Mediterranean Journal of Hematology and Infectious Diseases http://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><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 alt="" src="/public/site/images/fguidi/FRECCE0014.gif"></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 alt="" src="/public/site/images/fguidi/FRECCE0014.gif"></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 alt="" src="/public/site/images/fguidi/FRECCE0014.gif"></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 alt="" src="/public/site/images/fguidi/FRECCE0014.gif"></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 alt="" src="/public/site/images/fguidi/FRECCE0014.gif"></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 alt="" src="/public/site/images/fguidi/FRECCE0014.gif"></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 alt="" src="/public/site/images/fguidi/FRECCE0013.gif"></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 alt="" src="/public/site/images/fguidi/FRECCE0012.gif"></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 alt="" src="/public/site/images/fguidi/FRECCE0011.gif"></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 alt="" src="/public/site/images/fguidi/FRECCE001.gif"></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> en-US <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> gleone@mjhid.org (Giuseppe Leone) guidif@hotmail.com (Dr. PhD. Francesco Guidi) Tue, 01 Jan 2019 01:12:23 +0000 OJS 3.1.1.2 http://blogs.law.harvard.edu/tech/rss 60 NEW THERAPEUTIC OPTIONS FOR THE TREATMENT OF SICKLE CELL DISEASE http://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 http://mjhid.org/index.php/mjhid/article/view/2019.002 Tue, 01 Jan 2019 00:58:08 +0000 HIV AND LYMPHOMA: FROM EPIDEMIOLOGY TO CLINICAL MANAGEMENT http://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 http://mjhid.org/index.php/mjhid/article/view/2019.004 Tue, 01 Jan 2019 01:04:28 +0000 INTERNATIONAL MULTICENTER EXPERIENCE IN THE TREATMENT OF INVASIVE ASPERGILLOSIS IN IMMUNOCOMPROMISED CANCER PATIENTS http://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 http://mjhid.org/index.php/mjhid/article/view/2019.003 Tue, 01 Jan 2019 01:01:41 +0000 DETECTION OF CALR MUTATIONS USING HIGH RESOLUTION MELTING CURVE ANALYSIS (HRM-A); APPLICATION ON A LARGE COHORT OF GREEK ET AND MF PATIENTS http://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 http://mjhid.org/index.php/mjhid/article/view/2019.009 Tue, 01 Jan 2019 01:05:34 +0000 THE USE OF HPLC AS A TOOL FOR NEONATAL CORD BLOOD SCREENING OF HAEMOGLOBINOPATHY - A VALIDATION STUDY http://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 http://mjhid.org/index.php/mjhid/article/view/2019.005 Tue, 01 Jan 2019 01:06:14 +0000 RESPIRATORY VIRAL INFECTIONS IN CHILDREN AND ADOLESCENTS WITH HEMATOLOGICAL MALIGNANCIES http://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 http://mjhid.org/index.php/mjhid/article/view/2019.006 Tue, 01 Jan 2019 01:07:03 +0000 BONE MINERAL DENSITY AND VITAMIN D RECEPTOR GENETIC VARIANTS IN EGYPTIAN CHILDREN WITH BETA THALASSEMIA ON VITAMIN D SUPPLEMENTATION http://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 http://mjhid.org/index.php/mjhid/article/view/2019.013 Tue, 01 Jan 2019 01:07:56 +0000 SOLUBLE ST2 AND CD163 AS POTENTIALBIOMARKERS TO DIFFERENTIATE PRIMARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS FROM MACROPHAGE ACTIVATION SYNDROME http://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 http://mjhid.org/index.php/mjhid/article/view/2019.008 Tue, 01 Jan 2019 01:08:45 +0000 INCREASE IN CANDIDA PARAPSILOSIS CANDIDEMIA IN CANCER PATIENTS http://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 http://mjhid.org/index.php/mjhid/article/view/2019.012 Tue, 01 Jan 2019 01:09:47 +0000 HIGH PREVALENCE OF HEPATITIS C VIRUS ASSOCIATED B-CELL LYMPHOMA IN MANSOURA REGION (EGYPT), ANRS 12263 STUDY http://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 http://mjhid.org/index.php/mjhid/article/view/2019.011 Tue, 01 Jan 2019 01:10:35 +0000 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 http://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 http://mjhid.org/index.php/mjhid/article/view/2019.010 Tue, 01 Jan 2019 01:11:17 +0000 In Vivo Emergence of UL56 C325Y Cytomegalovirus Resistance to Letermovir in a Patient with Acute Myeloid Leukemia after Hematopoietic Cell Transplantation http://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 http://mjhid.org/index.php/mjhid/article/view/2019.001 Tue, 01 Jan 2019 01:02:34 +0000 Bortezomib maintenance for the treatment of Monoclonal Gammopathy of Renal Significance http://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 http://mjhid.org/index.php/mjhid/article/view/2019.007 Tue, 01 Jan 2019 00:00:00 +0000