Anemia in Heart Failure Patients

Heart failure is a very common disease, with severe morbidity and mortality, and a frequent reason of hospitalization. Anemia and a concurrent renal impairment are two major risk factors contributing to the severity of the outcome and consist of the cardio renal anemia syndrome. Anemia in heart failure is complex and multifactorial. Hemodilution, absolute or functional iron deficiency, activation of the inflammatory cascade, and impaired erythropoietin production and activity are some pathophysiological mechanisms involved in anemia of the heart failure. Furthermore other concomitant causes of anemia, such as myelodysplastic syndrome and chemotherapy, may worsen the outcome. Based on the pathophysiology of cardiac anemia, there are several therapeutic options that may improve hemoglobin levels, tissues' oxygenation, and probably the outcome. These include administration of iron, erythropoiesis-stimulating agents, and blood transfusions but still the evidence provided for their use remains limited

Coexistence of Plasma Cell Dyscrasia with Prefibrotic Stage of Primary Myelofibrosis: A Case Report

Introduction. Coexistence of myeloproliferative neoplasms with lymphoproliferative syndromes has been described in the past, whereas plasma cell dyscrasias seem to be the most common cases. Case Presentation. We present a case of a 59-year-old Caucasian female of Greek origin who presented with thrombocytosis. Clinical and laboratory investigation disclosed the presence of a smoldering myeloma with coexisting histological and molecular characteristics of primary myelofibrosis. The patient had the acquired point mutation V617F in the JAK2 gene but not the bcr-abl rearrangement and was treated for myelofibrosis with subsequent improvement of all haematological parameters without evidence of myelomatic evolution. Conclusion. We present the first case in the literature of a smoldering myeloma coexisting with primary myelofibrosis. The underlying pathogenetic mechanism could be either related to the presence of a pluripotent neoplastic stem cell capable to differentiate into both lymphoid and myeloid cells or be related to two separate nosologic entities

Miliary tuberculosis with no pulmonary involvement in myelodysplastic syndromes: a curable, yet rarely diagnosed, disease: case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Although tuberculosis is not uncommon among patients with myelodysplastic syndrome (MDS), only a few reports of such patients suffering from miliary tuberculosis (MT) exist. MT often presents as a fever of unknown origin and it is a curable disease, yet fatal if left untreated.</p> <p>Case presentation</p> <p>We report a case of MT with no clinical or laboratory indications of pulmonary involvement in a patient with MDS, and review the relevant literature. <it>Mycobacterium tuberculosis </it>was isolated from the liquid culture of a bone marrow aspirate.</p> <p>Conclusion</p> <p>Even if the initial diagnostic investigation for a fever of obscure etiology is negative, MT should not be excluded from the differential diagnosis list. Since it is a curable disease, persistent and vigorous diagnostic efforts are warranted. In suspected cases, mycobacterial blood cultures should be collected as soon as possible after hospital admission and early bone marrow aspirate with mycobacterial cultures is advocated.</p

Serum interleukin-17 and its relationship to angiogenic factors in multiple myeloma

Background: Interleukin-17 (IL-17) is a CD4 T-cell-derived mediator of angiogenesis that stimulates vascular endothelial cell migration and regulates the production of a variety of proangiogenic factors, such as tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial cell growth factor (VEGF). Angiogenesis is implicated in the progression of multiple myeloma (MM). Methods: We measured serum levels of IL-17, TNF-alpha, and VEGF, as well as microvessel density (MVD) in 40 untreated MM patients. Results: Levels of IL-17 in the sera of patients with MM were higher than those in matched controls; however, the difference did not reach statistical significance. Serum levels of both TNF-alpha and VEGF in MM patients were significantly higher than those in controls (P&lt;0.001 in both instances). Levels of IL-17 in MM patients, both stage 11 and stage 111, were significantly higher than those of stage I patients (p=0.001 and p&lt;0.001, respectively). Similarly, higher values of VEGF (p&lt;0.001), TNF-a (p&lt;0.001), and MVD (p&lt;0.035) were associated with advanced disease stage. Serum values of IL-17 in MM patients correlated positively not only with VEGF (Spearman’s rho=0.606) and TNF-alpha (r=0.552; p&lt;0.001 in both instances), but also with MVD (r=0.385, p=0.014). In addition, a positive correlation was found between serum values of VEGF and TNF-alpha (r=0.657, p&lt;0.001), MVD and VEGF (r=0.353, p=0.026), and between MVD and TNF-alpha (r=0.506,p=0.001) in MM patients. Conclusion: These results suggest that IL-17 plays a role in the promotion of angiogenesis and associated disease progression in MM. (C) 2006 European Federation of Internal Medicine. Published by Elsevier B.V All rights reserved

Positive correlation between bone marrow mast cell density and ISS prognostic index in patients with multiple myeloma

We evaluated mast cell density (MCD) in myeloma bone marrow biopsies and correlated it with stage of disease and markers of angiogenesis. Fifty-three untreated myeloma patients and 28 of them responded to therapy were studied. Mast cells were highlighted using immunohistochemical stain for tryptase. Angiogenesis was evaluated measuring microvascular density and serum levels of basic-fibroblast growth factor and tumor necrosis factor-alpha. MCD was higher in untreated patients, compared to healthy population and responders. Significant association was found between MCD with angiogenesis and clinical stage of disease, suggesting that mast cells could be used as target for myeloma treatment. (C) 2013 Elsevier Ltd. All rights reserved

Increased serum levels of MIP-1alpha correlate with bone disease and angiogenic cytokines in patients with multiple myeloma

Many cytokines possess variable roles in the pathogenesis of multiple myeloma. Macrophage inflammatory protein-1alpha (MIP-1alpha) is an osteoclast-activating factor with a major role in myeloma bone disease. The aim of the study was to examine its participation in the angiogenic process of the disease. We measured, by enzyme-linked immunosorbent assays, its serum levels in 56 newly diagnosed myeloma patients, in several skeletal grades and stages of the disease and in 25 healthy controls. Concurrently, we measured serum levels of the angiogenic cytokines basic-fibroblast growth factor, hepatocyte growth factor and interleukin-18. All the above cytokines were higher in myeloma patients (p &lt; 0.001 for all cases) and were increasing in parallel with disease stage (p &lt; 0.001 for all cases) and skeletal grade (p &lt; 0.04 for MIP-1alpha and p &lt; 0.001 for the other cases). Moreover, positive correlations between MIP-1alpha and all the angiogenic cytokines were noted (p &lt; 0.001 for all cases). MIP-1alpha seems to be a predominant factor responsible for the enhancement of bone resorption and increased angiogenesis. The positive correlation between MIP-1alpha and the angiogenic chemoattractants supports the involvement of these factors in the biology of myeloma cell growth. Moreover, they could be used as possible therapeutic targets as well as markers of disease activity

Histological expression of angiogenic factors: VEGF, PDGFR alpha, and HIF-1 alpha in Hodgkin lymphoma

Angiogenesis is a prerequisite for solid tumor growth, but there is relatively limited data regarding Hodgkin lymphoma. The purpose of this study was to examine the immunohistochemical expression of angiogenic and proliferation markers in Hodgkin biopsies in relation to clinical parameters. Immunostaining was performed on 65 Hodgkin biopsies with vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1 alpha), platelet-derived growth factor receptor alpha (PDGFR alpha), Ki-67, and p53. Microvessel density (MVD) was determined by CD31 staining. In all cases, neoplastic cells and reactive background cells were evaluated. The neoplastic population expressed VEGF in 48% of the cases, HIF-1 alpha in 54% of the cases, and PDGFR alpha in 95% of the cases. Both Ki-67 and p53 were positive in neoplastic cells in over 60% of the cases. The MVD had a median of 2.6/0.0625 mm(2) which was not different from normal lymph nodes. VEGF in the non-neoplastic compartment showed increased staining in Ann Arbor stage I-II versus III-IV. In conclusion, VEGF, HIF-1 alpha, and predominantly PDGFRa are expressed in neoplastic cells in the majority of Hodgkin lymphomas. As microvessel formation is not increased in Hodgkin, additional functions of these angiogenic molecules should be investigated. (C) 2008 Elsevier GmbH. All rights reserved