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Clinical Risks And Healthcare Utilization Of Hematopoietic Cell Transplantation For Sickle Cell Disease In The Usa Using Merged Databases., Staci D Arnold, Ruta Brazauskas, Naya He, Yimei Li, Richard Aplenc, Zhezhen Jin, Allistair Abraham, +several additional authors 2017 George Washington University

Clinical Risks And Healthcare Utilization Of Hematopoietic Cell Transplantation For Sickle Cell Disease In The Usa Using Merged Databases., Staci D Arnold, Ruta Brazauskas, Naya He, Yimei Li, Richard Aplenc, Zhezhen Jin, Allistair Abraham, +Several Additional Authors

Pediatrics Faculty Publications

Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 >years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of ...


Flow Cytometric And Demographic Analysis Of T Cell Acute Lymphoblastic Leukemia In Pakistani Population., M R. Khawaja, S S. Allana, N N. Akbaral, S N. Adil, M. Khurshid, Shahid Pervez 2017 Aga Khan University

Flow Cytometric And Demographic Analysis Of T Cell Acute Lymphoblastic Leukemia In Pakistani Population., M R. Khawaja, S S. Allana, N N. Akbaral, S N. Adil, M. Khurshid, Shahid Pervez

Mohammad Khurshid

Background: This study was carried out to analyze the proportion of T cell acute lymphoblastic leukemia (TALL) among all acute lymphoblastic leukemia (ALL) in Pakistani population and its correlation with the demographic features. Accuracy of cell surface markers used in flow cytometric analysis of the leukemic cells was also determined. Methods: Data of 209 consecutive cases of acute lymphoblastic leukemia (ALL) presenting between July 1995 and July 2003 was analyzed. Flow cytometry was performed on all ALL cases using the standard protocols. TALL markers included CD3, CD5 and CD7. Results: Proportion of TALL among known ALL Pakistani patients was 17 ...


Hydroxyurea Lowers The Frequency Of Sickle Cell Vaso-Occlusive Crises, Corey S. Macrander 2017 Wayne State University School of Medicine

Hydroxyurea Lowers The Frequency Of Sickle Cell Vaso-Occlusive Crises, Corey S. Macrander

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med 1995;(332):1317-1322 doi: 10.1056/nejm199505183322001


Chromatin Dynamics During The Differentiation Of Long-Term Hematopoietic Stem Cells To Multipotent Progenitors, Xiang Yu, Chao Wu, Dheeraj Bhavanasi, Hong Wang, Brian D. Gregory, Jian Huang 2017 University of Pennsylvania

Chromatin Dynamics During The Differentiation Of Long-Term Hematopoietic Stem Cells To Multipotent Progenitors, Xiang Yu, Chao Wu, Dheeraj Bhavanasi, Hong Wang, Brian D. Gregory, Jian Huang

Departmental Papers (Biology)

Hematopoietic stem cells (HSCs) are characterized by their self-renewal potential and ability to differentiate into multiple blood lineages.1,2 They are essential for lifelong blood production and represent 1 of the best-studied somatic stem cell systems.2-4 Several decades of successful bone marrow transplants have demonstrated the therapeutic importance of HSCs.5 Much progress has been made to understand the regulatory network of HSC self-renewal and differentiation.6,7 Several studies suggest that epigenetic mechanisms play an important role in controlling HSC renewal and lineage commitment.8-12 Understanding the regulatory mechanisms of HSC self-renewal and differentiation is important for ...


Identification Of A Functional Genetic Variant Driving Racially Dimorphic Platelet Gene Expression Of The Thrombin Receptor Regulator, Pctp., Xianguo Kong, Lukas M. Simon, Michael Holinstat, Chad A. Shaw, Paul F. Bray, Leonard C. Edelstein 2017 Thomas Jefferson University

Identification Of A Functional Genetic Variant Driving Racially Dimorphic Platelet Gene Expression Of The Thrombin Receptor Regulator, Pctp., Xianguo Kong, Lukas M. Simon, Michael Holinstat, Chad A. Shaw, Paul F. Bray, Leonard C. Edelstein

Cardeza Foundation for Hematologic Research

Platelet activation in response to stimulation of the Protease Activated Receptor 4 (PAR4) receptor differs by race. One factor that contributes to this difference is the expression level of Phosphatidylcholine Transfer Protein (PCTP), a regulator of platelet PAR4 function. We have conducted an expression Quantitative Trait Locus (eQTL) analysis that identifies single nucleotide polymorphisms (SNPs) linked to the expression level of platelet genes. This analysis revealed 26 SNPs associated with the expression level of PCTP at genome-wide significance (p < 5×10(-8)). Using annotation from ENCODE and other public data we prioritised one of these SNPs, rs2912553, for functional testing. The allelic frequency of rs2912553 is racially-dimorphic, in concordance with the racially differential expression of PCTP. Reporter gene assays confirmed that the single nucleotide change caused by rs2912553 altered the transcriptional potency of the surrounding genomic locus. Electromobility shift assays, luciferase assays, and overexpression studies indicated a role for the megakaryocytic transcription factor GATA1. In summary, we have integrated multi-omic data to identify and functionalise an eQTL. This, along with the previously described relationship between PCTP and PAR4 function, allows us to characterise a genotype-phenotype relationship through the mechanism of gene expression.


Targeting The Glucose Metabolism Of Myeloid-Derived Suppressor Cells (Mdscs) To Stimulate Cancer Immunity., Jaspreet Grewal 2017 University of Louisville

Targeting The Glucose Metabolism Of Myeloid-Derived Suppressor Cells (Mdscs) To Stimulate Cancer Immunity., Jaspreet Grewal

Electronic Theses and Dissertations

Myeloid derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells that are significantly increased in cancer patients and correlate with higher stage and poor prognosis. MDSCs negatively modulate anti-tumor immunity, suppress T cell activity, promote angiogenesis and increase the risk of metastasis. In this study, we report that monocytic-MDSCs (M-MDSCs) but polymorphonuclear-MDSCs (PMN-MDSCs) over-express 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatases 3 (PFKFB3), an important regulator of glycolysis. Furthermore in the melanoma model, M-MDSCs but not PMN-MDSCs suppressed T cell function which correlated with PFKFB3 over-expression and increased rate of glycolysis. PFKFB3 inhibition with the first-in-class small molecule inhibitor, PFK-158 reversed ...


Improved Survival After Acute Graft-Versus-Host Disease Diagnosis In The Modern Era., Hanna J. Khoury, Tao Wang, Michael T. Hemmer, Daniel Couriel, Amin Alousi, Corey Cutler, Mahmoud Aljurf, Joseph H Antin, Mouhab Ayas, Minoo Battiwalla, Jean-Yves Cahn, Mitchell Cairo, Yi-Bin Chen, Robert Peter Gale, Shahrukh Hashmi, Robert J. Hayashi, Madan Jagasia, Mark Juckett, Rammurti T. Kamble, Mohamed Kharfan-Dabaja, Mark Litzow, Navneet Majhail, Alan Miller, Taiga Nishihori, Muna Qayed, Helene Schoemans, Harry C. Schouten, Gerard Socie, Jan Storek, Leo Verdonck, Ravi Vij, William A. Wood, Lolie Yu, Rodrigo Martino, Matthew Carabasi, Christopher Dandoy, Usama Gergis, Peiman Hematti, Melham Solh, Kareem Jamani, Leslie Lehmann, Bipin Savani, Kirk R. Schultz, Baldeep M. Wirk, Stephen Spellman, Mukta Arora, Joseph Pidala 2017 Winship Cancer Institute of Emory University

Improved Survival After Acute Graft-Versus-Host Disease Diagnosis In The Modern Era., Hanna J. Khoury, Tao Wang, Michael T. Hemmer, Daniel Couriel, Amin Alousi, Corey Cutler, Mahmoud Aljurf, Joseph H Antin, Mouhab Ayas, Minoo Battiwalla, Jean-Yves Cahn, Mitchell Cairo, Yi-Bin Chen, Robert Peter Gale, Shahrukh Hashmi, Robert J. Hayashi, Madan Jagasia, Mark Juckett, Rammurti T. Kamble, Mohamed Kharfan-Dabaja, Mark Litzow, Navneet Majhail, Alan Miller, Taiga Nishihori, Muna Qayed, Helene Schoemans, Harry C. Schouten, Gerard Socie, Jan Storek, Leo Verdonck, Ravi Vij, William A. Wood, Lolie Yu, Rodrigo Martino, Matthew Carabasi, Christopher Dandoy, Usama Gergis, Peiman Hematti, Melham Solh, Kareem Jamani, Leslie Lehmann, Bipin Savani, Kirk R. Schultz, Baldeep M. Wirk, Stephen Spellman, Mukta Arora, Joseph Pidala

Department of Medical Oncology Faculty Papers

A cute graft-versus-host disease remains a major threat to a successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft-versus-host disease. We examined outcome following diagnosis of grade II-IV acute graft-versus-host disease according to time period, and explored effects according to original graft-versus-host disease prophylaxis regimen and maximum overall grade of acute graft-versus-host disease. Between 1999 and 2012, 2,905 patients with acute myeloid leukemia (56%), acute lymphoblastic leukemia (30%) or myelodysplastic syndromes (14%) received a ...


Low Molecular-Weight Heparin Is Better Than Warfarin For Prevention Of Recurrent Venous Thromboembolism In Cancer Patients, Sarah Choi 2017 Wayne State University School of Medicine

Low Molecular-Weight Heparin Is Better Than Warfarin For Prevention Of Recurrent Venous Thromboembolism In Cancer Patients, Sarah Choi

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lee AYY, Levin MN, Bake RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146-153. doi: 10.1056/NEJMoa025313


Diagnosis Of Lchad/Tfp Deficiency In An At Risk Newborn Using Umbilical Cord Blood Acylcarnitine Analysis, Donna Raval, Kristina Cusmano-Ozog, Omar Ayyub, Callie Jenevein, Laura Kofman, Brendan Lanpher, Natalie Hauser, Debra Regier 2017 George Washington University

Diagnosis Of Lchad/Tfp Deficiency In An At Risk Newborn Using Umbilical Cord Blood Acylcarnitine Analysis, Donna Raval, Kristina Cusmano-Ozog, Omar Ayyub, Callie Jenevein, Laura Kofman, Brendan Lanpher, Natalie Hauser, Debra Regier

Pathology Faculty Publications

Trifunctional protein deficiency/Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD/TFP) deficiency is a disorder of fatty acid oxidation and ketogenesis. Severe neonatal lactic acidosis, cardiomyopathy, and hepatic dysfunction are caused by the accumulation of toxic long-chain acylcarnitines. The feasibility of umbilical cord blood use in screening for acylcarnitine analysis and free carnitine has been hypothesized but not reported in LCHAD/TFP neonates.

We present a 4 week old female who was at risk of inheriting LCHAD/TFP deficiency and was diagnosed at the time of delivery using umbilical cord blood. Umbilical cord blood was collected at delivery and sent for acylcarnitine ...


Peritoneal Lymphomatosis: The Failure Of Occam’S Razor, Ranjit R. Nair MD, Nicole M. Agostino DO, Shereen M F Gheith MD, Usman Shah MD 2017 Lehigh Valley Health Network

Peritoneal Lymphomatosis: The Failure Of Occam’S Razor, Ranjit R. Nair Md, Nicole M. Agostino Do, Shereen M F Gheith Md, Usman Shah Md

Shereen M.F. Gheith, M.D., PhD.

No abstract provided.


A Hemodialysis Cohort Study Of Protocol-Based Anticoagulation Management, Steven Lamontagne, Tinzar Basein, Binyue Chang, Lakshmi Mallela 2017 University of Massachusetts Medical School

A Hemodialysis Cohort Study Of Protocol-Based Anticoagulation Management, Steven Lamontagne, Tinzar Basein, Binyue Chang, Lakshmi Mallela

Open Access Articles

BACKGROUND: Chronic hemodialysis patients frequently require anticoagulation treatment with warfarin for a variety of co-morbidities. The optimal method for monitoring and dose adjustment of warfarin-based anticoagulation in this population, however, remains unclear. To examine this more closely, we reviewed all hemodialysis patients at a single institution on chronic warfarin therapy for a 10-month period prior to and after the institution of a standardized protocol for warfarin dose adjustment and monitoring. Anticoagulation efficacy was assessed by time within the therapeutic INR range (TTR), and resource utilization was assessed by the number of weekly INR measurements required for monitoring.

RESULTS: We retrospectively ...


Aapt Diagnostic Criteria For Chronic Sickle Cell Disease Pain., Carlton Dampier, Tonya M Palermo, Deepika S Darbari, Kathryn Hassell, Wally Smith, William Zempsky 2017 George Washington University

Aapt Diagnostic Criteria For Chronic Sickle Cell Disease Pain., Carlton Dampier, Tonya M Palermo, Deepika S Darbari, Kathryn Hassell, Wally Smith, William Zempsky

Pediatrics Faculty Publications

Pain in sickle cell disease (SCD) is associated with increased morbidity, mortality, and high health care costs. Although episodic acute pain is the hallmark of this disorder, there is an increasing awareness that chronic pain is part of the pain experience of many older adolescents and adults. A common set of criteria for classifying chronic pain associated with SCD would enhance SCD pain research efforts in epidemiology, pain mechanisms, and clinical trials of pain management interventions, and ultimately improve clinical assessment and management. As part of the collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities ...


Dynamical System Modeling To Simulate Donor T Cell Response To Whole Exome Sequencing-Derived Recipient Peptides: Understanding Randomness In Alloreactivity Incidence Following Stem Cell Transplantation, Vishal Koparde, Badar Abdul Razzaq, Tara Suntum, Roy Sabo, Allison Scalora, Myrna Serrano, Max Jameson-Lee, Charles Hall, David Kobulnicky, Nihar Sheth, Juliana Feltz, Daniel Contaifer, Dayanjan Wijesinghe, Jason Reed, Catherine Roberts, Rehan Qayyum, Gregory Buck, Michael Neale, Amir Toor 2017 Virginia Commonwealth University, Center for the Study of Biological Complexity

Dynamical System Modeling To Simulate Donor T Cell Response To Whole Exome Sequencing-Derived Recipient Peptides: Understanding Randomness In Alloreactivity Incidence Following Stem Cell Transplantation, Vishal Koparde, Badar Abdul Razzaq, Tara Suntum, Roy Sabo, Allison Scalora, Myrna Serrano, Max Jameson-Lee, Charles Hall, David Kobulnicky, Nihar Sheth, Juliana Feltz, Daniel Contaifer, Dayanjan Wijesinghe, Jason Reed, Catherine Roberts, Rehan Qayyum, Gregory Buck, Michael Neale, Amir Toor

Massey Cancer Center Data

Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA) and graft versus host disease (GVHD) pathophysiology in stem cell transplant (SCT) donor-recipient pairs (DRP) is not established. In order to elucidate this relationship, whole exome sequencing (WES) was performed on 27 HLA matched related (MRD), & 50 unrelated donors (URD), to identify nonsynonymous single nucleotide polymorphisms (SNPs). An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p


Plasmablastic Lymphoma: Case Report Of Prolonged Survival Of An Advanced Human Immunodeficiency Patient And Literature Review, Hind Rafei, Ehab El-Bahesh, Antoine Finianos, Min-Ling Liu, Geraldine Schechter 2017 George Washington University

Plasmablastic Lymphoma: Case Report Of Prolonged Survival Of An Advanced Human Immunodeficiency Patient And Literature Review, Hind Rafei, Ehab El-Bahesh, Antoine Finianos, Min-Ling Liu, Geraldine Schechter

Medicine Faculty Publications

Clinical Practice Points. Plasmablastic lymphoma (PBL) is a rare and highly aggressive variant of diffuse large B cell lymphoma with median survival of advanced stage patients varying between 6 and 15 months in previous reports. We report here a human immunodeficiency virus-infected patient surviving over 12 years following treatment for advanced PBL with EPOCH chemotherapy and intrathecal therapy. This case highlights the potential for improved survival in PBL with intensive chemotherapy. Further, literature review suggests promising prospects utilizing novel targeted therapies to increase the rate of prolonged responses.


Post-Transfusion Purpura: A Case Report Of An Underdiagnosed Phenomenon, Hind Rafei, Raza Yunus, Samah Nassereddine 2017 George Washington University

Post-Transfusion Purpura: A Case Report Of An Underdiagnosed Phenomenon, Hind Rafei, Raza Yunus, Samah Nassereddine

Medicine Faculty Publications

Post-transfusion purpura is a rare transfusion-related complication that often goes undiagnosed. It is due to alloimmunization against platelet antigens which leads to acute profound thrombocytopenia following the transfusion of any platelet-containing product (red blood cells or platelets). It is commonly seen in multiparous women. Here, we report a case of post-transfusion purpura in a 56-year-old multiparous woman who developed acute thrombocytopenia seven days following a packed red blood cell transfusion. We will discuss the clinical presentation, diagnosis, workup and treatment of this rare disease. It is important to recognize this entity separately and to include it in the differential diagnosis ...


Hypercalcemia Due To Primary Hepatic Lymphoma, Andrew Hsu, Michael Gagnier, Elizabeth Ryer, Mohammed Salhab, Alan G. Rosmarin 2016 University of Massachusetts Medical School

Hypercalcemia Due To Primary Hepatic Lymphoma, Andrew Hsu, Michael Gagnier, Elizabeth Ryer, Mohammed Salhab, Alan G. Rosmarin

Open Access Articles

A 65-year-old female with a history of mixed connective tissue disease and pulmonary fibrosis on azathioprine, hydroxychloroquine, and prednisone (osteoporosis on teriparatide) presented with a 1-month history of hypercalcemia. After discontinuation of teriparatide, the patient's hypercalcemia persisted. Further evaluation revealed primary hepatic lymphoma as the source of her hypercalcemia.


Splenic Infarction: An Uncommon Presentation Of Acute Infectious Mononucleosis, Madhulika Urella, Roma Srivastava, Waseem Ahmed, Yehuda Lebowicz 2016 Marshall University Joan C.Edwards School of Medicine

Splenic Infarction: An Uncommon Presentation Of Acute Infectious Mononucleosis, Madhulika Urella, Roma Srivastava, Waseem Ahmed, Yehuda Lebowicz

Yehuda A. Lebowicz, MD

Contrast enhanced CT showing multiple splenic infarcts


Splenic Infarction: An Uncommon Presentation Of Acute Infectious Mononucleosis, Madhulika Urella, Roma Srivastava, Waseem Ahmed, Yehuda Lebowicz 2016 1. Joan C. Edwards School of Medicine, Marshall University

Splenic Infarction: An Uncommon Presentation Of Acute Infectious Mononucleosis, Madhulika Urella, Roma Srivastava, Waseem Ahmed, Yehuda Lebowicz

Marshall Journal of Medicine

Splenic infarction is a relatively uncommon diagnosis. It occurs when the splenic artery or one of its sub-branches is occluded with an infected or bland embolus or clot. Splenic infarction may be caused by atrial fibrillation, bacterial endocarditis, sickle cell disease, antiphospholipid syndrome, and trauma whereas an infectious etiology is uncommon. It is considered a rare presentation of acute infectious mononucleosis. Currently, its pathogenesis is still unclear. We describe a 24-year-old African American female who was admitted for evaluation of left-sided chest pain. Chest imaging, abdominal ultrasound, and initial laboratory data were normal, followed by a negative hypercoagulability panel. Signs ...


Primary Malignant Pleural Effusion With A Profound Type B Lactic Acidosis, Rachel Kinney DO, Christine Saraceni DO, Eliot L. Friedman MD 2016 Lehigh Valley Health Network

Primary Malignant Pleural Effusion With A Profound Type B Lactic Acidosis, Rachel Kinney Do, Christine Saraceni Do, Eliot L. Friedman Md

Department of Medicine

No abstract provided.


Feasibility Of A Community-Based Sickle Cell Trait Testing And Counseling Program, Ashley Housten, Regina Abel, Terianne Lindsey, Allison King 2016 Washington University School of Medicine in St. Louis

Feasibility Of A Community-Based Sickle Cell Trait Testing And Counseling Program, Ashley Housten, Regina Abel, Terianne Lindsey, Allison King

Journal of Health Disparities Research and Practice

Background: Sickle cell trait (SCT) screening is required at birth in the United States; however, adults rarely know their SCT status prior to having children.

Purpose: Assess feasibility of a community-based SCT education and testing intervention.

Methods: Participants were recruited from eight community sites to complete an educational program and offered a hemoglobin analysis. A genetic counselor met individually with participants to discuss lab results.

Results: Between July 14, 2010 and May 31, 2012, 637 participants completed the educational program. Five hundred seventy (89.5%) provided a blood sample, and 61 (10.9%) had SCT or other hemoglobinopathies. The genetic ...


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