Assessment of Factor VIII Activity and D-Dimer Levels in the Post-COVID Period.

Changes in the hemostatic system during COVID infection lead to hypercoagulability. Numerous studies have evaluated hemostatic abnormalities in COVID patients during acute infection, in the period of hospitalization. However, the hemostatic status following hospital discharge has not been sufficiently assessed. Considering the importance of FVIII and D-dimer levels as markers for the assessment of thrombosis, our study aimed to evaluate changes in these markers, as well as the influence of patient's age and clinical presentation of COVID infection on those hemostatic markers in the post-COVID phase. This prospective study (July 2020 to December 2022) included 115 COVID patients, 68 (59%) with asymptomatic/mild and 47 (41%) with moderate/severe clinical presentation. Patient follow-up included laboratory evaluation of FVIII and D-dimer levels at 1, 3, and 6 months following the COVID infection. Three months after the COVID infection, elevated FVIII was recorded in 44% of younger versus 65% of older individuals, p = 0.05, respectively, and 30 versus 57% (p = 0.008) 6 months post-COVID infection. With a focus on clinical presentation, a higher number of patients with moderate/severe COVID had elevated FVIII activity, but a statistically significant difference was observed only for the 6 months (32% mild vs. 53% moderate/severe, p = 0.041) post-infection time point. Following a COVID infection, an increase in FVIII activity suggests a continued hypercoagulable state in the post-COVID period and correlates with elevated D-dimer levels. This increase in FVIII is more pronounced in patients with moderate/severe clinical picture and those patients older than 50 years.

An evidence-based and risk-adapted GSF versus GSF plus plerixafor mobilization strategy to obtain a sufficient CD34+ cell yield in the harvest for autologous stem cell transplants.

BACKGROUND: Plerixafor is a bicyclam molecule with the ability to reversibly bind to receptor CXCR-4 thus leading to an increased release of stem cells (SC) into the circulation. This study aims to evaluate the efficacy of G-CSF plus plerixafor versus G-CSF alone mobilizing regimens on the basis of CD34+ cell yield and engraftment kinetics following hematopoietic SC transplants. METHODS: The study incorporated 173 patients with plasma cell neoplasms (PCN), Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), undergoing mobilization and following autologous SC-transplant. For patients with mobilization failure and those predicted to be at risk of harvesting inadequate CD34+ yields (poor-responders), plerixafor was administered. Data was collected and compared in relation to the harvesting protocols used, cell quantification, cell-engraftment potential and overall clinical outcome. RESULTS: A total of 101 patients received plerixafor (58.4 %) and the median CD34+increase was 312 %. Chemotherapy-mobilized PCN-patients required less plerixafor administration (p = 0.01), no difference was observed in lymphoma groups (p = 0.46). The median CD34+cell yield was 7.8 × 106/kg bm. Patients requiring plerixafor achieved lower, but still comparable cell yields. Total cell dose infused was in correlation with engraftment kinetics. Patients requiring plerixafor had delayed platelet engraftment (p = 0.029). CONCLUSIONS: Adequately selected plerixafor administration reduces "mobilization-related-failure" rate and assure a high-level cell dose for SC transplants, with superior "therapeutic-potential" and safety profile. The mobilization strategy that incorporates "just-in-time" plerixafor administration, also leads to a reduction of hospitalization days and healthcare resource utilization. For definitive conclusions, further controlled/larger clinical trials concerning correlation of CD34+ cell count/yield, with hematopoietic reconstitution are required.

Development and Validation of a Multivariable Predictive Model for Mortality of COVID-19 Patients Demanding High Oxygen Flow at Admission to ICU: AIDA Score.

INTRODUCTION: Risk stratification is an important aspect of COVID-19 management, especially in patients admitted to ICU as it can provide more useful consumption of health resources, as well as prioritize critical care services in situations of overwhelming number of patients. MATERIALS AND METHODS: A multivariable predictive model for mortality was developed using data solely from a derivation cohort of 160 COVID-19 patients with moderate to severe ARDS admitted to ICU. The regression coefficients from the final multivariate model of the derivation study were used to assign points for the risk model, consisted of all significant variables from the multivariate analysis and age as a known risk factor for COVID-19 patient mortality. The newly developed AIDA score was arrived at by assigning 5 points for serum albumin and 1 point for IL-6, D dimer, and age. The score was further validated on a cohort of 304 patients admitted to ICU due to the severe form of COVID-19. RESULTS: The study population included 160 COVID-19 patients admitted to ICU in the derivation and 304 in the validation cohort. The mean patient age was 66.7 years (range, 20-93 years), with 68.1% men and 31.9% women. Most patients (76.8%) had comorbidities with hypertension (67.7%), diabetes (31.7), and coronary artery disease (19.3) as the most frequent. A total of 316 patients (68.3%) were treated with mechanical ventilation. Ninety-six (60.0%) in the derivation cohort and 221 (72.7%) patients in the validation cohort had a lethal outcome. The population was divided into the following risk categories for mortality based on the risk model score: low risk (score 0-1) and at-risk (score > 1). In addition, patients were considered at high risk with a risk score > 2. By applying the risk model to the validation cohort (n = 304), the positive predictive value was 78.8% (95% CI 75.5% to 81.8%); the negative predictive value was 46.6% (95% CI 37.3% to 56.2%); the sensitivity was 82.4% (95% CI 76.7% to 87.1%), and the specificity was 41.0% (95% CI 30.3% to 52.3%). The C statistic was 0.863 (95% CI 0.805-0.921) and 0.665 (95% CI 0.598-0.732) in the derivation and validation cohorts, respectively, indicating a high discriminative value of the proposed score. CONCLUSION: In the present study, AIDA score showed a valuable significance in estimating the mortality risk in patients with the severe form of COVID-19 disease at admission to ICU. Further external validation on a larger group of patients is needed to provide more insights into the utility of this score in everyday practice.

Predictors of Mortality in Critically Ill COVID-19 Patients Demanding High Oxygen Flow: A Thin Line between Inflammation, Cytokine Storm, and Coagulopathy.

INTRODUCTION: Mortality among critically ill COVID-19 patients remains relatively high despite different potential therapeutic modalities being introduced recently. The treatment of critically ill patients is a challenging task, without identified credible predictors of mortality. METHODS: We performed an analysis of 160 consecutive patients with confirmed COVID-19 infection admitted to the Respiratory Intensive Care Unit between June 23, 2020, and October 2, 2020, in University Hospital Center Bezanijska kosa, Belgrade, Serbia. Patients on invasive, noninvasive ventilation and high flow oxygen therapy with moderate to severe ARDS, according to the Berlin definition of ARDS, were selected for the study. Demographic data, past medical history, laboratory values, and CT severity score were analyzed to identify predictors of mortality. Univariate and multivariate logistic regression models were used to assess potential predictors of mortality in critically ill COVID-19 patients. RESULTS: The mean patient age was 65.6 years (range, 29-92 years), predominantly men, 68.8%. 107 (66.9%) patients were on invasive mechanical ventilation, 31 (19.3%) on noninvasive, and 22 (13.8%) on high flow oxygen therapy machine. The median total number of ICU days was 10 (25th to 75th percentile: 6-18), while the median total number of hospital stay was 18 (25th to 75th percentile: 12-28). The mortality rate was 60% (96/160). Univariate logistic regression analysis confirmed the significance of age, CRP, and lymphocytes at admission to hospital, serum albumin, D-dimer, and IL-6 at admission to ICU, and CT score. Serum albumin, D-dimer, and IL-6 at admission to ICU were independently associated with mortality in the final multivariate analysis. CONCLUSION: In the present study of 160 consecutive critically ill COVID-19 patients with moderate to severe ARDS, IL-6, serum albumin, and D-dimer at admission to ICU, accompanied by chest CT severity score, were marked as independent predictors of mortality.

Systemic inflammatory response syndrome in dogs naturally infected with Babesia canis: Association with the parasite load and host factors.

The common signs of canine babesiosis caused by an infection with Babesia canis are fever, anorexia, lethargy, pulse alterations, anemia, and occasionally mild icterus. Dogs with these clinical signs can be divided into two groups: those with acute-phase reaction and those with systemic inflammatory response syndrome (SIRS). Factors associated with the occurrence of SIRS in canine babesiosis have not been thoroughly researched. This article outlines a cross-sectional study of 54 client-owned dogs with an acute B. canis infection, and evaluates the differences in age, gender, laboratory findings, parasite load, and seroreactivity against B. canis between the SIRS and the SIRS-free dogs. We have analyzed a complete blood count, serum biochemistry, serum amyloid A, ceruloplasmin, paraoxonase-1, serology, and PCR testing using standard methodologies. The frequency of SIRS among the investigated dogs reached 0.59. Male dogs and those seronegative against B. canis, were more frequent in the SIRS group, whilst age and parasite load could not be associated with the presence of SIRS. Dogs with SIRS had a lower count of total leukocytes, neutrophils, lymphocytes, and monocytes, and a lower concentration of iron and bilirubin compared with SIRS-free dogs. No significant differences in the concentration of acute-phase proteins have been noticed to exist between the groups of dogs. Further, the seronegative dogs had a lower count of lymphocytes and monocytes and a higher parasite load than the seroreactive dogs. Multivariate logistic regression analysis has identified leukopenia (<6 × 109/L) and monocytopenia (<0.2 × 109/L) as independent associates of SIRS in the investigated dogs, thus implying that these routine tests could be used as reliable markers for SIRS.

Early Selective C-Reactive Protein Apheresis in a Patient with Acute ST Segment Elevation Myocardial Reinfarction.

The patient was admitted for urgent coronary angiography following an acute anterior ST segment elevation myocardial reinfarction (STEMI) caused by acute stent thrombosis. A stent had been implanted 10 days prior to the reinfarction for an acute anterior STEMI. However, the patient had stopped taking ticagrelor post-discharge. Primary percutaneous coronary intervention of the left anterior descending artery was performed. Subsequently, due to a high C-reactive protein (CRP) level, 3 CRP apheresis sessions were performed, with the first session starting 12 h after the onset of symptoms. A significant drop in CRP was noted after each apheresis. The post-procedural course was uneventful.

A Promising Innovative Treatment for ST-Elevation Myocardial Infarction: The Use of C-Reactive Protein Selective Apheresis: Case Report.

BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI), C-reactive protein (CRP) levels are associated with larger infarct size, transmural extent, and poor function of left ventricle and independently predict 30-day mortality. CRP-apheresis following STEMI showed to be feasible, safe, and has significant beneficial effect both on myocardial infarction size and wall motion. To the best of our knowledge, this is only the second published clinical evaluation of the efficacy and safety of selective CRP-apheresis in the STEMI treatment using Spectra-Optia and Pentrasorb CRP-adsorber systems. CASE REPORT: A 53-year-old female was referred with anterior STEMI. After percutaneous coronary intervention, patient received standard post-STEMI therapy according to current guidelines. Selective therapeutic plasma exchange (TPE) was performed using Spectra-Optia (Terumo BCT; USA) and Pentrasorb CRP-adsorber (Pentracor GmbH; Germany) systems. Antecubital veins were used for vascular access and acid-citrate-dextrose solution (ACD formula A; total volume = 1,026 mL) was utilized as anticoagulant. The volume of processed blood was 15,600 mL. The removed "natural" plasma (total volume = 8,329 mL) was replaced with CRP-depleted autologous plasma (total volume = 8,085 mL). This intensive TPE-treatment was well tolerated, without adverse effects, or complications. The CRP plasma levels were: initial = 4.2 mg/L 6 h after acute myocardial infarction (AMI), pre-apheresis = 16.4 mg/L, and post-apheresis = 4.59 mg/L (CRP-depletion = 72%). There were neither significant changes observed in biochemistry nor any alterations in plasma hemostatic activity investigated before and after CRP-adsorption performed. CONCLUSION: Early performed CRP-apheresis is a promising innovative therapeutic approach for STEMI treatment that could provide a reduced size of infarction zone - with inferior occurrence of heart failure after AMI. However, precise and complete evaluation of the efficacy and safety of this treatment requires further multicenter randomized and larger clinical studies.

Flow cytometry analysis of platelet populations: usefulness for monitoringthe storage lesion in pooled buffy-coat platelet concentrates.

BACKGROUND: Early detection of the platelet storage lesion is still a challenge in transfusion practice. Using flow cytometry, we evaluated the appearance of the storage lesion, based on the expression of platelet activation markers, in total platelets and platelet populations. MATERIALS AND METHODS: Buffy-coat-derived platelet concentrates were stored under standard conditions for 5 days. The expression of activation antigens CD42b, CD36, CD62p and phosphatidylserine on total platelets and populations of small, medium-sized and large platelets was analysed by flow cytometry on storage days 1, 3 and 5. RESULTS: The activation/lesion on total platelets and each platelet population was detected on storage day 3, by the increased expression of CD36. On the same day, increased expression of CD42b and CD62p was detected, but only on large platelets. Small and medium-sized platelets had increased CD62p expression only on day 5. Externalisation of phosphatidylserine was not detected. DISCUSSION: Evaluation of the level of expression of various activation markers on different platelet populations could be an additional valid analysis in cell quality control of platelet concentrates, and in the assessment of novel approaches to platelet concentrate manipulation.

Novel insights into the polycythemia-paraganglioma-somatostatinoma syndrome.

Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A). This study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings into perspective these experiences with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11-46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8-38) and SOMs at 29 years (range 22-38). PGLs were multiple, recurrent and metastatic in 100, 100 and 29% of all cases, and SOMs in 40, 40 and 60%, respectively. All PGLs were primarily norepinephrine-producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel-Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA). Therefore, [18F]-FDOPA PET/CT, not [68Ga]-(DOTA)-[Tyr3]-octreotate ([68Ga]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The long-term prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges.

Autologous hematopoietic stem cell transplantation in combination with immunoablative protocol in secondary progressive multiple sclerosis--A 10-year follow-up of the first transplanted patient.

INTRODUCTION: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system that affects young individuals and leads to severe disability. High dose immunoablation followed by autologous hemopoietic stem cell transplantation (AHSCT) has been considered in the last 15 years as potentialy effective therapeutic approach for aggressive MS. The most recent long-time follow-up results suggest that AHSCT is not only effective for highly-aggressive MS, but for relapsing-remitting MS as well, providing long-term remission, or maybe even cure. We presented a 10-year follow-up of the first MS patient being treated by immunoablation therapy and AHSCT. CASE REPORT: A 27-year-old male experienced the first symptoms--intermitent numbness and paresthesia of arms and legs of what was treated for two years by psychiatrist as anxiety disorder. After he developed severe paraparesis he was admitted to the Neurology Clinic and diagnosed with MS. Our patient developed aggressive MS with frequent relapses, rapid disability progression and transition to secondary progressive form 6 years after MS onset[the Expanded Disability Status Scale (EDSS) 7.0 Ambulation Index (AI) 7]. AHSCT was performed, cyclophosphamide was used for hemopoietic stem cell mobilization and the BEAM protocol was used as conditionig regimen. No major adverse events followed the AHSCT. Neurological impairment improved, EDSS 6.5, AI 6 and during a 10-year follow-up remained unchanged. Brain MRI follow-up showed the absence of gadolinium enhancing lesions and a mild progression of brain atrophy. CONCLUSION: The patient with rapidly evolving, aggressive, noninflammatory MS initialy improved and remained stable, without disability progression for 10 years, after AHSCT. This kind of treatment should be considered in aggressive MS, or in disease modifying treatment nonresponsive MS patients, since appropriately timed AHSCT treatment may not only prevent disability progression but reduce the achieved level of disability, as well.

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses.

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach.

The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas.

Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC >2.6 in DLBCL and ALC/AMC ≥ 4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p < 0.05). In DLBCL, MVD > 42 blood vessels/0.36 mm(2) correlated with primary resistant disease (p < 0.0001), poorer EFS and OS (p = 0.014). High CD44s expression in FL correlated with inferior EFS and OS (p < 0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51-7.09, p = 0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08-1.79, p = 0.01). Furthermore, in FL, ALC/AMC mostly influenced OS (HR 5.21, 95 % CI 1.17-23.21, p = 0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06-14.95, p = 0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s).

The possible benefit from total tumour resection in primary diffuse large B-cell lymphoma of central nervous system - a one-decade single-centre experience.

BACKGROUND AND METHODS: The aim of the study was to evaluate retrospectively clinical course of 27 patients with primary central nervous system lymphoma (PCNSL) diagnosed and treated by different surgical approaches. Initial therapy-diagnostic approach included surgery with total tumour reduction (TTR) performed in 12 patients (44.4%), while partial reduction and biopsy were performed in 8 (29.7%) and 7 (25.9%) patients, respectively. All patients were treated with chemotherapy based on high-dose methotrexate (HD-MTX) with/without whole-brain radiotherapy (WBRT). RESULTS: The median overall survival (OS) and event-free survival were 37 and 31 months, respectively, with overall response rate of 74%. The patients who underwent an open surgery with TTR had significantly longer OS (median not reached), comparing with partial tumour reduction or biopsy only (Log-Rank χ(2) 6.08, p = 0.014) when median OS was 23 months. In patients with performance status according to Eastern Cooperative Oncology Group (ECOG PS) ≥ 3, OS was 23 months, contrary to ECOG PS 1-2 when median was not reached. The International Extranodal Lymphoma Study Group score (low, intermediate and high) also influenced OS between three risk groups (Log-Rank χ(2) 12.5, p = 0.002). CONCLUSION: The treatment of PCNSL still remains doubtful, however possible benefit from the TTR followed with HD-MTX with/without WBRT should be reconsidered.

Blood donors' positivity for transfusion-transmissible infections: the Serbian Military Medical Academy experience.

BACKGROUND: Members of armed forces worldwide are considered to be very susceptible to sexually transmitted infections, thus falling into a high-risk group of blood donors regarding transfusion-transmissible infections. In the Serbian Military Medical Academy a significant number (44% for the period 2005-2013) of blood donations were from members of the Serbian Army. The aim of this study was to determine the significance of military blood donors for the safety of blood transfusion. MATERIAL AND METHODS: Between January 2005 and December 2013, a total of 155,479 blood donations were tested for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and syphilis using serological assays (enzyme immunoassays, chemiluminescent microparticle immunoassay and western blot) and molecular testing (polymerase chain reaction analysis). RESULTS: The percentage of blood donations positive for transfusion-transmissible infections in the estimated period was 0.38%, and the percentage of HBV, HCV, HIV and syphilis positive blood donations was 0.20%, 0.12%, 0.005% and 0.06%, respectively. During that period, the percentage of all transfusion-transmissible infections, and in particular of HBV and HCV, declined significantly. In contrast, the percentage of HIV and syphilis positive blood donations remained unchanged. Higher rates of positivity for transfusion-transmissible infections in blood donations from members of the Serbian Army were not found, especially after mandatory military service was abolished in 2009. DISCUSSION: The reported rate of positivity for transfusion-transmissible infections in blood donations from the Military Medical Academy was considered low. This information is of great significance for further implementation of public health measures.

Functional recovery of patients with ischemic cardiomyopathy treated with coronary artery bypass surgery and concomitant intramyocardial bone marrow mononuclear cell implantation--a long-term follow-up study.

BACKGROUND/AIM: Intramyocardial bone marrow mononuclear cells (BMMNC) implantation concomitant to coronary artery bypass grafting (CABG) surgery as an option for regenerative therapy in chronic ischemic heart failure was tested in a very few number of studies, with not consistent conclusions regarding improvement in left ventricular function, and with a follow-up period between 6 months and 1 year. This study was focused on testing of the hypothesis that intramyocardial BMMNC implantation, concomitant to CABG surgery in ischemic cardiomyopathy patients, leads to better postoperative long-term results regarding the primary end-point of conditional status-functional capacity and the secondary endpoint of mortality than CABG surgery alone in a median follow-up period of 5 years. METHODS: A total of 30 patients with ischemic cardiomyopathy and the median left venticular ejection fraction (LVEF) of 35.9 ± 4.7% were prospectively and randomly enrolled in a single center interventional, open labeled clinical trial as two groups: group I of 15 patients designated as the study group to receive CABG surgery and intramyocardial implantation of BMMNC and group II of 15 patients as the control group to receive only the CABG procedure. All the patients in both groups received the average of 3.4 ± 0.7 implanted coronary grafts, and all of them received the left internal mammary artery (LIMA) to the left anterior descending (LAD) and autovenous to other coronaries. RESULTS: The group with BMMNC and CABG had the average of 17.5 ± 3.8 injections of BMMNC suspension with the average number of injected bone marrow mononuclear cells of 70.7 ± 32.4 x 10(6) in the total average volume of 5.7 ± 1.5 mL. In this volume the average count of CD34+ and CD133+ cells was 3.96 ± 2.77 x 10(6) and 2.65 ± 1.71 x 10(6), respectively. All the patients were followed up in 2.5 to 7.5 years (median, 5 years). At the end of the follow-up period, siginificantly more patients from the group that received BMMNC were in the functional class I compared to the CABG only group (14/15 vs 5/15; p = 0.002). After 6 months the results on 6-minute walk test (6-MWT) were significantly different between the groups (435 m in the BMMNC and CABG group and 315 m in the CABG only group; p = 0.001), and continued to be preserved and improved on the final follow-up (520 m in the BMMNC and CABG group vs 343 m in the CABG only group; p < 0.001). Cardiovascular mortality was also significantly reduced in the BMMNC and CABG group (p = 0.049). CONCLUSION: Implanatation of BMMNC concomitant to CABG is a safe and feasible procedure that demonstates not only the improved functional capacity but also a reduced cardiac mortality in a 5-year follow-up in patients with ischemic cardiomyopathy scheduled for CABG surgery.

Switching to BCL-6 Negativity in Relapsed Diffuse Large B Cell Lymphoma Correlated with More Aggressive Disease Course.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent, complex and heterogeneous lymphoma of adulthood. Heterogeneity is expressed at clinical, genetic, and molecular levels. It is known that BCL-6 expression is a favorable prognostic factor in DLBCL. However, the underlying mechanisms of BCL-6 expression in DLBCL relapse are not yet elucidated. Here, we present so far undescribed clinical phenomenon of switching BCL-6(+) protein expression into BCL-6(-) expression in 19 of 41 relapsed DLBCL patients. The switch in relapsed DLBCL was associated with more aggressive clinical course of the disease. Bone marrow infiltration and high IPI risk were more often present in BCL-6(-) patients. Significantly increased biochemical parameters, such as LDH, beta-2 macroglobulin, CRP, and ferritin have been found, as well as significantly decreased serum Fe, TIBC, and hemoglobin. A Ki-67 proliferation marker was considerably high in relapsed DLBCL, but without significant differences between BCL-6(+) and BCL-6(-) groups of patients. Thus, switching of the positive into negative BCL-6 expression during DLBCL relapse could be used as a prognostic factor and a valuable criterion for treatment decision.