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><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> RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA: CHEMOIMMUNOTHERAPY, TREATMENT UNTIL PROGRESSION WITH MECHANISM-DRIVEN AGENTS OR FINITE-DURATION THERAPY? https://mjhid.org/index.php/mjhid/article/view/2019.024 <p>Treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) has dramatically improved thanks to the development of mechanism-driven agents including drugs that inhibit kinases in the BCR pathway or BCL2. The treating physician has now the opportunity to decide i) which patient can be still offered chemoimmunotherapy as salvage treatment, ii) which patient is a candidate to receiving at relapse continuous treatment with ibrutinib, idelalisib and rituximab or venetoclax and iii) which patient may benefit from a fixed-duration treatment using the BCL2 antagonist venetoclax in association with rituximab.</p> <p>Ibrutinib is the most actively investigated drug in R/R CLL and data at a 7-year follow-up were reported, showing durable efficacy and favorable efficacy profile. The patients with &nbsp;cardiac disease, hypertension and on anticoagulant therapy are not ideal candidates for continuous therapy with this agent. Idelalisib and rituximab was tested in patients with unfavorable characteristics including cytopenias. The short follow-up and treatment emergent adverse events limit its role to patients unlikely to get a benefit with other agents. Venetoclax and rituximab is the only effective chemo-free approach for the treatment of R/R with a fixed duration (up to 24 months) schedule capable of inducing deep &nbsp;responses in the majority of cases with a reassuring safety profile.</p> <p>While a deep knowledge of the growing body of scientific evidence is required to inform and guide the appropriate treatment choice and management, physicians cannot disregard the growing problem of sustainability</p> Antonio Cuneo Robin Foà ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-27 2019-02-27 11 1 e2019024 e2019024 10.4084/mjhid.2019.024 NEW THERAPEUTIC OPTIONS FOR THE TREATMENT OF SICKLE CELL DISEASE https://mjhid.org/index.php/mjhid/article/view/2019.002 <p>Sickle cell disease (SCD; ORPHA232; OMIM # 603903) is a chronic and invalidating disorder distributed worldwide, with high morbidity and mortality.&nbsp; Given the disease complexity and the multiplicity of pathophysiological targets, development of new therapeutic options is critical, despite the positive effects of hydroxyurea (HU), for many years the only approved drug for SCD.</p> <p>New therapeutic strategies might be divided into (1) pathophysiology-related novel therapies and (2) innovations in curative therapeutic options such as hematopoietic stem cell transplantation and gene therapy. The pathophysiology related novel therapies are: a) Agents which reduce sickling or prevent sickle red cell dehydration; b) Agents targeting SCD vasculopathy and sickle cell-endothelial adhesive events; c) Anti-oxidant agents.</p> <p>This review highlights new therapeutic strategies in SCD and discusses future developments, research implications, and possible innovative clinical trials.</p> <p>&nbsp;</p> Alessandro Matte Filippo Mazzi Enrica Federti Oliviero Olivieri Lucia De Franceschi ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019002 e2019002 10.4084/mjhid.2019.002 HIV AND LYMPHOMA: FROM EPIDEMIOLOGY TO CLINICAL MANAGEMENT https://mjhid.org/index.php/mjhid/article/view/2019.004 <p class="western" lang="en-US" style="line-height: 200%; font-style: normal;"><span lang="en-GB">Patients infected with human immunodeficiency virus are at increased risk for developing both non Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL). Even if this risk has decreased for NHL after the introduction of combination antiretroviral therapy (cART), they remain the most common AIDS-related cancer in the developed world. They are almost always of B-cell origin, and some specific lymphoma types are more common than others. Some of these lymphoma types can occur in both HIV-uninfected and infected patients, while others preferentially develop in the context of AIDS. HIV-associated lymphoma differ from lymphoma in the HIV negative population in that they more often present with advanced disease, systemic symptoms, and extranodal involvement and are frequently associated with oncogenic viruses (EBV and/or HHV-8). Before the introduction of cART, most of these patients could not tolerate the treatment strategies routinely employed in the HIV-negative population. The widespread use of cART has allowed for the delivery of full-dose and dose-intensive chemotherapy regimens with improved outcomes that nowadays can be compared to those seen in non-HIV infected patients. However, a great deal of attention should be paid to opportunistic infections and other infectious complications, cART-chemotherapy interactions, and potential cumulative toxicity. In the context of relatively sparse prospective and randomized trials, the optimal treatment of AIDS-related lymphomas remains a challenge, particularly in patients with severe immunosuppression. This paper will address epidemiology, pathogenesis, and therapeutic strategies in HIV-associated NHL and HL.</span></p> Alessandro Re Chiara Cattaneo Giuseppe Rossi ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019004 e2019004 10.4084/mjhid.2019.004 PREGNANCY IN THALASSEMIA https://mjhid.org/index.php/mjhid/article/view/2019.019 <p>Therapeutic advances, including the availability of oral iron chelators and new non-invasive methods for early detection and treatment of iron overload, have significantly improved the life expectancy and quality of life of patients with thalassemia, with a consequent increase in their reproductive potential and desire to have children. Hundreds of pregnancies have been reported so far, highlighting that women carefully managed during preconception usually carry out a successful gestation and labour, both in case of spontaneous conception and use of assisted reproductive techniques. A multidisciplinary team including a cardiologist, an endocrinologist and a gynaecologist, with the supervision of an expert in beta-thalassemia should be involved.&nbsp;</p> <p>During pregnancy, a close follow-up of maternal disorders and of the baby's status is recommended. Haemoglobin should be maintained over 10 g/dL to to allow normal foetal growth. Chelators are not recommended during pregnancy; nevertheless, it may reasonable to consider restarting chelation therapy with desferrioxamine towards the end of the second trimester when the potential benefit outweighs the potential foetal risk.</p> <p>Women with non-transfusion-dependent thalassemia who have never previously been transfused or who have received only minimal transfusion therapy are at risk of severe alloimmune anaemia if blood transfusions are required during pregnancy. Since pregnancy increases the risk of thrombosis three-fold to four-fold and thalassemia is also a hypercoagulable state, the recommendation is to keep women who are at higher risk -such as those who are not regularly transfused and those splenectomised-&nbsp; on prophylaxis during pregnancy and during the postpartum period.</p> <p>&nbsp;</p> <p><strong>Keywords:</strong>Pregnancy, Thalassemia major, Thalassemia intermedia, Haemoglobin H disease, Counselling</p> Raffaella Origa Federica Comitini ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-26 2019-02-26 11 1 e2019019 e2019019 10.4084/mjhid.2019.019 FAMILIAL MEDITERRANEAN FEVER: ASSESSING THE OVERALL CLINICAL IMPACT AND FORMULATING TREATMENT PLANS https://mjhid.org/index.php/mjhid/article/view/2019.027 <p>Recurrent self-limited attacks of fever and short-lived inflammation in the serosal membranes, joints and skin are the leading features of familial Mediterranean fever (FMF), the most common autoinflammatory disorder in the world, transmitted as autosomal recessive trait caused by MEFV gene mutations. Their consequence is an abnormal function of pyrin, a natural repressor of inflammation, apoptosis and release of cytokines. FMF-related mutant pyrins are hypophosphorylated following RhoA&nbsp;GTPases’ impaired activity and show a propensity to relapsing uncontrolled systemic inflammation with inappropriate response to inflammatory stimuli and leukocyte spread to serosal membranes, joints or skin. Typical FMF phenotype 1 consists of brief episodes of inflammation and serositis, synovitis, and/or erysipelas-like eruption, whereas phenotype 2 is defined by reactive amyloid-associated (AA) amyloidosis, which is the most ominous complication of FMF, in otherwise asymptomatic individuals. Furthermore, FMF phenotype 3 is referred to the presence of two MEFV mutations with neither clinical signs of FMF, nor AA amyloidosis. The influence of epigenetic and/or environmental factors can contribute to the variable penetrance and phenotypic heterogeneity of FMF.&nbsp;Colchicine, a tricyclic alkaloid with anti-microtubule and anti-inflammatory properties, is the bedrock of FMF management: daily administration of colchicine prevents the recurrence of FMF attacks and the development of secondary AA amyloidosis. Many recent studies have also shown that anti-interleukin-1 treatment is actually the best therapeutic option for FMF patients nonresponsive or intolerant to colchicine. This review aims to catch readers’ attention on the clinical diversity of phenotypes, differential diagnosis, and management of patients with FMF.</p> Donato Rigante Raffaele Manna, Prof. ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-25 2019-04-25 11 1 e2019027 e2019027 10.4084/mjhid.2019.027 Guest Editor: Raffaella Origa THYROID DISORDERS IN HOMOZYGOUS β-THALASSEMIA: CURRENT KNOWLEDGE, EMERGING ISSUES AND OPEN PROBLEMS https://mjhid.org/index.php/mjhid/article/view/2019.029 <p><strong>Abstract. </strong>Changes in thyroid function and thyroid function tests occur in patients with β-thalassemia major (TM). The frequency of hypothyroidism in TM patients ranges from 4% to 29 % in different reports. The wide variation has been attributed to several factors such as patients' genotype, age, ethnic variations, treatment protocols of transfusions and chelation, and varying compliance to treatment. Hypothyroidism is the result of primary gland failure or insufficient thy­roid gland stimulation by the hypothalamus or pituitary gland. The main laboratory parameters of thyroid function are the assessments of serum thyroid-stimulating hor­mone (TSH) and serum free thyroxine (FT4). It is of primary importance to interpret these measure­ments within the context of the laboratory-specific normative range for each test. An ele­vated serum TSH level with a normal range of serum FT4 level is consistent with subclinical hypothyroidism. A low serum FT4 level with a low, or inappropriately normal, serum TSH level is consistent with secondary hypothyroidism. Doctors caring for TM patients most commonly encounter subjects with subclinical primary hypothy­roidism in the second decade of life. Several aspects remain to be elucidated as the frequency of thyroid cancer and the possible existence of a relationship between thyroid dysfunction on one hand, cardiovascular diseases, components of metabolic syndrome (insulin resistance) and hypercoagulable state on the other hand. Further studies are needed to explain these emerging issues. Following a brief description of thyroid hormone regulation, production and actions, this article is conceptually divided into two parts; the first reports the spectrum of thyroid disease occurring in patients with TM, and the second part focuses on the emerging issues and the open problems in TM patients with thyroid disorders.</p> Vincenzo De Sanctis ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-25 2019-04-25 11 1 e2019029 e2019029 10.4084/mjhid.2019.029 Guest Editor: Raffaella Origa IRON TOXICITY AND HEMOPOIETIC CELL TRANSPLANTATION: TIME TO CHANGE THE PARADIGM. https://mjhid.org/index.php/mjhid/article/view/2019.030 <p>The issue of iron overload in hemopoietic cell transplantation has been first discussed in the field of transplantation for thalassemia. Thalassemia major is characterized by ineffective erythropoiesis and hemolysis leading to anemia in the majority of patients. Patients require regular blood transfusion therefore they develop iron overload causing organ damage and hematopoietic cell transplantation (HCT) is a consolidated reliably curative option. <br>In this category of patients an important issue for transplant outcome is the iron burden before transplant and in the long-life post-transplant. Nevertheless, today the concept of the impact of iron overload / toxicity on the outcome of HCT) has been extended to other diseases characterized by periods of variable duration of transfusion dependence <br>Recent preclinical data has shown how increased production of reactive oxygen species (ROS) resulting under iron overload condition, could impair the stem cells clonality capacity, proliferation and maturation. Also, microenvironment cells could be affected through this mechanism. For this reason, iron overload is becoming an important issue also in the engraftment period post-transplant<br>The aim of this review is to update consolidated knowledge about the role of iron overload/iron toxicity in the HCT setting in non-malignant and in malignant diseases introducing the concept of exposition of free toxic iron forms and related cellular damage in the different stage of transplant.</p> Federica Pilo ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-25 2019-04-25 11 1 e2019030 e2019030 10.4084/mjhid.2019.030 SICKLE CELL DISEASE AND PREGNANCY https://mjhid.org/index.php/mjhid/article/view/2019.040 <p><strong><span style="text-decoration: underline;">Abstract</span></strong></p> <p>&nbsp;</p> <p>Sickle Cell Disease (SCD) is a group of inherited single-gene autosomal recessive disorders caused by the ‘sickle’ gene, which affects haemoglobin structure. Sickle cell anemia is the most common hemoglobinopathy worldwide. The burden of sickle cell disease in pregnancy has been exponentially increasing with more number of women reaching the reproductive age, and having successful pregnancies. It has been proven beyond doubt that SCD in pregnancy poses the pregnant woman and fetus to significantly higher risks than a lady without SCD. SCD is associated with both maternal and fetal complications and is associated with an increased incidence of perinatal mortality, premature labour,&nbsp; fetal growth restriction and acute painful crises during pregnancy.&nbsp; Some studies also describe an increase in spontaneous miscarriage, antenatal hospitalisation, maternal mortality, delivery by caesarean section, infection, thromboembolic events and antepartum haemorrhage.</p> <p>&nbsp;</p> <p>This review aims to discuss the risks of SCD in pregnancy - to the mother and fetus . It also reviews the difference between complications in SCD and sickle cell trait.</p> Dipty Jain Pooja Lodha Roshan Colah Prachi Atmapoojya Prachi Atmapoojya ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-24 2019-06-24 11 1 e2019040 e2019040 10.4084/mjhid.2019.040 ECONOMIC EVALUATION OF CHELATION REGIMENS FOR β--THALASSEMIA MAJOR: A SYSTEMATIC REVIEW https://mjhid.org/index.php/mjhid/article/view/2019.036 <p>Background:<br>Deferoxamine (DFO) or Deferiprone (DFP) or Deferasirox (DFX) monotherapy and DFO and DFP combination therapy were four commonly implemented now chelation regimens for the iron overloaded of β-thalassemia major. This systematic review aims to determine the cost-effectiveness of four chelation regimens and provide evidence for the rational use of chelation regimens for β-thalassemia major therapy in clinic.<br>Methods:<br>A systematic literature search in PubMed, EMBASE (Ovid), CENTRAL (Cochrane library), HTAD (Cochrane library), NHS EED (Cochrane library), CBM, CNKI, VIP, and Wanfang was conducted in April 2018. In addition, a manual search was performed. Two researchers, working independently, selected the papers, extracted the data and assessed the methodological quality of the included papers. Each included paper was evaluated using a checklist developed by Drummond et al. <br>Results:<br>The initial number of records was 968, and eight papers met the final eligibility criteria. All the included eight papers were cost-utility analyses. And the methodological quality of these papers was good. Nineteen studies were included in eight papers. Nine studies of DFX versus DFO had contradictory results. Out of the nineteen studies, three studies of DFX versus DFP established that using DFP was cost-effective. Three studies of DFP versus DFO established that using DFP was cost-effective. One study of DFP and DFO combination therapy versus DFO found that using DFO was cost-effective. One study of DFP and DFO combination therapy versus DFP found that using DFP was cost-effective. And there were two studies of DFP and DFO combination therapy versus DFX, but we cannot be sure which one of two chelation regimens was cost-effective. <br>Conclusion:<br>In brief, DFP is the best choice, followed by DFO or DFX, when an iron chelator is to be used alone for β-thalassemia major therapy. All studies that compared DFO and DFP combination therapy with DFO (or DFP or DFX) monotherapy established that the combination therapy with DFO and DFP was not cost-effective. However, due to the low number of related studies, more extensive, high-quality research is required for further analysis and confirmation of our findings. Moreover, the cost effectiveness is not an absolute issue when in different countries(regions) the results are opposite for other countries(regions). The specific region had a substantial influence on the economy of drugs.</p> <p>Key words: β-thalassemia major, Deferoxamine, Deferiprone, Deferasirox, cost-effectiveness, systematic review</p> Jialian Li ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-24 2019-06-24 11 1 e2019036 e2019036 10.4084/mjhid.2019.036 SICKLE CELL DISEASE AND INFECTIONS IN HIGH- AND LOW-INCOME COUNTRIES https://mjhid.org/index.php/mjhid/article/view/2019.042 <p>Infections, especially pneumococcal septicemia, meningitis, and <em>Salmonella</em> osteomyelitis, are a major cause of morbidity and mortality in patients with sickle cell disease (SCD). SCD increased susceptibility to infection, while infection leads to SCD-specific pathophysiological changes. The risk of infectious complications is highest in children with a palpable spleen before 6 months of age. Functional splenectomy, the results of repeated splenic infarctions, appears to be an important host-defense defect. Infection is the leading cause of death, particularly in less developed countries. Defective host-defense mechanisms enhance the risk of pneumococcal complications. Susceptibility to <em>Salmonella</em> infections can be explained at least in part by a similar mechanism. In high-income countries, the efficacy of the pneumococcal vaccine has been demonstrated in this disease. A decreased in infection incidence has been noted in SCD patients treated prophylactically with daily oral penicillin. Studies in low-income countries suggest the involvement of a different spectrum of etiological agents.</p> Giovanna Cannas ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-25 2019-06-25 11 1 02019042 02019042 10.4084/mjhid.2019.042 THERAPEUTIC TARGETING OF NOTCH SIGNALING PATHWAY IN HEMATOLOGICAL MALIGNANCIES https://mjhid.org/index.php/mjhid/article/view/2019.037 <p>The Notch pathway plays a key role in several processes including stem-cell self-renewal, proliferation, and cell differentiation. Several studies identified recurrent mutations in hematological malignancies making Notch one of the most desirable target in leukemia and lymphoma. The Notch signaling mediates resistance to therapy and controls cancer stem cells supporting the development of on-target therapeutic strategies to improve patients’ outcome. In this brief review, we outline the therapeutic potential of targeting Notch pathway in T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia and mantle cell lymphoma.</p> Giovanni Roti Claudia Sorrentino Antonio Cuneo ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-25 2019-06-25 11 1 e2019037 e2019037 10.4084/mjhid.2019.037 CORD BLOOD PLATELET LYSATE: IN VITRO EVALUATION TO SUPPORT THE USE IN REGENERATIVE MEDICINE. https://mjhid.org/index.php/mjhid/article/view/2019.021 <p>Platelet-rich plasma (PRP) is an inexpensive and safe substitute of recombinant growth factors in Vitro and <em>in vivo</em>. Due to its putative effect on tissue repair, the use of autologous PRP has become largely popular. Recently, a jellified PRP derivative obtained from umbilical cord blood (CB) has been utilized <em>in vivo&nbsp;</em>to treat mucosal and cutaneous lesions. Nevertheless, whether PRP derived from CB and adult blood display different potency in promoting cell growth in Vitro has been rarely investigated. In this study, we compared cytokine profile and mesenchymal cell growth supporting the ability of platelet lysate obtained from adult and cord blood. Our <em>in vitro&nbsp;</em>results strongly back the utilization of CB platelet lysate <em>in vivo</em>, as an efficacious, safe and inexpensive alternative to promote damaged tissue healing when the autologous PRP is contraindicated. Moreover, the policy of manufacturing CB platelet lysate can limit the current disposal of many collected CB units not suitable for transplant due to their low nucleated cell count.</p> <p>&nbsp;</p> <p>&nbsp;</p> Luciana Teofili ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-25 2019-02-25 11 1 e2019021 e2019021 10.4084/mjhid.2019.021 INTERNATIONAL MULTICENTER EXPERIENCE IN THE TREATMENT OF INVASIVE ASPERGILLOSIS IN IMMUNOCOMPROMISED CANCER PATIENTS https://mjhid.org/index.php/mjhid/article/view/2019.003 <p><strong>BACKGROUND: </strong>Invasive aspergillosis (IA) is a life-threatening infection in immunocompromised patients. In this study, we compared the efficacy of voriconazole containing regimen vs non-voriconazole containing regimen in patients with IA.</p> <p><strong>METHODS: </strong>In this retrospective study, we reviewed the medical records of all immunocompromised cancer patients diagnosed with proven or probable IA between February 2012 and March 2018. This trial included 26 patients from the American University of Beirut,&nbsp; Lebanon, 20 patients from&nbsp; Hospital das Clinicas da Faculdade de Medicina, Universidade de&nbsp; São Paulo, Brazil, and 10 patients from St. Luke's International Hospital Tokyo, Japan.</p> <p><strong>RESULTS:&nbsp; </strong>A total of 56 patients were analyzed. They were divided into 2 groups voriconazole containing regimen and non-voriconazole containing regimen (90% Amphotericin B&nbsp; based regimen) . Both groups had similar characteristic, age, gender, and immunocompromised status. The majority of patients had underlying leukemia 53%, lymphoma 18%, myeloma 15% and solid tumor 13%. Antifungal primary therapy with voriconazole-containing regimen was associated with better response to treatment (P = 0.003). Survival analysis showed that primary therapy with a voriconazole containing regimen was significantly associated with improved survival (p =0.006). By multivariate logistic regression analysis, mechanical ventilation was predictor of worse outcome (poor response to therapy and increased mortality at 6 weeks), whereas primary treatment with voriconazole containing regimen was associated with improved outcome (OR=0.14; 95% CI 0.03-0.64, P=0.01).</p> <p><strong>CONCLUSIONS: </strong>Based on international experience in immunocompromised cancer patients with IA, primary therapy with voriconazole-containing regimen is associated with improved response and survival compared with non-voriconazole amphotericin B based regimen.</p> R. Hachem Marjorie Batista Souha S Kanj Saaed El Zein Sara Haddad Ying Jiang Nobuyoshi Mori Rocha Vanderson Anne-Marie Chaftari Issam I Raad ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019003 e2019003 10.4084/mjhid.2019.003 DETECTION OF CALR MUTATIONS USING HIGH RESOLUTION MELTING CURVE ANALYSIS (HRM-A); APPLICATION ON A LARGE COHORT OF GREEK ET AND MF PATIENTS https://mjhid.org/index.php/mjhid/article/view/2019.009 <p><strong><em>Background and Objectives</em></strong></p> <p>Somatic mutations in the calreticulin gene (<em>CALR</em>) are detected in approximately 70% of patients with essential thrombocythemia (ET) and primary or secondary myelofibosis (MF), lacking the&nbsp;<em>JAK2</em>and&nbsp;<em>MPL</em>mutations. To determine the prevalence of&nbsp;<em>CALR</em>frameshift&nbsp;mutations in a population of MPN patients of Greek origin, we developed a rapid low-budget PCR-based assay and screened samples from 5 tertiary Haematology units. This is a first of its kind report of the Greek patient population that also disclosed novel&nbsp;<em>CALR</em>mutants.</p> <p>&nbsp;</p> <p><strong><em>Methods</em></strong></p> <p>MPN patient samples were collected from different clinical units and screened for&nbsp;<em>JAK2</em>and&nbsp;<em>MPL</em>mutations after informed consent was obtained. Negative samples were analyzed for the presence of&nbsp;<em>CALR</em>mutations. To this end, we developed a modified&nbsp;post Real Time PCR High Resolution Melting Curve analysis (HRM-A) protocol. Samples were subsequently confirmed by Sanger sequencing.</p> <p>&nbsp;</p> <p><strong><em>Results</em></strong></p> <p>Using this protocol we screened&nbsp;173 MPN,&nbsp;<em>JAK2</em>and&nbsp;<em>MP</em><em>L</em>mutation negative, patients of Greek origin, of whom 117 (67.63%) displayed a&nbsp;<em>CALR</em>exon 9 mutation. More specifically, mutations were detected in 90 out of 130 (69.23%) essential thrombocythaemia cases (ET), in 18 out of 33 (54.55%) primary myelofibrosis patients (pMF) and in 9 out of 10 (90%) cases of myelofibrosis secondary to ET (post-ET sMF). False positive results were not detected. The limit of detection (LoD) of our protocol was 2%. Furthermore, our study reavealed 6 rare novel mutations which are to be added in the COSMIC database.&nbsp;</p> <p>&nbsp;</p> <p><strong><em>Conclusions</em></strong></p> <p>Overall, our method could rapidly and cost-effectively detect the mutation status in a representative cohort of Greek patients; the mutation make-up in our group was not different from what has been published for other national groups.</p> Andreas Giannopoulos Niki Rougkala Theodoros Loupis Marina Mantzourani Nora-Athina Viniou Eleni Variami Theodoros Vassilakopoulos George Dryllis Ioannis Kotsianidis Theodora Gougopoulou Marianna Politou Konstantinos Konstantopoulos George Vassilopoulos ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019009 e2019009 10.4084/mjhid.2019.009 THE USE OF HPLC AS A TOOL FOR NEONATAL CORD BLOOD SCREENING OF HAEMOGLOBINOPATHY - A VALIDATION STUDY https://mjhid.org/index.php/mjhid/article/view/2019.005 <p><strong>Background</strong>: Newborn cord blood screening identifies infants with underlying haemoglobinopathies before they develop the characteristic symptoms or sequelae. </p><p><strong>Aims</strong>: This study was performed to validate the interpretation high-performance chromatography (HPLC) along with complete blood count (CBC) results as a tool for universal neonatal screening of hemoglobin disorders in Oman. </p><p><strong>Methods</strong>: HPLC and CBC data on subjects who participated in the National Neonatal screening program at birth were obtained from archival records. The results recorded at birth were compared with a second study performed on the same subjects, after approval from the local medical research and ethics committee.</p><p><strong>Results</strong>: Only 290 subjects from amongst the original cohort of 3740 newborns could be recalled between April 2010 to March 2011, to repeat HPLC and CBC, as well as perform confirmatory DNA studies, wherever necessary. All these subjects had been documented to show an initial abnormal result. 31 cases who had no HbA at birth on HPLC were confirmed as either homozygous β-thalassaemia major (n=5 subjects) or homozygous sickle cell anemia (n=26 subjects) by appropriate DNA analysis. Additionally, amongst 151 subjects, 72 subjects were studied in the initial study by Hb Bart’s quantitation using <strong>a</strong>alpha thalassaemia short program at birth. In this cohort, 42 subjects with Hb Bart’s &gt;1% at birth could be confirmed as having either deletional or non-deletional thalassaemia by GAP PCR studies. No case of HbH was detected in this cohort. Further, carrier status for structural hemoglobin variants (HbS, HbC, HbD, HbE) (n=67) and beta thalassaemia allele with low HbA at birth (n=29 out of 41) were confirmed by relevant molecular studies.</p><p><strong>Conclusions</strong>: The study validated the earlier observation by 100% concordance with results of CBC and HPLC. Presence of Hb Bart’s at birth does not always mean the presence of alpha thalassemia, as subjects with Hb Bart’s was below 1% by quantitation, were shown to be normal by molecular studies.</p><p><strong> </strong></p><p><strong>Key Words</strong>: Neonatal, screening, HPLC validation, haemoglobinopathy, sickle cell disease, thalassaemia</p><p><strong> </strong></p> A. Al-Madhani Anil Pathare Salam Alkindi ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019005 e2019005 10.4084/mjhid.2019.005 RESPIRATORY VIRAL INFECTIONS IN CHILDREN AND ADOLESCENTS WITH HEMATOLOGICAL MALIGNANCIES https://mjhid.org/index.php/mjhid/article/view/2019.006 <p>Abstract <br>Background: Despite the introduction of a polymerase chain reaction (PCR) test for the diagnosis of respiratory viral infection (RVI), guidance on the application of this test and the management of RVI in immunocompromised children is lacking. This study evaluated the clinical characteristics of RVI and established strategies for the PCR test in children and adolescents with hematological malignancies.<br>Methods: This study included children and adolescents with underlying hematological malignancies and respiratory symptoms, in whom a multiplex PCR test was performed. Patients in whom RVI was identified and not identified were categorized into Groups I and II, respectively. Group I was sub-divided into patients with upper and lower respiratory infections. The medical records of the enrolled patients were retrospectively reviewed.<br>Results: A total of 93 respiratory illnesses were included. Group I included 46 (49.5%) cases of RVI, including 31 (67.4%) upper and 15 (32.6%) lower respiratory infections. Rhinovirus (37.0%) was the most common viral pathogen. Significantly more patients in Group I had community-acquired respiratory illnesses (p=0.003) and complained of rhinorrhea (p&lt;0.001) and sputum (p=0.008) than those in Group II. In Group I, significantly more patients with lower respiratory infections had uncontrolled underlying malignancies (p=0.038) and received re-induction or palliative chemotherapy (p=0.006) than those with upper respiratory infections.<br>Conclusions: A multiplex PCR test should be considered for RVI diagnosis in immunocompromised children and adolescents with respiratory symptoms, especially in those with rhinorrhea or sputum prominent over a cough. The early application of the PCR test in patients with uncontrolled underlying malignancies may improve outcomes.</p> <p>Keywords: child, hematologic neoplasms, polymerase chain reaction, respiratory tract infections</p> Seung Beom Han Ju Ae Shin Seong koo Kim Jae Wook Lee Dong-Gun Lee Nack-Gyun Chung Bin Cho Dae Chul Jeong Jin Han Kang ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019006 e2019006 10.4084/mjhid.2019.006 BONE MINERAL DENSITY AND VITAMIN D RECEPTOR GENETIC VARIANTS IN EGYPTIAN CHILDREN WITH BETA THALASSEMIA ON VITAMIN D SUPPLEMENTATION https://mjhid.org/index.php/mjhid/article/view/2019.013 <p><strong>Background</strong>: Low bone mineral density (BMD) is a characteristic feature of Beta thalassemia major (βTM) patients. Vitamin D is important for bone mineralization. Vitamin D receptors (VDR) genetic variants may be related to vitamin D status and BMD.</p><p><strong>Objectives</strong><strong>:</strong>  To evaluate the effect of VDR genetic variants on vitamin D levels and BMD in βTM Egyptian patients supplemented with vitamin D.</p><p><strong>Methods</strong>: This study was conducted on forty children with βTM and forty unrelated healthy sex and age-matched controls. Serum calcium, phosphorus, ALP, ferritin and vitamin D were measured. VDR genetic variants (<em>BsmI</em>, <em>TaqI</em>, and <em>FokI</em>) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). BMD was measured by dual-energy X-ray densitometry (DEXA) of the lumbar spine.</p><p><strong>Results:</strong> In βTM patients, 22.5% had deficient, 50% had insufficient and only 27.5% had sufficient levels of vitamin D. BMD Z score was significantly lower in βTM patients compared to controls (p&lt;0.001). Osteopenia and osteoporosis of lumbar spines were observed in 70% and 22.5% of βTM patients respectively. <em>BsmI </em>bb and <em>FokI</em> Ff and ff genotypic variants were significantly associated with lower vitamin D and BMD Z score. No association was observed with <em>TaqI</em> genotypic variants.</p><p><strong>Conclusions:</strong> We reported a high prevalence of low BMD in βTM despite vitamin D supplementation. The <em>BsmI</em> bb, <em>FokI</em> Ff and ff genotypic variants of VDR can be considered as risk factors for the occurrence of osteoporosis in these children. Vitamin D doses should be adjusted individually according to the genetic makeup of each patient.<strong></strong></p> Hadeer A Abbassy Reham Abdel Haleem Abo Elwafa Omneya Magdy Omar ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019013 e2019013 10.4084/mjhid.2019.013 SOLUBLE ST2 AND CD163 AS POTENTIALBIOMARKERS TO DIFFERENTIATE PRIMARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS FROM MACROPHAGE ACTIVATION SYNDROME https://mjhid.org/index.php/mjhid/article/view/2019.008 <p>Abstract</p> <p><em>Background and Objective:</em> The differentiation of primary haemophagocytic lymphohistiocytosis (pHLH) and macrophage activation syndrome (MAS)&nbsp;poses&nbsp;a challenge&nbsp;to hematologists. The aim of this study was (1) to compare the levels of soluble ST2 (sST2), sCD163, IL-10, IFN-γ, TNF-α and IL-18 in patients with pHLH and MAS and (2) to investigate whether they can help differentiate the two diseases.</p> <p><em>Methods:</em> A total of 54 participants were recruited in this study, including 12 pHLH patients, 22 MAS patients and 20 healthy subjects. We measured the levels of sST2 and sCD163 in serum by ELISA. The serum levels of IL-10, IFN-γ, TNF-α and IL-18 were detected using a Luminex 200 instrument.</p> <p><em>Results:</em> The serum levels of sST2 and sCD163 in MAS patients were markedly higher than that in pHLH patients (363.13 ± 307.24 ng/ml vs 80.75 ± 87.04 ng/ml, <em>P</em> = 0.004; 3532.72 ± 2479.68 ng/ml vs 1731.96 ± 1262.07 ng/ml, <em>P</em> = 0.046). There was no significant difference in the expression of IFN-γ (306.89 ± 281.60 pg/ml vs 562.43 ± 399.86 pg/ml), IL-10 (20.40 ± 30.49 pg/ml vs 8.3 ± 13.14 pg/ml<strong>)</strong>, IL-18 (463.33 ± 597.04 pg/ml vs 1247.82 ± 1318.58 pg/ml) and TNF-α (61.48 ± 84.69 pg/ml vs 106.10 ±77.21 pg/ml) between pHLH and MAS.</p> <p><em>Conclusion:</em> Patients with pHLH and MAS show some differences in cytokine profiles. The elevated levels of IFN-γ, IL-10, IL-18 and TNF-α can contribute to the diagnosis of HLH, but may not discriminate pHLH from MAS. Levels of sST2 and sCD163 may serve as markers to distinguish pHLH from MAS.</p> Zhuo Gao Yini Wang Jingshi Wang Jia Zhang Zhao Wang ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019008 e2019008 10.4084/mjhid.2019.008 INCREASE IN CANDIDA PARAPSILOSIS CANDIDEMIA IN CANCER PATIENTS https://mjhid.org/index.php/mjhid/article/view/2019.012 <p><strong>Background:</strong> This study aimed to identify the risk factors of candidemia and asses possible clinically significant differences between <em>Candida parapsilosis</em> and other candida species among cancer patients.</p> <p><strong>Methods:</strong> A retrospective study was conducted in a Chinese tertiary cancer center over a 6-year period. A total of 323 cancer patients were enrolled and analyzed from 2012 to 2018. Data about demographic characteristics, underlying diseases, and risk factors of candidemia were collected. Univariate and multivariate logistic regression models were used to identify the risk factors associated with the development of candidemia.</p> <p><strong>Results:</strong> Among the isolates, the species most frequently isolated was <em>C. parapsilosis</em> (37.15%, 120/323), and <em>C. albicans </em>only accounted for 34.37%. Based on statistical analysis, when candidemia patients who had <em>C. parapsilosis</em> were compared with other <em>Candida</em> spp., the following factors were found to be significantly associated with <em>C. parapsilosis</em> fungemia: parenteral nutrition (p &lt; 0.001), neutropenia (p &lt; 0.001), receipt of chemotherapy (p = 0.002), and previous antifungal use (p &lt; 0.001). Parenteral nutrition was a factor that independently predicted <em>C. parapsilosis</em> candidemia (OR, 0.183; 95% CI, 0.098–0.340; p &lt; 0.001).</p> <p><strong>Conclusions:</strong> In short, <em>C. parapsilosis </em>as the leading non-<em>albicans Candida </em>spp. isolates in candidemia is posing a major threat for cancer patients. The study highlights the urgent need to evaluate the possibility of development of <em>C. parapsilosis</em> candidemia in cancer patients exposed to these risk factors effective and prevention strategies against this causative agent transmitted through nosocomial route should be implemented.</p> Mingyue Sun Chunguang Chen weiqiang xiao yanmin Chang cailin Liu Qingxia Xu ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019012 e2019012 10.4084/mjhid.2019.012 HIGH PREVALENCE OF HEPATITIS C VIRUS ASSOCIATED B-CELL LYMPHOMA IN MANSOURA REGION (EGYPT), ANRS 12263 STUDY https://mjhid.org/index.php/mjhid/article/view/2019.011 <p><strong><span style="text-decoration: underline;">Abstract&nbsp;:</span></strong>&nbsp;</p> <p><strong>Background:</strong> The prevalence of Hepatitis C virus in Egypt reaches 15%, which is considered the highest in the world. Genotype 4 represents 93 % of Egyptian HCV infections. Non-Hodgkin lymphoma (NHL) is the 5th most common cancer in Egypt. The association between HCV infection and occurrence of B-cell NHL is well known while data are scarce in Eastern countries. <strong>Objectives</strong>: We aimed to evaluate the prevalence of HCV infection among patients with B-cell NHL and the clinical characteristics of HCV associated B-cell NHL in Delta region (Mansoura-Egypt). <strong>Methods</strong>: Between March 2012 and March 2013, 110 adult patients newly diagnosed with B-cell NHL were enrolled in the current study. This study was carried out at Oncology Center, Mansoura University. Study subjects provided serum for HCV testing and for HCV RNA. <strong>Results: </strong>The prevalence of HCV infection among these patients was 61% (67/110 patients) which is the highest reported value in literature. Among them, 80% (32/40 tested patients) presented with viremia. Contrasting with the histological distribution previously described in Northern regions, the majority of HCV associated lymphomas were DLBCLs (72 %) followed by SLL/CLL (13 %), follicular lymphomas (7.5%) and 7.5% of marginal zone lymphomas. <strong>In conclusion</strong>: &nbsp;B-cell lymphomas are highly associated with HCV infection in Egypt. Further developments are needed to give access to antiviral treatment for those patients in Delta region.&nbsp;</p> Layla M. Saleh Danielle Canioni Sameh Shamaa Maha El-Zaafarany Ziad Emarah Sherin Abdel-Aziz Entsar Eladle Alsaeed Abdelaziz Olivier Hermine Caroline Besson Hasan Abdel-ghaffar ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019011 e2019011 10.4084/mjhid.2019.011 CHRONIC KIDNEY DISEASE AMONGST SICKLE CELL ANAEMIA PATIENT AT THE UNIVERSITY OF MAIDUGURI TEACHING HOSPITAL, NORTH EASTERN NIGERIA: A STUDY OF PREVALENCE AND RISK FACTORS https://mjhid.org/index.php/mjhid/article/view/2019.010 <p><strong>ABSTRACT</strong></p><p><strong>Introduction</strong>: Involvement of the kidneys in patient with sickle cell anaemia is a well recognized chronic complication of this disorder. The index study seeks to determine the prevalence of chronic kidney disease in patients with homozygous sickle cell disease (HbSS) and to identify risk factors associated with its development.</p><p><strong>Methodology</strong>: The subjects consisted of adolescents and adults with HbSS recruited sequentially from the adult haematology outpatient clinic and Day care ward of the unit. Clinical variables including age of diagnosis of SCA, frequency of vaso-occlusive crisis and transfusion therapy, as well as laboratory data including haematological profile, renal function test were obtained from routine blood result. The glomerular filtration rate was estimated (eGFR) using the ‘modification of diet in renal disease’ (MDRD) formula.<sup>.</sup></p><p><strong>Results</strong>: Two hundred and eighty-four HbSS patients were recruited. The prevalence of CKD amongst them was 38.9%.  Further stratification of the patients based on eGFR showed that sixty-nine (26.8%) had hyperfiltration; 35 (13.6%) stage 1 CKD; 53 (20.6%) stage 2 CKD; 61 (23.7%) stage 3 CKD; 30 (11.7%) stage 4 CKD and 9 (3.5%) had end stage renal disease. There was significant association between eGFR and clinical parameters such as age (r -0.353, p=0.000), SBP (r -0.148, p= 0.021), DBP (r -0.213, p=0.001) and total number of blood received (r -0.276, p=0.000); and laboratory parameters such as  PCV (r 0.371, p=0.000); urea ( r 0.527, p=000 ); creatinine (r 0.625, p=0.000) and uric acid  ( r -0.419, p=0.000).</p><p><strong>Conclusion</strong></p><p>The present study has revealed a high prevalence of CKD amongst patients with SCA in this region. Various clinical and laboratory predictors of eGFR were also identified. Monitoring and detection of early stages of these groups of patients may allow for interventions which may delay progression into advance stages and ESRD.</p> Audu Abdullahi Bukar Mohammad Maina Sulaiman Adama Isa Ladu Aisha Mohammed Abba Mohammed Kabir Ahmed Gideon Thomas Marama Usman Ali Medugu Abjah ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019010 e2019010 10.4084/mjhid.2019.010 CAN BASE EXCESS BE USED FOR PREDICT TO NEONATAL SEPSIS IN PRETERM NEWBORNS? https://mjhid.org/index.php/mjhid/article/view/2019.014 <p><strong>Background:</strong> Neonatal sepsis remains an important and potentially life-threatening clinical syndrome and a major cause of neonatal mortality and morbidity. The aim of this study to investigate whether values of base excess before the onset of clinical signs and symptoms of sepsis indicate infection in the early diagnosis of neonatal sepsis.</p> <p><strong>Methods:</strong> In this study a total of 118 infants were enrolled. The infants were classified into two groups: group 1 (sepsis, n=49) and group 2 (control, n=69). Blood gas analysis investigated for screening of neonatal sepsis.</p> <p><strong>Results:</strong> A total of 49 newborns with neonatal sepsis and 69 healthy controls were enrolled. A comparison of markers of sepsis revealed C-reactive protein, interleukin-6 level to be significantly higher and pH, pCO<sub>2</sub>, HCO<sub>3</sub> and base excess values to be significantly lower in newborns with sepsis compared healthy controls (p&lt;0.01). The optimum cut-off value in the diagnosis of neonatal sepsis was found to be -5 mmol/L for base excess. Sensitivity, specificity, positive predictive value and negative predictive value of this base excess cut-off for neonatal sepsis were 75, 91, 86 and 84% respectively.</p> <p><strong>Conclusion: </strong>This is the first study to determine the relationship between the decrease value of base excess and early stage of neonatal sepsis. If the value of base excess &lt;-5 mmol/L without an underlying another reason, may need close follow up of infants for neonatal sepsis and it may help early diagnosis.</p> Sema arayıcı ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-25 2019-02-25 11 1 e2019014 e2019014 10.4084/mjhid.2019.014 PROGNOSTIC IMPACT OF IMMUNOHISTOCHEMICAL P53 EXPRESSION IN BONE MARROW BIOPSY IN HIGHER RISK MDS: A PILOT STUDY https://mjhid.org/index.php/mjhid/article/view/2019.015 <p><strong>Background and objectives:</strong></p> <p>Mutations of the TP53 gene have an unfavorable prognosis in Myelodysplastic Syndromes (MDS). The product of the&nbsp;<em>TP53</em>gene is the p53 protein. Most of&nbsp;<em>TP53</em>mutations entail the accumulation of the protein in the nucleus of tumor cells. The immunohistochemical (IHC) staining for p53 can be a surrogate suggesting a mutational status and, if overexpressed, seems to be of prognostic value by itself. The best prognostic cut-off value of overexpression is controversial. The aim of this pilot study is to investigate about the correct value from a homogenous group of patients with higher IPSS-R risk MDS.</p> <p><strong>Methods:</strong></p> <p>In sixty consecutive patients diagnosed with MDS and categorized as IPSS-R risk “intermediate”, “high” and “very high”, the bone marrow biopsies performed at the diagnosis were retrospectively re-examined for IHC p53 expression. The result of p53 expression was subsequently related to survival.&nbsp;</p> <p><strong>Results:</strong></p> <p>A worst overall survival was observed both in patients whose IHC p53 expression was ≥5% and ≥ 10% compared to the patients with a p53 expression respectively below 5% (p= 0.0063) or 10% (p=0.0038).&nbsp;</p> <p><strong>Conclusions:</strong></p> <p>The ICH p53 expression in bone marrow biopsy in higher risk MDS was confirmed to have prognostic value.&nbsp;&nbsp;These results indicate more than 10% expression as the best cut off value.</p> Alfredo Molteni Emanuele Ravano Marta Riva Michele Nichelatti Laura Bandiera Lara Crucitti Mauro Truini Roberto Cairoli ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-26 2019-02-26 11 1 e2019015 e2019015 10.4084/mjhid.2019.015 SPECTRUM AND IMMUNOPHENOTYPIC PROFILE OF ACUTE LEUKEMIA: A TERTIARY CENTER FLOW CYTOMETRY EXPERIENCE https://mjhid.org/index.php/mjhid/article/view/2019.017 <p><strong>Introduction: </strong>For diagnosis, sub-categorization and follow up of Acute Leukemia (AL), phenotypic analysis using flow cytometry is mandatory.</p> <p><strong>Material and methods</strong>: We retrospectively analyzed immunophenotypic data along with cytogenetics/molecular genetics data (wherever available) from 631 consecutive cases of AL diagnosed at our flow cytometry laboratory from January 2014 to August 2017.</p> <p><strong>Results: </strong>Of the total 631 cases, 52.9% (n=334) were acute lymphoblastic leukemia (ALL), 43.9% (n=277) acute myeloid leukemia (AML), 2.2% (n=14) mixed phenotypic acute leukemia (MPAL) and0.5% (n=3) each of acute undifferentiated leukemia (AUL) and chronic myeloid leukemia in blast crisis (CML-BC). ALL cases comprised of 81.7% (n=273/334) B-cell ALLs (95.2%, n=260/273 common B-ALLs and 4.8%, n=13/273 Pro B-ALLs). CD13 was the commonest cross lineage antigen expressed in B-ALL (25.6%), followed by CD33 (17.9%) and combined CD13/CD33 (11.3%) expression. T-ALLs constituted 18.3% (n=61/334) of total ALLs and included 27.9% (n=17) cortical T- ALLs. CD13 was commonest (32.7%) aberrantly expressed antigen in T-ALLs, followed by CD117 (16.0%). AML cases included 32.1% (n=89/277) AML with recurrent genetic abnormalities, 9.0% (n=25/277) with FLT3/NPM1c mutation and 58.9% (n=163/277) AML NOS including 14.7% (n=24/163) AML M4/M5, 1.8% (n=3/163) AML M6 and 3.7% (n=6/163) AML M7. In AMLs, CD19 aberrancy was the most common (16.3%) followed by CD7 (11.9%).</p> <p><strong>Conclusion: </strong>In this study we document the spectrum; correlate the immunophenotype with genetic data of all leukemias, especially with respect to T-ALL where the data from India is scarce.</p> Nishit Gupta Ravikiran Pawar Sambhunath Banerjee Subhajit Brahma Asish Rath Sundar Shewale Mayur Parihar Manish Singh Arun SR Shekhar Krishnan Arpita Bhattacharyya Anirban Das Jeevan Kumar Saurabh Bhave Vivek Radhakrishnan Reena nair Mammen Chandy Neeraj Arora Deepak Kumar Mishra ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-26 2019-02-26 11 1 e2019017 e2019017 10.4084/mjhid.2019.017 DIFFERENCES IN EX-VIVO CHEMOSENSITIVITY TO ANTHRACYCLINES IN FIRST LINE ACUTE MYELOID LEUKEMIA https://mjhid.org/index.php/mjhid/article/view/2019.016 <h4>BACKGROUND: Induction schedules in acute myeloid leukemia (AML) are based on combinations of cytarabine and anthracyclines. The choice of the anthracycline employed has been widely studied in multiple clinical trials showing similar complete remission rates.</h4> <p><strong>MATERIALS AND METHODS:</strong> Using an <em>ex vivo</em> test we have analyzed if a subset of AML patients may respond differently to cytarabine combined with idarubicin, daunorubicin or mitoxantrone. &nbsp;Bone marrow (BM) samples of 198 AML patients were incubated for 48 hours in 96 well plates, each well containing different drugs or drug combinations at different concentrations. <em>Ex vivo</em> drug sensitivity analysis was made using the PharmaFlow platform maintaining the BM microenvironment. Drug response was evaluated as depletion of AML blast cells in each well after incubation. Annexin V-FITC was used to quantify the ability of the drugs to induce apoptosis, and pharmacological responses were calculated using pharmacokinetic population models.</p> <p><strong>RESULTS: </strong>Similar dose-respond graphs were generated for the three anthracyclines, with a slight decrease in EC<sub>50</sub> with idarubicin (p=1.462E-06), whereas the interpatient variability of either drug was large. To identify those cases of selective sensitivity to anthracyclines, potency was compared, in terms of area under the curve. Differences in anthracycline monotherapy potency greater than 30% from 3 pairwise comparisons were identified in 28.3% of samples. Furthermore, different sensitivity was detected in 8.2% of patients comparing combinations of cytarabine and anthracyclines.</p> <p><strong>DISCUSSION: </strong>A third of the patients could benefit of the use of this test in the first line induction therapy selection, although it should be confirmed in a clinical trial specifically designed.</p> Juan Eduardo Megias-Vericat David Martínez-Cuadrón Joaquin Martínez López Juan Miguel Bergua Mar Tormo Josefina Serrano Ataulfo González Jaime Pérez de Oteyza Susana Vives Belen Vidriales Pilar Herrera Juan Antonio Vera Aurelio López Martínez Adolfo De la Fuente María Lourdes Amador José Ángel Hernández-Rivas María Ángeles Fernández Carlos Javier Cerveró Daniel Morillo Pilar Hernández Campo Julián Gorrochategui Daniel Primo José Luis Rojas Margarita Guenova Joan Ballesteros Miguel Ángel Sanz Pau Montesinos ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-26 2019-02-26 11 1 e2019016 e2019016 10.4084/mjhid.2019.016 H1N1 INFECTION IN PREGNANCY; A RETROSPECTIVE STUDY OF FETO-MATERNAL OUTCOME AND IMPACT OF THE TIMING OF ANTIVIRAL THERAPY https://mjhid.org/index.php/mjhid/article/view/2019.020 <p><strong>Background and Objective:</strong> H1N1 infection carries an increased risk in pregnancy. Our aim was to study the fetomaternal outcome and the effect of early initiation of therapy.</p> <p><strong>Methods:</strong> This is a retrospective descriptive study. Confirmed infected cases were included. Maternal age, parity, gestational age at diagnosis, presenting symptoms, time between presentation and starting therapy, ICU admission, and maternal and perinatal outcome were evaluated.</p> <p><strong>Results: </strong>Nineteen confirmed patients were included. Most patients are 31 years old or more. Multiparous patients were 73.68% and 57.89% were in the third trimester. Most of our patients presented with cough, fever, and chills. Two patients were admitted to the ICU. One of them was a case of maternal mortality. 42.10% of patients were started on therapy only one day after clinical onset of symptoms. 26.31% delivered before 37 completed weeks. 73.68% delivered beyond term. Around one third delivered vaginally. 45% of babies weighed more than 3 kg. Four babies weighed less than 2 kg. Ninety percent had APGAR scores more than 8 at 1 and 5 minutes after delivery. Twenty five percent were admitted to the NICU with no neonatal mortalities.</p> <p><strong>Conclusions: </strong>H1N1 influenza A infection in pregnancy is associated with adverse maternal and perinatal outcomes. Medical and public awareness, low threshold for testing suspected pregnant patients, very early initiation of antiviral therapy, and multidisciplinary approach in our series decreased the overall adverse effects of this infection.</p> <p>&nbsp;</p> Naser Al-Husban, Dr. Prof. Nathir Obeidat, Dr. Prof. Oqba Al-Kuran, Dr. Prof. Khaled Al Oweidat, Dr. Prof. Faris Bakri, Dr. Prof. ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-26 2019-02-26 11 1 e2019020 e2019020 10.4084/mjhid.2019.020 SURVIVAL PROBABILITY IN PATIENTS WITH SICKLE CELL ANEMIA USING THE COMPETITIVE RISK STATISTICAL MODEL https://mjhid.org/index.php/mjhid/article/view/2019.022 <p>The clinical picture of patients with sickle cell anemia (SCA) is associated with several complications some of which could be fatal. The objective of this study is to analyze the causes of death and the effect of sex and age on survival of Brazilian patients with SCA. Data of patients with SCA who were seen and followed at HEMORIO for 15 years were retrospectively collected and analyzed. Statistical modeling was performed using survival analysis in the presence of competing risks estimating the covariate effects on a sub distribution hazard function. Eight models were implemented, one for each cause of death. The cause‐specific cumulative incidence function was also estimated. Males were most vulnerable for death from chronic organ damage (p = 0.0005) while females were most vulnerable for infection (p=0.03). Age was significantly associated (p ≤ 0.05) with death due to acute chest syndrome (ACS), infection, and death during crisis. The lower survival was related to death from infection, followed by death due to ACS. The independent variables age and sex were significantly associated with ACS, infection, chronic organ damage and death during crisis. These data could help Brazilian authorities strengthen public policies to protect this vulnerable population.</p> Samir Ballas Emilia Matos do Nascimento, PhD Clarisse Lopes de Castro Lobo, MD Basilio de Bragança Pereira, PhD ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-26 2019-02-26 11 1 e2019022 e2019022 10.4084/mjhid.2019.022 COMPARISON OF THE POWER OF PROCALCITONIN AND C-REACTIVE PROTEIN TO DISCRIMINATE BETWEEN DIFFERENT AETIOLOGIES OF FEVER IN PROLONGED PROFOUND NEUTROPENIA: A SINGLE-CENTRE PROSPECTIVE OBSERVATIONAL STUDY. https://mjhid.org/index.php/mjhid/article/view/2019.023 <p>Management of fever in prolonged profound neutropenia remains challenging with many possible infectious and non-infectious causes. We investigated whether procalcitonin (PCT) is superior to C-reactive protein (CRP) in discriminating between different etiologies of fever in this setting.</p> <p>CRP and PCT were tested daily during 93 neutropenic episodes in 66 patients. During this study period 121 febrile episodes occurred and were classified into four categories based on clinical and microbiological findings: microbiologically documented infection (MDI); clinically documented infection (CDI); proven or probable invasive fungal disease (IFD); fever of unknown origin (FUO). Values of PCT and CRP at fever onset as well as 2 days later were considered for analysis of their performance in distinguishing etiologies of fever.</p> <p>At fever onset no significant difference in PCT values was observed between different etiologies of fever, whereas median CRP values were significantly higher in case of IFD (median 98.8 mg/L vs 28.8 mg/L, p=0.027). Both PCT and CRP reached their peak at a median of 2 days after fever onset. Median PCT values on day 2 showed no significant difference between etiologies of fever. Median CRP values on day 2 were significantly higher in IFD (median 172 mg/L versus 78.4 mg/L, p=0.002). In MDI median CRP values rose &gt; 100 mg/L, whereas they did not in CDI or FUO.</p> <p>PCT has no added value over CRP for clinical management of fever in prolonged profound neutropenia. When performing reassessment 2 days after fever onset, CRP has better discriminatory power between etiologies of fever.</p> Anke Verlinden Veronique De Vroey Herman Goossens Ella Roelant Ann Van de Velde Zwi Berneman Wilfried Schroyens Alain Gadisseur ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-26 2019-02-26 11 1 e2019023 e2019023 10.4084/mjhid.2019.023 FINAL HEIGHT AND ENDORINE COMPLICATIONS IN PATIENTS WITH β-THALASSSEMIA INTERMEDIA: OUR EXPERIENCE IN NON-TRANSFUSED VERSUS INFREQUENTLY TRANSFUSED PATIENTS AND CORRELATIONS WITH LIVER IRON CONTENT https://mjhid.org/index.php/mjhid/article/view/2019.026 <p><strong>Abstract. <em>Backgrond: </em></strong><strong>β</strong><strong>-</strong>thalassemia intermedia (TI) spans a wide spectrum of severity and carries higher morbidity than previously recognized, including extramedullary hematopoeisis, leg ulcers, gallstones, thrombosis, secondary heart failure, pulmonary hypertension, skeletal deformity, growth retardation and endocrine abnormalities, such as diabetes mellitus, hypothyroidism, osteoporosis, and hypogonadism.</p> <p><strong><em>Objectives:</em></strong> To evaluate the final height and the endocrine complications encountered in young adult patients with TI followed at Hematology Section, Doha (Qatar) in relation to liver iron content in non-transfused versus infrequently transfused TI patients.</p> <p><strong><em>Patients and Methods: </em></strong>This retrospective cohort study was performed on 28 young adults with TI who were randomly selected from the Hematology Clinic of the Hematology Section, National Centre for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar).</p> <p>Eligibility criteria for this retrospective analysis included TI patients diagnosed by complete blood count, hemoglobin electrophoresis and young adult age ( ≥ 18 years).</p> <p>Group 1 included 9 patients who did not receive any blood transfusion and Group 2 included 19 patients who infrequently received blood transfusion.</p> <p>Data recorded from charts included demographic characteristics (gender, date of birth, ethnicity), disease and treatment characteristics (e.g., transfusion frequency, history of chelation therapy, and splenectomy), auxological and pubertal data [growth percentiles and pubertal stages, and body mass index (BMI)], laboratory data and target organ complications (including endocrinopathies and liver disease). Iron overload was assessed by direct (liver iron content; LIC) and indirect methods (SF), and bone mass index (BMA) by dual-energy X-ray absorptiometry (DXA).</p> <p><strong><em>Results:</em></strong> Short stature [Final Height (Ht) SDS &lt; -2] occurred in 25% of patients with no difference between the two groups of patients. Insulin growth factor 1 (IGF-1) SDS was low in 35.7 % of patients with no statistical difference among the two groups. Impaired fasting blood glucose occurred in 17.8% of patients, diabetes mellitus in 25% and hypogonadotropic hypogonadism in 10.7% of them. Morning cortisol was low in one patient. No thyroid or hypoparathyroid abnormalities were detected in any patient. Liver iron content (LIC) &gt; 15 mg/g dry weight and SF &gt; 2,000 ng/mL were detected in 75% of the patients. The values resulted significantly higher in the transfused group (Group 2). High liver enzyme level (ALT) was detected in 42.8 % of patients and the values were significantly higher in the transfused group (Group 2).Total and fetal Hb was significantly higher in group 1 versus group 2. Osteopenia was diagnosed in 14.3% of patients. Females had significantly better final height SDS, higher IGF-1 SDS, lower LIC and fasting blood glucose level compared to males. Ht-SDS was correlated significantly with IGF-1 SDS. LIC was correlated significantly with SF level. ALT concentrations were correlated significantly with LIC and SF levels. Total and fetal Hb did not correlate significantly with Ht-SDS or IGF-1 level.</p> <p>&nbsp;<strong><em>Conclusions:</em></strong> A significant number of TI patients have high LIC, short stature and endocrine disorders. Patients who require occasional transfusions have more liver iron overload and higher hepatic dysfunction. Females appear to attain better final adult height and have higher IGF1- SDS versus males. Our data emphasize the need for long term surveillance for identification of organ-specific risk factors and early disease manifestations.We also recommend a close monitoring of endocrine and other complications, according to the international guidelines.</p> Vincenzo De Sanctis Mohamed Yassin ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-25 2019-04-25 11 1 e2019026 e2019026 10.4084/mjhid.2019.026 LANGERANS CELL HISTIOCYTOSIS: SINGLE CENTER EXPERIENCE OF 25 YEARS https://mjhid.org/index.php/mjhid/article/view/2019.035 <p>Objectives: To review a single center outcome of patients with Langerhans Cell Histiocytosis diagnosed at a referral tertiary hospital from Turkey.<br>Methods: The files between 1989 and 2014 of 80 patients with LCH were retrospectively analyzed. <br>Results: During the 25 year period, 80 patients were diagnosed with LCH. The median age at diagnosis was 53 months (2-180 months) and median follow-up time of patients was 10 years and 9 months (24 months-25 years). Bone was the most frequently affected organ (n:60, 75%). Initially, 43 patients (54%) had single system (SS) disease, 20 patients (25%) had multisystem (MS) disease without risk organ involvement (MS-RO-), and 17 patients (21%) had multisystem disease with risk organ involvement (MS-RO+). The overall survival (OS) rate was 91% and event-free survival (EFS) rate was 67% at 10 years. The overall survival rate was lower in patients with RO involvement (p=&lt;0.001), lack of response to systemic chemotherapy on 12th week (p=&lt;0.001), younger age (&lt;2 years) at presentation (p=&lt;0.02), and skin involvement (&lt;0.001). <br>Discussion: Besides the known risk factors like younger age (&lt;2 years) at presentation, multi system risk organ involvement, and lack of response to initial chemotherapy, skin involvement was also associated with unfavorable outcome in our cohort. Evaluation of large cohorts of patients is needed to investigate this further.</p> Gulen Tuysuz İnci Yildiz Nihal Ozdemir Ibrahim Adaletli Sebuh Kurugoglu Hilmi Apak Sergulen Dervisoglu Selen Bozkurt Tiraje Celkan ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-25 2019-04-25 11 1 e2019035 e2019035 10.4084/mjhid.2019.035 TREATMENT PATTERNS IN PATIENTS WITH CHRONIC-PHASE CHRONIC MYELOID LEUKAEMIA IN ROUTINE CLINICAL PRACTICE: THE SIMPLICITY ITALIAN POPULATION https://mjhid.org/index.php/mjhid/article/view/2019.025 <h2>Background and Objectives</h2> <p>While tyrosine kinase inhibitors (TKIs) have transformed CP-CML management, limited data exist on their use in clinical practice.</p> <h2>Methods</h2> <p>SIMPLICITY (NCT01244750) is an observational study in CP-CML patients, exploring first‑line (1L) TKI use and management patterns in the US and Europe. Over half of the patients recruited in Europe are from Italy (n=266). This is an analysis of the Italian cohort and a comparison with the rest of the European SIMPLICITY population. Baseline demographic, factors influencing choice of first-line TKI, response monitoring patterns and predictors of monitoring, and treatment interruptions, discontinuations and switching by index TKIs are presented for the Italian cohort in the first year of treatment and compared with that for the overall European SIMPLICITY cohort.</p> <h2>Results</h2> <p>Italian patients received 1L imatinib (IM; retrospective [(n=31]; prospective [n=106]), dasatinib (DAS; n=56) or nilotinib (NIL; n=73). Documented cytogenetic response monitoring by 12 months was lower than expected, but almost all patients had documented molecular response monitoring. Fewer patients discontinued first-line TKI by 12 months in Italy compared with the rest of the European SIMPLICITY population (p=0.003). Of those with ≥12 months follow-up since start of 1L TKI, only 7.1% (n=19) of Italian patients switched to a second-line TKI, a third less than in the rest of the European SIMPLICITY population. Of interest, intolerance as opposed to resistance, was the main reason for switching.</p> <h2>Conclusion</h2> <p>This analysis provides valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice.</p> Elisabetta Abruzzese ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-26 2019-04-26 11 1 e2019025 e2019025 10.4084/mjhid.2019.025 CLINICAL PRESENTATION, LABORATORY ANALYSIS AND LINEAR GROWTH IN 50 NEONATES AND YOUNG INFANTS WITH ACUTE MENINGITIS: ONE YEAR EXPERIENCE OF A SINGLE CENTER IN QATAR https://mjhid.org/index.php/mjhid/article/view/2019.028 <p><strong>Abstract</strong></p> <p><strong>Introduction: </strong><strong>Meningitis occurs frequently in neonates and can lead to a number of acute, severe complications and long-term disabilities. Although, long term growth delay and abnormal weight gain appear to be risk factors following an acute attack of both bacterial and aseptic meningitis in children, especially during the fast phase of infantile growth, the long-term effects of acute meningitis occurring during the neonatal and early infantile periods on linear growth (length, weight and head growth) have not fully reported. </strong></p> <p><strong>Aim of the study:</strong><strong> The objective of this study is to describe the clinical presentation of neonates and young infants with acute meningitis with</strong><strong> different etiologies</strong><strong> and </strong><strong>to determine the clinical impact of </strong><strong>the effect of acute meningitis </strong><strong>on growth parameters. </strong></p> <p><strong>Material and methods: </strong><strong>We analyzed the clinical data and the growth parameters of 50 newborns and young infants (age: 1.6 ± 0.9 month) admitted to our hospital (Al Wakhra Hospital, Department of Pediatrics, Doha ,Qatar), between 1-1-2016 to 1-1-2017, with acute meningitis. Anthropometric measurements included weight, length, and head circumference. Length SDS (L-SDS) and body mass-index (BMI) were calculated and recorded at every clinic visit, every 3 months for 8 ± 2 months. </strong></p> <p><strong>Results: </strong><strong>In this age group of neonates&nbsp;and young infants with acute meningitis fever (84%) and hypoactivity (64%) were the major presenting manifestations. Acute bacterial meningitis (n: 10) was associated with higher morbidity [shock (n: 1), subdural empyema (n: 1) and hydrocephalus (n: 1)]. </strong><strong>Cerebrospinal fluid (CSF) examinations </strong><strong>showed that infants with bacterial meningitis had significantly higher pleocytosis</strong><strong> of mainly polymorphic leukocytes </strong><strong>and </strong><strong>protein levels, </strong><strong>compared to those with aseptic meningitis </strong></p> <p><strong>All infants showed normal linear growth and weight gain during the follow-up period (8 ± 2 months). The annualized growth rate of infants = 25.3 ± 3.5 cm per year. All had normal length standard deviation scores (LSDS) (-0.2 ± 0.9) and none of them had LSDS &lt; -2. All infants had normal BMI (16.7 ± 1.8 kg/m<sup>2</sup>). Head circumference growth was normal in 49/50 infants (43.8 ± 1.8 cm) at 8 ± 2 months. One infant developed hydrocephalus after GBS meningitis. There was no statistical difference in linear growth between infants with aseptic and bacterial meningitis. </strong></p> <p><strong>Conclusion: </strong><strong>Acute bacterial meningitis in newborns and young infants is still associated with considerably high morbidity and complications. Infantile linear growth appears to be normal in all newborns and young infants with both bacterial and aseptic meningitis.</strong></p> <p><strong>&nbsp;</strong></p> <p><strong>&nbsp;</strong></p> Vincenzo De Sanctis ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-26 2019-04-26 11 1 e2019028 e2019028 10.4084/mjhid.2019.028 DIRECT ACTING ANTIVIRAL TREATMENT FOR PATIENTS WITH END STAGE KIDNEY DISEASE WITH ACUTE HCV INFECTION https://mjhid.org/index.php/mjhid/article/view/2019.034 <p>Background: Hepatitis C virus (HCV) infection is a public health problem. Such an infection is prevalent and aggressive in patients with end-stage kidney disease (ESKD). The efficacy and the safety of direct acting antivirus (DAA) in patients with acute HCV and ESKD is under investigation. The aim of this study was to assess the safety and efficacy of sofosbuvir containing regimens in this difficult-to-treat population.</p> <p>Methods: A prospective and observational study was conducted to evaluate the efficacy and the safety of sofosbuvir containing regimen in patient with ESKD who were undergoing haemodialysis and were acutely infected with HCV. Subjects either received sofosbuvir 200 mg and daclatasvir 60 mg daily or sofosbuvir 400mg/ledipasvir 60mg daily for 12 weeks.&nbsp;&nbsp;</p> <p>Results: 19 Patients were recruited in this study who were infected with HCV genotype 1a. All subjects achieved sustained virologic response (SVR) twelve weeks after finishing the treatment course. No major adverse effects were reported and the treatment course was well tolerated.</p> <p>Conclusions: sofosbuvir containing regimens were effective and safe for the treatment of acute HCV in patients with ESKD who were on haemodialysis.</p> Nawfal R Hussein Zana Saleem Kais Abd ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-27 2019-04-27 11 1 e2019034 e2019034 10.4084/mjhid.2019.034 NUCLEOTIDE SUBSTITUTIONS IN HEPATITIS B VIRUSES DERIVED FROM CHRONIC HBV PATIENTS https://mjhid.org/index.php/mjhid/article/view/2019.046 <p><strong>Background</strong>: Mutations in the S gene (HBsAg), precore (PC) and basic core promoter (BCP) of the hepatitis B virus (HBV) are correlated with a wide spectrum of diseases. This study assessed the frequency of mutations in the S gene, PC and BCP regions in chronic hepatitis B (CHB) patients.</p> <p>&nbsp;</p> <p><strong>Methods</strong>: 104 CHB patients who visited Tehran Hepatitis centers, were included. The viral load of samples was determined based on the TaqMan method. Regions of the S gene, PC and BCP were amplified by the nested PCR. Positive PCR products were sequenced and analyzed.</p> <p>&nbsp;</p> <p><strong>Results</strong>: Successfully sequenced S gene region revealed all the derived strains were genotype D, with the majority (90%) belonging to the ayw2 subtype, and the rest (9%) to the ayw1 subtype. The prevalence of mutations was found to be 51% and 18% in the HBsAg and MHR regions, respectively. 70% of amino acid changes within HBsAg occurred in different immune epitopes, of which 27% and 72% were located in B cell and Th epitopes, respectively. Successfully sequenced PC and BCP regions showed at least one mutation in 84.6% of the patients. The PC and BCP mutations were G1896A (61%), G1899A (23%), A1762T/G1764A (23%) and G1764T/C1766G (26%). None of the strains with A1762T/G1764A mutation carried the G1764T/C1766G mutant.</p> <p>&nbsp;</p> <p><strong>Conclusion</strong><strong>s</strong>: Our results showed common mutations within HBsAg, occurring in immune epitopes, a high rate of G1896A mutations in the PC region, and a negative correlation between the emergence of A1762T/G1764A mutation and the G1764T/C1766G mutant in the BCP region.</p> <p>&nbsp;</p> Narjes Shokatpour Maryam Vaezjalali Graham R Foster Shahnaz Sali ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-24 2019-06-24 11 1 e2019046 e2019046 10.4084/mjhid.2019.046 HOMOZYGOUS DELETION ALFA-THALASSEMIA AND HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN, TWO GENETIC FACTORS PREDICTIVE THE REDUCTION OF MORBIDITY AND MORTALITY DURING PREGNANCY IN SICKLE CELL PATIENTS . A REPORT FROM DEMOCRATIC REPUBLIC OF CONGO https://mjhid.org/index.php/mjhid/article/view/2019.039 <p>FHb and alpha-thal are two genetic factors that modulate the clinical expression of sickle cell disease.</p> <p>Objective: to determine the beneficial role of FHb and alpha-thal on fetal and maternal morbidity during pregnancy in sickle cell patients.</p> <p>This is a documentary and analytical study that included 960 deliveries of homozygous sickle cell patients. The deliveries were divided into three genotype subgroups: Hb-SS / alpha-thal, HbSS / HPFH and HbSS. The diagnosis of SCD and the quantification of FHb were performed by the capillary electrophoresis technique. The diagnosis of SCD has been confirmed by the molecular test. The diagnosis of alpha-thal was made by the multiplex ligation dependent probe amplification (MLPA) technique. Sickle cell pregnancies were followed according to the protocol of care in force in our service. The variables of interest were: hematological variables, sickle cell crises during pregnancy, maternal and fetal complications. Statistical analyzes were performed with SPSS 20.0 software. Means and standard deviations were compared with the Student's t and Annova tests. The value of p &lt;0.05 was considered the significance level.</p> <p>The Hb-SS / alpha-thal and HbSS / HPFH genotypes were observed in 101 and 121 women respectively. Otherwise 758 women had the HbSS genotype. The morbidity related to sickle cell complications in the mother and fetus, were less frequent in the Hb-SS / alpha-thal and HbSS / HPFH groups. The statistical differences were statistically significant.</p> <p>This study showed a significant protective effect of alpa-thal and HPFH during pregnancy in sickle-cell pregnant women.</p> <p>FHb and alpha-thal are two genetic factors that modulate the clinical expression of sickle cell disease.</p> <p>Objective: to determine the beneficial role of FHb and alpha-thal on fetal and maternal morbidity during pregnancy in sickle cell patients.</p> <p>This is a documentary and analytical study that included 960 deliveries of homozygous sickle cell patients. The deliveries were divided into three genotype subgroups: Hb-SS / alpha-thal, HbSS / HPFH and HbSS. The diagnosis of SCD and the quantification of FHb were performed by the capillary electrophoresis technique. The diagnosis of SCD has been confirmed by the molecular test. The diagnosis of alpha-thal was made by the multiplex ligation dependent probe amplification (MLPA) technique. Sickle cell pregnancies were followed according to the protocol of care in force in our service. The variables of interest were: hematological variables, sickle cell crises during pregnancy, maternal and fetal complications. Statistical analyzes were performed with SPSS 20.0 software. Means and standard deviations were compared with the Student's t and Annova tests. The value of p &lt;0.05 was considered the significance level.</p> <p>The Hb-SS / alpha-thal and HbSS / HPFH genotypes were observed in 101 and 121 women respectively. Otherwise 758 women had the HbSS genotype. The morbidity related to sickle cell complications in the mother and fetus, were less frequent in the Hb-SS / alpha-thal and HbSS / HPFH groups. The statistical differences were statistically significant.</p> <p>This study showed a significant protective effect of alpa-thal and HPFH during pregnancy in sickle-cell pregnant women.</p> Tite Minga MIKOBI Prosper Tshilobo LUKUSA ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-24 2019-06-24 11 1 e2019039 e2019039 10.4084/mjhid.2019.039 MOLECULAR ANALYSIS OF NON-TRANSFUSION DEPENDENT THALASSEMIA ASSOCIATED WITH HEMOGLOBIN E-β-THALASSEMIA DISEASE WITHOUT α--THALASSEMIA https://mjhid.org/index.php/mjhid/article/view/2019.038 <p><strong>Background:</strong> The finding of many Thai Hb E-β<sup>0</sup>-thalassemia patients with non-transfusion dependent thalassemia (NTDT) phenotype without co-inheritance of α-thalassemia has prompted us to investigate the existence of other genetic modifying factors.</p> <p><strong>Methods:</strong> Study was done on 146 adult Thai patients with NTDT Hb E-β<sup>0</sup>-thalassemia and a homozygous β-thalassemia patient without co-inheritance of α-thalassemia. Multiple single-nucleotide polymorphisms (SNPs) associated with γ-globin gene expression including the <sup>G</sup>γ-<em>Xmn</em>I of HBG2 gene, rs2297339, rs4895441, and rs9399137 of the HBS1L-MYB gene, rs4671393 in the BCL11A gene, and G176AfsX179, T334R, R238H and -154 (C-T) in the KLF1 gene were investigated using PCR-and related techniques.</p> <p><strong>Results:</strong> Heterozygous and homozygous for <sup>G</sup>g-<em>Xmn</em>I of HBG2 gene were detected at 68.0% and 6.1%, respectively. Further DNA analysis identified the rs2297339 (C-T), rs4895441 (A-G), and rs9399137 (T-C) of HBS1L-MYB gene in 86.4%, 22.5% and 20.4%, respectively. The rs4671393 (G-A) of the BCL11A gene was found at 31.3%. For the KLF1 gene, the T334R and G176AfsX179 (+/-) were detected at 8.2% and 1.4%, respectively.</p> <p><strong>Conclusion:</strong> It was found that these SNPs when analyzed in combination could explain the mild phenotypic expression of all cases. These results underline the importance of these informative SNPs on phenotypic expression of Hb E-β-thalassemia patients.</p> Paramee Phanrahan Supawadee Yamsri Nattiya Teawtrakul Goonnapa Fucharoen Kanokwan Sanchaisuriya Supan Fucharoen ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-24 2019-06-24 11 1 e2019038 e2019038 10.4084/mjhid.2019.038 MALNUTRITION, SEPSIS AND TUMOR LYSIS SYNDROME ARE ASSOCIATED WITH INCREASED RATE OF ACUTE MORTALITY IN MATURE B CELL NON-HODGKIN LYMPHOMA IN PEDIATRIC POPULATION- STUDY FROM TERTIARY CARE HOSPITAL IN PAKISTAN https://mjhid.org/index.php/mjhid/article/view/2019.043 <p><u>Background:</u></p> <p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Outcomes of pediatric mature B cell NHL in resource challenged countries are negatively affected by increased rate of early and toxic deaths. Aim of this study is to assess rate of acute mortality and define significant risk factors present in children with mature B Cell NHL.</p> <p><u>Methods:</u></p> <p>A retrospective analysis was done of patients with B cell NHL from January 2012 till December 2016. Risk factors studied for acute mortality were malnutrition, stage, prior surgery with open laparotomy, LDH levels, tumor lysis syndrome, sepsis and fungal infection</p> <p><u>Results:</u></p> <p>Total 233 patients were enrolled in the study. Eighty five (36.4%) were below 15<sup>th</sup> percentile. &nbsp;Treatment was started in 226 patients. Eighty eight percent children showed 20% response after COP pre-phase. Tumor lysis syndrome was developed in 20.6 % (n = 48) children and 42.9% (n = 100) patients had sepsis, 71/100 patients had culture proven sepsis. 19.7% (n = 46) patients developed fungal infection. There was 19.7% (n = 46) acute mortality.&nbsp; Most common cause of death was sepsis (n = 22, 47.8%) followed by acute renal failure secondary to tumor lysis syndrome. On multivariate analysis, three independent variables found significant for early death are malnutrition, sepsis and tumor lysis syndrome.</p> <p><u>Conclusion:</u></p> <p>Rate of acute mortality in B cell NHL is high in our set up and significant risk</p> <p>factors are tumor lysis syndrome, sepsis and malnourishment at time of presentation.</p> Raheela Mansoor ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-24 2019-06-24 11 1 02019043 02019043 10.4084/mjhid.2019.043 PREVALENCE OF BLATEM, BLASHV, AND BLACTX-M GENES AMONG ESBL-PRODUCING KLEBSIELLA PNEUMONIAE AND ESCHERICHIA COLI ISOLATED FROM THALASSEMIA IN ERBIL, IRAQ https://mjhid.org/index.php/mjhid/article/view/2019.041 <p>Due to the recent appearance of organisms that are resistant to several drugs (multidrug-resistant) like Enterobacteriaceae that produce extended-spectrum β-lactamase (ESBL, concerns have remarkably increased regarding the suitable treatment of infections. The present study was an investigation into ESBL molecular characteristics among clinical isolates of <em>Klebsiella pneumoniae</em> and <em>Escherichia coli</em> resulting in UTIs and their pattern of antimicrobial resistance in order to come up with helpful information on the epidemiology of these infections and risk factors accompanied with them. In order to conduct the study, 20 <em>K. pneumoniae</em> and 48 <em>E. coli</em> were isolated and retrieved from thalassemia center in Erbil, Iraq during July 2016 and September 2016. The collected strains were analyzed and the profile of their antimicrobial susceptibility was specified. In order to spot β-lactamase genes (i.e. <em>bla</em>TEM, <em>bla</em>SHV, and <em>bla</em>CTX-M), polymerase chain reaction was conducted. The results obtained from multiplex PCR assay showed that out of the collected strains of ESBL-producing <em>E. coli</em>, 37 had 81% <em>bla</em>TEM, 16.2% <em>bla</em>SHV, and 32.4% <em>bla</em>CTX-M genes. Similarly, 64.7% <em>bla</em>TEM, 35.2% <em>bla</em>SHV, and 41.1% <em>bla</em>CTX-M genes existed in the isolates of<em> K. pneumoniae</em>. It was found that antibiotic resistance pattern of <em>E. coli</em> and <em>K. pneumoniae</em> isolates to 20 antibiotics varied widely. It was also concluded that the majority of the <em>K. pneumoniae </em>and <em>E. coli</em> isolates were multi-drug resistant (MDR). Moreover, 75% and 87.5% of respectively <em>K. pneumoniae</em> and <em>E. coli</em> isolates showed the MDR phenotypes. TEM prevalence was high among other types of ESBLs. Over all, the most active antimicrobial agents <em>in vitro</em> remained to be the carbapenems.</p> Pishtiwan Ahmad Hamad Khalil Mustafa Khadija ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-25 2019-06-25 11 1 e2019041 e2019041 10.4084/mjhid.2019.041 DIRECT ORAL ANTICOAGULANTS IN PATIENTS AFFECTED BY MAJOR CONGENITAL THROMBOPHILIA https://mjhid.org/index.php/mjhid/article/view/2019.044 <p><strong>Introduction</strong>: Thrombophilia is a condition that predisposes to a higher incidence of venous thromboembolisms (VTE), some also in atypical sites. Direct oral anticoagulants (DOACs) have proven to be effective in the treatment of deep vein thrombosis (DVT). However, their use can be sometimes challenging in particular settings of patients such as those with major thrombophilia - antithrombin, protein C and protein S deficiency, homozygous mutation of Factor V Leiden, homozygous mutation of Factor II G20210A, combined heterozygous mutation of factor V Leiden and Factor II G20210A – carrying a high thrombotic risk.</p> <p><strong>Patients and methods</strong>: At our Center, 45 patients with major thrombophilia were treated with DOACs: 33 after an initial treatment with vitamin K antagonists (VKA) and 12 as first line therapy for VTE. The median follow-up of DOACs treatment was 29 months.</p> <p><strong>Conclusions</strong>: No patient presented hemorrhagic or thrombotic complications during DOAC therapy. DOACs have proven to be effective and safe in this real-life series of patients with major thrombophilia.</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;</p> alessandra serrao benedetta lucani davide mansour antonietta ferretti erminia baldacci cristina santoro robin foà antonio chistolini ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-25 2019-06-25 11 1 e2019044 e2019044 10.4084/mjhid.2019.044 Seroprevalence of Toxocara canis in the city of Catania, Italy. https://mjhid.org/index.php/mjhid/article/view/2019.031 <p>Toxocariasis is one of the most common helminthiases worldwide. However, there is a lack of data regarding Southern Italy. We have evaluated the seroprevalence and associated environmental factors of toxocariasis in a sample of adults living in the city of Catania.</p> <p>Presence of anti-<em>Toxocara canis</em> IgG antibodies was searched using an ELISA test using excretory/secretory antigens. Environmental risk factors have beene valuated with a face-to-face questionnaire.</p> <p>Two hundred eighty-seven subjects (mean age of 48.1±15.6 years) were enrolled, and presence of anti <em>T. canis</em> antibodies was found in 23 participants, of whom 18 (78.3%) were women with a mean age of 51.1±14.0 years, giving a seroprevalence of 8.0% (95%CI 5.4-11.7). At multivariate analysis a positive association for subjects with more than 3 siblings (adjOR 3.17; 95%CI 1.09-9.25) was recorded.</p> <p>Our study confirms that exposition to <em>T. canis</em> is common also in urban areas of western countries.</p> Alessandra Nicoletti Calogero Edoardo Cicero Antonia Mantella Loretta Giuliano Cristina Rascunà Vincenza Paradisi Alessandro Bartoloni Mario Zappia Vito Sofia ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-27 2019-04-27 11 1 e2019031 e2019031 10.4084/mjhid.2019.031 A real-world study on Clofarabine and Cytarabine combination in patients with relapsed/refractory acute myeloid leukemia https://mjhid.org/index.php/mjhid/article/view/2019.032 <p>NA</p> Claudio Fozza Valeria Crobu Giovanni Caocci Giorgio La Nasa Giovanni Sotgiu Laura Saderi ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-29 2019-04-29 11 1 e2019032 e2019032 10.4084/mjhid.2019.032 Azacytidine failure revisited: an appraisal based on real life data from the MDS registry of the Hellenic Myelodysplastic Syndrome Study Group (HMDS). https://mjhid.org/index.php/mjhid/article/view/2019.045 <p>N/A</p> IOANNIS KOTSIANIDIS ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-06-25 2019-06-25 11 1 e2019045 e2019045 10.4084/mjhid.2019.045 In Vivo Emergence of UL56 C325Y Cytomegalovirus Resistance to Letermovir in a Patient with Acute Myeloid Leukemia after Hematopoietic Cell Transplantation https://mjhid.org/index.php/mjhid/article/view/2019.001 <p>CMV associated tissue-invasive disease is associated with a considerable risk of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Recently, the terminase inhibitor letermovir (LMV) has been approved for prophylaxis of CMV infection in HSCT. We hereby report a 60-year-old female experiencing CMV reactivation after HSCT in a CMV seronegative donor-constellation. Due to ongoing elevated CMV viral load and drug-associated myelosuppression, which prevented ganciclovir therapy, treatment was replaced by foscarnet. Due to nephrotoxicity, foscarnet was switched to LMV. The patient developed skin GvHD and prednisolone was started. Subsequently, CMV viremia worsened despite LMV therapy. Genotyping revealed the mutation C325Y of the CMV UL56 terminase being associated with high-level resistance against LMV. Prolonged uncontrolled low-level viremia due to prednisolone treatment may have favored the selection of drug-resistant CMV. Despite the excellent toxicity profile of LMV, physicians should be aware of risk factors for the emergence of resistance.</p> Jochen J Frietsch Detlef Michel Thomas Stamminger Friederike Hunstig Sebastian Birndt Ulf Schnetzke Sebastian Scholl Andreas Hochhaus Inken Hilgendorf ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019001 e2019001 10.4084/mjhid.2019.001 Bortezomib maintenance for the treatment of Monoclonal Gammopathy of Renal Significance https://mjhid.org/index.php/mjhid/article/view/2019.007 <p>Monoclonal gammopathy of renal significance (MGRS) defines renal disease resulting from monoclonal proteins that are secreted from clonal B cells, that does not meet criteria for lymphoma or multiple myeloma. Recognizing MGRS in clinical practice is important because renal outcomes are poor and treatments targeting the underlying clonal disease have been associated with improved renal survival. In this case report, we present a case of a patient with membranoproliferative glomerulonephritis (MPGN) with IgG-kappa deposition who underwent clone directed treatment in a phased approach with induction and maintenance to achieve renal response. This is one of the first cases to report on MGRS treatment that required extended maintenance therapy.</p> Holly Lee Peter Duggan Ernesta Paola Neri Jason Tay Victor Jimenez Zepeda ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-01-01 2019-01-01 11 1 e2019007 e2019007 10.4084/mjhid.2019.007 Novel deleterious sequence change in the NLRP12 gene in a child with autoinflammatory syndrome, joint hypermobility and cutis laxa from India. https://mjhid.org/index.php/mjhid/article/view/2019.018 <p>An otherwise healthy male child of 9 years presented with paroxysmal fever and diffuse abdominal pain along with loss of appetite and nausea lasting for 3-4days every 4-6 weeks for last 2 years. He also has stretchable skin and hypermobile joint which he inherited from his mother who never suffered any paroxysmal attack of the kind.&nbsp; Work up for acute intermittent porphyria, lead poisoning and familial mediterranean fever was negative. A novel harmful sequence change in NLRP12 gene was detected and a diagnosis of NLRP12 associated autoinflammatory syndrome was made. This sequence change with disease has not yet been reported in the literature and is the first such case of NLRP12 related autoinflammatory syndrome from India.</p> Kanjaksha Ghosh Kanchan Mishra Avani Shah Parizad Patel Shrimati Shetty ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-02-26 2019-02-26 11 1 e2019018 e2019018 10.4084/mjhid.2019.018 West Nile virus encephalitis in haematological setting: report of two cases and brief review of the literature https://mjhid.org/index.php/mjhid/article/view/2019.033 <p>West Nile virus is a zoonotic agent causing life-threatening encephalitis in a proportion of infected patients. Older age, immunosuppression and mutations in specific host genes (e.g. CCR5 delta-32 mutation) predispose to neuroinvasive infection. We report on two cases of severe West Nile encephalitis in recently-treated, different-aged, chronic lymphocytic leukemia patients. Both patients developed high-grade fever associated with severe neurological impairment. The younger one harboured germ-line CCR5 delta-32 mutation, which might have played a role in the pathogenesis of its neuroinvasive manifestations.</p> Isacco Ferrarini Antonella Rigo Alberto Gandini Fabrizio Vinante ##submission.copyrightStatement## http://creativecommons.org/licenses/by-nc/4.0 2019-04-27 2019-04-27 11 1 e2019033 e2019033 10.4084/mjhid.2019.033