Does Double Mean Trouble? Coexistence of Myeloproliferative and Lymphoproliferative Neoplasms.

Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients after long term follow-up. Methods: Fourteen patients with MPN/LPN coexistence were diagnosed and treated according to guidelines at a single university center across two decades. Results: The overall median age was 53 years (22-69). MPNs patients with subsequent LPNs had a shorter period of second malignancy development and a more aggressive course of LPN, which can cause fatal outcomes. Polycythemia vera and chronic lymphocytic leukemia were most commonly associated (36%). The JAK2V617F mutation had 2/3 and cytogenetic abnormalities occurred in 1/3 of patients. MPN/LPN coexistence cases had significantly higher thrombotic potential (42.8%) and a higher third malignancy accruement frequency (21.4%) versus those without such malignancies. Conclusions: Considering the younger ages at MPN diagnosis, it is recommended to check regularly for blood lymphocytosis or lymphadenopathy occurrences and organomegaly progression faster than expected for MPN, with the aim of timely LPN diagnoses. The presence of molecular-cytogenetic abnormalities in a majority of patients indicate possible genetic instability and increased risk of development of multiple neoplasms, thus elevating thrombotic risk.

Social Accountability and Legal Empowerment Initiatives: Improving the Health of Underserved Roma Communities in Eastern Europe.

Improving the protection of the right to health of ethnic Roma people is one of the most pressing public health challenges in contemporary Europe, as their life expectancy and health status remain significantly lower than their non-Roma counterparts.1 This paper analyzes Roma-led accountability initiatives that embrace social accountability and legal empowerment approaches to advocate for equitable fulfillment of the right to health. While these initiatives have led to the elimination of some harmful health practices (such as illegal cash bribes and violent and abusive treatment by medical professionals) and to improvements in health care, and some Roma communities have become driving forces for local and national health system reforms for advancing the fulfillment of health rights, the health inequalities affecting Roma communities remain significant. This issue also remains largely overlooked by European health research and policy experts, who are mostly reluctant to incorporate analyses of ethnicity and racialization into their research on health inequalities in Europe. The COVID-19 pandemic has further exacerbated these health inequalities.

The Occurrence of Acute Pancreatitis in Adult Patients during a Measles Outbreak from November 2017 to May 2018 in Southeastern Serbia.

Background and Objectives: Although it is believed that measles infections are under control, there is a global reappearance, and their treatment has become more complex as the disease is followed by a relatively high incidence of complications. This study, conducted on patients during a measles outbreak from November 2017 to May 2018, aims to evaluate a rarely reported complication of measles, acute morbilous pancreatitis (AMP), which has been reported in several cases to date. Materials and Methods: A total of 207 patients admitted and treated at the Clinic for Infectious Diseases, Clinical Center Nis, for measles infection were included in the analysis. The data collected from the patient's medical records included the demographic characteristics, disease duration, full blood, serum, and urine biochemical analysis, general measles-associated symptoms, and disease outcome. Results: According to the serum and urine amylase activity, and some clinical symptoms AMP were diagnosed in 14% (29/207) of the studied patients. These patients had significantly higher levels of ALT and vomited more frequently than the patients without AMP. Only slight differences in measles duration, changes in RBC count, and CRP levels were found between the males and females with AMP. Conclusions: Acute morbillous pancreatitis should not be underestimated as a complication, even though according to the results of our survey, it was not associated with a fatal outcome or disease severity as the course of it can be frequently rapid and fatal.

MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.

We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.

Modelling Voluntary General Population Vaccination Strategies during COVID-19 Outbreak: Influence of Disease Prevalence.

A novel statistical model based on a two-layer, contact and information, graph is suggested in order to study the influence of disease prevalence on voluntary general population vaccination during the COVID-19 outbreak. Details about the structure and number of susceptible, infectious, and recovered/vaccinated individuals from the contact layer are simultaneously transferred to the information layer. The ever-growing wealth of information that is becoming available about the COVID virus was modelled at each individual level by a simplified proxy predictor of the amount of disease spread. Each informed individual, a node in a heterogeneous graph, makes a decision about vaccination "motivated" by their benefit. The obtained results showed that disease information type, global or local, has a significant impact on an individual vaccination decision. A number of different scenarios were investigated. The scenarios showed that in the case of the stronger impact of globally broadcasted disease information, individuals tend to vaccinate in larger numbers at the same time when the infection has already spread within the population. If individuals make vaccination decisions based on locally available information, the vaccination rate is uniformly spread during infection outbreak duration. Prioritising elderly population vaccination leads to an increased number of infected cases and a higher reduction in mortality. The developed model accuracy allows the precise targeting of vaccination order depending on the individuals' number of social contacts. Precisely targeted vaccination, combined with pre-existing immunity, and public health measures can limit the infection to isolated hotspots inside the population, as well as significantly delay and lower the infection peak.

Prediction of optimal cytogenetic responses at 6 and 12 months in patients with chronic myeloid leukemia in chronic phase treated with imatinib.

PURPOSE: Imatinib mesylate transformed the treatment and paradigms of chronic myeloid leukemia. European LeukemiaNet (ELN) group has defined specific treatment milestones with an optimal outcome to be achieved in patients. METHODS: In a retrospective cohort study, we evaluated the impact of clinical and biological variables on achieving an optimal response at 6 and 12 months according to ELN recommendations. We included 106 patients with chronic phase chronic myeloid leukemia (CML) with appropriate bone marrow aspirate and biopsy for immunohistochemistry. RESULTS: The number of white blood cells (WBC), the percentage of peripheral blast, the values of Sokal and ELTS scores and the percentage of Ki-67+ cells in the bone marrow predicted a complete cytogenetic response (CCyR) at 6 months, but only WBC and EUTOS score predicts CCyR at 12 months. We found that Sokal score below 0.775 was very sensitive to achieve of CCyR at 6 months (m) and that all patients with a value <0.550 achieved CCyR-6m. Patients with a low percentage of blast in the peripheral blood (≤1.5%) or in the bone marrow (≤5%) together with lower WBC (≤100×109/L) were likely to have significantly higher CCyR rates at 6 and 12 months respectively. Also, patients with a higher number of Ki67+ cells in the leukemic areas of the bone marrow had a significantly better outcome. Unfortunately, our investigation did not reveal that bone marrow fibrosis (MF grade), microvascular density, percentage of CD34+, CD61+ or PTCH1+ cells could have any effect on achievement of CCyR at 6 or 12 months. CONCLUSION: Our investigation has shown that only a few biological characteristics in patients with CML can predict the optimal treatment outcome after imatinib.

Micro-elimination of HCV as a possible therapeutic strategy: our experience and a review of literature.

BACKGROUND: Serbia has an intermediate estimated prevalence of chronic hepatitis C (CHC) infection, approximately 1.13%, with hepatitis C remaining one of the leading causes of liver-related morbidity and mortality in Serbia with impaired quality of life and overwhelming cost of treating its complications As the availability of new treatment options and resources for screening remains limited, micro-elimination of CHC becomes a top priority. METHODS: Review of the available published data related to the clinical and epidemiological situation of the hepatitis C infection in Serbia, including the unpublished data from the databases of four major reference centres in Serbia (Clinical Center Serbia, Clinical Center Nis, Clinical Center Vojvodina and Clinical Center Kragujevac). RESULTS: Currently in Serbia, micro-elimination appears to be realistic in the patients with haemophilia, who represent a small, well-defined subpopulation, under constant monitoring by the healthcare system. Other feasible targets for micro-elimination of CHC infection in Serbia are patients on hemodialysis, prisoners and people who inject drugs. CONCLUSIONS: Micro-elimination is feasible in Serbia, especially in the subpopulation of patients with haemophilia. This may represent an initial step towards achieving the WHO objective to eliminate hepatitis C infection by 2030.

Comparison of fine particulate matter level, chemical content and oxidative potential derived from two dissimilar urban environments.

Urban airborne particles contain a wide spectrum of components, known to have harmful effects on human health. This study reports a detailed investigation of fine particulate matter (PM2.5), chemical content and oxidative potential derived from two different urban environments. During summer and winter, 20-day campaigns were conducted at Belgrade city center (urban-background site - UB) and Bor (urban-industrial site - UI). Using various analytical techniques, carbonaceous compounds, water-soluble inorganic ions, major and trace elements were determined, while the oxidative potential of PM2.5 was estimated by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay (OPDCFH values). The mean PM2.5 concentrations in both urban environments were above the recommended daily value, and the dominant PM2.5 mass contributor was organic matter (29-55%). The OC/EC ratio was significantly higher at UB site during winter, which was an indication of a considerable contribution of secondary organic carbon to the overall organic carbon (OC). Water-soluble organic carbon (WSOC) was also higher at UB than at UI site, and it probably came from the same sources as OC. In general, the different partition of secondary organic aerosol (SOA) in warm and cold periods affected the number of organic components. Sulfates and nitrates were the most abundant ions at both sites and they counted approximately 40% (summer) and 50% (winter) of total ions. Further, the concentrations of the most elements, particularly some potentially carcinogenic elements such as As, Cd and Pb were significantly higher at UI, due to the emissions from the copper smelter complex in the vicinity. The mean OPDCFH values were similar during the summer at both sampling sites, whereas a statistically significant difference between sites was noticed in favor of UB environment in winter.

Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.

We investigated the role of autophagy, a controlled lysosomal degradation of cellular macromolecules and organelles, in glutamate excitotoxicity during nutrient deprivation in vitro. The incubation in low-glucose serum/amino acid-free cell culture medium synergized with glutamate in increasing AMP/ATP ratio and causing excitotoxic necrosis in SH-SY5Y human neuroblastoma cells. Glutamate suppressed starvation-triggered autophagy, as confirmed by diminished intracellular acidification, lower LC3 punctuation and LC3-I conversion to autophagosome-associated LC3-II, reduced expression of proautophagic beclin-1 and ATG5, increase of the selective autophagic target NBR1, and decreased number of autophagic vesicles. Similar results were observed in PC12 rat pheochromocytoma cells. Both glutamate-mediated excitotoxicity and autophagy inhibition in starved SH-SY5Y cells were reverted by NMDA antagonist memantine and mimicked by NMDA agonists D-aspartate and ibotenate. Glutamate reduced starvation-triggered phosphorylation of the energy sensor AMP-activated protein kinase (AMPK) without affecting the activity of mammalian target of rapamycin complex 1, a major negative regulator of autophagy. This was associated with reduced mRNA levels of autophagy transcriptional activators (FOXO3, ATF4) and molecules involved in autophagy initiation (ULK1, ATG13, FIP200), autophagosome nucleation/elongation (ATG14, beclin-1, ATG5), and autophagic cargo delivery to autophagosomes (SQSTM1). Glutamate-mediated transcriptional repression of autophagy was alleviated by overexpression of constitutively active AMPK. Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, as well as genetic or pharmacological autophagy induction by TFEB overexpression or lithium chloride, reduced the sensitivity of nutrient-deprived SH-SY5Y cells to glutamate excitotoxicity. These data indicate that transcriptional inhibition of AMPK-dependent cytoprotective autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.

Measurements of Oxidative Potential of Particulate Matter at Belgrade Tunnel; Comparison of BPEAnit, DTT and DCFH Assays.

To estimate the oxidative potential (OP) of particulate matter (PM), two commonly used cell-free, molecular probes were applied: dithiothreitol (DTT) and dichloro-dihydro-fluorescein diacetate (DCFH-DA), and their performance was compared with 9,10-bis (phenylethynyl) anthracene-nitroxide (BPEAnit). To the best of our knowledge, this is the first study in which the performance of the DTT and DCFH has been compared with the BPEAnit probe. The average concentrations of PM, organic carbon (OC) and elemental carbon (EC) for fine (PM2.5) and coarse (PM10) particles were determined. The results were 44.8 ± 13.7, 9.8 ± 5.1 and 9.3 ± 4.8 µg·m-3 for PM2.5 and 75.5 ± 25.1, 16.3 ± 8.7 and 11.8 ± 5.3 µg·m-3 for PM10, respectively, for PM, OC and EC. The water-soluble organic carbon (WSOC) fraction accounted for 42 ± 14% and 28 ± 9% of organic carbon in PM2.5 and PM10, respectively. The average volume normalized OP values for the three assays depended on both the sampling periods and the PM fractions. The OPBPEAnit had its peak at 2 p.m.; in the afternoon, it was three times higher compared to the morning and late afternoon values. The DCFH and BPEAnit results were correlated (r = 0.64), while there was no good agreement between the BPEAnit and the DTT (r = 0.14). The total organic content of PM does not necessarily represent oxidative capacity and it shows varying correlation with the OP. With respect to the two PM fractions studied, the OP was mostly associated with smaller particles.

Clinicopathological and fluorescence in situ hibridisation analysis of primary testicular diffuse large B-cell lymphoma: a single-centre case series.

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) represents a rare and aggressive extranodal non-Hodgkin's lymphoma (NHL) with some specific features that differ from other NHLs. Formalin fixed, paraffin wax embedded (FFPE) samples of 21 PT-DLBCLs and 30 comparative patients with DLBCL were analysed. All PT-DLBCL patients were treated with rituximab-containing regimens, intrathecal prophylaxis (10 patients), and irradiation of the contralateral testis (9 patients). FFPE samples were additionally analysed by immunohistochemistry (Bcl-2, c-Myc protein expression) and fluorescence in situ hybridisation (FISH) (BCL2 and MYC). The patients with PT-DLBCL (median age 48.5 years), had low frequency of B symptoms (28.6%) and were often diagnosed in I and II Ann Arbor clinical stage (66.0%). The majority of PT-DLBCL (80.9%) had a non-germinal centre B-cell-like immunophenotype. Immunohistochemical staining showed increased c-Myc protein expression in the PT-DLBCL group compared to the control group (p = 0.016). MYC rearrangement was detected in 1 of 14 (7.0%), and MYC amplification in 3 of 14 (21.0%) patients. One of the 14 cases (7.0%) in the PT DLBCL group showed BCL2 rearrangement, and four of 14 (28.05%) cases showed BCL2 amplification. Complete remission (CR) was achieved in 75.0% of PT-DLBCL patients who had superior survival compared to those who did not achieve CR (median 48 vs. 21 months, p = 0.012). Patients with PT-DLBCL express some immunohistochemical, biological, and clinical features that might differentiate them from nodal and extranodal DLBCL patients, indicating the need for a more personalised treatment approach.

The WHO diagnostic criteria for polycythemia vera-role of red cell mass versus hemoglobin/hematocrit level and morphology.

Regarding diagnosis of polycythemia vera (PV), discussion persists about hemoglobin (Hb) and/or hematocrit (Hct) threshold values as surrogate markers for red cell mass (RCM) and the diagnostic impact of bone marrow (BM) morphology. We performed a retrospective study on 290 patients with PV (151 males, 139 females; median age 65 years) presenting with characteristic BM features (initial biopsies, centralized evaluation) and endogenous erythroid colony (EEC) formations. This cohort included (1) a group of 229 patients when following the 2008 versus 256 patients diagnosed according to the 2016 World Health Organization (WHO) guidelines, all presented with increased RCM; (2) masked PV patients with low Hb (n = 143)/Hct (n = 45) recruited from the 2008 WHO cohort; (3) a cohort of 17 PV patients with elevated diagnostic Hb/Hct levels but low RCM; and (4) nine PV patients with increased RCM, opposing low Hb/Hct values. All patients were treated according to current PV guidelines (phlebotomies 87%, hydroxyurea 79%, and acetylsalicylic acid 87%). Applying the 2016 WHO criteria significantly increased concordance between RCM and Hb values compared with the 2008 WHO criteria (90 vs. 43% in males and 83 vs. 64% in females). Further analysis of the WHO 2016 PV cohort revealed that increased RCM is associated with increased Hb/Hct (93.8/94.6%). Our study supports and extends the diagnostic impact of the 2016 revised WHO classification for PV by highlighting the importance of characteristic BM findings and implies that Hb/Hct threshold values may be used as surrogate markers for RCM measurements.

The Revised International Staging System Compared to the Classical International Staging System Better Discriminates Risk Groups among Transplant-Ineligible Multiple Myeloma Patients.

BACKGROUND: The Revised International Staging System (R-ISS) has recently been introduced as a comprehensive prognostic score for multiple myeloma (MM). Validation of the R-ISS in patients treated outside of clinical trials is the focus of current investigations. The aim of this study was to test the prognostic role of the R-ISS in MM patients ineligible for autologous stem cell transplantation. PATIENTS AND METHODS: A total of 102 newly diagnosed MM patients were analyzed. All patients were initially treated with thalidomide-based combinations. RESULTS: An overall response rate was achieved in 77.4% patients. Both the International Staging System (ISS) and the R-ISS influenced the event-free survival and the overall survival (OS). However, the ISS was unable to discriminate patients in stages ISS1 and ISS2 regarding OS. On the contrary, the R-ISS clearly differentiated risk categories regarding OS and provided an improved discriminative power of 6.3% compared to the ISS. Furthermore, among the parameters that were significant in univariate analysis (presence of renal impairment, anemia, platelet count < 130 × 109/l, and R-ISS), the multivariate model pointed to the R-ISS (p = 0.001) as the most important parameter influencing OS. CONCLUSION: The R-ISS represents a useful tool for risk stratification of transplant-ineligible MM patients and should be considered as a prognostic index in daily clinical practice.

Two-Year Complete Remission of Diffuse Large B-Cell Lymphoma in an Immunological Nonresponder HIV-Infected Patient: Case Report.

INTRODUCTION: HIV-infected patients are affected significantly more frequently by all types of lymphoma, with diffuse large B-cell lymphoma (DLBCL) as the most prevalent histological type. Since the introduction of combination antiretroviral therapy (cART) morbidity and mortality of DLBCL has been markedly reduced, which is primarily interpreted as a result of the drug-mediated immune reconstitution. CASE REPORT: We present a previously healthy, 44-year-old HIV-infected man with DLBCL of the oral cavity, treated with immunochemotherapy and cART. During HIV-directed treatment, despite the successful virologic response, a satisfactory immunological response was not achieved. However, the patient had a 2-year complete remission after first-line treatment of DLBCL. CONCLUSION: Response to cART strongly predicts outcome in patients with DLBCL. Close monitoring of HIV-directed therapy efficacy, especially as to achievement of successful virologic response, independently associated with prolonged survival, is essential for estimating future DLBCL treatment strategies.

Primary Intestinal Hodgkin Lymphoma Mimicking Intraabdominal Abscess in a Renal Transplant Recipient: A Case Report.

INTRODUCTION: Post-transplant lymphoproliferative disease (PTLD) comprises a variety of lymphoid and plasma cell disorders arising in patients with a solid organ transplant. Monomorphic lymphomas represent the most significant part of this wide spectrum, with the overall risk rising with the aggressiveness of lymphoid proliferation in comparison to the general population. The development of Hodgkin lymphoma is very rare in transplant recipients, comprising less than 6% of all monomorphic PTLD, while cases of primary intestinal Hodgkin lymphoma in these circumstances are anecdotal. CASE REPORT: We describe an exceptional case of intestinal Hodgkin lymphoma mimicking an intra-abdominal abscess that developed in a transplant recipient 19 years after kidney transplantation. By presenting this case, we wish to emphasize the importance of suitable diagnostic pathways in transplant recipients experiencing prolonged fever episodes or masses of unknown origin, thus raising the awareness of possible PTLD development in such patients. CONCLUSION: The lack of information about transplant recipients with Hodgkin PTLD regarding the site of involvement and type of treatment suggests the necessity of conducting larger international studies aimed at providing further insight into this particular group of patients.

FCG (FLIPI, Charlson comorbidity index, and histological grade) score is superior to FLIPI in advanced follicular lymphoma.

The Follicular Lymphoma International Prognostic Index (FLIPI) is widely used in the identification of risk groups among follicular lymphoma (FL) patients. The aim of the present study was to evaluate the prognostic value of FLIPI combined with the Charlson comorbidity index (CCI) and histological grade of lymphoma. 224 newly diagnosed FL patients (median age 56 years) treated with immunochemotherapy were retrospectively analysed. Low FLIPI had 21.0 % of patients, intermediate 28.1 % and high 46.9 %. 50.9 % of patients had no comorbidities. Only 7.1 % of patients had a high CCI score (≥2), while 25.9 % of patients were histological grade 3. Parameters that influenced overall survival were evaluated using Cox regression analysis, in which CCI, FLIPI and histological grade (p < 0.05) retained prognostic significance. By combining these parameters, we have developed the FCG score, which incorporates FLIPI, CCI, and histological grade. This score defines three risk categories (low: 41.5 %; intermediate: 37.5 %; high: 13.4 %), associated with significantly different survival (p < 0.0001); this consequently improves discriminative power by 9.1 % compared to FLIPI. FCG score represents a possible new prognostic index, highlighting the role of the patient's clinical state and the histological characteristics of disease, as indicated by comorbidity index and histological grade of lymphoma.

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).

Prognostic value of lymphocyte/monocyte ratio in advanced Hodgkin lymphoma: correlation with International Prognostic Score and tumor associated macrophages.

We studied the prognostic significance of the absolute lymphocyte/monocyte count ratio (ALC/AMC), its contribution to the prognostic value of the International Prognostic Score (IPS), and evaluated if ALC/AMC could serve as a proxy for the frequency of CD68 + tumor-associated macrophages (TAMs) in 101 patients with advanced Hodgkin lymphoma (HL). The receiver operating characteristic (ROC) curve identified best cut-off values of 2.0 for ALC/AMC and 25% for CD68 + TAM. Patients with ALC/AMC < 2, IPS > 2 and > 25% CD68 + TAM had an inferior overall survival (OS) and event-free survival (EFS). Spearman's test also uncovered a significant correlation between the ALC/AMC and TAM. Multivariate analysis identified ALC/AMC < 2, IPS > 2 and > 25% CD68 + TAM as poor prognostic factors of OS and EFS. After evaluating ALC/AMC and IPS, we stratified patients into three progressively-worse-outcome groups (low-risk: 0 risk factors; intermediate: 1 risk factor; high: 2 risk factors). Our study encourages the combination of ALC/AMC with IPS, for refining risk prediction in advanced HL patients.

Evaluation of the effects of different supplementation on oxidative status in patients with rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory disease. Reactive oxygen species have been considered as aggravating factors for autoimmune diseases. Fatty acids had been linked in reduction of various diseases by augment of their antioxidant potential and antiinflammatory mechanisms. The aim of this study was to assess the oxidative status in patients with rheumatoid arthritis who used concentrated fish oil only or concentrated fish oil in combination with evening primrose oil in a period of 3 months. Subjects were divided into three groups. The group I consists of patients who had been taking only their regular rheumatologic therapy; group II, patients who had been taking concentrated fish oil; and group III, patients who had been taking concentrated fish oil and evening primrose oil. Peripheral blood samples were used for all the assays. We assessed the following oxidative stress markers: index of lipid peroxidation (thiobarbituric acid-reactive substances (TBARS)), hydrogen peroxide (H2O2), superoxide anion radical (O2 (-)), nitric oxide (NO), superoxide dismutase activity (SOD), catalase activity (CAT), and glutathione levels (GSH) in erythrocytes. There were no statistically significant changes for any of the oxidative stress parameters in group I. In group II, levels of TBARS, NO2 (-), and GSH were increased, while levels of H2O2 decreased. Increased values of TBARS, NO2 (-), and SOD were found in group III. Our findings indicate that intakes of fish oil and evening primrose oil may be of importance in mitigation of inflammation, disease activity, and oxidative stress biomarkers, through increased activities of antioxidant enzymes.

Hyperparathyroidism as a cause of recurrent acute pancreatitis: A case report.

Introduction: One of the more uncommon etiological factors responsible for the development of acute pancreatitis (AP) is hypercalcemia. Hyperparathyroidism (HPT), as a cause of hypercalcemia, is responsible for 1.5­13% of AP according to a number of studies. A mechanism of the development of AP in hyperparathyroidism is still unclear. Case report: We presented a 47-year-old female patient, who had five episodes of AP in total before the etiological factors were finally determined. The patient had certain comorbidities which were considered to be potential causes of AP. She had chronic renal insufficiency (she was on a regular hemodialysis program), systemic lupus erythematosus and mioma uteri. She used to regularly take an antiepileptic drug (combination of sodium valproate and valproic acid). During the fifth episode of AP, the serum calcium level was for the first time elevated to twice the normal value. Level of parathyroid hormone was several times higher. A static scintigraphy found hyperplasia or hyperfunctional adenoma of the right inferior and superior parathyroid glands. Abdominal multislice computed tomography (MSCT) scan verified the enlargement of the entire pancreas, as well as the presence of heterogeneous structures with diffuse amorphous calcifications. The lytic lesions in the pelvic bones could be seen in both sides. Parathyroidectomy was being postponed by an endocrine surgeon because of the poor overall condition of the patient. In the next period the patient had five more episodes of AP. The condition was significantly contributed by increasingly more frequent and longer episodes of metrorrhagia. Despite all therapeutic measures that were taken, systemic inflammatory response syndrome (SIRS) developed, and fatal outcome occurred. Conclusion: In case of recurrent pancreatitis, hyperparathyroidism is to be considered even if a significant elevation of serum calcium is not present. This is especially the case for patients with chronic renal insufficiency or impaired vitamin D metabolism, who have a higher risk of secondary hyperthyroidism.