Mediterranean Journal of Hematology and Infectious Diseases https://mjhid.org/index.php/mjhid <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 </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 <strong>2017 <strong>official</strong> </strong>Impact Factor: 1.183</strong></p> <p><strong>♦ Official Impact Factor 2018. 1.586</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; background-color: #ffffff;">ISI Journal Citation Reports @ Ranking: 2017</span></strong></span></p> <p><strong>List of contents:</strong></p> <p>&nbsp;</p> <p><strong>12:(1) (2020): </strong><strong><a title="Volume 12, Year 2020" href="https://www.mjhid.org/index.php/mjhid/issue/view/91"><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>&nbsp;</p> <p><strong>11:(1) (2019): </strong><strong><a title="Volume 11, Year 2019" href="https://www.mjhid.org/index.php/mjhid/issue/view/90"><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p><strong>Reviews Series</strong></p> <ul> <li class="show">UPDATE ON THALASSEMIA AND HEMOGLOBINOPATHIES. Guest Editor: Raffaella Origa<strong>. </strong><a href="/index.php/mjhid/announcement/view/82">More...</a></li> </ul> <p><strong>10:(1) (2018): <a title="Volume 10, Year 2018" href="https://www.mjhid.org/index.php/mjhid/issue/view/Volume%2010%2C%202018"><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 <a href="/index.php/mjhid/announcement/view/73">More...</a></li> </ul> <p><strong>9:(1) (2017): </strong><strong><a title="Volume 9, Year 2017" href="https://www.mjhid.org/index.php/mjhid/issue/view/9%281%29"><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 <a href="/index.php/mjhid/announcement/view/59">More...</a></li> <li class="show">UPDATE on “Rare Plasma Cell Dyscrasias” Guest Editor M.T. PETRUCCI <a href="/index.php/mjhid/announcement/view/49">More...</a></li> </ul> <p><strong>8:(1) (2016): <a title="Volume 8, Year 2016" href="https://www.mjhid.org/index.php/mjhid/issue/view/78"><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">HEMATOPOIETIC STEM CELL TRANSPLANTATION AND INFECTIONS. Guest Editor: Miguel Sanz <a href="/index.php/mjhid/announcement/view/37">More...</a></li> <li class="show">REVIEW SERIES: UPDATE ON FOLLICULAR LYMPHOMA. Guest Editor: Corrado Tarella <a href="/index.php/mjhid/announcement/view/39">More...</a></li> </ul> <p><strong>8:(Supplementary Issue) (2016): <a href="https://www.mjhid.org/index.php/mjhid/issue/view/79"><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a> Fifth International Symposium on Secondary Leukemia and Leukemogenesis</strong></p> <p><strong>7:(1) (2015): <a title="Volume 7, Year 2015" href="https://www.mjhid.org/index.php/mjhid/issue/view/75"><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a> 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. <a href="https://www.mjhid.org/index.php/mjhid/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 <a href="https://www.mjhid.org/index.php/mjhid/announcement/view/25">More...</a></li> </ul> <p><strong>6:(1) (2014): <a title="Volume 6, Year 2014" href="https://www.mjhid.org/index.php/mjhid/issue/view/39"><img src="/public/site/images/fguidi/FRECCE0013.gif" alt=""></a> 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. <a href="https://www.mjhid.org/index.php/mjhid/announcement/view/21">More...</a></li> <li class="show">UPDATE IN HODGKIN LYMPHOMA. Guest Editor: A. Gallamini <a href="https://www.mjhid.org/index.php/mjhid/announcement/view/22">More...</a></li> <li class="show">ACUTE LYMPHOID LEUKEMIA IN ADULTS: AN UPDATE. Guest Editors: R. Bassan and A.Rambaldi <a href="https://www.mjhid.org/index.php/mjhid/announcement/view/23">More...</a></li> </ul> <p><strong>5:(1) (2013): <a title="Volume 5, Year 2013" href="https://www.mjhid.org/index.php/mjhid/issue/view/20"><img src="/public/site/images/fguidi/FRECCE0012.gif" alt=""></a> 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. <a href="https://www.mjhid.org/index.php/mjhid/announcement/view/19">More...</a></li> <li class="show">VON WILLEBRAND FACTOR UPDATE. Guest Editors: A. Federici and F. Rodeghiero. <a href="https://www.mjhid.org/index.php/mjhid/announcement/view/18">More...</a></li> <li class="show">TUBERCULOSIS UPDATE. Guest Editors: R. Cauda and A. Matteelli. <a href="https://www.mjhid.org/index.php/mjhid/announcement/view/20">More...</a></li> </ul> <p><strong>4:(1) (2012): <a title="Malaria In The World, Chronic Lymphoid Leukemia, Autologous Hemopoietic Stem Cell Transplantation In Leukemia And Lymphoma" href="https://www.mjhid.org/index.php/mjhid/issue/view/19"><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 <a href="https://www.mjhid.org/index.php/mjhid/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 <a href="https://www.mjhid.org/index.php/mjhid/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 <a href="https://www.mjhid.org/index.php/mjhid/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="https://www.mjhid.org/index.php/mjhid/issue/view/18"><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="https://www.mjhid.org/index.php/mjhid/announcement/view/8">More...</a></li> <li class="show">THROMBOSIS IN THE MEDITERRANEAN AREA. Guest Editor: V. De Stefano <a style="color: #990000;" href="https://www.mjhid.org/index.php/mjhid/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="https://www.mjhid.org/index.php/mjhid/announcement/view/10">More...</a></li> <li class="show">THERAPY-RELATED MYELOID NEOPLASMS: Guest Editor: R. Larson <a style="color: #990000;" href="https://www.mjhid.org/index.php/mjhid/announcement/view/11">More...</a></li> </ul> Università Cattolica Sacro Cuore, Rome, Italy en-US Mediterranean Journal of Hematology and Infectious Diseases 2035-3006 <p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<a href="https://creativecommons.org/licenses/by-nc/4.0" target="_blank" rel="noopener">https://creativecommons.org/licenses/by-nc/4.0</a>) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p><strong>Transfer of Copyright and Permission to Reproduce Parts of Published Papers.</strong>&nbsp;Authors will grant copyright of their articles to the Institute of Hematology, Catholic University, Rome . No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent.&nbsp;<strong>Reproductions with commercial intent will require written permission and payment of royalties.</strong></p> <div class="grammarly-disable-indicator">&nbsp;</div> CONCISE REVIEW ON THE FREQUENCY, MAJOR RISK FACTORS AND SURVEILLANCE OF HEPATOCELLULAR CARCINOMA (HCC) IN Β-THALASSEMIAS: PAST, PRESENT AND FUTURE PERSPECTIVES https://mjhid.org/index.php/mjhid/article/view/2020.006 <p>Due to the recent alarming increase in the incidence of hepatocellular carcinoma (HCC) in thalassemias, the aim of the present report is to review briefly the frequency, the major risk factors and the surveillance of HCC in β-thalassemias. Over the past 33 years, 153 cases of HCC were reported in patients with thalassemia, mainly in Italy, and Greece. Among HCV-infected patients additional factors promoting development of&nbsp; HCC, included: advanced age, male sex, chronic hepatitis B (CHB) coinfection, and iron overload. For early diagnosis of HCC sequential ultrasound screening&nbsp; is recommended&nbsp; especially for thalassemia patients with chronic hepatitis C (CHC), that coincide with (one or more) additional risk factors for HCC. &nbsp;Here we report also the preliminary data of thalassemic patients, above the age of 30 years, followed in 13 different centers. The total number of enrolled patients was 1,313 (males: 612 and 701 females). The prevalence of HCC in thalassemia major patients [characterized by transfusion-dependency (TDT)] and thalassemia intermedia [characterized by nontransfusion dependency (NTDT)] was 1.68 % and 1.98 % ,respectively The lowest age at diagnosis was 36 years in TDT and 47 years in NTDT patients.We hope that our review can be used to develop more refined and prospective analyses of HCC magnitude and risk in patients with thalassemia, and to define specific international guidelines to support clinicians for an early diagnosis and treatment of HCC in thalassemic patients.</p> Vincenzo De Sanctis Copyright (c) 2020 Vincenzo De Sanctis https://creativecommons.org/licenses/by-nc/4.0 2020-01-01 2020-01-01 12 1 e2020006 e2020006 10.4084/mjhid.2020.006 MOLECULAR MECHANISMS OF INHIBITOR DEVELOPMENT IN HEMOPHILIA https://mjhid.org/index.php/mjhid/article/view/2020.001 <p>The development of neutralizing antibodies in hemophilia is a serious complication of factor replacement therapy. These antibodies, also known as “inhibitors”, significantly increase morbidity within the hemophilia population and lower the quality of life for these patients. People with severe hemophilia A have an overall 25-40% lifetime risk of inhibitor development, compared to that of 5-15% lifetime risk in those with moderate/mild hemophilia A. The risk is lower in hemophilia B population (about 1-5%) and occurrence of inhibitors is almost only seen in patients with severe hemophilia B. The understanding of the pathophysiological mechanism leading to the development of inhibitors in patients with hemophilia has improved considerably over the last 2 decades. Identification of early biomarkers which predict inhibitor development in previously untreated patients with hemophilia will assist in risk identification and possible early intervention strategies. In this review, we aim to summarize the molecular mechanisms of inhibitor development in hemophilia and to identify potential areas in need of further investigation.</p> Davide Matino Paul Tieu Antony Chan Copyright (c) 2019 Davide Matino, Paul Tieu, Dr., Antony Chan https://creativecommons.org/licenses/by-nc/4.0 2020-01-01 2020-01-01 12 1 e2020001 e2020001 10.4084/mjhid.2020.001 THE HISTORY OF DEFERIPRONE (L1) AND THE COMPLETE TREATMENT OF IRON OVERLOAD IN THALASSAEMIA https://mjhid.org/index.php/mjhid/article/view/2020.011 <p>Deferiprone (L1) was originally designed, synthesised and screened in vitro and in vivo in 1981 by Kontoghiorghes G J following his discovery of the novel alpha-ketohydroxypyridine class of iron chelators (1978-1981), which were intended for clinical use. The journey through the years for the treatment of thalassaemia with L1 has been a very difficult one with intriguing turn of events, which continue until today. Despite many complications, such as the wide use of L1 suboptimal dose protocols, the aim of chelation therapy- namely the complete removal of excess iron in thalassaemia major patients, has been achieved following the introduction of specific L1 and L1/deferoxamine combinations. Many such patients continue to maintain normal iron stores. As a result of the introduction of L1, thalassaemia has changed from a fatal to a chronic disease and thalassaemia patients are active professional members in all sectors of society, have their own families with children and grandchildren and their lifespan is approaching that of normal individuals. No changes in the low toxicity profile of L1 have been observed in more than 30 years of clinical use. Thousands of thalassaemia patients are still denied the cardioprotective and other beneficial effects of L1 therapy. The safety of L1 in thalassaemia and other non-iron loaded diseases resulted in its selection as one of the leading therapeutics for the treatment of Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration and other&nbsp;similar cases. There are also increasing prospects for the application of L1 as a main, alternative or adjuvant therapy in many pathological conditions including cancer, infectious diseases and as a general antioxidant for diseases related to free radical pathology.</p> George J Kontoghiorghes Marios Kleanthous Christina N. Kontoghiorghe Copyright (c) 2020 George J Kontoghiorghes, Marios Kleanthous, Christina N. Kontoghiorghe https://creativecommons.org/licenses/by-nc/4.0 2020-01-01 2020-01-01 12 1 e2020011 e2020011 10.4084/mjhid.2020.011 THE EVOLVING PHARMACOTHERAPEUTIC LANDSCAPE FOR THE TREATMENT OF SICKLE CELL DISEASE https://mjhid.org/index.php/mjhid/article/view/2020.010 <p>Sickle cell disease (SCD) is an extremely heterogeneous disease that has been associated with global morbidity and early mortality. More effective and inexpensive therapiesare needed. During the last five years the landscape of the pharmacotherapy of SCD has changed dramatically. Currently, there are at least 50 drugs that have been used or under consideration to use for the treatment of SCD. These fall into 3 categories: the first category includes the three drugs (Hydroxyurea, L-Glutamine and Crizanlizumab tmca) that have been approved by the United States Food and Drug Administration (FDA) based on successful clinical trials. The second category includes 22 drugs that failed, discontinued or terminated for now and the third category includes 25 drugs that are actively being considered for the treatment of SCD. New therapies targeting multiple pathways in its complex pathophysiology have been achieved or are under continued investigation. The emerging trend seems to be the use of multimodal drugs (i.e. drugs that have different mechanisms of action) to treat SCD similar to the use of multiple chemotherapeutic agents to treat cancer.</p> Samir Ballas Copyright (c) 2020 Samir Ballas https://creativecommons.org/licenses/by-nc/4.0 2020-01-01 2020-01-01 12 1 e2020010 e2020010 10.4084/mjhid.2020.010 FEBRILE NEUTROPENIA IN ACUTE LEUKEMIA. EPIDEMIOLOGY, ETIOLOGY, PATHOPHYSIOLOGY AND TREATMENT https://mjhid.org/index.php/mjhid/article/view/2020.009 <p>Acute leukemias are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. An important cause of both the latter is infectious complications. Patients with acute leukemia are highly susceptible to infectious diseases due to factors related to the disease itself, factors attributed to treatment, and specific individual risk factors in each patient. Patients with chemotherapy-induced neutropenia are at particularly high risk, and microbiological agents include viral, bacterial and fungal agents. The etiology is often unknown in infectious complications, although adequate patient evaluation and sampling have diagnostic, prognostic and treatment-related consequences. Bacterial infections include a wide range of potential microbes, both Gram-negative and Gram-positive species, while fungal infections include both mold and yeast. A recurring problem is increasing resistance to antimicrobial agents, and in particular, this applies to extended-spectrum beta-lactamase resistance (ESBL), <em>Pseudomonas aeruginosa</em>, methicillin-resistant <em>Staphylococcus aureus</em> (MRSA), vancomycin-resistant <em>Enterococcus</em> (VRE) and even carbapenemase-producing <em>Enterobacteriaceae</em> (CPE). International guidelines for the treatment of sepsis in leukemia patients include the use of broad-spectrum Pseudomonas-acting antibiotics. However, one should implant the knowledge of local microbiological epidemiology and resistance conditions in treatment decisions. Here, we discuss infectious diseases in acute leukemia with a major focus on febrile neutropenia and sepsis, and we problematize the diagnostic, prognostic, and therapeutic aspects of infectious complications in this patient group. Meticulously and thorough clinical and radiological examination combined with adequate microbiology samples are cornerstones of the examination. Diagnostic and prognostic evaluation includes patient review according to the multinational association for supportive care in cancer (MASCC) and sequential organ failure assessment (SOFA) scoring system. Antimicrobial treatments for important etiological agents are presented. The main challenge for reducing the spread of resistant microbes is to avoid unnecessary antibiotic treatment, but without giving to narrow treatment to the febrile neutropenic patient that reduce the prognosis.</p> Bent-Are Hansen Øystein Wendelbo Øyvind Bruserud Anette Lodvir Hemsing Knut Anders Mosevoll Håkon Reikvam Copyright (c) 2020 Bent-Are Hansen, Øystein Wendelbo, Øyvind Bruserud, Anette Lodvir Hemsing, Knut Anders Mosevoll, Håkon Reikvam https://creativecommons.org/licenses/by-nc/4.0 2019-12-30 2019-12-30 12 1 e2020009 e2020009 10.4084/mjhid.2020.009 CARDIOVASCULAR RISK IN ESSENTIAL THROMBOCYTHEMIA AND POLYCYTHEMIA VERA: THROMBOTIC RISK AND SURVIVAL https://mjhid.org/index.php/mjhid/article/view/2020.008 <p class="western"><span style="color: #1c1d1e;"><span style="font-family: Arial, serif;"><span style="font-size: large;"><span lang="en-US"><strong>Abstract</strong></span></span></span></span></p> <p class="western" align="justify"><a name="tw-target-text"></a> <span style="color: #000000;"><span style="font-family: Arial, serif;"><span style="font-size: large;"><span lang="en-US">Thromboembolic and bleeding events pose a severe risk for patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Many factors can contribute to determine the thrombotic event, including the interaction between platelets, leukocytes and endothelium alterations. Moreover, a very important role can be played by cardiovascular risk factors (CV.R) such as cigarette smoking habits, hypertension, diabetes, obesity and dyslipidemia. In this study we evaluated the impact that CV.R plays on thrombotic risk and survival in patients with PV and ET.</span></span></span></span></p> Vincenzo Accurso Marco Santoro Salvatrice Mancuso Angelo Davide Contrino Paolo Casimio Mariano Sardo Simona Raso Florinda Di Piazza Alessandro Perez Marco Bono Antonio Russo Sergio Siragusa Copyright (c) 2020 Vincenzo Accurso, Maro Santoro, Salvatrice Mancuso, Angelo Davide Contrino, Paolo Casimio, Mariano Sardo, Simona Raso, Florinda Di Piazza, Alessandro Perez, Marco Bono, Antonio Russo, Sergio Siragusa https://creativecommons.org/licenses/by-nc/4.0 2020-01-01 2020-01-01 12 1 e2020008 e2020008 10.4084/mjhid.2020.008 CANDIDEMIA IN PATIENTS WITH ACUTE LEUKEMIA: ANALYSIS OF SEVEN YEARS’ EXPERIENCE AT A SINGLE CENTER IN CHINA https://mjhid.org/index.php/mjhid/article/view/2020.003 <p>The study of candidemia in Chinese leukemia patients has been limited. This retrospective study aims to investigate the characteristics and prognostic factors of candidemia among leukemia patients in a Chinese chemotherapy center.</p> <p>From 2009 to 2015, 30 isolates of candidemia were detected in 19 patients with acute leukemia after chemotherapy. The overall incidence of candidemia was 2.12 episode per 1000 admissions<em>. </em><em>Candida tropicalis</em> was the most common <em>Candida</em> species (n = 17; 89.5%), followed by <em>Candida albicans</em> (n = 2; 10.5%). The most common underlying disease was acute myeloid leukemia (94.7%) and induction chemotherapy phase was the most susceptible stage. The vast majority of candidal infections are endogenous rather than central venous catheter-related. The overall 30-day crude mortality rate was 31.6%. Neutrophil recovery (P = 0.000) and initiation of empiric antifungal treatment before first positive blood culture (P = 0.041) were associated with a significant improvement in overall survival.</p> <p>Although the incidence of candidaemia appears to be quite low in patients with leukemia submitted to intensive chemotherapy, its high mortality rate continues to be a crucial problem despite the availability of new effective antifungal drugs. Early diagnosis followed by rapid antifungal treatment remains the cornerstone of successful management. Catheter removal should be considered on an individual basis. The widespread use of newer antifungal agents as prophylaxis among patients with acute leukemia may result in a decreased candidemia incidence.</p> Xiaoyuan Gong mianzeng yang Dong Lin Hui Wei Ying Wang Bingchen Liu Chunlin Zhou Kaiqi Liu Shuning Wei Benfa Gong Guancji Zhang Yuntao Liu Yan Li Xingli Zao Shaowei Qiu Ruxia Gu Yingchang Mi Jianxiang Wang Copyright (c) 2020 Xiaoyuan Gong, mianzeng yang, Dong Lin, Hui Wei, Ying Wang, Bingchen Liu, Chunlin Zhou, Kaiqi Liu, Shuning Wei, Benfa Gong, Guancji Zhang, Yuntao Liu, Yan Li, Xingli Zao, Shaowei Qiu, Ruxia Gu, Yingchang Mi, Jianxiang Wang https://creativecommons.org/licenses/by-nc/4.0 2020-01-01 2020-01-01 12 1 e2020003 e2020003 10.4084/mjhid.2020.003 THE PROGNOSTIC SIGNIFICANCE OF TET2 SINGLE NUCLEOTIDE POLYMORPHISM IN EGYPTIAN CHRONIC MYELOID LEUKEMIA https://mjhid.org/index.php/mjhid/article/view/2020.004 <p><strong>Background: </strong>Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. The pathogenesis of CML is based on the oncoprotein termed BCR‐ABL1. TET2 initiates DNA demethylation and is frequently mutated in hematological malignancies including CML.<sup>(1)</sup> The relation between TET2 acquisition and CML transformation and/or imitinab resistance is needed to be investigated. <strong><sup>(2)</sup></strong></p> <p><strong>Aim:</strong> To evaluate Ten Eleven Translocation 2 gene (TET2) single nucleotide polymorphism (SNP) (rs2454206, rs34402524, rs61744960) in chronic myeloid leukemia (CML) in relation to the disease prognostic criteria.</p> <p><strong>Materials &amp; Method:</strong> The study included 84 subjects; 54 CML in chronic phase and 30 healthy subjects as control group matched for age and sex. Routine investigations including CBC, bone marrow aspiration, biochemical investigations and molecular study were performed in CML patients to identify the disease stage. DNA extraction and SNP assay for TET2 gene polymorphism was done using (Thermo-Fisher predesigned SNP, USA) PCR prism 7500.</p> <p><strong>Results:</strong> The mean age was 45.98±15.7 yrs in CML patients and&nbsp;&nbsp; 39.3±6.587 yrs in control group (p&gt;0.05). TET2 SNP rs 34402524 was either heterozygous and homozygous in CML (48%,and 46.2%) but was mainly homozygous among control (80%) group (p=0.012). TET2 SNP rs 2454206 cases within CML (65.4%) and control (63.3%) group had wild patterns (p=0.046). TET2 SNP rs 61744960 showed a homozygous pattern among all groups (CML and control) showing no statistical significance (p=0.528). TET2 SNP in CML cases did not alter the prognostic criteria as no statistical significance was noted (p&gt;0.05) yet, it was significantly related to spleen size in rs 34402524 where homozygous group had huger sizes and higher BCR-ABL1 levels 6 months after starting TKIs (p&lt;0.05).</p> <p><strong>Conclusions/Recommendation:</strong> TET2 SNP is a common in Egyptian chronic myeloid leukemia. TET2 SNP rs 3442524 was associated with huger spleen size and higher BCR-ABL1 levels after 6 months of starting TKIs suggesting disease progression.</p> Enas A Dammag Nahla A.M. Hamed Nabil A El Halawani Heba S Kassem Mona W Ayad Copyright (c) 2020 Enas A Dammag, Nahla A.M. Hamed, Professor, Nabil A El Halawani, Professor, Heba S Kassem, Professor, Mona W Ayad, Professor https://creativecommons.org/licenses/by-nc/4.0 2020-01-01 2020-01-01 12 1 e2020004 e2020004 10.4084/mjhid.2020.004 MICRORNA-181A-3P AS A DIAGNOSTIC AND PROGNOSTIC BIOMARKER FOR ACUTE MYELOID LEUKEMIA https://mjhid.org/index.php/mjhid/article/view/2020.012 <p><strong>Background:</strong> Micro (mi)RNAs play an important role in the pathogenesis and development of acute myeloid leukemia (AML), and their abnormal expression may be sufficient to predict the prognosis and outcomes in AML patients. We evaluated the clinical diagnostic value of miRNA-181a-3p in predicting prognosis and outcomes in patients with AML.</p> <p><strong>Methods: </strong>A total of 119 newly diagnosed adult patients with AML and 60 healthy controls were recruited. Blood specimens were obtained from all AML patients at diagnosis, and 10 blood specimens were obtained on day 28 after induction chemotherapy. The controls also provided blood samples. MiR-181a-3p expression was quantified by PCR, and relative&nbsp;miRNA&nbsp;expression&nbsp;was determined using the comparative Ct method.</p> <p><strong>Results:</strong> Compared with healthy controls, the expression of miRNA-181a-3p was significantly increased in patients with AML. MiR-181a-3p expression could be used to discriminate AML patients from controls, with up-regulated expression correlating with favorable prognosis. Moreover, miRNA-181a-3p expression was significantly decreased in patients who achieved a complete response after induction chemotherapy. The multivariate Cox analysis highlighted the prognostic value of miR-181a-3p for patients with AML.</p> <p><strong>Conclusions:</strong> MiR-181a-3p may be clinically useful as a disease marker for AML, and enhanced the prediction of patient outcomes to chemotherapy.</p> Xiaoling Ma Copyright (c) 2020 Xiaoling Ma http://creativecommons.org/licenses/by-nc/4.0 2020-02-26 2020-02-26 12 1 e2020012 e2020012 10.4084/mjhid.2020.012 The PARTIAL ACHIEVEMENT OF THE 90-90-90 UNAIDS TARGET IN A COHORT OF HIV INFECTED PATIENTS FROM CENTRAL ITALY. https://mjhid.org/index.php/mjhid/article/view/2020.017 <p>Despite progress in the prevention and treatment of HIV, persistent issues concerning the evaluation of continuum in care from the serological diagnosis to virologic success remain.</p> <p>Considering the UNAIDS target 90-90-90 for 2020 for treatment and viral suppression of people living with HIV (PLVH), our purpose was to verify if, starting from diagnosis, the viral suppression rate of our cohort of new PLWH satisfied the above targets.</p> <p>The aim of this retrospective study was to compare 2005-2017 data collected at the Perugia Infectious Diseases Clinic with the 2020 UNAIDS 90 targets and to identify risk factors that could be associated with failure to reach these targets.</p> <p>Methods:&nbsp; We included all patients aged ≥15 undergoing HIV test at our clinic between January 2005 and December 2017. We evaluated the unclaimed tests, linkage to care, retention in ART and the viral suppression at 1 and 2 years from starting ART. Data were analyzed between Italians and foreigners.</p> <p>Results: We observed 592 new diagnoses for HIV infection: 61.4% on Italian-natives, 38.5% on foreigners. Considering the continuum of care from diagnosis, 88 (15%) PLWHIV were lost to engagement in care: 55 (9.2%) patients didn’t withdraw the test and 33 (5.5%) &nbsp;didn’t link to care.</p> <p>An antiretroviral treatment was started only on 78.8% of the new diagnoses (467/592) and a viral suppression was obtained at 2 years on 82% of PLWH who had started ART (383/467) namely only 64.7% of the new diagnoses instead of the hoped-for 81% of the UNAIDS target. We found no significant differences between Italians and foreigners</p> <p>Conclusions</p> <p>UNAIDS goal was very far to be reached. The main challenges were unreturned tests as well as the retention in ART. Rapid tests for a test-treat strategy and frequent phone communications in the first ART years could facilitate UNAIDS target achievement.</p> Elisabetta Schiaroli Copyright (c) 2020 Elisabetta Schiaroli http://creativecommons.org/licenses/by-nc/4.0 2020-02-26 2020-02-26 12 1 e2020017 e2020017 10.4084/mjhid.2020.017 CHARACTERISTICS AND PROGNOSIS OF HEPATOCELLULAR CARCINOMA IN MULTI-TRANSFUSED PATIENTS WITH THALASSEMIA MAJOR. EXPERIENCE OF A SINGLE TERTIARY CENTER. https://mjhid.org/index.php/mjhid/article/view/2020.013 <p><strong>Background: </strong>In this retrospective study, records of patients with thalassemia major (TM) diagnosed with hepatocellular carcinoma (HCC) from 2008‐2018 were reviewed in order to determine the survival rate and evaluate possible etiological factors associated with survival.</p> <p><strong>Methods:</strong> Forty-two TM patients who were diagnosed with HCC have been included in the study. Most of our patients (78.5%) were anti-HCV positive, while 16.5% had evidence of resolved HBV infection. At the time of HCC diagnosis, 78.5% of our patients were diagnosed with cirrhosis, while the vast majority (98%) had normal or mild elevated liver iron concentration (LIC) values. According to Barcelona Clinic Liver Cancer (BCLC) grading system patients were classified as 0-A: 28.5%, B: 57% and as C-D: 14.5%.&nbsp; HCC has been treated with loco-regional treatment in 78.5% of our patients, while the rest have been treated with sorafenib.</p> <p><strong>Results:</strong> Twenty-eight patients (66.5%) have eventually died with a median survival time of 6 months (range: 2-60). Using the Cox proportional hazard model, the only factors who have been associated with poor survival were BCLC stages C and D.</p> <p><strong>Conclusions:</strong> In conclusion, BCLC staging is the main prognostic factor of survival in patients with TM who develop HCC, with a median survival time of six months.</p> Nikolaos Papadopoulos Dimitrios Kountouras Katerina Malagari Maria Tampaki Maria Theochari John Koskinas Copyright (c) 2020 Nikolaos Papadopoulos, Dimitrios Kountouras, Katerina Malagari, Maria Tampaki, Maria Theochari, John Koskinas http://creativecommons.org/licenses/by-nc/4.0 2020-02-26 2020-02-26 12 1 e2020013 e2020013 10.4084/mjhid.2020.013 FINE MAPPING OF GLUCOSE 6 PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY IN RURAL AREA OF SOUTH WEST ODISHA USING THE CLINICAL, HEMATOLOGICAL AND MOLECULAR APPROACH https://mjhid.org/index.php/mjhid/article/view/2020.015 <p><strong>Introduction</strong>: The aim of the study was to enumerate the clinical, hematological and molecular spectrum of G6PD deficiency in malaria endemic regions of south west Odisha.</p> <p><strong>Methods</strong>: Diagnosis of G6PD deficiency was made by using the Di-chloroindophenol Dye test in from two south west districts (Kalahandi and Rayagada) of Odisha State. Demographic and clinical history was taken from each individual using a pre-structured questionnaire. Molecular characterization of G6PD deficiency was done using PCR-RFLP and Sanger sequencing.</p> <p><strong>Results</strong>:&nbsp; A total of 1981 individuals were screened, out of which 59 (2.97%) individuals were found G6PD deficient. Analysis revealed that G6PD deficiency was more in males (4.0%) as compared to females (2.3%). G6PD deficiency was significantly higher in tribal population (4.8%) as compared to non-tribal populations (2.4%) (p=0.012, OR=2.014, 95%CI =1.206-3.365). Individuals with history of malaria and G6PD deficiency have high risk of need of blood transfusion than G6PD normal individuals (p=0.026, OR=3.816, 95%CI=1.079-13.496). Molecular analysis revealed G6PD Orissa as the most common (88%) mutation 88% in the studied cohort. G6PD Kaiping (n=3), G6PD Coimbra (n=2) and G6PD Union (n=1) were also identified in studied cohort.&nbsp;</p> <p><strong>Conclusion</strong>: The cumulative prevalence of G6PD deficiency the present is below the estimated national prevalence. G6PD deficiency was higher in tribes as compared to non-tribes. Rare G6PD Kaiping and G6PD Union variants have been identified.</p> Ravindra Kumar MPSS Singh Soumendu Mahapatra Sonam Chourasia Malay Kumar Tripathi John Oommen Praveen Kumar Bharti Rajasubramaniam Shanmugam Copyright (c) 2020 Ravindra Kumar, MPSS Singh, Soumendu Mahapatra, Sonam Chourasia, Malay Kumar Tripathi, John Oommen, Praveen Kumar Bharti, Rajasubramaniam Shanmugam http://creativecommons.org/licenses/by-nc/4.0 2020-02-26 2020-02-26 12 1 e2020015 e2020015 10.4084/mjhid.2020.015 THE IMPACT OF CHEMOTHERAPY AFTER PEDIATRIC MALIGNANCY ON HUMORAL IMMUNITY TO VACCINE-PREVENTABLE DISEASES https://mjhid.org/index.php/mjhid/article/view/2020.014 <div>Abstract.Background/Aim: The antibody titer of vaccine-preventable disease in pediatric patients who underwent chemotherapy was assessed in order to evaluate the seroprotection after treatment and the feasibility and the efficacy of a policy of revaccination.Methods: Serum antibody titers of55 patients for hepatitis B (HBV), rubella, varicella-zoster (VZV), measles, mumps, polioviruses, Clostridium tetani(C. tetani)and Streptococcus pneumoniae(S. pneumoniae) were analysed.Results: After chemotherapy, a lack of protective antibody titers against HBV, rubella, VZV, measles, mumps, polioviruses, C. tetani, and S. pneumonia was found in 53%, 45%, 46%, 46%, 43%, 21-26%, 88% and 55% of patients, respectively. In 49 of 55 patients who were tested both before and after chemotherapy for at least a pathogen, the loss of immunity for HBV, rubella, VZV, measles, mumps, polioviruses and C. tetani was respectively 39%, 43%, 38%, 42%, 32%, 33%, and 80%. A low number of B-lymphocytes was associated with the loss of immunity against measles (p=0.04) whereas a high number of CD8+ T-lymphocytes was associated with the loss of immunity against VZV (p=0.03). A single booster of vaccine dose resulted in a seroprotection for HBV, rubella, VZV, measles, mumps, polioviruses, C. tetani and S. pneumoniae in 67%, 83%, 80%, 67%, 33%, 100%, 88% and 67% of patients, respectively. Conclusions: We confirm that seroprotection for vaccine-preventable diseases is affected by treatment for pediatric malignancy. A single booster dose of vaccine might be a practical way to restore vaccine immunity in patients after chemotherapy.</div> <div>&nbsp;</div> Chiara Garonzi Rita Balter Gloria Tridello Anna Pegoraro Manuela Pegoraro Monia Pacenti Novella Scattolo Simone Cesaro Copyright (c) 2020 Chiara Garonzi, Rita Balter, Gloria Tridello, Anna Pegoraro, Manuela Pegoraro, Monia Pacenti, Novella Scattolo, Simone Cesaro http://creativecommons.org/licenses/by-nc/4.0 2020-02-26 2020-02-26 12 1 e2020014 e2020014 10.4084/mjhid.2020.014 DEVELOPMENT OF AN IMPROVED EPSTEIN-BARR VIRUS (EBV) NEUTRALIZING ANTIBODY ASSAY TO FACILITATE DEVELOPMENT OF A PROPHYLACTIC GP350-SUBUNIT EBV VACCINE https://mjhid.org/index.php/mjhid/article/view/2020.016 <p>No licensed vaccine is available for prevention of EBV-associated diseases, and robust, sensitive, and high-throughput bioanalytical assays are needed to evaluate immunogenicity of gp350 subunit-based candidate EBV vaccines. Here we have developed and improved analytical tools for such a vaccine’s pre-clinical and clinical validation including a gp350-specific antibody detection assay and an EBV-GFP based neutralization assay for measuring EBV specific antibodies in human donors. The sensitivity of our previously published high-throughput EBV-GFP fluorescent focus (FFA)-based neutralization assay was further improved when guinea pig complement was supplemented using a panel of healthy human sera. Anti-gp350 antibody titers, which were evaluated using an anti-gp350 IgG ELISA assay optimized for capture and detection conditions, were moderately correlated to the FFA-based neutralization titers. Overall, these sensitive, and high-throughput bioanalytical assays are capable of characterizing the serologic response to natural EBV infection, with applications in evaluating EBV antibody status in epidemiologic studies and immunogenicity of candidate gp350-subunit EBV vaccines in clinical studies.</p> Hui Liu Lorraine Gemmell Rui Lin Fengrong Zuo Henry H. Balfour Jennifer C. Woo Gregory M. Hayes Copyright (c) 2020 Hui Liu, Henry H. Balfour, Gregory M. Hayes http://creativecommons.org/licenses/by-nc/4.0 2020-02-26 2020-02-26 12 1 e2020016 e2020016 10.4084/mjhid.2020.016 DISCOVERY OF TYPE 3 VON WILLEBRAND DISEASE IN A COHORT OF PATIENTS WITH SUSPECTED HEMOPHILIA A IN CÔTE D’IVOIRE https://mjhid.org/index.php/mjhid/article/view/2020.019 <p><strong>Abstract</strong></p> <p><strong>Aim&nbsp;:</strong> Type 3 von Willebrand disease (VWD) is the most severe form of VWD, characterized by a near-total absence of von Willebrand factor (vWF) leading to a huge deficiency in plasmatic factor VIII (FVIII). VWD may be confused with hemophilia A, sometimes leading to misdiagnosis. The purpose of this work was to finalize the biological diagnosis of patients with FVIII activity deficiency in Abidjan, in order to guide the best type of management. <strong>Methods:</strong> We conducted a cross-sectional descriptive study from June 2018 to April 2019. Forty-nine patients, all of whom had lower FVIII levels or had been referred for bleeding disorder, were monitored in the clinical hematology service. Pro-coagulant activity of coagulation factors was performed in Abidjan. The assays for von Willebrand antigen and activity were performed at Nîmes University Hospital in France. <strong>Results:</strong> The mean age of patients was 13.8 years (1 – 65) and 86% were Ivorian. FVIII deficiency was discovered during a biological checkup, circumcision or post-traumatic bleeding, in 33%, 31% and 29% respectively. The FVIII level of patients was classified as severe (89.8%), moderate (8.2%) and mild (2%). Only one patient had a quantitative deficiency of von Willebrand factor (vWF: Ag &lt;3%) with undetectable von Willebrand factor activity (vWF: Ac) and an FVIII level &lt;1%. <strong>Conclusion:</strong> Not all of the constitutive deficits of FVIII are hemophilia A. It was very important to assess the Willebrand factor of these patients followed in Côte d'Ivoire for whom hemophilia A had been suspected.</p> Adia Eusèbe Adjambri Sylvie Bouvier Roseline N'guessan Emma N’draman-Donou Mireille Yayo-Ayé Marie-France Meledje Missa Louis Adjé Duni Sawadogo Copyright (c) 2020 Adia Eusèbe Adjambri, Sylvie Bouvier, Roseline N'guessan, Emma N’draman-Donou, Mireille Yayo-Ayé, Marie-France Meledje, Missa Louis Adjé, Duni Sawadogo http://creativecommons.org/licenses/by-nc/4.0 2020-02-26 2020-02-26 12 1 e2020019 e2020019 10.4084/mjhid.2020.019 Archi-Prevaleat project. A National Register of color-Doppler ultrasonography of the epi-aortic vessels in Patients Living with HIV https://mjhid.org/index.php/mjhid/article/view/2020.018 <p>Persons Living with HIV (PLWH) are at higher risk of cardiovascular disease (CVD) than the general population. &nbsp;Carotid ultrasound is a non-invasive diagnostic tool, aimed at the assessment of vascular anatomy and function.&nbsp; Our present aim is to generate a National Register of color-Doppler ultrasonography (Archi-Prevaleat) to better evaluate the characteristics of vascular lesions in PLWH on a large number of data.</p> S Martini S Ferrara C Bellacosa B M Ceresia F Taccari G Di Filippo A Tartaglia G Gaeta Paolo Maggi Copyright (c) 2020 S Martini, S Ferrara, C Bellacosa, B M Ceresia, F Taccari, G Di Filippo, A Tartaglia, G Gaeta, Paolo Maggi http://creativecommons.org/licenses/by-nc/4.0 2020-02-26 2020-02-26 12 1 e2020018 e2020018 10.4084/mjhid.2020.018 Chronic-graft-versus-host-disease-related polymyositis: a 17-months-old child with a rare and late complication of haematopoietic stem cell transplantation. https://mjhid.org/index.php/mjhid/article/view/2020.002 <p align="justify"><a name="__DdeLink__174_756140867"></a> <span style="color: #000000;"><span style="font-family: Courier, 'Courier New', serif;"><span style="font-size: small;"><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB"><strong>Background: </strong></span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">Chronic graft versus host disease (cGVHD) occurs in 20-30% of paediatric patients receiving haemopoietic stem cell transplantation (HSCT). Neuromuscular disorders such as polymyositis are considered a rare and distinctive but non-diagnostic manifestation of cGVHD and, in absence of other characteristic signs and symptoms, biopsy is highly recommended to exclude other causes. </span></span></span></span></span></span></p> <p align="justify"><span style="color: #000000;"><span style="font-family: Courier, 'Courier New', serif;"><span style="font-size: small;"><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB"><strong>Case report:</strong></span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB"> We report a case of a 17-months-old child </span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">affected by hemophagocytic </span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">lymphohistiocytosis who</span></span></span> <span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">underwent a matched </span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">unrelated donor </span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">haematopoietic stem cell transplantation (</span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">HSCT). She </span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">developed a severe cGVHD-related polymyositis that was successfully treated with high-dose steroid therapy, rituximab and sirolimus. </span></span></span></span></span></span></p> <p class="western" lang="en-GB" align="justify"><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><strong>Conclusions: </strong></span></span><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;">This is the first case of cGVHD-related-polymyositis described in a pediatric patient which was successfully treated with rituximab.</span></span></span></p> Matteo Chinello Rita Balter Massimiliano De Bortoli Virginia Vitale Ada Zaccaron Elisa Bonetti Paola Tonin Gaetano Vattemi Valeria Guglielmi Simone Cesaro Copyright (c) 2020 Matteo Chinello, Rita Balter, Massimiliano De Bortoli, Virginia Vitale, Ada Zaccaron, Elisa Bonetti, Paola Tonin, Gaetano Vattemi, Valeria Guglielmi, Simone Cesaro https://creativecommons.org/licenses/by-nc/4.0 2020-01-01 2020-01-01 12 1 e2020002 e2020002 10.4084/mjhid.2020.002 Successful planned pregnancy through vitrified-warmed embryo transfer in a woman with chronic myeloid leukemia: case report and literature review https://mjhid.org/index.php/mjhid/article/view/2020.005 <p>A 35-year-old female patient with chronic myeloid leukemia wanted to have a child. She had been treated with imatinib and had achieved major molecular remission, after which imatinib was intentionally discontinued and interferon-α treatment was initiated. After three failed cycles of artificial insemination with her husband’s semen, the patient underwent treatment with assisted reproductive technology. After two cycles of <em>in vitro</em> fertilization, two embryos (8-cell stage and blastocyst) were cryopreserved. The patient again had elevated <em>BCR/ABL</em> mRNA levels; thus, infertility treatment was discontinued. After 18 months of dasatinib treatment, major molecular remission was observed and the patient underwent vitrified–warmed embryo transfer with a single blastocyst. Thereafter, she became pregnant. Discontinuation of tyrosine kinase inhibitors combined with the timely initiation of infertility treatments, including assisted reproductive technology, may be useful for treating women with CML who wish to become pregnant.</p> Toshifumi Takahashi Copyright (c) 2020 Toshifumi Takahashi https://creativecommons.org/licenses/by-nc/4.0 2020-01-01 2020-01-01 12 1 e2020005 e2020005 10.4084/mjhid.2020.005 Hepatic Infiltration with Malignant T-cells Manifesting as Impending Acute Liver failure in Mycosis Fungoides with Large Cell Transformation https://mjhid.org/index.php/mjhid/article/view/2020.007 <p>Here we described a patient with a history of mycosis fungoides who developed large cell transformation manifesting with generalized erythroderma, lymphocytosis, lymphadenopathy and impending acute liver failure (ALF). Three-phase computed tomography of the liver showed neither mass nor hepatomegaly. Liver biopsy confirmed infiltration with malignant CD4+ clonal T-cells. Combination chemotherapy with gemcitabine, dexamethasone, and cisplatin (GDP) resulted in the recovery of liver function and resolution of skin involvement. In Foundation Medicine Hematology Gene Panel, 31 genetic alterations with 11 clinically relevant mutations were identified including ARID2 mutation frequently observed in hepatocellular carcinoma but rarely observed in hematologic malignancies.</p> Yumeng Zhang Jinming Song David Rutenberg Lubomir Sokol Copyright (c) 2020 Yumeng Zhang, Jinming Song, David Rutenberg, Lubomir Sokol https://creativecommons.org/licenses/by-nc/4.0 2020-01-01 2020-01-01 12 1 e2020007 e2020007 10.4084/mjhid.2020.007 Cover https://mjhid.org/index.php/mjhid/article/view/2020.000 <p>Printable Cover Vol 12, Year 2020</p> Francesco Guidi Copyright (c) 2020 Francesco Guidi http://creativecommons.org/licenses/by-nc/4.0 2020-03-14 2020-03-14 12 1