventeen studies comprising 3249 patients were included in the final analysis. Patients experiencing hemorrhage had a longer activated partial thromboplastin time (aPTT), a longer ECMO duration, and higher mortality. We could not find strong evidence of any aPTT threshold association with the bleeding occurrence, as less than half of authors reported a potential relationship. Finally, we identified the acute kidney injury (66%, 233/356) and hemorrhage (46%, 469/1046) to be the most frequent adverse events, while almost one-half of patients did not survive to discharge (47%, 1192/2490). Conclusion: The aPTT-guided anticoagulation is still the standard of care in ECMO patients. We did not find strong evidence supporting the aPTT-guided monitoring during ECMO. Based on the weight of the available evidence, further randomized trials are crucial to clarify the best monitoring strategy. © 2023 The Authors

Many studies have reported insufficient support from surgical services, resulting in nephrologists creating arteriovenous fistulas in many centers. The aim of this study was to compare risk factors of arteriovenous fistula dysfunction in patients whose fistulas were created by nephrologists versus vascular surgeons. Methods: This was a retrospective, analytical study of interventions by nephrologists and vascular surgeons during a period of 15 years. Out of a total of 1,048 fistulas, 764 (72.9%) were created by nephrologists patients, while vascular surgeons were responsible for 284 (27.1%) fistulae. Laboratory, demographic, and clinical parameters which might affect functioning of these arteriovenous fistulae were analyzed. Results: Patients whose arteriovenous fistula was formed by nephrologists differed significantly from those created by vascular surgeons in relation to the preventive character of the arteriovenous fistula (p = 0.011), lumen of the vein (p < 0.001) and systolic blood pressure (p = 0.047). Multivariate logistic regression of arteriovenous fistula dysfunction showed that risk factors were female gender (odds ratio [OR] = 1.56, 95% CI 1.16-2.07), whether the fistulae were created by vascular surgeons or nephrologists (OR = 1.38; 95% CI 1.01-1.89) and the site of the arteriovenous fistula (OR = 0.64; 95% CI 0.48-0.85). Conclusions: Arteriovenous fistulae created by vascular surgeons, female gender, and the location are risk factors of dysfunction. © 2021 S. Karger AG. All rights reserved.

Background: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. Aim: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Results: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23–6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581–63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329–13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212–23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948–21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092–5.007). Conclusions: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30. © 2023 by the authors.

Background: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. Aim: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Results: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23–6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581–63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329–13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212–23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948–21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092–5.007). Conclusions: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30. © 2023 by the authors.

Introduction: Nearly sixty percent of patients with prostate cancer (PCa) undergo radiation therapy (RT). During the course of treatment patients may experience normal tissue reactions. It is a well established fact that genetic and epigenetic mechanisms, such as microRNA (miRNA) level changes might be associated with radiotoxicity, as a response to irradiation. Materials and methods: This is the first study that has investigated levels of radiosensory miRNAs in association with acute genitourinary radiotoxicity extracted from peripheral blood mononuclear cells (PBCs), in three points; before RT (BRT), after RT (ART) and on the first control examination (FCONT). We measured levels of miR-21/146a/155 expression by quantitative real-time PCR (qRT-PCR), comparative ΔΔCt method, in fifteen patients with localized prostate cancer, treated with three-dimensional conformal radiotherapy (3DCRT). Nine subjects have experienced acute genitourinary (GU) radiotoxicity whereas six where without GU radiotoxicity. Results: Firstly, we detected the highest levels of miR-21 in ART group (p = 0.043) in the patients with acute GU radiotoxicity. Secondly, we found trend towards higher miR-21 levels and significantly higher levels of miR-146a/155 within the patients with acute GU toxicity than in patients without (p = 0.068, p = 0.016, and p = 0.010, respectively). Thirdly, we detected significant change in miR-146a/155 levels within the patients without acute GU radiotoxicity during RT p = 0.042, and p = 0.041, respectively). Conclusion: miR-21/146a/155 might be useful potential factors of radiosensitivity and acute genitourinary radiotoxicity in prostate cancer patients. miRNA might have great potential as predictors of various pathological conditions extracted from PBMCs. © 2018 Elsevier GmbH

Introduction: Nearly sixty percent of patients with prostate cancer (PCa) undergo radiation therapy (RT). During the course of treatment patients may experience normal tissue reactions. It is a well established fact that genetic and epigenetic mechanisms, such as microRNA (miRNA) level changes might be associated with radiotoxicity, as a response to irradiation. Materials and methods: This is the first study that has investigated levels of radiosensory miRNAs in association with acute genitourinary radiotoxicity extracted from peripheral blood mononuclear cells (PBCs), in three points; before RT (BRT), after RT (ART) and on the first control examination (FCONT). We measured levels of miR-21/146a/155 expression by quantitative real-time PCR (qRT-PCR), comparative ΔΔCt method, in fifteen patients with localized prostate cancer, treated with three-dimensional conformal radiotherapy (3DCRT). Nine subjects have experienced acute genitourinary (GU) radiotoxicity whereas six where without GU radiotoxicity. Results: Firstly, we detected the highest levels of miR-21 in ART group (p = 0.043) in the patients with acute GU radiotoxicity. Secondly, we found trend towards higher miR-21 levels and significantly higher levels of miR-146a/155 within the patients with acute GU toxicity than in patients without (p = 0.068, p = 0.016, and p = 0.010, respectively). Thirdly, we detected significant change in miR-146a/155 levels within the patients without acute GU radiotoxicity during RT p = 0.042, and p = 0.041, respectively). Conclusion: miR-21/146a/155 might be useful potential factors of radiosensitivity and acute genitourinary radiotoxicity in prostate cancer patients. miRNA might have great potential as predictors of various pathological conditions extracted from PBMCs. © 2018 Elsevier GmbH

Objective: Extracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to reduce the risk of thromboembolic events. Despite its historic role, activated clotting time (ACT) remains a widely used heparin monitoring method. Systematic evidence on the association of ACT-guided monitoring with hemorrhagic or thromboembolic complications does not exist. Design: Systematic literature review and meta-analysis (Scopus and PubMed, July 2023). Setting: All cohort studies. Participants: Patients receiving ECMO support. Intervention: Anticoagulation monitoring with ACT. Measurements and Main Results: We identified 3,177 publications, with 8 studies reporting the average ACT values for patients with and without bleeding. Meta-analysis revealed no significant difference in the compared groups (SMD = 0.69; 95% CI −0.05 to 1.43, p = 0.069; I2 = 87.4%). Three studies (n = 117 patients) reported on the average ACT values for patients with thrombosis, without significant differences in ACT between patients with and without thrombosis (SMD = 0.47; 95% CI −0.50 to 1.44, p = 0.342; I2 = 81.1%). Conclusions: Even though ACT is a widely used heparin monitoring tool, the evidence on its association with hemorrhagic or thromboembolic events is still controversial and limited. Further studies are essential to elucidate the role of ACT in anticoagulation monitoring during ECMO support. © 2024 The Author(s)

Background: The use of extracorporeal membrane oxygenation (ECMO) is associated with complex hemostatic changes. Systemic anticoagulation is initiated to prevent clotting in the ECMO system, but this comes with an increased risk of bleeding. Evidence on the use of anti-Xa-guided monitoring to prevent bleeding during ECMO support is limited. Therefore, we aimed to analyze the association between anti-factor Xa-guided anticoagulation and hemorrhage during ECMO. Methods: A systematic review and meta-analysis was performed (up to August 2023). PROSPERO: CRD42023448888. Results: Twenty-six studies comprising 2293 patients were included in the analysis, with six works being part of the meta-analysis. The mean anti-Xa values did not show a significant difference between patients with and without hemorrhage (standardized mean difference −0.05; 95% confidence interval [CI]: −0.19; 0.28, p =.69). We found a positive correlation between anti-Xa levels and unfractionated heparin dose (UFH; pooled estimate of correlation coefficients 0.44; 95% CI: 0.33; 0.55, p <.001). The most frequent complications were any type of hemorrhage (pooled 36%) and thrombosis (33%). Nearly half of the critically ill patients did not survive to hospital discharge (47%). Conclusions: The most appropriate tool for anticoagulation monitoring in ECMO patients is uncertain. Our analysis did not reveal a significant difference in anti-Xa levels in patients with and without hemorrhagic events. However, we found a moderate correlation between anti-Xa and the UFH dose, supporting its utilization in monitoring UFH anticoagulation. Given the limitations of time-guided monitoring methods, the role of anti-Xa is promising and further research is warranted. © 2024 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.

Background: The initiation of extracorporeal membrane oxygenation (ECMO) is associated with complex inflammatory and coagulatory processes, raising the need for systemic anticoagulation. The balance of anticoagulatory and procoagulant factors is essential, as therapeutic anticoagulation confers a further risk of potentially life-threatening bleeding. Therefore, our study aims to systematize and analyze the most recent evidence regarding anticoagulation monitoring and the thromboembolic events in patients receiving veno-arterial ECMO support. Methods: Using the PRISMA guidelines, we systematically searched the Scopus and PubMed databases up to October 2022. A weighted effects model was employed for the meta-analytic portion of the study. Results: Six studies comprising 1728 patients were included in the final analysis. Unfractionated heparin was used for anticoagulation, with an activated partial thromboplastin time (aPTT) monitoring goal set between 45 and 80 s. The majority of studies aimed to investigate the incidence of adverse events and potential risk factors for thromboembolic and bleeding events. None of the authors found any association of aPTT levels with the occurrence of thromboembolic events. Finally, the most frequent adverse events were hemorrhage (pooled 43%, 95% CI 28.4; 59.5) and any kind of thrombosis (pooled 36%, 95% CI 21.7; 53.7), and more than one-half of patients did not survive to discharge (pooled 54%). Conclusions: Despite the tremendous development of critical care, aPTT-guided systemic anticoagulation is still the standard monitoring tool. We did not find any association of aPTT levels with thrombosis. Further evidence and new trials should clarify the true incidence of thromboembolic events, along with the best anticoagulation and monitoring strategy in veno-arterial ECMO patients. © 2023 by the authors.

Objectives: We sought to determine whether blended learning is an effective strategy for acquiring competence in public health biostatistics. Methods: The trial was conducted with 69 Masters’ students of public health attending the School of Public Health at University of Belgrade. Students were exposed to the traditional and blended learning styles. Blended learning included a combination of face-to-face and distance learning methodologies integrated into a single course. Curriculum development was guided by competencies as suggested by the Association of Schools of Public Health in the European Region (ASPHER). Teaching methods were compared according to the final competence score. Results: Forty-four students were enrolled in the traditional method of education delivery, and 25 to the blended learning format. Mean exam scores for the blended learning group were higher than for the on-site group for both the final statistics score (89.65 ± 6.93 vs. 78.21 ± 13.26; p < 0.001) and knowledge test score (35.89 ± 3.66 vs. 22.56 ± 7.12; p < 0.001), with estimated large effect size (d > 0.8). Conclusions: A blended learning approach is an attractive and effective way of acquiring biostatistics competence for Masters of Public Health (MPH) graduate students. © 2017, Swiss School of Public Health (SSPH+).

Background: Cytarabine-anthracycline-based induction chemotherapy remains the standard of care for remission induction among patients with newly diagnosed acute myeloid leukaemia (AML). There are remarkable differences in therapy response among AML patients. This fact could be partly explained by the patients’ genetic variability related to the metabolic paths of cytarabine and anthracyclines. This study aims to evaluate the effect of variants in pharmacogenes SLC29A1, DCK, ABCB1, GSTM1, and GSTT1, as well as laboratory and AML-related parameters on clinical outcomes in adult AML patients. Methods: A total of 100 AML patients were included in the study. Pharmacogenetic variants SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582, and GSTM1 and GSTT1 gene deletions were detected by methodology based on PCR, fragment analysis and direct sequencing. The methods of descriptive and analytic statistics were used. Survival analysis was done using the Kaplan-Meier method using the Log-Rank test. Results: This is the first study of adult AML pharmacogenetics in the Serbian population. Clinical outcomes in our cohort of AML patients were not impacted by analysed variants in SLC29A1, DCK, ABCB1 and GSTT1, and GSTM1 genes, independently or in combinations. Achievement of complete remission was identified as an independent prognostic indicator of clinical outcome. Conclusions: The population-specific genomic profile has to be considered in pharmacogenetics. Since the data on AML pharmacogenetics in European populations is limited, our results contribute to knowledge in this field and strongly indicate that a high-throughput approach must be applied to find particular pharmacogenetic markers of AML in the European population. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.

Background: Cytarabine-anthracycline-based induction chemotherapy remains the standard of care for remission induction among patients with newly diagnosed acute myeloid leukaemia (AML). There are remarkable differences in therapy response among AML patients. This fact could be partly explained by the patients’ genetic variability related to the metabolic paths of cytarabine and anthracyclines. This study aims to evaluate the effect of variants in pharmacogenes SLC29A1, DCK, ABCB1, GSTM1, and GSTT1, as well as laboratory and AML-related parameters on clinical outcomes in adult AML patients. Methods: A total of 100 AML patients were included in the study. Pharmacogenetic variants SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582, and GSTM1 and GSTT1 gene deletions were detected by methodology based on PCR, fragment analysis and direct sequencing. The methods of descriptive and analytic statistics were used. Survival analysis was done using the Kaplan-Meier method using the Log-Rank test. Results: This is the first study of adult AML pharmacogenetics in the Serbian population. Clinical outcomes in our cohort of AML patients were not impacted by analysed variants in SLC29A1, DCK, ABCB1 and GSTT1, and GSTM1 genes, independently or in combinations. Achievement of complete remission was identified as an independent prognostic indicator of clinical outcome. Conclusions: The population-specific genomic profile has to be considered in pharmacogenetics. Since the data on AML pharmacogenetics in European populations is limited, our results contribute to knowledge in this field and strongly indicate that a high-throughput approach must be applied to find particular pharmacogenetic markers of AML in the European population. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.

Background: The aim of this study was to evaluate the effects of pneumoperitoneum on liver function during and after laparoscopic cholecystectomy. Methods: This prospective study comprised a total of 165 patients, who were divided into two groups: The first group had low-pressure pneumoperitoneum (12 mm Hg; N = 78) and the second group had high-pressure pneumoperitoneum (14 mm Hg; N = 87). A detailed statistical analysis included sex, age, operation time, and liver function tests including total bilirubin, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, fibrinogen, and lactate dehydrogenase (LDH), which were obtained preoperatively and 24 h, 7 days, and 30 days postoperatively. The statistical hypotheses were tested with a t test, Mann–Whitney test, chi-square test, Friedman test, and Wilcoxon’s test. Results: There was no statistical difference between the two groups considering age, gender, and operation time (p = 0.740, p = 0.255, and p = 0.480, respectively). There was also no statistical difference in the median values of bilirubin, AST, GGT, LDH, albumin, and fibrinogen between the two groups. There was a significant statistical difference between the two groups in the median values of ALT on the 30th postoperative day (p = 0.045). There was a statistical difference for all hematochemical parameters as a function of time, independent of the level of intra-abdominal pressure (IAP). Conclusion: There were no statistically significant differences in the values of parameters of structural damage to the liver between the two groups, but within the groups themselves. From this we conclude that both values of elevated IAP cause microstructural and functional damage to the liver. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature.

Over the years, a rising incidence of liver cirrhosis and lymphoma has been observed. Therefore, the risk of having cirrhosis as a comorbidity increases, thus challenging treatment approaches as data on the management of these patients is lacking. We performed a systematic review to summarize papers that analyzed patients with liver cirrhosis that occurred before and/or concomitantly to lymphoma. We identified 153 papers (230 patients) through Pubmed and/or Embase search. Publications comprised predominantly of case reports and/or case series. Most patients had HCV-related cirrhosis (62.6%), and aggressive lymphoma histology (59.6%). Data on liver status was available in 55.7% of all patients, with 46.1% having decompensated liver cirrhosis. These patients experienced more often treatment reductions and/or modifications, treatment side effects, and inferior survival than those with compensated cirrhosis (median 18 months vs. median not reached). Dose reductions and/or treatment modifications primarily due to concomitant liver disease were common. Moreover, liver toxicity was observed in 33.6% of patients with provided information on treatment side effects, ranging from mild toxicity to liver failure with fatal outcomes. Again, despite treatment modification/reduction, patients with decompensated liver cirrhosis developed hepatic toxicity more frequently than patients with compensated liver disease. Although patients suffering from cirrhosis and lymphoma can tolerate standard chemoimmunotherapy, a cautious multidisciplinary approach is needed to evaluate the risks and benefits. © 2022