Mediterranean Journal of Hematology and Infectious Diseases 2018-12-16T13:24:54+00:00 Giuseppe Leone Open Journal Systems <p style="font-size: 14px;">The Journal publishes original articles and topical reviews concerning both clinical hematology and infectious diseases. A particular attention will be deserved to original articles focusing on the relationship between blood and infectious diseases.</p> <p><strong>The Mediterranean Journal of Hematology and Infectious Diseases has been selected for coverage in&nbsp;</strong><strong>Clarivate Analytics products and services. <br>Beginning with V. 7 (1) 2015, this publication is indexed and abstracted in:</strong><br><strong>♦ Science Citation Index Expanded</strong><br><strong>♦ Journal Citation Reports/InCites</strong></p> <p><strong>♦ First&nbsp;&nbsp;<strong>2017&nbsp;<strong>official</strong>&nbsp;</strong>Impact Factor: 1.183</strong></p> <p><span style="font-size: 12px;"><strong><span class="info_label" style="color: #757472; text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: 'Open Sans', sans-serif, icomoon; font-style: normal; word-spacing: 0px; white-space: normal; box-sizing: border-box; background-color: #ffffff; font-variant-ligatures: normal; font-variant-caps: normal; -webkit-text-stroke-width: 0px; text-decoration-style: initial; text-decoration-color: initial;">ISI Journal Citation Reports @ Ranking: 2017</span></strong></span></p> <p><strong>List of contents</strong></p> <p><strong>10:(1) (2018):&nbsp;<a title="Volume 10, Year 2018" href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a>ORIGINAL ARTICLES, REVIEWS:</strong></p> <p><strong>Review Topics:</strong></p> <ul> <li class="show">UPDATE ON VIRAL INFECTIONS AND LYMPHOPROLIFERATIVE DISEASES. Guest Editors: M. Luppi and L. Arcaini&nbsp;<a href="/index.php/mjhid/announcement/view/73">More...</a></li> </ul> <p><strong>9:(1) (2017):&nbsp;</strong><strong><a title="Volume 9, Year 2017" href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a>ORIGINAL ARTICLES, REVIEWS:</strong></p> <p><strong>Review Topics:</strong></p> <ul> <li class="show">UPDATE ON SECONDARY LEUKEMIAS. Guest Editor: Richard Larson&nbsp;<a href="/index.php/mjhid/announcement/view/59">More...</a></li> <li class="show">UPDATE on &nbsp;“Rare Plasma Cell Dyscrasias” Guest Editor M.T. PETRUCCI&nbsp;<a href="/index.php/mjhid/announcement/view/49">More...</a></li> </ul> <p><strong>8:(1) (2016):&nbsp;<a title="Volume 8, Year 2016" href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a>&nbsp;ORIGINAL ARTICLES, REVIEWS:</strong></p> <p><strong>Review Topics:</strong></p> <ul> <li class="show">HEMATOPOIETIC STEM CELL TRANSPLANTATION AND INFECTIONS. Guest Editor: Miguel Sanz&nbsp;<a href="/index.php/mjhid/announcement/view/37">More...</a></li> <li class="show">REVIEW SERIES: UPDATE ON FOLLICULAR LYMPHOMA. Guest Editor: Corrado Tarella&nbsp;<a href="/index.php/mjhid/announcement/view/39">More...</a></li> </ul> <p><strong>8:(Supplementary Issue) (2016):&nbsp;<a href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a>&nbsp;Fifth International Symposium on Secondary Leukemia and Leukemogenesis</strong></p> <p><strong>7:(1) (2015):&nbsp;<a title="Volume 7, Year 2015" href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a>&nbsp;ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>Review Topics:</p> <ul> <li class="show">MYELODYSPLASTIC SYNDROMES. AN UPDATE. SINCE 2015. Guest Editors: C. Mecucci and M.T. Voso.&nbsp;<a href="/announcement/view/24">More...</a></li> <li class="show">BACTERIAL INFECTIONS IN HEMATOLOGIC PATIENTS: AN UPDATE. SINCE 2015.Guest Editors F. Aversa and M. Tumbarello&nbsp;<a href="/announcement/view/25">More...</a></li> </ul> <p><strong>6:(1) (2014):&nbsp;<a title="Volume 6, Year 2014" href=""><img src="/public/site/images/fguidi/FRECCE0013.gif" alt=""></a>&nbsp;ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>Review Topics:</p> <ul> <li class="show">CHRONIC MYELOID LEUKEMIAS: AN UPDATE. Guest Editors: M. Baccarani and F. Pane.&nbsp;<a href="/announcement/view/21">More...</a></li> <li class="show">UPDATE IN HODGKIN LYMPHOMA. Guest Editor: A. Gallamini&nbsp;<a href="/announcement/view/22">More...</a></li> <li class="show">ACUTE LYMPHOID LEUKEMIA IN ADULTS: AN UPDATE. Guest Editors: R. Bassan and A.Rambaldi&nbsp;<a href="/announcement/view/23">More...</a></li> </ul> <p><strong>5:(1) (2013):&nbsp;<a title="Volume 5, Year 2013" href=""><img src="/public/site/images/fguidi/FRECCE0012.gif" alt=""></a>&nbsp;ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>Review Topics:</p> <ul> <li class="show">ACUTE MYELOID LEUKEMIA IN THE ELDERLY. Guest Editors: S. Amadori and A. Venditti.&nbsp;<a href="/announcement/view/19">More...</a></li> <li class="show">VON WILLEBRAND FACTOR UPDATE. Guest Editors: A. Federici and F. Rodeghiero.&nbsp;<a href="/announcement/view/18">More..</a></li> <li class="show">TUBERCULOSIS UPDATE. Guest Editors: R. Cauda and A. Matteelli.&nbsp;<a href="/announcement/view/20">More...</a></li> </ul> <p><strong>4:(1) (2012):&nbsp;<a title="Malaria In The World, Chronic Lymphoid Leukemia, Autologous Hemopoietic Stem Cell Transplantation In Leukemia And Lymphoma" href=""><img src="/public/site/images/fguidi/FRECCE0011.gif" alt=""></a>ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>Review Topics:</p> <ul> <li class="show">MALARIA IN THE WORLD: 2012 Update. Guest Editors: F. Castelli and E. Pizzigallo&nbsp;<a href="/announcement/view/12">More...</a></li> <li class="show">CHRONIC LYMPHOID LEUKEMIA: Update on Immunological Dysfunctions and Infections. Guest Editors: D. Efremov and L. Laurenti&nbsp;<a href="/announcement/view/17">More...</a></li> <li class="show">AUTOLOGOUS HEMOPOIETIC STEM CELL TRANSPLANTATION IN LEUKEMIA AND LYMPHOMA: 2012 UPDATE. Guest Editors: G. Meloni and G. Visani&nbsp;<a href="/announcement/view/13">More...</a></li> </ul> <p><strong>3:(1) (2011): <a title="Fungal Infections, Thrombosis In The Mediterranean Area, Acute Promyelocytic Leukemia In The Mediterranean Area And In The Developing Countries, Therapy-Related Myeloid Neoplasms." href=""><img src="/public/site/images/fguidi/FRECCE001.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>Review Topics:</p> <ul> <li class="show">FUNGAL INFECTIONS. Guest Editor: L. Pagano <a style="color: #990000;" href="/announcement/view/8">More...</a></li> <li class="show">THROMBOSIS IN THE MEDITERRANEAN AREA. Guest Editor: V. De Stefano <a style="color: #990000;" href="/announcement/view/9">More...</a></li> <li class="show">ACUTE PROMYELOCYTIC LEUKEMIA IN THE MEDITERRANEAN AREA AND IN THE DEVELOPING COUNTRIES: Guest Editors: F. Lo-Coco and G. Avvisati <a style="color: #990000;" href="/announcement/view/10">More...</a></li> <li class="show">THERAPY-RELATED MYELOID NEOPLASMS: Guest Editor: R. Larson <a style="color: #990000;" href="/announcement/view/11">More...</a></li> </ul> WALDENSTROM’S MACROGLOBULINEMIA: AN UPDATE 2018-12-16T13:24:54+00:00 Maddalena Mazzucchelli Anna Maria Frustaci Marina Deodato Roberto Cairoli Alessandra Tedeschi <p lang="en-GB" align="justify"><span style="font-family: Arial, serif;">Waldenstrom Macroglobulinemia is a rare lymphoproliferative disorder with distinctive clinical features.</span></p><p lang="en-GB" align="justify"><span style="font-family: Arial, serif;">Diagnostic and prognostic charactrization in WM significantly changed with the discovery of two molecular markers: MYD88 and CXCR4. Mutational status of these latter influences both clinical presentation and prognosis and demonstrated therapeutic implications.</span></p><p lang="zxx" align="justify"><span style="font-family: Arial, serif;"><span lang="en-GB">Treatment choice in Waldemstrom disease is strictly guided by </span></span><span style="font-family: Arial, serif;"><span lang="en-US">patients age and characteristics, specific goals of therapy, necessity for rapid disease control, risk of treatment-related neuropathy, disease characteristics, risk of immunosuppression or secondary malignancies and potential for future autologous stem cell transplantation.</span></span></p><p lang="en-US" align="justify"><span style="font-family: Arial, serif;">Therapeutic landscape has expanded during the last years and the approval of ibrutinib, the first drug approved for Waldenstrom Macroglobulinemia, represents an important step forward for a better management of the disease. </span></p> 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## HEAVY-CHAIN DISEASES AND MYELOMA-ASSOCIATED FANCONI SYNDROME: AN UPDATE 2018-09-14T09:19:37+00:00 Roberto Ria Franco Dammacco Angelo Vacca The heavy chain diseases (HCDs) are rare B-cell malignancies characterized by the production of a monoclonal immunoglobulin heavy chain without an associated light chain. There are three types of HCD, defined by the class of immunoglobulin heavy chain produced: IgA (α-HCD), IgG (γ-HCD), and IgM (μ-HCD). Alpha-HCD is the most common and usually occurs as intestinal malabsorption in a young adult from a country of the Mediterranean area. Gamma- and μ-HCDs are more rare and associated to a B-cell non-Hodgkin lymphoma that produces an abnormal Ig heavy chain. These patients may occasionally be diagnosed with a monoclonal gammopathy of undetermined significance (MGUS). Fanconi syndrome, on the other hand, can be primary (inherited) or secondary (acquired). The only exception to this rule is the idiopathic form. Adult acquired Fanconi syndrome can be a rare complication of a monoclonal gammopathy. At diagnosis, most patients have a MGUS or smoldering multiple myeloma, with renal failure and evidence of osteomalacia. During follow-up, patients can develop end-stage renal disease. Chemotherapy provides little benefit on renal function. 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## ELOTUZUMAB FOR THE TREATMENT OF RELAPSED OR REFRACTORY MULTIPLE MYELOMA, WITH SPECIAL REFERENCE TO ITS MODES OF ACTION AND SLAMF7 SIGNALING 2018-10-27T17:21:36+00:00 Masafumi Taniwaki Mihoko Yoshida Yosuke Matsumoto Kazuho Shimura Junya Kuroda Hiroto Kaneko <p>Elotuzumab, targeting signaling lymphocytic activation molecule family 7 (SLAMF7), has been approved in combination with lenalidomide and dexamethasone   (ELd)   for relapsed/refractory  multiple myeloma (MM) based on the findings of the phase III randomized trial  ELOQUENT-2 (NCT01239797). Four-year  follow-up  analyses  of  ELOQUENT-2 have demonstrated  that  progression-free survival was 21%  in  ELd  versus  14%  in  Ld. Elotuzumab binds a unique epitope on the membrane IgC2 domain of SLAMF7, exhibiting a dual mechanism of  action:  natural  killer  (NK)  cell-mediated  antibody-dependent  cellular  cytotoxicity  (ADCC) and  enhancement  of  NK  cell  activity.  The  ADCC  is  mediated  through  engagement  between  Fc portion  of  elotuzumab  and  FcgRIIIa/CD16  on  NK  cells. Enhanced NK cell cytotoxicity results fromm phosphorylation  of  the  immunoreceptor  tyrosine-based  switch  motif  (ITSM)  that  is induced via elotuzumab binding and recruits the SLAM-associated adaptor protein EAT-2.The coupling of EAT-2 to the phospholipase Cg enzymes SH2 domain leads to enhanced Ca<sup>2+</sup>. Influx and MAPK/Erk pathway activation, resulting in granule polarization and enhanced exocytosis inNK  cells. Elotuzumab  does not stimulate the  proliferation of MM cells due to a lack of EAT-2.The  inhibitory  effects  of  elotuzumab  on  MM  cell  growth  are  not  induced by  the lack  of  CD45, even  though  SHP-2,  SHP-1,  SHIP-1,  and  Csk may be  recruited  to  phosphorylated  ITSM  of SLAMF7.  ELd  improves PFS in patients  with  high-risk  cytogenetics,  i.e.  t(4;14),  del(17p),  and 1q21  gain/amplification. Since  the immune  state  is  paralytic  in  advanced  MM,  the  efficacy  of ELd with minimal toxicity may bring forward for consideration of its use in the early stages of the disease.</p> 2018-02-15T00:00:00+00:00 ##submission.copyrightStatement## LIGHT CHAIN AMYLOIDOSIS 2018-10-27T17:21:35+00:00 Paolo Milani Giampaolo Merlini Giovanni Palladini <p>Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic lights chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by response to therapy. The specific treatment is chemotherapy targeting the underlying plasma-cell clone. This needs be risk adapted, according to the severity of cardiac and/or multi-organ involvement. Autologous stem cell transplant (preceded by induction and/or followed by consolidation with bortezomib-based regimens) can be considered for low-risk patients (~20%). Bortezomib combined with alkylators is used in the majority of intermediate-risk patients, and with possible dose escalation in high-risk subjects. Novel, powerful anti-plasma cell agents were investigated in the relapsed/refractory setting, and are being moved to upfront therapy in clinical trials. In addition, the use of novel approaches based on antibodies targeting the amyloid deposits or small molecules interfering with the amyloidogenic process gave promising results in preliminary studies. Some of them are under evaluation in controlled trials. These molecules will probably add powerful complements to standard chemotherapy. The understanding of the specific molecular mechanisms of cardiac damage and the characteristics of the amyloidogenic clone are unveiling novel potential treatment approaches, moving towards a cure for this dreadful disease.</p> 2018-03-01T00:00:00+00:00 ##submission.copyrightStatement## APPROPRIATE DURATION OF INTRAVENOUS TREATMENT OF CANDIDEMIA AND TIMING OF STEP DOWN TO ORAL THERAPY IN NON-NEUTROPENIC PATIENTS 2018-08-31T21:43:11+00:00 Rita Wilson Dib Ray Hachem Anne-Marie P Chaftari Issam I Raad <p>In this review we have analyzed the available literature pertaining to the total duration of intravenous (IV) therapy and the appropriate timing of step down to oral therapy in the management of candidemia. Overview of the guidelines and literature seem to indicate that a minimum of 14 days of antifungal therapy is required in the treatment of candidemia without deep seated infection. However, this was never based on evidence. Furthermore, step down to oral therapy seems to be dependent on the clinical stability criteria of the patient with candidemia after 4 to 7 days of IV therapy.  Further studies are required to evaluate the appropriate total duration of IV therapy, appropriate timing of step down to oral therapy and to validate the clinical criteria that would allow the switch to happen.</p> 2018-05-01T00:00:00+00:00 ##submission.copyrightStatement## PERIOPERATIVE MANAGEMENT OF SICKLE CELL DISEASE: A NARRATIVE REVIEW 2018-08-31T21:43:12+00:00 Kwame Ofori Adjepong Folashade Otegbeye Yaw Amoateng ADJEPONG <p>An estimated 30 million people worldwide have sickle cell disease (SCD).  Emergent and non-emergent surgical procedures in SCD have been associated with relatively increased risks of peri-operative mortality, vaso-occlussive (painful) crisis, acute chest syndrome, post-operative infections, congestive heart failure, cerebrovascular accident and acute kidney injury.  Pre-operative assessment must include careful review of the patient’s known crisis triggers, baseline hematologic profile, usual transfusion requirements, pre-existing organ dysfunction and narcotic use. Use of preoperative blood transfusions should be selective and decisions individualized based on the baseline hemoglobin, surgical procedure and anticipated volume of blood loss.  Intra- and post-operative management should focus on minimizing hypoxia, hypothermia, acidosis, and intravascular volume depletion. Pre- and post-operative incentive spirometry use should be encouraged. </p> 2018-05-01T00:00:00+00:00 ##submission.copyrightStatement## LYMPHOPROLIFERATIVE SYNDROMES ASSOCIATED WITH HUMAN HERPESVIRUS-6A AND HUMAN HERPESVIRUS-6B 2018-08-31T21:43:12+00:00 Eva Eliassen Gerhard R Krueger Mario Luppi Dharam Ablashi <p>Human herpesvirus 6A and 6B (HHV-6A and HHV-6B) have been noted since their discovery for their T-lymphotropism. Although it has proven difficult to determine the extent to which HHV-6A and HHV-6B are involved in the pathogenesis of many diseases, evidence suggests that primary infection and reactivation of both viruses may induce or contribute to the progression of several lymphoproliferative disorders, ranging from benign to malignant and including infectious mononucleosis-like illness, drug induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), and nodular sclerosis Hodgkin’s lymphoma. Herein, we discuss the conditions associated with the lymphoproliferative capacity of HHV-6, as well as the potential mechanisms behind them. Continued exploration on this topic may add to our understanding of the interactions between HHV-6 and the immune system and may open the doors to more accurate diagnosis and treatment of certain lymphoproliferative disorders. </p> 2018-05-01T00:00:00+00:00 ##submission.copyrightStatement## INFECTIONS IN MYELODYSPLASTIC SYNDROME IN RELATION TO STAGE AND THERAPY 2018-10-31T11:43:59+00:00 Giuseppe Leone Livio Pagano <p>Infections remain a significant problem in myelodysplastic syndromes in treated as well in non-treated patients and assume a particular complexity. The susceptibility to infections is due, in the absence of intensive chemotherapies, mainly to functional defects in the myeloid lineage with or without neutropenia. Furthermore, MDS include a heterogeneous group of patients with very different prognosis, different therapy and various risk factors regarding survival and infections. You should distinguish risk factors related to the disease, like as neutrophils function impairment, neutropenia, unfavorable cytogenetics and bone marrow insufficiency; factors related to the patient, like as age and comorbidities, and factors related to the therapy. When the patients with MDS are submitted to intensive chemotherapy with and without HSCT, they have a risk factor for infection very similar to that of patients&nbsp;with AML, and mostly related to neutropenia. Patients with MDS treated with supportive therapy only or with demethylating agent or lenalidomide or immunosuppressive drugs should have a tailored approach. Most of the infections in MDS originate from bacteria, and the major risk factors are represented by neutropenia, thrombocytopenia, and unfavorable cytogenetics. Thus it is reasonable to give antibacterial prophylaxis in patients who start the therapy with demethylating agents with a number of neutrophils &lt;500, or with thrombocytopenia and unfavorable cytogenetics. The antifungal prophylaxis is not considered cost/benefit adequate and should be taken into consideration only when there is an antecedent fungal infection or presence of filamentous fungi in the surveillance cultures. Subjects submitted to immunosuppression with ATG+CSA have a high number of infections, and when severely neutropenic should ideally be nursed in isolation, should be given prophylactic antibiotics and antifungals, regular mouth care including an antiseptic mouthwash.&nbsp;</p> <p>&nbsp;</p> 2018-07-01T00:00:00+00:00 ##submission.copyrightStatement## DISSEMINATED HISTOPLASMOSIS AS AIDS PRESENTATION. CASE REPORT AND COMPREHENSIVE REVIEW OF CURRENT LITERATURE 2018-08-31T22:34:11+00:00 Paola Zanotti Claudia Chirico Maurizio Gulletta Laura Ardighieri Salvatore Casari Eugenia Quiros Roldan Ilaria Izzo Gabriele Pinsi Giovanni Lorenzin Fabio Facchetti Francesco Castelli Emanuele Focà <p><span style="font-family: Times New Roman;"><span style="font-size: medium;">Progressive disseminated</span><span style="font-size: medium;"> histoplasmosis (PDH) is an AIDS</span><span style="font-size: medium;">-defining illness with a high lethality rate if not promptly treated. The wide range of its possible clinical manifestations represents the main barrier to diagnosis in non-endemic countries. Here we present a case of PDH with haemophagocytic syndrome in a newly diagnosed HIV patient and a comprehensive review of disseminated histoplasmosis focused on epidemiology, clinical features, diagnostic tools and treatment options in HIV-infected patients.</span><span style="font-size: medium;">  </span></span></p> 2018-07-01T00:00:00+00:00 ##submission.copyrightStatement## THROMBOCYTOPENIA IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES - STILL AN UNSOLVED PROBLEM 2018-08-31T22:34:14+00:00 May Basood Howard S. Oster Moshe Mittelman <p>The myelodysplastic syndromes (MDS) are a group of clonal bone marrow (BM) stem cell disorders, characterized by ineffective hematopoiesis, peripheral cytopenias and hematologic cellular dysfunction, as well as potential transformation to acute leukemia.</p><p>Thrombocytopenia is common in MDS and is associated with bleeding complications, occasionally life threatening. Low platelet count (PLT), as well declining PLT also serves as a prognostic marker. Understanding thrombopoiesis led to the cloning of thrombopoietin, resulting in the development of platelet stimulating agents, thrombomimetics, romiplostim and eltrombopag.</p><p>Both agents have been shown to increase PLT, decrease the need for platelet transfusions and reduce the number of bleeding episodes, with a reasonable tolerance. They are already approved for immune thrombocytopenia and thrombocytopenia related to liver disease.</p><p>Romiplostim and eltrombopag have proven efficacy in lower- and higher-risk MDS with thrombocytopenia, as monotherapy, as well as a part of a combination, either with lenalidomide, and mainly combined with hypomethylating agents. However, safety concerns have been raised: while several trials have been completed with no evidence of disease progression, others have been early terminated due to increased number of BM blasts and possible leukemic transformation in treated-patients. The jury is still out regarding this safety concern, although recent publications are more encouraging. </p><p>Keywords: Myelodysplastic syndrome, Thrombocytopenia, Thrombomimetics,</p><p>Romiplostim, Eltrombopag.</p> 2018-07-01T00:00:00+00:00 ##submission.copyrightStatement## INVASIVE ASPERGILLOSIS IN CHILDREN: UPDATE ON CURRENT GUIDELINES 2018-10-27T17:21:34+00:00 Athanasia Apsemidou Nikolaos Petridis Timoleon-Achilleas Vyzantiadis Athanasios Tragiannidis <p>Invasive aspergillosis (IA) is an important cause of infectious morbidity and mortality in immunocompromised paediatric patients. Despite improvements in diagnosis, prevention and treatment, IA is still associated with high mortality rates. To address this issue, several international societies and organisations have proposed guidelines for the management of IA in the paediatric population. In this article, we review current recommendations of the Infectious Diseases Society of America, the European Conference on Infection in Leukaemia and the European Society of Clinical Microbiology and Infectious Diseases for the management and prevention of IA in children.</p> 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## PERIPHERAL NERVOUS SYSTEM INVOLVEMENT IN LYMPHOPROLIFERATIVE DISORDERS 2018-09-07T12:28:25+00:00 Mario Sabatelli Luca Laurenti Marco Luigetti <p>Peripheral neuropathies are a vast group of diseases with heterogeneous aetiologies, including genetic and acquired causes. Several haematological disorders may cause an impairment of the peripheral nervous system, with diverse mechanisms and variable clinical, electrophysiological and pathological manifestations. In this practical review we considered the main phenotypes of peripheral nervous diseases and examined the haematological disorders which may associate with each of them.</p><p>The area of intersection of neurological and haematological fields is of particular complexity and raises several problems in clinical practice. The personal crosstalk between neurologists and haematologists remains a fundamental tool for  a proper diagnostic process  which  may lead to successful treatments in  most cases.  <strong></strong></p> 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## INVASIVE FUNGAL INFECTIONS IN PATIENTS WITH CHRONIC LYMPHOPROLIFERATIVE DISORDERS IN THE ERA OF TARGET DRUGS 2018-12-16T13:24:53+00:00 Livio Pagano Davide Facchinelli, Dr. <p>This review summarizes the more recent evidence about epidemiology and risk factors for invasive fungal infections (IFI) in patients affected by Chronic Lymphocytic Leukemia (CLL), indolent Non Hodgkin Lymphoma (iNHL) and Multiple Myeloma (MM).</p> <p>Despite advances in the prognosis and treatment of hematological malignancies in recent years, susceptibility to infection remains a significant challenge to patient care. A large amount of data regarding patients with acute leukemia has been published while little information is available on the incidence of IFI in chronic lymphoproliferative disorders (CLD).</p> <p>New drugs are now available for treatment of lymphoproliferative disorders which may cause suppression of humoral immunity, cellular immunity, and deficiency of white blood cells, increasing the risk for infections which remain the leading cause of mortality in these patients.</p> 2018-10-27T15:36:07+00:00 ##submission.copyrightStatement## THE BROAD-RANGING PANORAMA OF SYSTEMIC AUTOINFLAMMATORY DISORDERS WITH SPECIFIC FOCUS ON ACUTE PAINFUL SYMPTOMS AND HEMATOLOGIC MANIFESTATIONS IN CHILDREN 2018-12-16T13:24:53+00:00 Donato Rigante <p>Systemic autoinflammatory disorders (SAIDs) are inherited defects of innate immunity characterized by recurrent sterile inflammatory attacks involving skin, joints, serosal membranes, gastrointestinal tube and other tissues, which recur with variable rhythmicity and display reactive amyloidosis as a potential long-term complication. Dysregulated inflammasome activity leading to overproduction of many proinflammatory cytokines, such as interleukin-1 (IL-1), and delayed shutdown of inflammation are considered crucial pathogenic keys in the vast majority of SAIDs. Progresses of cellular biology have partially clarified the mechanisms behind monogenic SAIDs, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndrome, mevalonate kinase deficiency, hereditary pyogenic diseases, idiopathic granulomatous diseases and defects of the ubiquitin-proteasome pathway, whereas little is clarified for the polygenic SAIDs, such as periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy (PFAPA) syndrome. The puzzle of symptomatic febrile attacks recurring over time in children requires evaluating the mixture of clinical data, inflammatory parameters in different disease phases, therapeutic efficacy of specific drugs such as colchicine, corticosteroids or IL-1 antagonists, and genotype analysis in selected cases. Long-term history of periodic fevers should also need to rule out chronic infections and malignancies. This review is conceived as a practical template for a proper classification of children with recurring fevers and includes tips useful for the diagnostic approach to SAIDs, focusing on the specific acute painful symptoms and blood manifestations encountered in childhood.</p> 2018-10-30T09:45:08+00:00 ##submission.copyrightStatement## DEFERASIROX: OVER A DECADE OF EXPERIENCE IN THALASSEMIA 2018-12-16T13:24:52+00:00 Ali Taher <p>Thalassemia incorporates a broad clinical spectrum characterized by decreased or absent production of normal hemoglobin leading to decreased red blood cell survival and ineffective erythropoiesis. Chronic iron overload remains an inevitable complication resulting from regular blood transfusions (transfusion-dependent) and/or increased iron absorption (mainly non-transfusion-dependent thalassemia), requiring adequate treatment to prevent the significant associated morbidity and mortality. Iron chelation therapy has become a cornerstone in the management of thalassemia patients, leading to improvements in their outcome and quality of life. Deferasirox, an oral iron chelating agent is approved for use in transfusion dependent and non-transfusion-dependent thalassemia and has shown excellent efficacy in this setting. We herein present an updated review of the role of deferasirox in thalassemia, exploring over a decade of experience, which has documented its effectiveness and convenience; in addition to its manageable safety profile.</p> <p><strong>Keywords:</strong> iron overload, iron chelation therapy, transfusion-dependent thalassemia, non-transfusion dependent thalassemia, serum ferritin, liver iron concentration, deferasirox</p> 2018-11-01T11:16:21+00:00 ##submission.copyrightStatement## Megakaryocyte contribution to bone marrow fibrosis: many arrows in the quiver 2018-12-16T13:24:52+00:00 Alessandro Malara Vittorio Abbonante Maria Zingariello Anna Rita Franco Migliaccio Alessandra Balduini In Primary Myelofibrosis (PMF), megakaryocyte dysplasia/hyperplasia determines the release of inflammatory cytokines that, in turn, stimulate stromal cells and induce bone marrow fibrosis. The pathogenic mechanism and the cells responsible for progression to bone marrow fibrosis in PMF are not completely understood. This review article aims to provide an overview of the crucial role of megakaryocytes in myelofibrosis by discussing the role and the altered secretion of megakaryocyte-derived soluble factors, enzymes and extracellular matrices that are known to induce bone marrow fibrosis. Additionally, we describe recent evidences showing that the role of megakaryocytes in tissue fibrosis is not limited to the bone marrow. 2018-11-01T11:19:24+00:00 ##submission.copyrightStatement## HUMAN HERPESVIRUS 8 AND LYMPHOPROLIFERATIVE DISEASES 2018-12-16T13:24:52+00:00 Maria Luisa Calabrò Ronit Sarid <p style="margin: 0cm 0cm 0pt; text-align: justify; line-height: 200%;"><span style="line-height: 200%; font-family: 'Times New Roman','serif'; font-size: 12pt;">The spectrum of lymphoproliferative disorders linked to human herpesvirus 8 (HHV-8) infection has been constantly increasing since the discovery of its first etiologic association with primary effusion lymphoma (PEL). PEL is a rapidly progressing non-Hodgkin’s B-cell lymphoma that develops in body cavities in an effusional form. With the increase in the overall survival of PEL patients, as well as the introduction of HHV-8 surveillance in immunocompromised patients, the extracavitary, solid counterpart of PEL was later identified. Moreover, virtually all plasmablastic variants of multicentric Castleman’s disease (MCD) developing in HIV-1-infected individuals harbor HHV-8, providing a strong etiologic link between MCD and this oncogenic herpesvirus. Two other pathological conditions develop in HIV-1-infected persons concomitantly with MCD: MCD with plasmablastic clusters and MCD-associated plasmablastic lymphoma, the first likely representing an intermediate stage preceding the full neoplastic stage. MCD in leukemic phase has also been described, albeit much less commonly. The germinotropic lymphoproliferative disorder (GLPD) may resemble extracavitary PEL, but develops in immune competent HHV8-infected individuals, and, unlike the disorders described above, it responds well to conventional therapies. Almost all HHV-8-mediated lymphoproliferative disorders </span><span style="line-height: 200%; font-family: 'Times New Roman','serif'; font-size: 12pt; mso-bidi-language: HE;">are the result of</span><span style="line-height: 200%; font-family: 'Times New Roman','serif'; font-size: 12pt;"> an interaction between HHV-8 infection and a dysregulated immunological system, leading to the formation of inflammatory niches in which B cells, at different developmental stages, are infected, proliferate and may eventually shift from a polyclonal state to a monoclonal/neoplastic disorder. H</span><span style="line-height: 200%; font-family: 'Times New Roman','serif'; font-size: 12pt; mso-bidi-language: HE;">erein</span><span style="line-height: 200%; font-family: 'Times New Roman','serif'; font-size: 12pt;">, we describe the association between HHV-8 and lymphoproliferative disorders and highlight the predominant distinctive features of each disease. </span></p> 2018-11-01T11:23:55+00:00 ##submission.copyrightStatement## MOLECULAR HETEROGENEITY IN ACUTE PROMYELOCYTIC LEUKEMIA - A SINGLE CENTRE EXPERIENCE FROM INDIA 2018-08-31T21:43:12+00:00 Nikhil Rabade Goutham Raval Shruti Chaudhary PG Subramanian Rohan Kodgule Swapnali Joshi Prashant Tembhare Hasmukh Jain Manju Sengar Syed Hasan K Pratibha Amare Kadam Dhanalaxmi Shetty Gaurav Narula Shripad Banavali Sumeet Gujral Nikhil Patkar Atypical breakpoints and variant APL cases involving alternative chromosomal aberrations are seen in a small subset of acute promyelocytic leukemia (APL) patients. Over 7 different partner genes for RARA have been described. Although rare, these variants prove to be a diagnostic challenge and require combination of advanced cytogenetic and molecular techniques for accurate characterization. Heterogeneity occurs not only at the molecular level but also at clinico-pathological level influencing treatment response and outcome. In this case series we describe the molecular heterogeneity of APL seen in a single tertiary referral centre with a focus on seven variant APL cases from a single tertiary cancer center in India over a period of two and a half years. We discuss five cases with <em>PLZF-RARA</em> fusion and two novel <em>PML-RARA</em> variants, including a Bcr3 variant involving fusion of <em>PML</em> exon4 and <em>RARA</em> exon3 with an additional 40 nucleotides originating from <em>RARA</em> intron2, another involving exon 6 of <em>PML</em> and exon 3 of <em>RARA</em> with addition of 126 nucleotides, which mapped to the central portion of <em>RARA</em> intron 2  To the best of our knowledge this is the first of kind case series from India 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THERAPY-RELATED MYELOID NEOPLASMS (t-MN) OF THE ADULT: MONOCENTRIC OBSERVATIONAL STUDY AND REVIEW OF THE LITERATURE. 2018-08-31T21:43:13+00:00 Elisabetta Metafuni Patrizia Chiusolo Luca Laurenti Federica Sorà Sabrina Giammarco Andrea Bacigalupo Giuseppe Leone Simona Sica <p><strong>Abstract</strong></p><p><strong> </strong></p><p><em>Background:</em> Therapy-related myeloid neoplasms (t-MN) occur due to direct mutational events of chemotherapeutic agents and radiotherapy. Disease latency, mutational events, and prognosis vary with drugs categories.</p><p><em>Methods:</em><strong> </strong>We describe a cohort of 30 patients, 18 females and 12 males, with a median age of 52.5 years (range, 20 to 64), submitted to allogeneic stem cell transplantation (HSCT) in our department between September 1999 and March 2017. Patients had a history of a solid tumor in 14 cases, a hematological disease in 15 cases and both of them in one case. After a median of 36.5 months (range, 4 to 190) from the first neoplasm, patients developed t-AML in 19 cases and t-MDS in 11 cases. Molecular abnormalities were detected in 5 patients, while karyotype aberrations were found in 17 patients. Patients received conventional chemotherapy in 14 cases, azacitidine in 10 cases and both of them in one case. Five patients were submitted to HSCT without previous treatment except for supportive therapy.</p><p><em>Results:</em> Seventeen patients obtained sustained CR after SCT, while 8 patients showed resistant or relapsed disease. The remaining five patients died early after SCT. At follow up time (May 2017) 13 patients were alive with a median OS of 48 months (range 3-195), while 17 patients died after a median of 4 months (range 1-27) by relapse mortality in 6 cases and non-relapse mortality in the other 11 patients.</p><p><em>Conclusions:</em> Global OS was 43%. After SCT 56.7% of patients with t-MN obtained and maintained CR.</p><p><strong>Keywords: Therapy-related myeloid neoplasm; Hematopoietic stem cell transplantation; </strong><strong>Secondary leukemia.</strong></p><div class="grammarly-disable-indicator"> </div><div class="grammarly-disable-indicator"> </div><div class="grammarly-disable-indicator"> </div> 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## TREATMENT OF EARLY STAGES HODGKIN LYMPHOMA DURING PREGNANCY 2018-08-31T21:43:13+00:00 Agustin Avilès Maria-Jesus Nambo Natividad Neri <p>Objetive. To assess maternal and fetal outcome of women who receiving chemotherapy during pregnancy to treat Hodgkin lymphoma(HL) in early stages (IA and IIA), we performed an retrospective analysis of 44 women with HL at early stage, diagnosed and treated between 1988 to 2010, in a tertiary reference cancer center.</p><p>Methods:We analyze data of HL: clinical characteristics and treatment; and special attention to maternal and fetal complications ; children : physical development, assess scholar performance phsycological, cardiac and neurological function and intellegence tests.</p><p>Results:  Forty-four pregnant women were enrolled. Median age was 29.4 (range 21-37)years; most patients were stage IIA (86%), had mediastinal bulky disease (78%) and &gt; 3 nodal sites involved; thus these patients were recorded to have a not favourable condition. Abortion was refused when proposed. All patients received combined chemotherapy: ABVD) ( adryamicin, bleomycin, vinblastine and dacarbazine), even during first trimester, at standar doses and schedules. Radiotherapy, when necessary was administered after delivery in 39 patients. No obstetrical complications were observed. Delivery ocurred between 31 to 36 weks in 10 patients (22%) and &gt; 37 weeks in 34 cases (77%). Four newborns were low-weight: 2012 (median) (range:1750 -2350) g. No clinical malformations were observed and development of children were normal without evidence of cardiac, neurological damage. Behavior, scholar attendance and intellegence tests were normal. With a median follow-up of 120.4 (range 48-299) months, progression-free survival and overall survival were 93% and 95 %, respectively.</p><p>Conclusion: Chemotherapy as initial therapy appear to be thes best therapeutic approach in these setting of patients, with a excelent outcome to both: mother and children. If radiotherapy is necessary, could be administered after delivery</p><p> </p> 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## OCCULT HEPATITIS B VIRUS INFECTION AND ASSOCIATED GENOTYPES AMONG HBSAG-NEGATIVE SUBJECTS IN BURKINA FASO 2018-08-31T21:43:13+00:00 Birama DIARRA Albert Théophane YONLI Pegdwendé Abel SORGHO Tegwinde rebecca COMPAORE Dorcas Obiri -Yeboah Abdoul Karim OUATTARA Traore Lassina Wendpagnangdé Arsène ZONGO Serge Théophile Soubeiga Virginio Pietra Bolni-Marius Nagalo Wendkuuni Florencia Djigma Issoufou Tao Rokia Sanogo Jacques SIMPORE <p><strong>Background</strong>: Occult Hepatitis B virus infection (OBI), is characterized by the absence of detectable HBsAg in the blood of a person assumed to be healthy. It remains a potential transmission threat and risk to HBV chronic infection. The purpose of this study was to determine the OBI prevalence among HBsAg negative subjects and to characterize associated genotypes.</p><p><strong>Methods</strong>: Blood samples of 219 HBsAg-negative subjects tested by ELISA were collected. HBV DNA was investigated in all samples. Viral loads were determined using quantitative real-time PCR. All samples were screened for HBV markers (anti-HBc, anti-HBe, HBsAg). The Pre-S/S region of the HBV genome was sequenced. The database was analyzed using the SPSS and Epi info softwares. Phylogenetic analysis was performed using the BioEdit and MEGA softwares.</p><p><strong>Results</strong>: Of the 219 samples, 20.1 % were anti-HBc positive, 1.8 % HBeAg and 22.8 % were anti-HBe positive. Fifty-six 56 (25.6 %) of the samples had a detectable HBV DNA and viral loads ranging from 4 IU/mL to 13.6 10<sup>6</sup> IU/mL. Sixteen of them (16/56) had a viral load &lt; 200 IU/mL, resulting in an OBI prevalence of 7.3 % (16/219) in our study. The remaining 40 subjects had viral loads ˃ 200 IU/mL, resulting in a “false OBI” prevalence of 18.3% (40/219). HBV genotype E was predominant followed by the quasi-sub-genotype A3. A single "false OBI" strain had the characteristic mutation G145R. Other mutations were observed and all located in the major hydrophilic region (MHR) of the S gene.</p><p><strong>Conclusion:</strong> The study reported a prevalence of 7.3% of occult hepatitis B infection. It confirms the predominance of genotype E and the existence of a subgroup of quasi-sub-genotype A3 of HBV in Burkina Faso. It further provides information on the existence of “false OBI “. This study has found mutations in the major hydrophilic region (MHR) of the pre-S/S gene of HBV. </p><p><strong>Key words</strong>: HBV, OBI, Genotypes, Real-time PCR, Sequencing</p> 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## DETECTION OF Β THALASSEMIA CARRIERS BY RED CELL PARAMETERS OBTAINED FROM AUTOMATIC COUNTERS USING MATHEMATICAL FORMULAS 2018-08-31T21:43:13+00:00 Idit Lachover Roth Boaz Lachover Guy Koren Carina Levin Luci Zalman Ariel Koren <p><span style="font-size: medium;"><span style="font-family: Times New Roman;"><span>BACKGROUND and Objective: β thalassemia major is a severe disease with high morbidity</span><strong><span>.</span></strong><span> The world prevalence of carriers is around 1.5–7%. The aim of the present study was to find a reliable formula for detecting β thalassemia carriers using a large database of more than 22,000 samples obtained from a homogeneous population of childbearing age women with 14% of β thalassemia carriers and to check previously published formulas. </span></span></span><strong></strong></p><p><span style="font-size: medium;"><span style="font-family: Times New Roman;"><span>METHODS: We applied a mathematical method based on the support vector machine (SVM) algorithm </span>in the search for a reliable formula that can differentiate between <span>thalassemia carriers</span> and non-carriers, including normal counts or counts suspected to belong to iron-deficient women.</span></span></p><p><span style="font-size: medium;"><span style="font-family: Times New Roman;"><span>RESULTS: </span>Shine's <span>formula and ours showed &gt;98% sensitivity and &gt;99.77% NPV. All other published formulas gave inferior results. </span></span></span></p><p><span style="font-family: Times New Roman; font-size: medium;">CONCLUSIONS: We found a reliable formula that can be incorporated into any automatic blood counter to alert health providers to the possibility of a woman being a <span>β</span> thalassemia carrier. A further simple hemoglobin characterization by HPLC analysis should be performed to confirm the diagnosis, and subsequent family studies should be carried out. Our SVM formula is currently limited to women of fertility age until further analysis in other groups can be performed.</span></p> 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## NEGATIVE IMPACT OF PROLONGED ANTIBIOTICS OR PERSISTENT DIARRHEA ON VITAMIN K1 LEVELS IN 2-24 WEEKS AGED EGYPTIAN INFANTS 2018-08-31T21:43:13+00:00 Mohsen Elalfy Fatma S E Ebeid Iman Elagouza Fatma Ibrahim Noura Hassan Beshoy Botros <p><strong><em>Ob</em></strong><strong><em>jectives:</em></strong> To evaluate the hazard of prolonged antibiotic therapy and/or persistent diarrhea on vitamin K1 (VK1) level and bleeding profile in infants (2-24 weeks). <strong><em>Methods:</em></strong> A one-year case-control study, conducted at Ain Shams University, Egypt. 338 infants (2-24 weeks) were recruited and divided into 3 groups (1:1:3 ratios); group A (n= 67) patients who received antibiotics for ≥10 days, group B (n= 67) who had persistent diarrhea ≥ 14 days and group C (n=204) age- and gender-matched infants who were not either received antibiotics nor had diarrhea. All subjected to clinical assessment, bleeding history and had their complete blood count (CBC), PT and PTT, liver transaminases and VK1 level assayed.  <strong><em>Results:</em></strong> There was a significant increase in the frequency of VKDB (vitamin K deficiency bleeding) and abnormal bleeding profile in cases than the control group. There was a significant negative correlation between VK1 level and duration of diarrhea, length of antibiotics used and bleeding profile. Antibiotic usage has a dangerous effect on the VK1 level in those with diarrhea; more patients were receiving antibiotic in those with persistent diarrhea and VKDB (N=55) than those with persistent diarrhea and normal VK1 (N=12). The longer duration of antibiotic therapy the lower level of VK1.  Combining cephalosporins/penicillins therapy and/or diarrhea, in particular, had an impact on the VK1 level. <strong><em>Conclusion:</em></strong> VKDB, a preventable cause of life-threatening hemorrhage, is still a major health problem in Egyptian infants, where persistent diarrhea and misuse of antibiotics are prevalent, necessitate a booster dose of VK in those high risk infants.</p><p>Keyword: Prolonged Antibiotics; Persistent Diarrhea; Vitamin K1; Egyptian</p><p> </p><p> </p> 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## AN OBSERVATIONAL STUDY OF THE EFFECT OF HEMOGLOBINOPATHY, ALPHA THALASSEMIA AND HEMOGLOBIN E ON P. VIVAX PARASITEMIA 2018-10-27T17:21:35+00:00 Suparak Para Puncharee Mungkalasut Makamas Chanda Issarang Nuchprayoon Srivicha Krundsood Chalisa Louicharoen Cheepsunthorn <p>Background: The protective effect of α-thalassemia, a common hematological disorder in Southeast Asia, against <em>P</em><em>lasmodium</em><em> falciparum</em> malaria has been well established. However, there are much less well understood the effect of α-thalassemia against <em>P</em><em>.</em><em>vivax</em>. Here, we aimed to investigate the proportion of α-thalassemia including the effect of α-thalassemia and HbE on the parasitemia of <em>P</em><em>.</em><em>vivax</em> in Southeast Asian malaria patients in Thailand.</p><p>Methods: A total of 210 malaria patients, admitted to the Hospital for Tropical Diseases, Thailand during 2011-2012, consist of 159 Myanmeses, 13 Karens, 26 Thais, 3 Mons, 3 Laotians, and 6 Cambodians were recruited. <em>Plasmodium spp</em><em>. </em>and parasite densities were determined. Group of deletion mutation (--<sup>SEA</sup>, -α<sup>3</sup><sup>.</sup><sup>7</sup>, -α<sup>4</sup><sup>.</sup><sup>2</sup>deletion) and substitution mutation (HbCS and HbE) were genotyped using multiplex gap-PCR and PCR-RFLP, respectively.</p><p>Results: In our malaria patients, 17/210 homozygous and 74/210 heterozygous -α<sup>3</sup><sup>.</sup><sup>7</sup> deletion were found. Only 3/210 heterozygous -α<sup>4</sup><sup>.</sup><sup>2</sup> deletion and 2/210 heterozygous--<sup>SEA</sup> deletion were detected. HbE is frequently found with 6/210 homozygote and 35/210 heterozygote. The most common thalassemia allele frequencies in Myanmar population were -α<sup>3</sup><sup>.</sup><sup>7 </sup>deletion (0.282), followed by HbE (0.101), HbCS (0.016), -α<sup>4</sup><sup>.</sup><sup>2 </sup>deletion (0.009), and --<sup>SEA</sup> deletion (0.003). Only density of <em>P</em><em>.</em><em>vivax</em> in α-thalassemia trait patients (-α<sup>3</sup><sup>.</sup><sup>7</sup>/-α<sup>3</sup><sup>.</sup><sup>7</sup>, --<sup>SEA</sup>/αα, -α<sup>3</sup><sup>.</sup><sup>7</sup>/-α<sup>4</sup><sup>.</sup><sup>2</sup>) but not in silent α-thalassemia (-α<sup>3</sup><sup>.</sup><sup>7</sup>/αα, -α<sup>4</sup><sup>.</sup><sup>2</sup>/αα, αα<sup>CS</sup>/αα) were significantly higher compared with non α-thalassemia patients (<em>p</em>=0.027). Density of <em>P</em><em>.</em><em>falciparum</em> significantly increased in heterozygous HbE patients (<em>p</em>=0.046).</p><p>Conclusions: Alpha-thalassemia trait is associated with high level of <em>P.vivax</em> parasitemia in malaria patients in Southeast Asia. </p> 2018-02-16T00:00:00+00:00 ##submission.copyrightStatement## CHARACTERIZATION AND ANTIMICROBIAL SUSCEPTIBILITY PROFILE OF SEPTICAEMIA-CAUSING PATHOGENS ISOLATED FROM FEBRILE CHILDREN WITH SICKLE CELL DISEASE IN KANO, NIGERIA. 2018-10-27T17:21:36+00:00 Ibrahim Yusuf <p><strong>Background and Objectives</strong>: Bacterial infection in sickle cell anaemic patients is a major cause of mortality and require proper treatment with appropriate antibiotics. However, continue defiant of these infections causing pathogens to many antibiotics and inadequate screening methods in overburden health care facilities such as our in Kano, Nigeria necessitates the conduct of this study. A research was therefore conducted on the characterizations and antimicrobial susceptibility of septicaemia-causing pathogens isolated from febrile children with sickle cell disease in Kano, Nigeria.</p><p><strong>Method</strong>: A total of 225 venous blood samples from suspected sickle cell anaemicchildren attending three selected hospitals within Kano metropolis were collected and screened for sickle cell disease, followed by blood culture using automated <a href="">blood culture system</a> (BD BACTEC) respectively. The bacteria isolated from confirmed SCD patients were characterized using microscopic, biochemical and serological techniques. <strong>Results</strong>: Results showed that of the 225 specimens collected,68 (30.22%) were SCD positive, with the highest percentage (16%) among subjects within 1-2 years of age.  A total of 11 genera of bacteria were isolated from the SCD confirmed bloods, with  <em>Salmonella typhi</em> having highest occurring rate 27 (39.71%), followed by <em>Streptococcus pneumoniae</em>10 (14.71%), <em>Salmonella Group B </em>9(13.24%), <em>Staphylococcus aureus</em> 4 (5.88%),and<em> Escherichia coli </em>3 (4.41%).Majority of the isolates 59 (86.76%) were highly susceptible to ciprofloxacin followed by cefuroxime 45 (66.18%), gentamicin 38 (55.88%), ceftriaxone 30 (44.12%), augmentin 39 (57.35%), ampicillin 25 (36.77%) and co-trimoxazole (22.06%). </p><p><strong>Conclusion</strong>: Septicaemia in SCD confirmed children in the three hospitals are caused by a combination of 11 genera of bacteria. Resistance to commonly used antibiotics are on increase, but treatment with ciprofloxacin is still promising.</p> 2018-02-15T00:00:00+00:00 ##submission.copyrightStatement## ADULT SICKLE CELL ANAEMIA PATIENTS IN BONE PAIN CRISIS HAVE ELEVATED PRO-INFLAMMATORY CYTOKINES 2018-10-27T17:21:35+00:00 Adekunle Emmanuel Alagbe John Ayodele Olaniyi Oladapo Wale Aworanti <p><strong>Background and Objective: </strong>Inflammatory markers that influence bone pain crisis (BPC) and other complications of sickle cell anaemia (SCA) are numerous and play various roles. This study determined the plasma levels of tumour necrosis factor (TNF) - α, interleukin - 8 (IL-8), and endothelin - 1 (ET-1) in adult SCA patients during BPC and in steady state. In addition, the plasma levels of these cytokines were correlated with the severity of BPC of the patients.<strong></strong></p><p><strong>Methods and Materials: </strong>Sixty adult SCA patients (30 during BPC and 30 during steady state) and 30 haemoglobin A controls were enrolled for this cross-sectional study. The severity of BPC was assessed clinically, and questionnaires were filled. Plasma levels of TNF- α, IL-8 and ET-1 were quantified by ELISA, and haematological parameters were determined using a 5-part auto-analyzer. Plasma levels were correlated with the severity of bone pain crisis. Results were considered statistically significant if p&lt;0.05.</p><p><strong>Results:</strong> Plasma TNF-α, IL-8, and ET-1 were significantly elevated in the BPC group than in the steady state group and the controls. Plasma TNF-α, IL-8 and ET-1 were markedly higher in the severe BPC groups than the steady state and control groups, There was a positive correlation between TNF-α and ET-1 in the bone pain crisis group.</p><p><strong>Conclusion: </strong>Elevated levels of plasma TNF-α, IL-8, and ET-1 further establish the chronic inflammatory state in SCA and equally affirm their significant contribution, not only to pathogenesis but also to the severity of pain in SCA.</p><p> </p><p><strong>Keywords</strong><strong>: </strong>Sickle cell anaemia, Cytokines, Bone pain crisis, Severity, Steady state.</p><p> </p><p> </p> 2018-03-01T00:00:00+00:00 ##submission.copyrightStatement## OUTCOME AND TOXICITY PATTERNS IN CHILDREN AND ADOLESCENTS WITH NON-HODGKIN LYMPHOMA: A SINGLE INSTITUTION EXPERIENCE 2018-10-27T17:21:35+00:00 Paola Angelini Laura Rodriguez Mohammed Zolaly Ahmed Naqvi Sheila Weitzman oussama Abla Angela Punnett <p><strong>Background</strong>: The incidence and biology of non-Hodgkin lymphoma (NHL) vary according to age. Some data suggest that the impact of age in pediatric and adolescent NHL patients depends on the histological subtype. <strong>Objectives</strong>: We aimed to analyze the impact of age at diagnosis on clinical characteristics and treatment-related toxicity in children and adolescents with NHL.</p><p><strong>Methods</strong>: Retrospective review of medical records of children and adolescents diagnosed with NHL at the Hospital for Sick children, Toronto, between January 1995 and December 2008.</p><p><strong>Results: </strong>164 children were diagnosed with NHL during the study period, with a median age at diagnosis of 10 years. With a median follow-up of 6.2 years, 5-year OS in patients aged &lt;15 and 15-18 years was 89± 2% <em>vs</em> 82% ± 6%, respectively (<em>P </em>= 0.30), and 5-year EFS was 84% ± 3% <em>vs. </em>77% ± 7%  (<em>P</em>= 0.37). In Burkitts lymphoma (BL) and lymphoblastic lymphoma (LL) there was a trend towards better outcomes in children compared to adolescents, with EFS of  91% ± 4% <em>vs.</em> 75% ± 15%, respectively in BL (<em>P</em>= 0.17),  and 82% ± 7% <em>vs.</em> 51.4% ± 2% respectively in LL (<em>P</em>= 0.16). Late effects occurred in 21 patients (12.8%).</p><p><strong>Conclusions: </strong>Children with NHL aged &lt; 15 years tend to have better survival rates and less long-term toxicity than adolescents aged 15-18 years.</p> 2018-03-01T00:00:00+00:00 ##submission.copyrightStatement## CLINICAL AND HEMATOLOGICAL PROFILE OF PATIENTS WITH DENGUE FEVER AT A TERTIARY CARE HOSPITAL – AN OBSERVATIONAL STUDY 2018-10-27T17:21:35+00:00 Vishal Vishnu Tewari Kunal Tewari Ritu Mehta <p><strong><span style="text-decoration: underline;"><span style="font-family: Times New Roman; font-size: medium;">Abstract</span></span></strong></p><p><span style="font-size: medium;"><span style="font-family: Times New Roman;"><strong>Background: </strong>Dengue is a major health issue with<strong> </strong>seasonal rise in dengue fever cases imposing an additional burden on hospitals, necessitating bolstering of services in the emergency department, laboratory with creation of additional dengue fever wards.</span></span></p><p><span style="font-size: medium;"><span style="font-family: Times New Roman;"><strong>Objectives:</strong> To study the clinical and hematological profile of dengue fever cases presenting to a hospital.</span></span></p><p><span style="font-size: medium;"><span style="font-family: Times New Roman;"><strong>Methods:</strong> Patients with fever and other signs of dengue with either positive NS1 antigen test or IgM or IgG antibody were included. Age, gender, clinical presentation, platelet count and hematocrit were noted and patients classified as dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Duration of hospitalization, bleeding manifestations, requirement for platelet component support and mortality were recorded.</span></span></p><p><span style="font-size: medium;"><span style="font-family: Times New Roman;"><strong>Results:</strong> There were 443 adults and 57 children between 6 months to 77 year age. NS1 was positive in 115 patients (23%). Fever (99.8%) and severe bodyache (97.4%) were the commonest presentation. DF was seen in 484 (96.8 %), DHF in 10 (2%) and DSS in 6 cases (1.2%). OPD treatment was needed in 412 (82%) and hospitalization in 88 (18%). Intravenous fluid resuscitation was needed in 16 (3.2%) patients. Thrombocytopenia was seen in 335 (67%) patients at presentation. Platelet transfusion was needed in 46 (9.2%). PRC transfusion was given in 3 patients with DF and 10 of DHF. Death occurred in 03 DSS and 2 DHF patients. </span></span></p><p><span style="font-size: medium;"><span style="font-family: Times New Roman;"><strong>Conclusions:</strong> Majority of DF cases can be managed on OPD basis. DHF and DSS carry high mortality. Hospitals can analyze annual data for resource allocation for capacity expansion.</span></span></p> 2018-03-01T00:00:00+00:00 ##submission.copyrightStatement## ROLE OF CYTOKINES AS MOLECULAR MARKER OF DENGUE SEVERITY 2018-08-31T21:43:14+00:00 Priyanka Sehrawat Ashutosh Biswas Prabhat Kumar Paras Singla Naveet Wig Lalit Dar Rita Sood <p><strong>Objective:</strong> Dengue infection is a rapidly spreading vector-borne disease and is endemic in Indian subcontinent. It has varied manifestations ranging from subclinical infection to severe fatal shock syndrome. This study aimed to estimate cytokine level in dengue patients and correlate them with dengue severity.</p><p><strong>Methods:</strong> Cases of Dengue fever diagnosed in the Department of Medicine of our institute from July 2015 to November 2016 were included in the study. The clinical features, biochemical, hematological and radiological parameters along with cytokine levels (Interferon-gamma, Interleukin-6 and Tumour Necrosis Factor-alpha) were recorded in all patients.</p><p><strong>Results:</strong> Out of 80 confirmed cases of dengue included in the study, 50 had non severe dengue (Group 1) and 30 patients had severe dengue (Group 2). The mean levels of serum TNF-α in group 2 (213.17±266.9 pg/mL, median= 62.5 pg /ml) were significantly higher than the mean levels in patients in dengue group 1 (112.8±213.1 pg/mL, median=20pg/ml) (<em>p</em>&lt;0.043). Similarly, the mean levels of serum IFN-γ in group 2 (28.4±56.2 pg/mL, median=10.5pg/ml) were significantly higher than the mean levels in patients in group 1 (11.8 ± 9.2pg/mL, median=8.5pg/ml) (<em>p</em>&lt;0.002). The levels of IL-6 were also higher in severe dengue group as compared to non severe dengue but these results were not significant (p&gt;0.05).</p><strong>Conclusion:</strong> Increased cytokines may play a role in pathogenesis of severe manifestations of dengue and can be targeted to halt the progression of disease severity 2018-04-20T00:00:00+00:00 ##submission.copyrightStatement## GUT COLONIZATION WITH CARBAPENEM RESISTANT ENTEROBACTERIACEAE ADVERSELY IMPACTS THE OUTCOME IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES: RESULTS OF A PROSPECTIVE SURVEILLANCE STUDY 2018-08-31T21:43:14+00:00 SUPARNO CHAKRABARTI <p><strong>Background</strong>: Gut colonisation with Carbapenem Resistant Enterobacteriaceae (CRE) is a risk factor for CRE bacteremia and patients with haematological malignancies (HM) are at the highest risk of mortality.</p><p><strong>Methods</strong>: We conducted a prospective surveillance study of gut colonisation with CRE and its impact on the outcome on  225 consecutive patients of HM over 28 months.                                                                                                                                                                                                                                                                                                                   <strong>Results</strong>: The median age of the cohort was 46 years, majority with Acute Leukemia.  48 (21%) patients were colonized with CRE on admission (CAD). Another 46 patients were colonized with CRE in the hospital (CIH). The risk factors for CAD and CIH were diagnosis of acute leukemia and duration of hospital stay respectively. CRE accounted for 77% of non-relapse mortality (NRM). CRE bacteremia occurred only in colonized patients with 100% mortality. NRM was 35.3% in CIH group compared to 10.5% in the CAD group (p=0.0001). NRM was highest in those with AML and CIH (54.9% p=0.0001). On multivariate analysis, CIH was the most important risk factor for NRM (HR-7.2).</p><p><strong>Conclusion</strong>: Our data demonstrates that a substantial proportion of patients with HM are colonized with CRE without prior hospitalization, but those with nosocomial colonization have the highest risk of mortality, particularly in those with Acute Myeloid Leukemia.</p> 2018-05-01T00:00:00+00:00 ##submission.copyrightStatement## INFECTIOUS RISKS AND COMPLICATIONS IN ADULT LEUKEMIC PATIENTS RECEIVING BLINATUMOMAB 2018-08-31T21:43:14+00:00 Wonhee So Shuchi Pandya Rod Quilitz John Greene <p><span style="font-family: Times New Roman;"><strong><span style="font-size: medium;">Background:</span></strong><span style="font-size: medium;"> Blinatumomab is an anti-CD19 immunotherapy approved for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) with significantly increased survival rate. While blinatumomab showed lower rates of infection, neutropenia and mucosal barrier injury versus chemotherapy, its infection risks are not well described. </span></span></p><p><span style="font-family: Times New Roman;"><strong><span style="font-size: medium;">Methods:</span></strong><span style="font-size: medium;"> All patients who received blinatumomab for ≥ 7 days at an academic cancer center from </span><span style="font-size: medium;">May 2015 to April 2017 were included. Patient characteristics pertinent to infectious risks and complications were examined.</span></span></p><p><span style="font-family: Times New Roman;"><strong><span style="font-size: medium;">Results:</span></strong><span style="font-size: medium;"> Twenty patients with refractory (25%), relapsed (70%), or remitted (5%) B-ALL who received a total of </span><span style="font-size: medium;">35</span><span style="font-size: medium;"> cycles were included. Ten of the 35 cycles were interrupted, none of which were due to infections. Twenty six infections (n) were observed with lower respiratory (9), gastrointestinal (6) and bacteremia (5) being most common. Compared to patients without nodular, possible mold pneumonia (n=16), patients with nodular pneumonia (n=4) had significantly lower baseline absolute neutrophil count (ANC) (2319 v. 208/µL, p=0.011</span><span style="font-size: medium;">). There were no differences in baseline characteristics including ANC between bacteremic and non-bacteremic patients. One patient was discharged with no antibacterial prophylaxis since ANC recovered to &gt;500cells/µL, but developed Pseudomonal bacteremia within a week with ANC ~100cells/µL. </span></span></p><p><span style="font-family: Times New Roman;"><strong><span style="font-size: medium;">Conclusion:</span></strong><span style="font-size: medium;"> Despite blinatumomab’s relatively modest myelosuppression and the lack of mucotoxicity, host factors (e.g., duration and degree of neutropenia/lymphopenia) play a key role and should be considered when choosing anti-microbial prophylaxis. In relapsed/refractory disease, the ANC should be monitored closely post blinatumomab since neutropenia can unexpectedly develop after treatment which may be compounded by the underlying disease and recent chemotherapy effects.</span></span></p> 2018-05-01T00:00:00+00:00 ##submission.copyrightStatement## DECOLONIZATION OF INTESTINAL CARRIAGE OF MDR/XDR GRAM-NEGATIVE BACTERIA WITH ORAL COLISTIN IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES: RESULTS OF A RANDOMIZED CONTROLLED TRIAL 2018-08-31T21:43:14+00:00 Igor Stoma Igor Karpov Igor Iskrov Svetlana Krivenko Anatoly Uss Svetlana Vlasenkova Irina Lendina Veronika Cherniak Dmitrii Suvorov <p><strong>Background</strong></p><p>Intestinal colonization by MDR/XDR gram-negative bacteria leads to an increased risk of subsequent bloodstream infections (BSI) in patients receiving chemotherapy as a treatment for hematologic malignancies.</p><p><strong>Objectives</strong></p><p>The objective of this study was to evaluate the efficacy of oral colistin in eradicating the intestinal carriage of MDR/XDR Gram-negative bacteria in patients with hematological malignancies.</p><p><strong>Methods</strong></p><p>In a tertiary hematology center adult patients with intestinal colonization by MDR/XDR Gram-negative bacteria were included in a randomized controlled trial (RCT) during a period from November 2016 to October 2017. Patients were treated with oral colistin for 14 days or observed with the primary outcome set as a decolonization on day 21 post-treatment. Secondary outcomes included treatment safety and changes in MICs of isolated microorganisms. Identifier: NCT02966457.</p><p><strong>Results</strong></p><p>Short-time positive effect (61.3% vs 32.3%; OR 3.32; 95% CI 1.17–9.44; p=0.0241) was demonstrated on the day 14 of colistin treatment, without any statistical difference on day 21 post-treatment. The incidence of BSI in decolonization group was lower in the first 30 days after the intervention (3.2% vs 12.9%), but overall in the 90-day observation period it did not show any advantages comparing to control group (log-rank test; p=0.4721). No serious adverse effects or increase in resistance to colistin was observed.</p><p><strong>Conclusions</strong></p><p>This study suggests that in hematological patients the strategy of selective intestinal decolonization by colistin may be beneficial to decrease the rate of MDR/XDR Gram-negative intestinal colonization and the risk of BSI in the short-term period, having no long-term sustainable effects.</p> 2018-05-01T00:00:00+00:00 ##submission.copyrightStatement## GROWTH AND ENDOCRINE FUNCTION IN TUNISIAN THALASSEMIA MAJOR PATIENTS 2018-08-31T21:43:14+00:00 Naouel GUIRAT Beta-thalassemia major (TM) is among prevalent hereditary disorders imposing high expenses on health-care system worldwide. The patient’s survival is dependent on lifetime blood transfusion which leads to iron overload and its toxicity on various organs including endocrine glands. This article provides an overview of  endocrine disorders in beta-TM patients. This single center investigation enrolled 28 beta-TM patients (16 males, 12 females)  regularly transfused with packed red cell since early years of life. For each patient were determined: age, sex, number of transfusions received, history of splenectomy and anthropometric parameters. Evaluation for hormonal status including growth, gonadal, thyroid, adrenal cortex, and parathyroid glands was done for all patients. Dual energy X-ray absorptiometry was used to diagnose osteoporosis. Assessment of iron overload status was performed by measuring the serum ferritin concentration and the results of magnetic resonance imaging T<sub>2</sub>*. Growth retardation was found in 16 of the 28 studied patients (57 %).Thirteen among them had delayed puberty. Spontaneous puberty was achieved in 16 cases. Growth hormone (GH) deficiency was found in 10 cases (35 %). Seventeen among the studied patients (60 %) developed disorders of glucose homeostasis. Subclinical hypothyroidism was found in six patients (21 %). Intensive chelation therapy had allowed the reversibility of this complication in five cases. Adrenal Insufficiency was found in 9 cases (32%). Hypoparathyroidism has occurred in one case. Ten of the 28 studied patients had osteoporosis (35%). Twenty-three of the 28 studied patients (82%) had at least one endocrine complication. 2018-05-01T00:00:00+00:00 ##submission.copyrightStatement## LABORATORY BIOMARKERS TO FACILITATE DIFFERENTIAL DIAGNOSIS BETWEEN MEASLES AND KAWASAKI DISEASE IN A PEDIATRIC EMERGENCY ROOM: A RETROSPECTIVE STUDY 2018-08-31T21:43:14+00:00 Danilo Buonsenso Giulia Macchiarulo Maria Chiara Supino Francesco La Penna Simona Scateni Alessandra Marchesi Antonino Reale Elena Boccuzzi <p>This retrospective study was conducted to analyze clinical and laboratoristic parameters to individuate specific differences and facilitate differential diagnosis between Measles and Kawasaki Disease (KD) at first evaluation in a emergency room. We found similar clinical features as duration of fever and number of KD criteria (p &gt;0.5) but significant differences in white blood cell count, neutrophils, CRP and LDH levels (p &lt; 0.001). LDH value ≥ 800 mg/dl had sensibility of 89% and specificity of 90% for Measles while CRP ≥ 3 mg/dl had sensibility 89% and specificity of 85% for KD. The combined use of CRP, LDH and AST showed accuracy of 86.67%.</p> 2018-05-01T00:00:00+00:00 ##submission.copyrightStatement## ORAL/ENTERAL NUTRITIONAL SUPPLEMENTATION IN CHILDREN TREATED FOR CANCER IN LOW-MIDDLE-INCOME COUNTRIES IS FEASIBLE AND EFFECTIVE: THE EXPERIENCE OF THE CHILDREN'S HOSPITAL MANUEL DE JESUS RIVERA "LA MASCOTA" IN NICARAGUA. 2018-08-31T22:34:10+00:00 Nicolò Peccatori Roberta Ortiz Emanuela Rossi Patricia Calderon Valentino Conter Yesly Garcia Andrea Biondi Darrel Espinoza Francesco Ceppi Luvy Mendieta Maria Luisa Melzi <p><strong>Background and objectives</strong>. The prevalence of malnutrition in children diagnosed with malignant tumors in Nicaragua has been reported to be 67%. Thus, a nutritional program for children with cancer has been developed at the Children’s Hospital Manuel de Jesus Rivera (Managua, Nicaragua).</p><p><strong>Methods</strong><strong>.</strong> A qualified nutritionist evaluated all patients and prescribed oral/enteral supplementation. The nutritional assessment was based on weight, height or length, mid upper arm circumference (MUAC) and triceps skin fold thickness (TSFT). In this descriptive study, pre and post-nutritional intervention data were compared and analyzed in terms of event free survival.</p><p><strong>Results</strong><strong>.</strong> 104 patients (median age 7.0 years, 52 with leukemia/lymphoma and 52 with solid tumor) underwent oral/enteral nutritional supplementation; 64 of these patients had pre and post supplementation nutritional assessment. Overall, 55% of patients in the leukemia/lymphoma group and the 35% in the solid tumor group improved their condition or remained in an adequately nourished status.</p><strong>Conclusion</strong>. This experience demonstrates that nutritional supplementation in pediatric cancer patients who are inadequately nourished is feasible also in countries with limited resources and is effective in improving the nutritional conditions. 2018-06-23T00:00:00+00:00 ##submission.copyrightStatement## IMPACT OF MULTIPLEX PCR IN REDUCING THE RISK OF RESIDUAL TRANSFUSION-TRANSMITTED HUMAN IMMUNODEFICIENCY AND HEPATITIS B AND C VIRUSES IN BURKINA FASO 2018-08-31T22:34:12+00:00 Arzouma Paul YOODA Serge Theophile SOUBEIGA Kompingnin Yacouba NEBIE Birama DIARRA Salam SAWADOGO Abdoul Karim OUATTARA Dorcas OBIRI-YEBOAH Albert Theophane YONLI Issoufou TAO Pegdwende Abel SORGHO Honorine DAHOUROU Jacques SIMPORE <p><strong>Background and Objective</strong></p><p>The improved performance of serological tests has significantly reduced the risk of human immunodeficiency and hepatitis B and C viruses transmission by blood transfusion, but there is a persistence of residual risk. The objective of this study was to evaluate the impact of multiplex PCR in reducing the risk of residual transmission of these viruses in seronegative blood donors in Burkina Faso.</p><p><strong>Methods</strong></p><p>This cross-sectional study was conducted from March to September 2017. The serological tests were performed on sera using ARCHITECT<sub>SR</sub> <em>i</em>1000 (Abbot diagnosis, USA). Detection of viral nucleic acids was performed by multiplex PCR on mini-pools of seronegative plasma for HBV, HCV and HIV using SaCycler-96 Real Time PCR v.7.3 (Sacace Biotechnologies). Multiplex PCR-positive samples from these mini-pools were then individually tested by the same method.</p><p><strong>Results<br /> </strong>A total of 989 donors aged 17 to 65 were included in the present study. "Repeat donors" accounted for 44.79% (443/989). Seroprevalences for HIV, HBV, and HCV were 2.53% (25/989), 7.28% (72/989) and 2.73% (27/989), respectively. Of the 14 co-infections detected, HBV/HCV was the most common with 0.71% (7/989) of cases. Of 808 donations tested by multiplex PCR, 4.70% (38/808) were positive for HBV while no donation was positive for HIV or HCV.</p><p><strong>Conclusion</strong>: Our study showed a high residual risk of HBV transmission through blood transfusion. Due to the high prevalence of blood-borne infections in Burkina Faso, we recommend the addition of multiplex PCR to serologic tests for optimal blood donation screening.</p> 2018-07-01T00:00:00+00:00 ##submission.copyrightStatement## PREVALENCE OF ß-THALASSEMIA MUTATIONS AMONG NORTHEASTERN IRANIAN POPULATION AND THEIR IMPACTS ON HEMATOLOGICAL INDICES AND APPLICATION OF PRENATAL DIAGNOSIS, A SEVEN-YEARS STUDY 2018-08-31T22:34:11+00:00 Mohammad Ehsan Jaripour Kourosh Hayatigolkhatmi Vahid Iranmanesh Farhad Khadivi Zand Zahra Badiei Hamid Farhangi Ali Ghasemi Abdollah Banihashem Reza Jafarzadeh Esfehani Ariane Sadr-Nabavi <p><span style="font-size: medium;"><strong><span>Background and objective</span></strong><span>: ß-thalassemia results from a diverse range of mutations inside the hemoglobin subunit β (<em>HBB</em>) gene. In a study of β-thalassemia carriers and some of their at-risk fetuses in the Khorasan province of Iran we aimed to recognize the most common mutations in the region and to find a possible link between these mutations and some of the relevant hematological indices.</span></span></p><p><span style="font-size: medium;"><strong><span>Methods</span></strong><span>: Amplification-refractory mutation system-PCR (ARMS-PCR) was used to detect the typical <em>HBB</em> mutations among 1593 individuals, suspected of having a mutated <em>HBB</em> allele from March/2011 to January/2018. Sanger sequencing of <em>HBB</em> had been performed, where ARMS-PCR was uninformative. In some cases, reverse dot blot was utilized. Analysis of variance was used to compare parametric variables.</span></span></p><p><span style="font-size: medium;"><strong><span>Results</span></strong><span>: Among 1273 ß-thalassemia carriers, the prevalence of the mutations were reported as follows: IVS-I-5 (42.03%), IVS-II-1 (11.23%), Codons 8/9 (4.79%), Codon 44 (4.56%), codon 15 (3.53%), Los Angeles (2.91%), Codon 5 (2.75%), IVS-I-110 (2.51%), -88 (2.20%) and other mutations were less than 2% of all of the reported mutations. 644 conceptions were subjected to prenatal diagnosis, using chorionic villus sampling. 118 cases were reported as normal. 352 cases were detected as carriers. 174 cases were diagnosed as affected. There was a significant difference in mean corpuscular volume and hemoglobin A2 levels between the 9 most commonly reported mutation types (p&lt;0.001).</span></span></p><p><span style="font-size: medium;"><strong><span>Conclusion</span></strong><span>: This study makes a reliable guide for ß-thalassemia diagnosis in the region. The possibility of a correlation between <em>HBB</em> mutations and hematological indices opens a gate of future investigations.</span></span></p> 2018-07-01T00:00:00+00:00 ##submission.copyrightStatement## DETECTION OF AMINOGLYCOSIDE AND QUINOLONE RESISTANCE GENES AND EVALUATION OF POLYMYXIN B SUSCEPTIBILITY PROFILE IN ACINETOBACTER BAUMANNII CLINICAL ISOLATES IN TEHRAN, IRAN DURING 2015-2016 2018-08-31T22:34:11+00:00 Mohsen Heidary <p><strong> </strong></p><p><strong>ABSTRACT</strong></p><p><em>Acinetobacter baumannii</em> is an important opportunistic pathogen, responsible for approximately 10% of all gram-negative nosocomial infection. The main aims of this study were to detect aminoglycoside and quinolone resistance genes among clinical isolates of <em>A. baumannii</em> and determine the antimicrobial susceptibility profiles. Current study was performed from February 2015 to April 2016, at two teaching hospitals. One-hundred <em>A. baumannii</em> isolates were collected from different clinical samples. Antimicrobial susceptibility tests were done by disk diffusion method according to CLSI guidelines. Detection of the <em>qnrA, anrB, qnrS, aac(3)-IIa, </em>and<em> aac(6′)-Ib </em>genes was done by PCR assay. The results of antibiotic susceptibility tests indicated that polymyxin B was the most effective drug against isolates<em> </em>of<em> A. baumannii </em>and the<em> </em>isolates were most resistant to cefepime (97%), ceftriaxone (95%), and amikacin (82%). The <em>aac(3)-IIa, aac(6′)-Ib, </em>and <em>qnrA </em>genes<em> </em>were found in 45%, 50%, and 50% of isolates, respectively.<em> </em>However,<em> qnrB and qnrS </em>genes<em> </em>could not be detected in any<em> </em><em>A. baumannii </em>isolate<em>.</em>This study showed that there is a high level of resistance genes among clinical isolates of <em>A. baumannii</em> circulating in hospitals in Iran. This high prevalence rate highlights the necessity for establishing rapid diagnostic assays, more antimicrobial susceptibility tests, continuous antibiotic resistance monitoring.<strong></strong></p><p><strong><em>Keywords:</em></strong><strong> </strong><em>Acinetobacter baumannii</em>, Aminoglycoside, Quinolone, Iran</p> 2018-07-01T00:00:00+00:00 ##submission.copyrightStatement## ACUTE PROMYELOCYTIC LEUKEMIA IN CHILDREN: A SINGLE CENTRE EXPERIENCE FROM TURKEY 2018-08-31T22:34:10+00:00 Tekin Aksu <p>Background and objectives: Acute promyelocytic leukemia (APL), characterized by tendency to hemorrhage and excellent response to all-trans retinoic acid (ATRA), is a distinct subtype of acute myeloid leukemia (AML). In this retrospective study, we aimed to determine the incidence, clinical symptoms, toxicities and outcome of children with APL in our center. Methods: We retrospectively reviewed the medical records of children (age &lt; 18 years) diagnosed with APL at our pediatric hematology department between January 2006-December 2016.</p><p>Results: Pediatric APL represents 20.5% of AML cases in this cohort. Most of the cases presented as classical M3, albeit hypogranular variant was described in 12% of the cohort. Patients with hypogranular variant APL were differed from classical APL by co-expression of CD2 and CD34. About ¾ of APL patients had hemorrhagic findings at admission or at initial phase of the treatment. Severe bleeding manifested as intracranial hemorrhage was present in three patients and intracranial arterial thrombosis was present in one. Five patients showed side effects of ATRA such as pseudotumor cerebri, dilated cardiomyopathy, and pulmonary infiltrates. Six year overall survival (OS) and early death rate was found to be 82.5% and 12% respectively.</p><p>Conclusions: A high frequency (20.5%) of APL was noted among children with AML in this single center study. The overall mortality rate was 17.5%. Since the induction death rate was 12% and life threatening bleeding was the major problem, awareness and urgent treatment are critical factors to reduce early losses.  </p> 2018-07-01T00:00:00+00:00 ##submission.copyrightStatement## HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN ADULTS: LOW INCIDENCE OF PRIMARY NEOPLASM AS A TRIGGER IN A CASE SERIES FROM TURKEY 2018-10-27T17:18:51+00:00 Ferhat Arslan <p>This study aimed to investigate the clinical and laboratory features and outcomes of Turkish patients with Hemophagocytic Lymphohistiocytosis. The medical records of 26 HLH adult patients (≥ 16 years of age) were retrospectively analyzed. Gender, age, the duration of fever, time to diagnosis, etiology and laboratory data were extracted from the records. The mean age was 38 ± 18 years, and 15 (58%) patients were female. A total of nine cases had infectious diseases, four cases had rheumatologic diseases, three cases had hematological malignancies while nine cases could not be obtained a definitive diagnosis. The median time to detection of HLH was 20 days (IQR: 8-30 d). Of the 25 patients, 11 (44%) died. The erythrocyte sedimentation rates of the surviving and non-surviving patients were 39 ± 22 mm/h and 15 ± 13 mm/h, respectively. When a long-lasting fever is complicated by bicytopenia or pancytopenia (especially), clinicians must promptly consider the possibility of HLH syndrome to improve patients’ prognosis </p> 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## TRANSIENT ELASTOGRAPHY (TE) IS A USEFUL TOOL FOR ASSESSING THE RESPONSE OF LIVER IRON CHELATION IN SICKLE CELL DISEASE PATIENTS 2018-09-07T12:28:24+00:00 SOPHIA DELICOU <p>Sickle cell disease patients often need regular blood transfusions to improve both the quality of life and survival from the veno-occlusive complications of the disease. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with promising efficacy.</p><p>This study aims to evaluate the association of liver stiffness and possible fibrosis with iron deposition and confirm the use of elastography as a validated test of responding to chelation with low cost and easy access.<em> </em></p><p>15 patients with sickle cell disease and systemic or occasional transfusionswere evaluated with MRI,transient elastography and biochemistry<span style="font-size: medium;">, </span>for liver iron(LIC) and liver stiffness(LSM) before onset and one year after taking Deferasirox.All patients completed the study.</p><p>Our results showed improvement in hepatic iron and hepatic stiffness after chelation therapy; Furthermore ALT, AST, LDH and ferritin levels have improved after 12 months of therapy with deferasirox.During the study no serious adverse events were encountered indicating the safety of the drug.</p><p>Transient liver elastography findings correlate with serum ferritin and LIC in patients with sickle cell disease and it is a useful tool for assessing the response of liver iron chelation therapy.</p><p> </p><p> Keywords: Sickle cell disease, iron chelation, transient elastography, transfusion, iron overload</p> 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## EPIDEMIOLOGY OF MALARIA IN THE STATE OF QATAR, 2008-2015 2018-09-07T12:28:25+00:00 Elmoubasher Farag eabdfarag@MOPH.GOV.QA Devendra Bansal Mohamad Abdul Halim Chehab Ayman Al-Dahshan Mohamed Bala Nandakumar Ganesan Yosuf Abdulla Al Abdulla Mohammed Al Thani Ali H. Sultan Hamad Al-Romaihi <p><strong>Background and Objectives</strong></p><p>Imported malaria poses a serious public health problem in Qatar because its population is “naïve” to such infection; where local transmission might lead to serious life-threatening infection and might even trigger epidemics.</p><p><strong>Methods</strong></p><p>This study is a retrospective review of the imported malaria cases in Qatar reported by the malaria surveillance program at the Ministry of Public Health (MoPH), during the period between January 2008 and December 2015. All cases were imported and underwent parasitological confirmation through microscopy.</p><p><strong>Results</strong></p><p>A total of 4092 malaria cases were reported during 2008-2015 in Qatar. The demographic features of the imported cases show that the majority of cases were males (93%), non-Qatari(99.6%), and aged 15 to 44 years(82.1%). Moreover,<em> P. vivax</em> was found to be the main etiologic agent accounting for more than three-quarters (78.7%) of the imported cases. In addition, almost a third (33.1%) of the cases were reported during the months of July, August, and September.<strong></strong></p><p><strong>Conclusions</strong></p><p>Imported malaria in Qatar has witnessed an increase during the past 7 years, despite a long period of constant reduction; where the people most affected were adult male migrants from endemic countries. Many challenges need to be overcome to prevent the reintroduction of malaria into the country.</p> 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## OUTBREAK OF BURKHOLDERIA CEPACIA INFECTION: A SYSTEMATIC STUDY IN A HEMATOLOGY-ONCOLOGY UNIT OF A TERTIARY CARE HOSPITAL FROM EASTERN INDIA. 2018-10-27T17:21:34+00:00 Shuvra Neel Baul Rajib De PRAKAS KUMAR MANDAL Swagnik Roy Tuphan Kanti Dolai Prantar Chakrabarti <p><strong>Background: </strong><em>Burkholderia cepacia</em>, an aerobic gram-negative bacillus, is a frequent colonizer of fluids used in the hospital ward. It poses little risk of infection to healthy people; however it is a known important opportunistic pathogen causing morbidity and mortality due to its intrinsic resistance to most of the antibiotics in hospitalized patients. Small hospital outbreaks are frequent. <em>B. cepacia</em> may occur as an opportunistic infection in hemato-oncology patients. <sup> </sup>Here we present an outbreak of  <em>Burkholderia cepacia</em> infection in hematology ward of our institute.</p><p><strong>Methods</strong>: Febrile episodes as defined by IDSA guideline, 2010 were followed, and blood for culture and sensitivity was sent in all the events. The culture was done by an automated method using Bactalert 3d  Biomeriux  &amp; sensitivity pattern by Microscan Siemens method and subsequently detected by  PCR based method.</p><p><strong>Results</strong>: During   September 2016 to February 2017 (six months), a total of 498 blood cultures were sent during febrile episodes. Out of which 60 (12%) came out to be positive for different microorganisms. Out of all positive cultures, Burkholderia cepacia was detected in 29 (48%)  patients, which reduced drastically following the change in antibiotic administration practice.  All isolates showed sensitivity to pipercillin+tazobactum, cefoperazone+sulbactum, fluoroquinolones, cotrimoxazole and carbapenems and resistance to polymyxin B and colistin. With timely intervention by appropriate intravenous antibiotics as per culture sensitivity result and change in antibiotic preparation practice, overall mortality was low 1 (4%) out of 29 culture positive episodes.  </p> 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## THE SPECTRUM OF HYPEREOSINOPHILIA AND ASSOCIATED CLONAL DISORDERS – A REAL WORLD DATA FROM A TROPICAL SETTING. 2018-10-27T17:21:34+00:00 Sreejesh Sreedharanunni Neelam Varma Man Updesh Singh Sachdeva Shano Naseem Pankaj Malhotra Deepak Bansal Amita Trehan Subhash Varma <p><strong>Objective:</strong> To determine the frequency, etiological spectrum and treatment outcome of hypereosinophilia (HE) and hypereosinophilic syndrome (HES) in a tropical setting.</p><p><strong>Methods:</strong>  A retrospective analysis of hospital data of five years and a comprehensive prospective evaluation of patients presenting with HE/HES over a period of 33 months was performed.</p><p><strong>Results</strong>: HE/HES was diagnosed in total of 125 patients during study period with an estimated prevalence of 0.5-1 case per one lakh population in our hospital settings. Infections, especially helminthes were the commonest cause (34%) followed by primary/clonal HE/HES (24%) and reactive HE/HES secondary to various clonal disorders (14.3%). Lymphocytic variant of HES and <em>FIP1L1-PDGFRA</em> positive HES were diagnosed in 3.6% each.  Imatinib responsive <em>BCR-ABL1</em> negative HE/HES constitute 7.1% in our patients.</p><p><strong>Conclusions: </strong>None of the clinical or routine laboratory features including the age of patients, duration of HE, presence or absence of organomegaly, hemoglobin levels, eosinophil %, absolute eosinophil count, total leukocyte count, platelet counts, serum IgE levels or presence of myelofibrosis can be used to predict or exclude malignancy in patients with HE/HES. The absence of blasts in peripheral blood or the absence of &gt;5% blasts in bone marrow does not exclude primary/clonal HES. Clonal disorders (Primary HES and reactive HES secondary to clonal disorders; 38%) are diagnosed with nearly equal frequency compared to infections (34%) in tropical settings necessitating a thorough follow-up and comprehensive work-up in these patients.</p> 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## MOLECULAR CHARACTERIZATION OF VANCOMYCIN, MUPIROCIN AND ANTISEPTIC RESISTANT STAPHYLOCOCCUS AUREUS STRAINS. 2018-10-27T17:21:34+00:00 Mahtab Hadadi Hamid Heidari Hadi Sedigh Ebrahim-Saraie Mohammad Motamedifar <p><strong>Background:</strong><em> Staphylococcus aureus</em> is a common cause of nosocomial infections that leads to broad spectrum of diseases. Increasing antibiotic resistance among <em>S. aureus </em>strains, particularly methicillin-resistant <em>S. aureus</em> (MRSA) is a serious concern. In addition, the emergence of antiseptics resistance in MRSA helps organism to easily persist and spread in healthcare environments. The aim of this study was to determine the molecular characteristics of vancomycin, mupirocin and antiseptic resistant <em>S. aureus</em> strains.</p><p><strong>Materials and Methods:</strong> This cross-sectional study was performed on a total of 120 MRSA isolates collected from two major hospitals in Shiraz, Iran. Minimum inhibitory concentrations (MICs) of vancomycin and mupirocin were determined by E-test method according to CLSI and Eucast guidelines. Presence of resistance genes were investigated by PCR method.</p><p><strong>Results:</strong> Antibacterial susceptibility tests for MRSA isolates showed that 7 isolates (5.8%) were vancomycin-resistant <em>S. aureus</em> (VRSA) and 15 isolates (12.5%) were high-level mupirocin resistant (MuH). None of the isolate had vancomycin resistance gene (<em>vanA</em>), but the frequency of mupirocin resistance gene was significant and 55 (45.8%) isolates carried <em>mupA</em> gene.</p><p>Moreover, <em>norA</em>, <em>smr</em> and <em>qacA/B</em> genes were detected in 110 (91.7%), 55 (45.8%) and 36 (30%) strains, respectively.</p><p><strong>Conclusion:</strong> This study showed the existence of VISA and VRSA strains in our region, and we also found high frequency of mupirocin and biocide resistance genes among strains.</p> 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## PREVALENCE OF THALASSEMIA AMONG NEWBORNS: A RE-VISITED AFTER 20 YEARS OF A PREVENTION AND CONTROL PROGRAM IN NORTHEAST THAILAND. 2018-09-07T12:28:25+00:00 Goonnapa Fucharoen <p><strong>Background: </strong>To provide accurate prevalence information of thalassemia in northeast Thailand after 20 years implementation of a prevention and control program, thalassemia screening was carried out in newborns.   <strong></strong></p><p><strong>Methods: </strong>Study was done on 350 cord blood specimens collected consecutively at Maternal and Child Hospital, Regional Health Promotion Center 7, Khon Kaen, Thailand. All kinds of a- and β-thalassemias were identified using combined hemoglobin (Hb) and DNA analyses. </p><p><strong>Results: </strong>Among 350 newborns examined, subjects with thalassemia genes were identified in 184 (52.6%) cases with as many as 22 different genotypes. The most prevalent one was Hb E (39.1%). The incidence of 3.1% a<sup>0</sup>-thalassemia, 25.9% a<sup>+</sup>-thalassemia, 5.4% Hb Constant Spring and 1.4% of Hb Paksé were encountered. Heterozygous β-thalassemia was found in 2 cases (0.6%). Hb capillary electrophoresis could demonstrate Hb E in all cases with Hb E and detected different levels of Hb Bart’s for different a-thalassemia genotypes but not in all cases with a-thalassemia. No newborn with severe thalassemia diseases was encountered.</p><strong>Conclusion: </strong>This study reveals that a-thalassemia, β-thalassemia and Hb E carriers as well as complex thalassemia syndromes are still prevalence and indicates a need for continuing a prevention and control program in the region. 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## THE EMERGING RESISTANCE IN NOSOCOMIAL URINARY TRACT INFECTIONS: FROM THE PEDIATRICS PERSPECTIVE. 2018-09-07T12:28:24+00:00 Fatma Devrim Erkin Serdaroğlu İlknur Çağlar Yeliz Oruç Nevbahar Demiray Nuri Bayram Hasan Ağın Şebnem Çalkavur Yelda Sorguç Nida Dinçel Yüce Ayhan Ebru Yılmaz İlker Devrim <p><strong>Background:</strong> Healthcare–associated infections results increased healthcare costs and mortality. There are limited studies concerning the distribution of the etiologic agents and the resistance patterns of the microorganisms causing healthcare–associated urinary tract infections (HA-UTI) in pediatric settings.</p><p><strong>Objectives:</strong> The aim of this study was to evaluate the distribution and antibiotic susceptibility patterns of pathogens causing HA-UTI in children.</p><p><strong>Material and Methods:</strong> Isolates from 138 children with UTI who were hospitalized in pediatric, neonatal and pediatric surgery intensive care units were reviewed.</p><p><strong>Results:</strong> Most common isolated organism was <em>Kleibsella pneumoniae</em> (34.1%) and <em>Escherichia coli </em>(26.8%). Among the <em>Pseudomonas aeruginosa,</em> Meropenem and imipenem resistance rates were 46.2% and 38.5%. Extended spectrum beta-lactamase (ESBL) production was present in 48 <em>Klebsiella</em> species (82.75%). Among ESBL positive <em>Klebsiella</em> species, the rate of meropenem and  imipenem resistance was 18.8% and ertapenem resistance was 45.9%. Extended spectrum beta-lactamase production was present in 27 (72.9%) <em>Escherichia coli</em> species. Among ESBL positive <em>E.coli</em>, the rate of meropenem and imipenem resistance was 7.4% and ertapenem resistance was 14.8%</p><p><strong>Conclusions:</strong> Emerging meropenem resistance in <em>P. aeruginosa</em>, higher rates of ertapenem resistance in ESBL positive ones in <em>E.coli</em> and <em>Klebsiella</em> species in pediatric nosocomial UTI are important  notifying signs for superbug infections.</p> 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## MUTATIONAL PROFILES OF F8 AND F9 IN A COHORT OF HAEMOPHILIA A AND HAEMOPHILIA B PATIENTS IN THE MULTI-ETHNIC MALAYSIAN POPULATION 2018-09-07T12:28:24+00:00 Maimiza Zahari Siti Aishah Sulaiman Zulhabri Othman Yasmin Ayob Faraizah Abd Karim Rahman Jamal <p><span style="font-family: Times New Roman; font-size: medium;">Background: Haemophilia A (HA) and Haemophilia B (HB) are X-linked blood disorders that are caused by various mutations in the factor VIII (F8) and factor IX (F9) genes respectively. Identification of mutations is essential as some of the mutations are associated with the development of inhibitors. This study is the first comprehensive study of the <em>F8</em> mutational profile in Malaysia.</span></p><p><span style="font-family: Times New Roman; font-size: medium;">Materials and methods: We analysed 100 unrelated HA and 15 unrelated HB patients for genetic alterations in the <em>F8</em> and <em>F9</em> genes by using the long-range PCR, DNA sequencing, and the multiplex-ligation-dependent probe amplification assays. The prediction software was used to confirm the effects of these mutations on factor VIII and IX proteins.</span></p><p><span style="font-family: Times New Roman; font-size: medium;">Results: 44 (53%) of the severe HA patients were positive for <em>F8</em> intron 22 inversion, and three (3.6%) were positive for intron 1 inversion. There were 22 novel mutations in <em>F8</em>, including missense (8), frameshift (9), splice site (3), large deletion (1) and nonsense (1) mutations. In HB patients, four novel mutations were identified including the splice site (1), small deletion (1), large deletion (1) and missense (1) mutation.</span></p><p><span style="font-family: Times New Roman; font-size: medium;">Discussion: The mutational spectrum of <em>F8</em> in Malaysian patients is heterogeneous, with a slightly higher frequency of intron 22 inversion in these severe HA patients when compared to other Asian populations. Identification of these mutational profiles in <em>F8</em> and <em>F9</em> genes among Malaysian patients will provide a useful reference for the early detection and diagnosis of HA and HB in the Malaysian population.</span></p><p><span style="font-family: Times New Roman; font-size: medium;"><br /></span></p><p> </p> 2018-09-01T00:00:00+00:00 ##submission.copyrightStatement## THE JAK2V617F POINT MUTATION INCREASES THE OSTEOCLAST FORMING ABILITY OF MONOCYTES IN PATIENTS WITH CHRONIC MYELOPROLIFERATIVE NEOPLASMS AND MAKES THEIR OSTEOCLASTS MORE SUSCEPTIBLE TO JAK2 INHIBITION 2018-12-16T13:24:54+00:00 Emmanouil Spanoudakis Menelaos Papoutselis Ioanna Bazntiara Eleftheria Lamprianidou Xrisa Kordella Constantinos Tilkeridis Constantinos Tsatalas Ioannis Kotsianidis <p>JAK2V617F is a gain of function point mutation that occurs in Myeloproliferative Neoplasm (MPN) patients and deranges their hemopoiesis at cellular level. We speculate that hyperfunctioning JAK2 can modify osteoclast (OCL) homeostasis in MPN patients. We studied 18 newly diagnosed MPN patients and four age-matched normal donors (ND). Osteoclast forming assays started from selected monocytes also and under titrated concentrations of the JAK2 Inhibitor AG-490 (Tyrphostin). Genomic DNA was extracted from the formed osteoclasts, and the JAK2V617F/JAK2WT genomic DNA ratio was calculated. OCLs formed from monocytes derived from heterozygous (Het) for the JAK2V617F mutation MPN patients, were three times more compared to those from JAK2 wild type (WT) MPN patients (p=0,05) and from ND as well (p=0,03). The ratio of JAK2V617F/JAK2WT genomic DNA was increased in OCLs compared to the input monocyte cells showing a survival advantage of the mutated clone. In comparison to ND and JAK2 WT MPN patients, OCLs from patients JAK2V617F (Het) were more susceptible to JAK2 inhibition. These alterations in osteoclast homeostasis, attributed to mutated JAK2, can deregulate the hemopoietic stem cell niche in MPN patients.</p> 2018-10-27T10:45:48+00:00 ##submission.copyrightStatement## SEVERE LIVER IRON CONCENTRATIONS (LIC) IN 24 PATIENTS WITH Β-THALASSEMIA MAJOR: CORRELATIONS WITH SERUM FERRITIN, LIVER ENZYMES AND ENDOCRINE COMPLICATIONS 2018-12-16T13:24:54+00:00 Vincenzo De Sanctis <p><strong>Abstract.</strong> <strong>Introduction:</strong> Chronic blood transfusion is the mainstay of care for individuals with β-thalassemia major (BTM). However, it causes iron-overload that requires monitoring and management by long-term iron chelation therapy in order to prevent endocrinopathies and cardiomyopathies, that can be fatal. Hepatic R2 MRI method (FerriScan®) has been validated as the gold standard for evaluation and monitoring liver iron concentration (LIC) that reflects the total body iron-overload. Although adequate oral iron chelation therapy (OIC) is promising for the treatment of transfusional iron-overload, some patients are less compliant with it and others suffer from long-term effects of iron overload.</p> <p><strong>Objective: </strong>The aim of our study was to evaluate the prevalence of endocrinopathies and liver dysfunction, in relation to LIC and serum ferritin level, in a selected group of adolescents and young adult BTM patients with severe hepatic iron overload (LIC from 15 to 43 mg Fe/g dry weight).</p> <p><strong>Patients and </strong><strong>Methods:</strong> Twenty-four selected BTM patients with severe LIC, due to transfusion-related iron-overload, followed at the Hematology Section, National Center for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar), from April 2015 to July 2017, were retrospectively evaluated. The prevalence of short stature, hypogonadism, hypothyroidism, hypoparathyroidism, impaired fasting glucose (IFG), diabetes, and adrenal insufficiency was defined and assessed according to the International Network of Clinicians for Endocrinopathies in Thalassemia (ICET) and American Diabetes Association criteria.</p> <p><strong>Results:</strong></p> <p>Patients have been transfused over the past 19.75 ± 8.05 years (ranging from 7 to 33 years). The most common transfusion frequency was every 3 weeks (70.8%).&nbsp; At the time of LIC measurements, the mean age of patients was 21.75 ± 8.05 years, mean LIC was 32.05 ± 10.53 mg Fe/g dry weight (range: 15 to 43 mg Fe/g dry weight). Their mean serum ferritin level was 4,488.6 ± 2,779 µg/L. The overall prevalence of growth failure was 26.1% (6/23), IFG was 16.7% (4/24), sub-clinical hypothyroidism was 14.3% (3/21), hypogonadism was 14.3% (2/14), diabetes mellitus was 12.5% (3/24), and biochemical adrenal insufficiency was 6.7% (1/15). The prevalence of hepatitis C positivity was 20.8% (5/24). No case of clinical hypothyroidism, adrenal insufficiency or hypoparathyroidism was detected in this cohort of patients. The prevalence of IFG impaired fasting glucose was significantly higher in BTM patients with very high LIC (&gt;30 mg Fe/g dry liver) versus those with lower LIC (p = 0.044). LIC was correlated significantly with serum ferritin levels (r = 0.512; p = 0.011), lactate dehydrogenase (r = 0.744; p = 0.022) and total bilirubin (r = 0.432; p = 0.035).</p> <p><strong>Conclusions:</strong> A significant number of BTM patients, with high LIC and endocrine disorders, still exist despite the recent developments of new oral iron chelating agents. Therefore, physicians’ strategies shall optimize early identification of those patients in order to optimise their chelation therapy and to avoid iron-induced organ damage. We believe that further studies are needed to evaluate if serial measurements of quantitative LIC may predict the risk for endocrine complications. Until these data are available, we recommend a close monitoring of endocrine and other complications, according to the international guidelines.</p> <p>&nbsp;</p> 2018-10-27T11:17:18+00:00 ##submission.copyrightStatement## JADENU® SUBSTITUTING EXJADE® IN IRON OVERLOADED Β- THALASSEMIA MAJOR (BTM) PATIENTS: A PRELIMINARY REPORT OF THE EFFECTS ON THE TOLERABILITY, SERUM FERRITIN LEVEL, LIVER IRON CONCENTRATION AND BIOCHEMICAL PROFILES 2018-12-16T13:24:54+00:00 Vincenzo De Sanctis <p><strong>Abstract. Introduction</strong>: Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu <sup><span style="font-size: small;">® </span></sup>is a new oral formulation of deferasirox (Exjade <sup><span style="font-size: small;">®</span></sup>) tablets for oral suspension. While Exjade<span style="font-size: small;"><sup>® </sup><sup>&nbsp;</sup></span>is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu <sup><span style="font-size: small;">® </span></sup>can be taken in a single step, with or without a light meal, simplifying administration for the treatment of&nbsp; patients with chronic iron overload. This may significantly improve the compliance to treatment of patients withβ-thalasemia major (BMT). The aim of this study was to evalute the drug tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload.</p> <p><strong>Patients and Methods:</strong> Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular packed cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade <sup><span style="font-size: small;">®</span></sup> therapy (30 mg/kg per day) for 2 years or more before starting Jadenu ® therapy (14-28 mg/kg/day). The reason for&nbsp; shifting from Deferasirox <sup><span style="font-size: small;">®</span></sup> to Jadenu <sup><span style="font-size: small;">® </span></sup>therapy was lack of tolerability,&nbsp; since most of the patients described Deferasirox <sup><span style="font-size: small;">®</span></sup> as not palatable. Lab investigations included montly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan <sup><span style="font-size: small;">®</span></sup>. Thyroid function, vitamin D and serum parathormone, before and one year&nbsp; after starting&nbsp; Jadenu <sup><span style="font-size: small;">®</span></sup> therapy, were also assessed.</p> <p><strong>Results:</strong> Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment.&nbsp; Subjectively, patients reported an improvement in the palatability of Jadenu<sup><span style="font-size: small;">® </span></sup>compared to Exjade <sup><span style="font-size: small;">®</span></sup> therapy in 8 out of 12 BMT patients.&nbsp; A non-significant decrease in LIC and&nbsp; serum ferritin levels was observed after 1 year of&nbsp; treatment with Jadenu <sup><span style="font-size: small;">® </span></sup>. A positive significant correlation was found between serum ferritin level and LIC measured by FerriScan <sup><span style="font-size: small;">®</span></sup> method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p &lt; 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters.</p> <p><strong>Conclusion:</strong> Our study shows that short-term treatment with Jadenu <sup><span style="font-size: small;">®</span></sup> is safe but is associated with&nbsp; a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and&nbsp; the long-term outcomes of new deferasirox formulation.</p> 2018-10-27T11:23:46+00:00 ##submission.copyrightStatement## CUTANEOUS MANIFESTATIONS OF PRIMARY IMMUNODEFICIENCY DISEASES IN TUNISIAN CHILDREN 2018-12-16T13:24:52+00:00 Naouel GUIRAT Monia Ben Khaled Monia Ouederni Imen Ben-Mustapha Ridha Kouki Habib Besbes Mohamed Ridha Barbouche Fethi Mellouli mohamed bejaoui <p><strong>Abstract.&nbsp;</strong>Skin manifestations are frequent among patients with primary immunodeficiency diseases (PIDs). Their prevalence varies according to the type of immunodeficiency. This review provides the reader with an up-to-date summary of the common dermatologic manifestations of PIDs among Tunisian children. We conducted a prospective study on two hundred and ninety children with immune deficiency. Demographic details (including age, sex, and consanguinity) with personal and family history were recorded. Special attention was paid to cutaneous manifestations. Dermatological involvements were grouped according to the etiology of their most prominent sign. Cutaneous manifestations were found in 164 patients (56.5%). They revealed the diagnosis of PIDs in 71 patients (24.5 %). The mean age at presentation was 21 months. Overall the most prominent cutaneous alterations were infectious. They accounted for 106 cases (36.55%). The most prevalent causes of cutaneous infections were bacterial: 93 cases (32.06%). Immuno-allergic skin diseases were among the common findings in our study. These include eczematous dermatitis found in 62 cases (21.38%). Malignancy related PIDs was seen in a boy with Wiskott Aldrich syndrome. He developed Kaposi’s sarcoma at the age of 14 months. Cutaneous changes are common among children with PIDs. In pediatric patients with failure to thrive, chronic refractory systemic manifestations often present in other family members, recurrent cutaneous infections unresponsive to adequate therapy, atypical forms of eczematous dermatitis or unusual features should arouse the suspicion of PIDs and prompt specialized immunologic consultation should be made.</p> 2018-10-30T18:53:33+00:00 ##submission.copyrightStatement## INSIGHTS INTO THE INTERPLAY BETWEEN KIR GENE FREQUENCIES AND CHRONIC HBV INFECTION IN BURKINA FASO 2018-12-16T13:24:51+00:00 Abel Pegdwendé SORGHO Jeremy James MARTINSON Florencia Wendkuuni Djigma Albert Théophane YONLI Bolni Marius NAGALO Rebeca Tégwindé COMPAORE Dorcas OBIRI-YEBOAH Diarra BIRAMA Herman Karim SOMBIE Arsène Wendpagnangdé ZONGO Abdoul Karim OUATTARA Serge Théophile R. SOUBEIGA Lassina TRAORE Lewis R. ROBERTS Jacques SIMPORE <p><strong>Background/Objective</strong>: The receptors of natural killer cells "Killer Cell Immunoglobulin-Like Receptor" (KIR) regulate the activity of Natural killer cells in the innate response against viral infections. To date there is no accurate method to identify high risk groups for cirrhosis and HCC in Sub-Saharan Africa. Therefore, this investigation was undertaken to assess the association between KIR genes frequencies and chronic infection HBV infection in Burkina Faso’s population.</p> <p><strong>Methods: </strong>Chronic HBV carriers and healthy patients were selected for this study. The viral load for HBV were performed to confirm the serological status for HBV of the studied cohort. In addition, SSP-PCR was used to characterize the frequencies of KIR genes.</p> <p><strong>Results</strong>: The study suggested that inhibitory genes KIR2DL2, KIR2DL3 and activator gene KIR2DS2 (p˂0.001 for all and OR = 2.82; 2.48 and 3.84 respectively) might be associated with chronic stages of HBV infection. &nbsp;While inhibitory genes KIR3DL1 (p = 0.0018 OR = 0.49), KIR3DL2 (p = 0.005 OR = 0.40), the activator gene KIR2DS1 (p = 0.014 OR = 0.47) and the pseudo gene KIR2DP1 (p = 0.011 OR = 0.49) could be associated with immunity against HBV infection. Patients who carried the KIR3DL2 gene had a high HBV viral load compared to the rest of the study population.</p> <p><strong>Conclusion: </strong>Our data showed an evidence of correlation between the propensity of developing chronic HBV infection and certain KIR gene frequencies and that KIR3DL1, KIR3DL2, KIR2DS1 and KIR2DP1 might confer a protective status against chronic HBV infection in Burkina Faso’s patients.</p> 2018-11-01T13:17:06+00:00 ##submission.copyrightStatement## Association of the SOD2 polymorphism (Val6Ala) and SOD activity with vaso-occlusive crisis and acute splenic sequestration in children with sickle cell anemia 2018-08-31T21:43:16+00:00 Isabela Cristina Cordeiro Farias Taciana Furtado Mendonça-Belmont Andreia Soares Silva Kleyton Palmeira do Ó Felipe Borba Ferreira Fernanda Silva Medeiros Luydson Richardson Silva Vasconcelos Moacyr Jesus Barreto de Melo Rego Marcos Andre Cavalcanti Bezerra Aderson Silva Araujo Patricia Muniz Mendes Freire Moura Ana Claudia Mendonça Anjos Betânia Lucena Domingues Hatzlhofer Maria do Socorro Mendonça Cavalcanti <p>The <em>SOD2</em> polymorphism Val16Ala TàC influences the antioxidative response. This study investigated the association of the <em>SOD2 </em>polymorphism and superoxide dismutase (SOD) activity with vaso-occlusive crisis (VOC) and acute splenic sequestration (ASS) in children with sickle cell anemia (SCA). One hundred ninety-five children aged 1-9 years old were analyzed. The TC and CC genotypes were associated with lower SOD activity compared with the TT genotype (<em>p</em>=0.0321; <em>p</em>=0.0253, respectively). Furthermore, TC/CC were more frequent in patients with VOC or ASS (<em>p</em>=0.0285; <em>p</em>=0.0090, respectively). These results suggest that the <em>SOD2 </em>polymorphism associated with low SOD activity could be involved in SCA physiopathology. <strong></strong></p> 2018-02-21T00:00:00+00:00 ##submission.copyrightStatement## Human T-cell leukemia virus type І associated with an increased risk of primary malignant neoplasm 2018-08-31T21:43:16+00:00 Aya Nakaya Shinya Fujita Atsushi Satake Takahisa Nakanishi Yoshiko Azuma Yukie Tsubokura Akiko Konishi Masaaki Hotta Hideaki Yoshimura Kazuyoshi Ishii Tomoki Ito Shosaku Nomura <p><span lang="EN-US">The correlation between human T-cell leukemia virus type І (HTLV-І) infection and malignant neoplasms other than adult T-cell lymphoma (ATL) remains unknown. We analyzed the frequency of primary malignant neoplasm in HTLV-І-seropositive patients. From January 2006 to December 2016, 203 patients were diagnosed as HTLV-І-seropositive at Kansai Medical University Hospital. Among them, 32 developed a primary malignant neoplasm. Their median age was 64 years old, 63% of them were male, and 69% of them were HTLV-I carriers. This group had the following distribution of ATL subtypes: 31% smoldering type, 0% chronic type, 3% acute type, and 3% lymphoma type. Among them, 53% was hematology malignancy, and solid tumor was 47%. The most frequent type of hematological malignancy was T-cell lymphoma (23%), followed B-cell lymphoma (16%), and myelodysplastic syndromes (6%). The most frequent primary solid tumor locations were the lung (15%), followed by the colon (9%), prostate (6%), kidney (6%), cervix (2%), breast (2%), liver (2%), pancreas (2%), and oral cavity (2%). Our results suggest that HTLV-Іinfection is often associated with the development of other malignant neoplasms. Therefore, HTLV-І<span>-</span>positive patients should be made aware of their increased risk for the onset of a malignant neoplasm and undergo increased surveillance.</span></p> 2018-04-20T00:00:00+00:00 ##submission.copyrightStatement## Molecular Expression of bone marrow angiogenic factors, cell-cell adhesion molecules and matrix-metallo-proteinase plasma cellular disorders: a molecular panel to investigate disease progression 2018-12-16T13:24:52+00:00 Maria Cristina Rapanotti <p>Increasing levels of angiogenesis play an important role in the pathogenesis and progression of multiple myeloma (MM). Malignant plasma cells promote a gradual increase in the degree of angiogenesis, modulation of specific cell-cell adhesion molecules and secretion of matrix-metallo-proteinases (MMPs), changing the BM composition from benign conditions, such as MGUS, to smouldering multiple myeloma (SM) and to active MM. We aimed to identify a gene expression profile, helpful to discriminate the “angiogenic potential” in BM and PB plasma cells from MGUS, SMM and active MM patients analyzed at diagnosis. We analyzed the expression of cell-cell adhesion molecules such as VE-Cadherin, E-Cadherin MCAM/MUC18/CD146 and of the MMP-2 and MMP-9. MCAM/MUC18 expression resulted mostly associated with that of the pivotal angiogenic factors VEGF and Ang2, and in MGUS the pattern was different in steady state, compared to progression towards SM. Furthermore, E-Cadherin, the main epithelial cell-cell-adhesion molecule, unexpectedly resulted overexpressed in MM.</p> <p>&nbsp;</p> <p><strong>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <br></strong></p> 2018-10-30T10:55:54+00:00 ##submission.copyrightStatement## Phenotyping of Rh, Kell, Duffy and Kidd blood group antigens among non-tribal and tribal population of South Gujarat and its implication in preventing alloimmunisations in multitransfused patients. 2018-12-16T13:24:53+00:00 Avani Shah Kanjaksha Ghosh Preeti Sharma Kanchan Mishra <p><strong>Background:</strong>Sickle cell anaemia is common amongst Tribal population of south Gujrat. Alloimmunisation in multitransfused sickle cell anaemia patient is 10 times commoner in these patients than beta Thalassemia&nbsp; major &nbsp;patients from regular blood donor communities.</p> <p><strong>Study design &amp; methodology: </strong>Red cell antigen typing of Rh (D,C,E,c,e ), Kell (K, k), Duffy (Fy<sup>a</sup>, Fy<sup>b</sup>) and Kidd (Jk<sup>a</sup>, Jk<sup>b</sup>) were carried out in 222 regular voluntary blood donors who belonged to non-tribal population and in 113 samples of tribal population using conventional antisera.</p> <p><strong>&nbsp;</strong><strong>Results: </strong>Rh D antigen frequency was 96.6% in non-tribal and 96.5% in tribal population. 2.4% of K antigen was found in non-tribal population whereas the antigen was absent in tribal population&nbsp; .Amongst Rh antigens, e was the most common (100%) followed by D, C (91.0%, 85.8%), c (50.5%, 44.2%) and E (16.5%, 17.0%) with DCe/DCe (R1R1, 48.0%, 55.8%) being the most common phenotype in both the groups. In Kell antigens&nbsp; k antigen was 100% ,Kidd and Duffy antigens &nbsp;Jk (a+b-) (39.2%, 46.9%) and Fy (a+b-) (64.2%, 52.2%) were the most common phenotypes in non-tribal and tribal population respectively.</p> <p>&nbsp;<strong>Conclusion: </strong>There is significant difference in Duffy , Kidd and Kell (k) antigen distribution between non tribal and tribal population . Total absence of Kell antigen in tribalsalong with. E antigen in a significant portion of blood donors and its absence in large number of tribals also increase the risk of alloimmunisation.&nbsp;</p> <p>&nbsp;</p> 2018-10-30T00:00:00+00:00 ##submission.copyrightStatement## Late-onset hepatic veno-occlusive disease after allografting: report of two cases with atypical clinical features successfully treated with defibrotide. 2018-08-31T21:43:17+00:00 Alessia Castellino Stefano Guidi Chiara Dellacasa Antonella Gozzini Irene Donnini Chiara Nozzoli Sara Manetta Semra Aydin Luisa Giaccone Moreno Festuccia Lucia Brunello Enrico Maffini Benedetto Bruno Ezio David Alessandro Busca <p>Hepatic Veno-occlusive disease (VOD) is a potentially severe complication of hematopoietic stem cell transplantation (HSCT). Here we report two patients receiving an allogeneic HSCT  who developed late onset VOD with atypical clinical features. The two  patients presented with only few risk factors, namely, advanced acute leukemia, a myeloablative busulphan-containing regimen and received grafts from an unrelated donor. The first patient did not experience painful hepatomegaly and weight gain and both  patients showed only a mild elevation in total serum bilirubin level. Most importantly, the two patients developed clinical signs beyond day 21 post-HSCT. Hepatic transjugular biopsy confirmed the diagnosis of VOD. Intravenous defibrotide was promptly started leading to a marked clinical improvement. Based on our experience, liver biopsy may represent a useful diagnostic tool when the clinical features of VOD are ambiguous. Early therapeutic intervention with defibrotide  represents a crucial issue for the successful outcome of patients with VOD.</p> 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## Genomic integration of HHV-6 mimicking viral reactivation after autologous stem cell transplantation 2018-10-27T17:21:36+00:00 rossana mineri Jacopo Mariotti Barbara Sarina Lucio Morabito roberto crocchiolo stefania bramanti tiziana sarno federica tordato carmelo carlo-stella armando santoro Luca Castagna <p>The monitoring of HHV-6 after allogeneic hematopoietic stem cell transplantation (HSTC) has proven to be useful in preventing life-threatening complications; however, the pathogenic role of HHV-6 after autologous HSCT is not well-characterized, although viral reactivation might be responsible for significant complications even after autologous HSCT. Here we report for the first time to our knowledge the case of a patient with genomic integration of HHV-6, presenting with high titers of HHV-6 after autologous HSCT, mimicking HHV-6 reactivation. The presence of viral DNA in the follicle bulb confirmed the genomic integration and allowed the discontinuation of the antiviral treatment to the patient.  This case might be helpful for discriminate HHV-6 reactivation from viral integration, thus avoiding unnecessary and potentially toxic antiviral therapy once the genomic integration is confirmed.</p> 2018-02-15T00:00:00+00:00 ##submission.copyrightStatement## Chemotherapy-colchicine interaction in a child with Familial Mediterranean Fever and Hodgkin Lymphoma 2018-10-27T17:21:35+00:00 Karin Petra Sabine Langenberg-Ververgaert Ronald M. Laxer Angela S. Punnett Lee L Dupuis Yaron Finkelstein Oussama Abla <p>Familial Mediterranean Fever (FMF) has been associated with hematological malignancies, but has not been reported in association with Hodgkin lymphoma (HL). We hereby describe the first pediatric patient with FMF and stage IIA nodular sclerosis HL. She was treated with prednisone, doxorubicin, vincristine and etoposide (OEPA). However, she suffered more than expected treatment-related toxicity due to interaction with colchicine. Colchicine had to be discontinued during her second cycle of chemotherapy which was well tolerated. She is currently in remission at 17 months after her HL diagnosis, and her FMF is under control with colchicine without any signs of toxicity.</p> 2018-03-01T00:00:00+00:00 ##submission.copyrightStatement## Parvovirus B19-triggered acute hemolytic anemia and thrombocytopenia in a child with Evans syndrome 2018-10-27T17:21:35+00:00 ELPIS MANTADAKIS <p><em><strong>Background:</strong></em><strong> </strong>Human parvovirus B19 (HPV-B19) is the etiologic agent of erythema infectiosum, of transient aplastic crises in individuals with underlying chronic hemolytic disorders, and of chronic pure red cell aplasia in immunocompromised individuals.</p><p><em><strong>Case report</strong></em>. We describe a 14-year-old girl with long-standing Evans syndrome, who presented with severe anemia, reticulocytopenia and thromocytopenia. A bone marrow aspirate revealed severe erythroid hypoplasia along with presence of giant pronormoblasts, while serological studies and real-time PCR of whole blood were positive for acute parvovirus B19 infection. The patient was initially managed with corticosteroids, but both cytopenias resolved only after administration of intravenous gamma globulin 0.8g/kg.</p><p><strong>Conclusion: </strong>Acute parvovirus B19 infection should be suspected in patients with immunologic diseases, who present with reticulocytopenic hemolytic anemia and thrombocytopenia. In this setting, intravenous gamma globulin is effective for both cytopenias.</p> 2018-03-01T00:00:00+00:00 ##submission.copyrightStatement## Breastfeeding in patients with chronic myeloid leukaemia: case series with measurements of drug concentrations in maternal milk and review of literature 2018-08-31T21:43:17+00:00 Ekaterina Chelysheva Sergey Aleshin Evgenia Polushkina Roman Shmakov Igor Shokhin Ghermes Chilov Anna Turkina Breastfeeding in patients with chronic myeloid leukaemia (CML) who take tyrosine kinase inhibitors (TKIs) is not recommended but interruption of TKI treatment may cause the loss of remission. We observed the kinetics of the leukaemic clone in 3 women with CML in accordance with treatment interruptions for pregnancy and breastfeeding. The concentrations of nilotinib and imatinib in maternal milk were measured when the breastfeeding period was over. Nilotinib transfer into human breast milk was demonstrated for the first time and had a maximum concentration (Cmax) 129 ng/ml after 4 hours of the drug intake at a dose of 400 mg. The Cmax of imatinib in maternal milk ranged from 420 to 1411 ng/ml after 4-8 hours of the drug intake at a dose of 400-600 mg. Breastfeeding without TKI treatment may be safe with molecular monitoring, but preferably in those patients with CML who have durable deep molecular response. 2018-05-01T00:00:00+00:00 ##submission.copyrightStatement## Parasitic hypereosinophilia in childhood: a diagnostic challenge 2018-08-31T21:43:17+00:00 Roberto Antonucci Nadia Vacca Giulia Boz Cristian Locci Rosanna Mannazzu Claudio Cherchi Giacomo Lai Claudio Fozza <p class="western" align="justify"><span style="font-size: medium;"><span lang="en-GB">Severe hypereosinophilia (HE) in children is rare, and its etiological diagnosis is challenging. We describe a case of </span></span><span style="font-size: medium;"><span lang="en-GB">a 30-month-old boy</span></span><span style="font-size: medium;"><span lang="en-GB">, living in a rural area, who was admitted</span></span><span style="font-size: medium;"><span lang="en-GB"> to our Clinic with a 7-day history of fever</span></span><span style="font-size: medium;"><span lang="en-GB"> and severe hypereosinophilia. A comprehensive diagnostic work-up could not identify the cause of this condition. </span></span><span style="font-size: medium;"><span lang="en-GB">On day 6, the rapidly increasing eosinophil count (maximum value of 56,000/mm</span></span><sup><span style="font-size: medium;"><span lang="en-GB">3</span></span></sup><span style="font-size: medium;"><span lang="en-GB">), the risk of developing hypereosinophilic syndrome, and the patient’s history prompted us to undertake an empiric treatment with albendazole.</span></span><span style="font-size: medium;"><span lang="en-GB">The eosinophil count progressively decreased following treatment. On day 13, clinical condition and hematological data were satisfactory, therefore the treatment was discontinued and the patient was discharged. Three months later, anti-nematode IgG antibodies were detected in patient serum, thus establishing the etiological diagnosis. </span></span><span style="font-size: medium;"><span lang="en-GB">In conclusion, an empiric anthelmintic treatment seems to be justified when parasitic </span></span><span style="font-size: medium;"><span lang="en-GB">hypereosinophilia</span></span><span style="font-size: medium;"><span lang="en-GB"> is strongly suspected, and other causes have been excluded.</span></span></p> 2018-05-01T00:00:00+00:00 ##submission.copyrightStatement## T-cell Large Granular Lymphocytic Leukemia Manifesting in Patients with HIV-1 Infection: Cases Series and Review of the Literature 2018-08-31T22:34:09+00:00 Ashley M Rose Leidy Isenalumhe Magali VanDenBergh Lubomir Sokol We report five patients with human immunodeficiency virus-1/acquired immunodeficiency syndrome (HIV-1/AIDS) who developed T-cell large granular lymphocytic leukemia (T-LGLL). None of the patients fulfilled criteria for diagnosis of diffuse infiltrative lymphocyte syndrome (DILS) or HIV-associated CD8+ lymphocytosis syndrome at the time of diagnosis of LGLL. The immunophenotype of malignant T-cells was identical in three patients with co-expression of CD3, CD8, CD57, and T-cell receptor (TCR) alpha/beta. Three out of five patients were also diagnosed with clonal disorders of B-cell origin including diffuse large B-cell lymphoma, Burkitt’s lymphoma, and monoclonal gammopathy of undetermined significance (MGUS).  Two patients developed cytopenias due to T-LGLL prompting initiation of therapy. Our study suggests that chronic viral infection with HIV can contribute to evolution of T-LGLL. Clinical and laboratory characteristics of T-LGLL associated with HIV-1/AIDS resemble those of immunocompetent  patients. 2018-06-21T00:00:00+00:00 ##submission.copyrightStatement## Very early development of typical signs of Kawasaki Disease with transient coronary involvement. 2018-08-31T22:34:10+00:00 Danilo Buonsenso Sebastian Cristaldi Antonino Reale Isabella Tarissi de Jacobis Laura Granata Alessandra Marchesi <p>Kawasaki disease (KD) is an acute, self-limited, inflammatory disease affecting medium-sized arteries and particularly the coronary arteries in about 25% of untreated cases. KD is a clinical diagnosis based on the presence of ≥5 days of fever and the presence of ≥4 of the 5 principal clinical criteria. We described, for the first time to our knowledge, a case of a very early development (on day 1) of typical KD with transient coronary involvement, diagnosed on day 2 of disease and treated with aspirin and steroids on day 3, with complete resolution of clinical signs and coronary involvement.<strong></strong></p> 2018-06-20T00:00:00+00:00 ##submission.copyrightStatement## Successful management of Kaposiform Hemangioendothelioma with long-term sirolimus treatment: a case report and review of the literature 2018-08-31T22:34:13+00:00 Matteo Chinello Daniela Di Carlo Francesca Olivieri Rita Balter Massimiliano De Bortoli Virginia Vitale Ada Zaccaron Elisa Bonetti Alice Parisi Simone Cesaro <p class="western" lang="en-GB" align="justify"><span><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB"><strong>Background:</strong></span></span></span><span><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB"> Kaposiform Hemangioendothelioma (KHE) is a rare vascular tumour of the infancy and of the first decade of life. It is locally aggressive and potentially life threatening when associated to consumptive coagulopathy, known as Kasabach-Merritt syndrome (KMS). </span></span></span><span><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB">No consensus or guideline for the therapy has been reached because of the lack of prospective trials and the different standard care suggestions are based on retrospective case series.</span></span></span></p><p class="western" align="justify"><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB"><strong>Case report:</strong></span></span></span><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB"> We report the case of a</span></span></span><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB"> 9-month-old male</span></span></span><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB"> with KHE and KMS in which the initial response, obtained with prednisone and vincristine, was subsequently consolidated and strengthened by long-term treatment with sirolimus, </span></span></span><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB">an mTOR inhibitor. A</span></span></span><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB"> summary of the published data is presented as well.</span></span></span></p><p class="western" align="justify"><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB"><strong>Conclusions: </strong></span></span></span><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB">The inhibition of mTOR pathway represents the most important therapeutic innovation introduced in the last few years for KHE. </span></span></span><span style="color: #212121;"><span style="font-family: 'Times New Roman', serif;"><span><span lang="en-GB">Our case shows the effectiveness and good tolerance of long-term therapy with sirolimus.</span></span></span></span></p><p class="western" align="justify"><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB"><strong>Keywords: </strong></span></span><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span lang="en-GB">Kaposiform Hemangioendothelioma, Kasabach-Merrit syndrome, sirolimus, prednisone, vincristine</span></span></span></p> 2018-07-01T00:00:00+00:00 ##submission.copyrightStatement## Sterile "Abscess" of the Spleen and the Sickle Cell Trait 2018-08-31T21:43:18+00:00 Lucio Luzzatto <p>Dear Editor:</p><p>I read with interest the case report by Dr P Magro <em>et al</em>. [<em>MJHID</em> <strong>9</strong>: e2017023, 2017] regarding a boy with sickle cell trait (AS), who was appropriately treated for <em>Plasmodium</em> <em>falciparum</em> malaria and who, upon ultrasound imaging, was thought to have multiple abscesses in the spleen, eventually interpreted as splenic infarction. </p> 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## Increased mortality in male recipients of red cells from ever pregnant female donors : mHAGs on red cells to blame ? 2018-08-31T21:43:18+00:00 Kanjaksha Ghosh N/A 2018-01-01T00:00:00+00:00 ##submission.copyrightStatement## Formulas for the Detection β-Thalassemia Carriers Are Affected by Changes in Red Cell Parameters 2018-08-31T21:43:18+00:00 Deniz Aslan 2018-04-20T00:00:00+00:00 ##submission.copyrightStatement## Cardiac toxicity associated with HCV direct antiviral agents 2018-12-16T13:24:53+00:00 Claudio Ucciferri Alessandro Occhionero Jacopo Vecchiet Katia Falasca 2018-10-29T13:10:16+00:00 ##submission.copyrightStatement##