Ascites as First Atypical and Only Clinical Manifestation of De Novo Follicular Lymphoma.

Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma and is usually initially detected in lymph nodes. Primary extranodal NHL is most commonly primarily localized in the gastrointestinal tract. We present one unusual case of ileum FL with ascites as the first clinical sign. The 73-year-old female patient was presented to the emergency department for evaluation of mild abdominal pain and abdominal swelling that had been going on for three days followed by bloating and occasional pain in the spine. The abdominal contrast-enhanced CT revealed the contrast stagnation in the distal part of the ileum. The ileum wall about 11 cm in length was thickened up to 2.9 cm and the tumor mass infiltrated all layers of ileum mesenteric lymphadenopathy up to 2 cm in diameter and significant ascites. On the upper ileum wall, the vegetative mass was described 3 cm in diameter. The patient had an emergent laparotomy with the ileocolic resection and latero-lateral ileocolic anastomosis. The microscopy finding of terminal ileum and the regional lymph nodes showed domination of cleaved cells with irregular nuclei which correspond to centrocytes. There were 0-15 large non-cleaved cells corresponding to centroblast in the microscopy high-power field. The final diagnosis was follicular lymphoma, the clinical stage 2E and histological grade by Berard and Mann criteria 1-2.

A Phase II Study to Assess the Safety and Efficacy of the Dual mTORC1/2 and PI3K Inhibitor Bimiralisib (PQR309) in Relapsed, Refractory Lymphoma.

Bimiralisib is an orally bioavailable pan-phosphatidylinositol 3-kinase and mammalian target of rapamycin inhibitor which has shown activity against lymphoma in preclinical models. This phase I/II study evaluated the response rate to bimiralisib at 2 continuous dose levels (60 mg and 80 mg) in patients with relapsed/refractory lymphoma. Fifty patients were enrolled and started treatment. The most common histologies were diffuse large B-cell lymphoma (n = 17), follicular lymphoma (n = 9), T-cell lymphoma (n = 8), and others (mostly indolent). Patients had been treated with a median of 5 prior lines of treatment and 44% were considered refractory to their last treatment. Mean duration of treatment (and standard deviations) with 60 mg once daily (o.d.) was 1.3 ± 1.2 months, and with 80 mg o.d. 3.7 ± 3.9 months. On an intention to treat analysis, the overall response rate was 14% with 10% achieving a partial response and 4% a complete response. Thirty-six percent of patients were reported as having stable disease. No dose-limiting toxicities were observed during the phase I portion of the study. Overall, 70% of patients had a grade 3 treatment emergent adverse events (TEAE) and 34% had a grade 4 TEAE; 28% of patients discontinued treatment due to toxicity. The most frequent TEAEs grade ≥3 was hyperglycemia (24%), neutropenia (20%), thrombocytopenia (22%), and diarrhea (12%). Per protocol, hyperglycemia required treatment with oral antihyperglycemic agents in 28% and with insulin in 14%. At 60 mg or 80 mg continuous dosing, bimiralisib showed modest efficacy with significant toxicity in heavily pretreated patients with various histological subtypes of lymphoma.

Standardized Aronia melanocarpa extract regulates redox status in patients receiving hemodialysis with anemia.

The aim of our study was to investigate the effects of one-month consumption of polyphenol-rich standardized Aronia melanocarpa extract (SAE) on redox status in anemic hemodialysis patients. The study included 30 patients (Hb < 110 g/l, hemodialysis or hemodiafiltration > 3 months; > 3 times week). Patients were treated with commercially available SAE in a dose of 30 ml/day, for 30 days. After finishing the treatment blood samples were taken to evaluate the effects of SAE on redox status. Several parameters of anemia and inflammation were also followed. After the completion of the treatment, the levels of superoxide anion radical and nitrites significantly dropped, while the antioxidant capacity improved via elevation of catalase and reduced glutathione. Proven antioxidant effect was followed by beneficial effects on anemia parameters (increased hemoglobin and haptoglobin concentration, decreased ferritin and lactate dehydrogenase concentration), but SAE consumption didn't improve inflammatory status, except for minor decrease in C-reactive protein. The consumption of SAE regulates redox status (reduce the productions of pro-oxidative molecules and increase antioxidant defense) and has beneficial effects on anemia parameters. SAE could be considered as supportive therapy in patients receiving hemodialysis which are prone to oxidative stress caused by both chronic kidney disease and hemodialysis procedure. Additionally, it could potentially be a good choice for supplementation of anemic hemodialysis patients. TRN: NCT04208451 December 23, 2019 "retrospectively registered".

Influence of different supplementation on platelet aggregation in patients with rheumatoid arthritis.

INTRODUCTION: Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) have been reported to reduce platelet aggregation. Our aim was to prospectively assess the potential influence of different supplementation omega-3 PUFA on the antiplatelet effects in rheumatoid arthritis (RA) patients. METHODS: The study included 60 patients with RA at the Department of Rheumatology, Clinical Center Kragujevac. Patients were divided into three groups depending on who used concentrated fish oil only or concentrated fish oil in combination with evening primrose oil or control group without supplementation in a period of 3 months. Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test, aranchidonic acid-induced aggregation (ASPI) test, thrombin receptor-activating peptide (TRAP) test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP representing the degree of inhibition of platelet aggregation compared to the basal value. The platelet function analysis in whole blood was performed 18-24 h before starting supplementation and after 90 days. Considerations were taken in the representation of demographic, clinical characteristics, and laboratory parameters between the groups. RESULTS: Patients who used concentrated fish oil only had a significantly lower value of the ratio of ADP/TRAP (0.68 ± 0.20) compared to patients without supplementation (0.83 ± 0.12; p = 0.008), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups. CONCLUSIONS: Co-administration of supplementation-concentrated fish oil may reduce platelet aggregation in adults with RA. KEY POINTS: • Omega-3 PUFAs are essential for health and are known to possess anti-inflammatory properties, improving cardiovascular health as well as benefiting inflammatory diseases.. • In this paper, we report on anti-aggregation effects n-3 PUFAs and ɤ-linolenic acid in RA. • The risk of cardiovascular morbidity and mortality is increased in RA, and dietary supplementation of n-3 PUFA may have preventive potential for the cardiovascular management in rheumatoid arthritis.

Rituximab in the therapy of stage III and IV follicular lymphoma: Results of the REFLECT 1 study of the Serbian Lymphoma Group.

PURPOSE: Follicular lymphoma (FL) is an indolent lymphoma that responds well to rituximab+chemotherapy. We evaluated the prognosis and efficacy of immunochemotherapy in patients with previously untreated, advanced FL. METHODS: REFLECT 1 is a multicentre, prospective study of 99 patients with previously untreated FL stage III-IV. All patients were treated with rituximab+chemotherapy x 6 cycles, plus 2 cycles of rituximab monotherapy. Clinical assessment was performed at baseline, after completion of the first 6 cycles of therapy and every 3 months from the end of immunochemotherapy to the end of the study period. RESULTS: Eighty-nine out of 99 patients with complete documentation were included. Complete remission (CR) was achieved in 61.6%, partial remission (PR) in 11.6% and progressive disease (PD) in 24.4% of the patients. Time to progression (TTP) and overall survival (OS) after the 1st, 2nd and 3rd year were 89.9, 72.7, 57.8%, and 94.2, 92,6 and 92.6%, respectively. The probability of achieving CR was significantly lower in the high risk group according to Follicular Lymphoma Prognostic Index (FLIPI) score. Expression of CD43 antigen had a significant impact on the probability of 2-year TTP and OS, and ECOG performance status had a significant impact on OS. CONCLUSIONS: Treatment with rituximab plus chemotherapy is effective in advanced stages of FL. Significant prognostic factors are FLIPI score for induction therapy outcome, CD43 antigen expression for OS and TTP and ECOG performance status for OS.

Influence of Different ß-Blockers on Platelet Aggregation in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy.

INTRODUCTION: The use of ß-blockers in the treatment of patients with coronary heart disease is associated with a decrease in the frequency of angina pectoris and mortality of patients. Due to the severity of the disease and previous cardiovascular interventions, many patients with coronary artery disease (CAD) use dual antiplatelet therapy to achieve greater inhibition of platelet aggregation. The influence of ß-blockers on platelet aggregation in patients using antiplatelet therapy is not well understood. OBJECTIVE: To examine the effect of different ß-blockers on platelet aggregation in patients on dual antiplatelet therapy. METHODOLOGY: The study included 331 patients who were treated at the Department of Cardiology, Clinical Center Kragujevac during 2011. Patients were divided into 4 groups depending on the type of ß-blockers that were used (bisoprolol, nebivolol, metoprolol, and carvedilol). Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test (to assess the effect of clopidogrel), ASPI test (to assess the effect of acetyl salicylic acid), TRAP test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP ASPI/TRAP (ASPI - aranchidonic acid induced aggregation, TRAP - thrombin receptor activating peptide) representing the degree of inhibition of platelet aggregation compared to the basal value. In consideration were taken the representation of demographic, clinical characteristics, laboratory parameters, and cardiovascular medications between the groups. RESULTS: Patients who used nebivolol had a significantly lower value of the ratio of ADP/TRAP (0.39 ± 0.30) compared to patients who used bisoprolol (0.48 ± 0.26; P = .038), and trend toward the lower values of ADP test (328.0 ± 197.3 vs 403.7 ± 213.2; P = .059), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups. CONCLUSION: Patients with CAD on dual antiplatelet therapy who used nebivolol had significantly lower levels of residual ADP-induced platelet aggregation compared to baseline than patients who used bisoprolol.

Possible role of CD22, CD79b and CD20 expression in distinguishing small lymphocytic lymphoma from chronic lymphocytic leukemia.

AIM OF THE STUDY: Flow cytometry has an important role in diagnosis and classification of B-cell lymphoproliferative disorders (BCLPDs). However, in distinguishing chronic lymphocytic leukemia (CLL) from small lymphocytic lymphoma (SLL) only clinical criteria are available so far. Aim of the study was to determine differences in the expression of common B cell markers (CD22, CD79b and CD20) on the malignant lymphocytes in the peripheral blood samples of CLL and SLL patients. MATERIAL AND METHODS: Peripheral blood samples of 56 CLL and 11 SLL patients were analyzed by 5-color flow cytometry on the CD45/CD19/CD5 gate for CD22, CD79b and CD20. RESULTS: In the samples collected from the CLL patients, CD22 expression was detected in only 20% of patients in the low pattern, while in SLL patients the expression was medium and present in 90.9% of patients (p < 0.0001). For CD79b expression, statistical significance is reached both in the expression pattern, which was low/medium for CLL and high for SLL, and expression level (p = 0.006). The expression of CD20 was counted as the CD20/CD19 ratio. The average ratio was 0.512 in the CLL patients vs. 0.931 in the SLL patients (p = 0.0001). CONCLUSIONS: The pattern of expression and expression level of CD22, CD79b and CD20 in peripheral blood could be used for distinguishing SLL from CLL patients.

Nitroglycerine effects on portal vein mechanics and oxidative stress in portal hypertension.

AIM: Тo examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension. METHODS: Thirty healthy controls and 39 patients with clinically verified portal hypertension and increased vascular resistance participated in the study. Liver diameters, portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection. Cross-section area, portal flow and index of vascular resistance were calculated. In collected blood samples, superoxide anion radical (O(2) (-)), hydrogen peroxide (H(2)O(2)), index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO(2) (-)) were determined. Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration. RESULTS: Oxidative stress parameters changed significantly during the study. H(2)O(2) decreased at the end of study, probably via O(2) (-) mediated disassembling in Haber Weiss and Fenton reaction; O(2) (-) increased significantly probably due to increased diameter and tension and decreased shear rate level. Consequently O(2) (-) and H(2)O(2) degradation products, like hydroxyl radical, initiated lipid peroxidation. Increased blood flow was to some extent lower in patients than in controls due to double paradoxes, flow velocity decreased, shear rate decreased significantly indicating non Newtonian characteristics of portal blood flow. CONCLUSION: This pilot study could be a starting point for further investigation and possible implementation of some antioxidants in the treatment of portal hypertension.

Von Willebrand factor and oxidative stress parameters in acute coronary syndromes.

Considering the role of von Willebrand factor (vWf) in hemostasis, and the role of oxidative stress in the development of endothelial dysfunction and atherosclerotic disease, the aim of our study was to investigate the relationship between vWf, parameters of oxidative stress and different types of acute coronary syndromes (ACS). Levels of vWf activity (vWfAct), vWf antigen (vWfAg), nitric oxide (estimated through nitrites-NO(2)-), superoxide anion radical (O(2)-), hydrogen peroxide (H2O2), index of lipid peroxidation (estimated through thiobarbituric acid reactive substances-TBARS), superoxide dismutase (SOD) and catalase (CAT) activity of 115 patients were compared with those of 40 healthy controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well as TBARS levels, while their levels of NO(2)-, H2O2, SOD and CAT activities were lower than controls'. vWfAg showed high specificity and sensitivity as a test to reveal healthy or diseased subjects. Multivariant logistic regression marked only vWfAg and TBARS as parameters that were under independent effect of ACS type. The results of our study support the implementation of vWf in clinical rutine and into therapeutic targets, and suggest that ACS patients are in need of antioxidant supplementation to improve their impaired antioxidant defence.

[Autologous stem cell transplantation in the treatment of multiple myeloma--single center experience].

BACKGROUND/AIM: In comparison to standard therapy autologous stem cell transplant (ASCT) with high doses mel-phalane has improved treatment of multiple myeloma (MM) patients. The aim of this study was to evaluate the results of treatment of MM patients in our center with ASCTconditioning with melphalane or combining busulphane, cyclophosphamide and melphalane. METHODS: We performed 62 ASCT procedures in 47 patients from 1998 till 2008. Single ASCT were performed in 32 patients (68%), after 3-6 cycles of (26% patients. RESULTS: Median engraftment was on 12th day. In a 50-month follow-up period 64% patients were alive. The overall response rate (ORR), wich was reached in 38 (80%) patients, was better in the group of patients treated in the early phase of MM. Totally 25 (53%) patients were without progression in a 25-month follow-up period. Twenty patients met criteria for CR + VGPR (very good partial remission), that was 5 patients more than in the period before ASCT. Fourteen (30%) patients died and median time till death was 17 months. CONCLUSION: The ASCT perfomed in early phase of MM after V A D induction had a significant influence onthe treatment of MM patients. Reaching CR + VGPR before and after the ASCT is predictive factor for overall survival (OS) or prolongation of period till recidive appears, progression, therapy withdrowal or death.

[Updated criteria for diagnosis and risk stratification in patients with multiple myeloma].

Search and disclosure of most adequate diagnostic criteria and prognostic indicators of disease represents one of the most difficult tasks in the understanding of any disease, which creates the way toward a more successful treatment and longer survival. The recent advances in research techniques that have helped refine the diagnostic work up and prognosis of myeloma include serum-free light chains, especially in oligosecretory myeloma, magnetic resonance and positron emission tomography in the diagnosis of bone diseases, cytogenetics and fluorescent in situ hibridization (FISH) technique to determine prognosis. The International Staging System and Durie/Salmon PLUS system are the current standards for staging myeloma. Newer risk stratification protocols are based on international staging system and chromosomal changes detected by conventional cytogenetics and FISH. These improved predictive risk stratification models have enabled the determination of prognosis in patients with myeloma which has a considerable influence on the choice of therapeutic algorism. Novel therapies enable a significant increase in achieving complete remission in a significant number of patients which also results in the definition of more precise criteria regarding the response to therapy. A firm and complete remission with a very good partial remission represent new categories defined by the international uniform criteria of response to therapy. This paper provides the current criteria for diagnosis, staging, risk stratification and response assessment of myeloma.

Oxidative stress in fetal distress: potential prospects for diagnosis.

Our aim was to investigate the relation between fetal distress and oxidative stress. Fetal distress was associated with increased concentration of superoxide in the fetal blood and with significant increase of the level of H2O2 in both maternal and fetal blood. The activity of superoxide dismutase was increased roughly sixfold (p<0.01) in the maternal (7330 +/- 2240 U/g of hemoglobin in controls (C) and 36811 +/- 16862 U/g in fetal distress (FD)) and fetal blood (C: 5930 +/- 2641 U/g; FD: 41912 +/- 17133 U/g). In contrast, fetal distress was related to a considerable decrease of catalase activity in both maternal (C: 26011 +/- 8811 U/g; FD: 7212 +/- 1270 U/g) and fetal blood (C: 37194 +/- 9191 U/g; FD: 6173 +/- 1965 U/g). From this we concluded that in fetal distress, the maternal and fetal bloods are exposed to superoxide- and H2O2-mediated oxidative stress, which could be initiated by hypoxic conditions in the fetal blood and placenta. A tremendous increase/decrease of the activities of superoxide dismutase/catalase in the blood of women bearing a distressed fetus in comparison to healthy subjects implies that the assessment of superoxide dismutase/catalase activity could be of use for establishing a timely and accurate ante- or intrapartum diagnosis of fetal distress.

Monitoring of cytomegalovirus infection after allogeneic stem cell transplantation.

BACKGROUND/AIM: More than 90% of worldwide population is infected with human cytomegalovirus (CMV), one of the most common agents which complicate immunocompromised patients. Viral infections, in particular CMV ones are still a major cause of moratality and morbidity after stem cell transplantation (SCT). Monitoring is performed by detecting CMV-Ag or virus DNA in peripheral blood. Risk factors are donor/recipient CMV status, type of transplant and acute graft versus host disease. The aim of the study was to determine the extent of validity of CMV infection monitoring after transplantation as a reliable parameter of further CMV replication course in patients with hematopoietic stem cell transplantation. METHODS: A total of 49 patients with stem cell transplantation were studied prospectively during a 2-year period after transplantation for the presence of CMV DNA. Polymerase chain reaction (PCR) CMV DNA was performed on 222 full blood samples using Cobas Amplicor assay. RESULTS: Activation of CMV was detected in 10/49 (20.48%) of the patients. The median posttransplantation time for the first positive PCR result was 6 weeks for the stem cell transplant patients. Viremia became negative in all the cases after the antiviral therapy with ganciclovir. CONCLUSION: Our data show that the level of CMV-DNA load at the time of initial CMV detection after transplantation could be a possible predictor for further course of CMV replication in patients receiving hematopoietic stem cell.

Human platelets perfusion through isolated guinea-pig heart: the effects on coronary flow and oxidative stress markers.

Present study was designed to evaluate effect of perfusion with human platelets reach plasma (PRP) on coronary flow (CF) and oxidative stress markers in coronary vascular bed of the isolated guinea-pig heart. In coronary venous effluent the following oxidative stress markers were estimated: nitrite as a measure of nitric oxide (NO) production, superoxide anion (O2(-)), and index of lipid peroxidation (TBARS). Isolated guinea-pig hearts (n = 6, b.m. 250-300 g) were perfused according to a Langendorff's technique at different (30, 70, and 120 cmH2O) coronary perfusion pressures (CPP). Samples were collected at control conditions and during perfusion with platelets rich plasma (PRP) obtained either from healthy volunteers or from patients with acute myocardial infarction (PRP (AMI)) with/or without previous inhibition of NO synthase (NOS) by Nomega-nitro-L-arginine monomethyl ester (L-NAME, 30 micromol/l). PRP and PRP (AMI) perfusion induced reduction of CF and all evaluated oxidative stress parameters. The reduction of CF was more potentiated in PRP (AMI) as in PRP group, while oxidative stress parameters where significantly decreased only in PRP (AMI). In addition, previous blockade of NOS by L-NAME potentiated these effects only in PRP (AMI) group. It can be concluded that non-activated and activated platelets interact with coronary endothelium in similar way, with more significant influence of activated platelets on CF and oxidative stress markers.