Hemic and Lymphatic Diseases Commons^™

Conditional Screening For Ultra-High Dimensional Covariates With Survival Outcomes, Hyokyoung Grace Hong, Jian Kang, Yi Li

The University of Michigan Department of Biostatistics Working Paper Series

Identifying important biomarkers that are predictive for cancer patients' prognosis is key in gaining better insights into the biological influences on the disease and has become a critical component of precision medicine. The emergence of large-scale biomedical survival studies, which typically involve excessive number of biomarkers, has brought high demand in designing efficient screening tools for selecting predictive biomarkers. The vast amount of biomarkers defies any existing variable selection methods via regularization. The recently developed variable screening methods, though powerful in many practical setting, fail to incorporate prior information on the importance of each biomarker and are less powerful in …

Pharmacokinetics And Bioequivalence Of A Liquid Formulation Of Hydroxyurea In Children With Sickle Cell Anemia., Jeremie H. Estepp, Chiara Melloni, Courtney D. Thornburg, Paweł Wiczling, Zora Rogers, Jennifer A. Rothman, Nancy S. Green, Robert Liem, Amanda M. Brandow, Shelley E. Crary, Thomas H. Howard, Maurine H. Morris, Andrew Lewandowski, Uttam Garg, William J. Jusko, Kathleen A. Neville, Best Pharmaceuticals For Children Act-Pediatric Trials Network Administrative Core Committee

Manuscripts, Articles, Book Chapters and Other Papers

Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability …

Hydroxycarbamide Versus Chronic Transfusion For Maintenance Of Transcranial Doppler Flow Velocities In Children With Sickle Cell Anaemia-Tcd With Transfusions Changing To Hydroxyurea (Twitch): A Multicentre, Open-Label, Phase 3, Non-Inferiority Trial., Russell E Ware, Barry R Davis, William H Schultz, R Clark Brown, Banu Aygun, Sharada Sarnaik, Lori Luchtman-Jones, +Several Additional Authors

Pediatrics Faculty Publications

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions.

METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible …

Surgeon's Guide To Anticoagulant And Antiplatelet Medications Part Two: Antiplatelet Agents And Perioperative Management Of Long-Term Anticoagulation., Louise Y Y Yeung, Babak Sarani, Jordan A Weinberg, Paul B Mcbeth, Addison K May

Surgery Faculty Publications

An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two part review, agents commonly encountered by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part one, we review warfarin and the new direct oral anticoagulants. In part two, we review …

Examination Of Reticulocytosis Among Chronically Transfused Children With Sickle Cell Anemia., Megha Kaushal, Colleen Byrnes, Zarir Khademian, Natalie Duncan, Naomi L. Luban, Jeffery L Miller, Ross Fasano, Emily R. Meier

Pediatrics Faculty Publications

Sickle cell anemia (SCA) is an inherited hemolytic anemia with compensatory reticulocytosis. Recent studies have shown that increased levels of reticulocytosis during infancy are associated with increased hospitalizations for SCA sequelae as well as cerebrovascular pathologies. In this study, absolute reticulocyte counts (ARC) measured prior to transfusion were analysed among a cohort of 29 pediatric SCA patients receiving chronic transfusion therapy (CTT) for primary and secondary stroke prevention. A cross-sectional flow cytometric analysis of the reticulocyte phenotype was also performed. Mean duration of CTT was 3.1 ± 2.6 years. Fifteen subjects with magnetic resonance angiography (MRA) -vasculopathy had significantly higher …

Dental Extraction Is Probably Safe For Patients With Thrombocytopenia: The Standard Of Care Is A Guide For Clinical Decision Making Related To Platelet Transfusion., Phillip So

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Fillmore WJ, Leavitt BD, Arce K. Dental extraction in the thrombocytopenic patient is safe and complications are easily managed. J Oral Maxillofac Surg. 2013 Oct;71(10):1647-1652. doi:10.1016/j.joms.2013.05.011.

Antithyroid Drug-Induced Agranulocytosis, Elizabeth Spears

Nursing Student Class Projects (Formerly MSN)

We live in a culture that is busy and constantly on the go. With little time to spare, often symptoms of an alteration in bodily function are pushed to the side and attribute to the stress of everyday life. With symptoms including nausea, fatigue, weight loss, nervousness, and irritability, one may be more inclined to disregard these symptoms, only to attribute them to effects of a busy lifestyle. The presentation of the previously listed symptoms can formulate a medical diagnosis of hyperthyroidism. According to the American Thyroid Association, 20 million Americans will develop some type of alteration in thyroid function …

Multiple Myeloma, Matthew Crowley

Nursing Student Class Projects (Formerly MSN)

Multiple myeloma a rare and largely incurable malignant disease the affects the plasma cells. (Bilotti, Gleason, McNeill, and the International Myeloma Foundation Nurse Leadership Board, 2011). Understanding the pathophysiology of Multiple Myeloma (MM) and treatment options in Oncology and Hematology nursing can be difficult. It is the goal of this poster to outline the pathophysiology, prognosis, treatment options available to multiple myeloma patients. Multiple myeloma accounts for about 10% of hematologic malignancies in the U.S. (Kuo, Fenves, Mehta, 2011). MM is the second most common hematologic malignancy with twenty-four thousand new MM cases each year (Bianchi, and Anderson, 2014 )

Tslp-Induced Mechanisms And Potential Therapies For Crlf2 B-Cell Acute Lymphoblastic Leukemia, Olivia L. Francis

Loma Linda University Electronic Theses, Dissertations & Projects

Childhood CRLF2 B-cell Acute Lymphoblastic Leukemia (CRLF2 B-ALL) is a high-risk form of leukemia that is associated with poor patient survival outcomes. CRLF2 B-ALL is five times more prevalent in Hispanic children than others and is associated with a higher rate of relapse, thus contributing significantly to childhood cancer health disparities. This disease occurs due to alterations of the CRLF2 gene, leading to overexpression of the CRLF2 protein- a component of the receptor signaling complex for the cytokine Thymic Stromal LymphoPoietin (TSLP) on the surface of B-ALL cells. TSLP has been shown to induce proliferation of human and mouse B-cell …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Clinical Outcomes Of Splenectomy In Children: Report Of The Splenectomy In Congenital Hemolytic Anemia Registry., Henry E. Rice, Brian R. Englum, Jennifer Rothman, Sarah Leonard, Audra Reiter, Courtney Thornburg, Mary Brindle, Nicola Wright, Matthew M. Heeney, Charles Smithers, Rebeccah L. Brown, Theodosia Kalfa, Jacob C. Langer, Michaela Cada, Keith T. Oldham, J Paul Scott, Shawn D. St Peter, Mukta Sharma, Andrew M. Davidoff, Kerri Nottage, Kathryn Bernabe, David B. Wilson, Sanjeev Dutta, Bertil Glader, Shelley E. Crary, Melvin S. Dassinger, Levette Dunbar, Saleem Islam, Manjusha Kumar, Fred Rescorla, Steve Bruch, Andrew Campbell, Mary Austin, Robert Sidonio, Martin L Blakely, Splenectomy In Congenital Hemolytic Anemia (Sicha) Consortium

Manuscripts, Articles, Book Chapters and Other Papers

The outcomes of children with congenital hemolytic anemia (CHA) undergoing total splenectomy (TS) or partial splenectomy (PS) remain unclear. In this study, we collected data from 100 children with CHA who underwent TS or PS from 2005 to 2013 at 16 sites in the Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium using a patient registry. We analyzed demographics and baseline clinical status, operative details, and outcomes at 4, 24, and 52 weeks after surgery. Results were summarized as hematologic outcomes, short-term adverse events (AEs) (≤30 days after surgery), and long-term AEs (31-365 days after surgery). For children with hereditary spherocytosis, …

Hereditary Spherocytosis, Dolores Loeser

Nursing Student Class Projects (Formerly MSN)

Hereditary Spherocytosis (HS) is a hemolytic anemia where red blood cell membranes are spherical unlike common red blood cells, which are flat and round. In individuals with HS the spleen does not recognize these amorphous cells and destroys—rather filters—them them, making the individual anemic (MedlinePlus, 2013). HS is an autosomal dominant, or recessive autosomal inherited blood disease (Huq, Pietroni, Rahman & Alam, 2010) HS happens in 1 in 2,000 of the Caucasian population in or from Northern Europe (MedlinePlus, 2013). The proteins involved in HS are ankyrin-1, ά-spectrin, β-spectrin, band 3, and protein 4.2. Hyperbilirubinemia is a common symptoms in …

Hemophilia A: Pathophysiology And Treatment Strategies, Daniel Dinneen

Nursing Student Class Projects (Formerly MSN)

Hemophilia is a sex-linked recessive coagulation disorder that varies in severity. The implications and complications of hemophilia can be life threatening; pathology is usually diagnosed during childhood and adequate management is essential in maintaining health. Advanced practice nurses treat a variety of hemophilia patients in varying roles throughout the lifespan as hemostasis is a constant physiologic process. Thorough knowledge of the pathophysiology, signs/symptoms, and treatment modalities related to hemophilia is necessary to provide the highest level of comprehensive medical care to such patients. Hemophilia care is continued throughout the lifespan, and newer research indicates that current treatment modalities can initiate …

Lymphedema: Pathophysiology, Diagnosis & Management, Bernadine Cruz

Nursing Student Class Projects (Formerly MSN)

Lymphedema is a disfiguring condition whose hallmark is progressive, increasing swelling which occurs as a result of the accumulation of protein rich fluid in interstitial spaces. Those individuals who are affected suffer from either primary lymphedema or secondary lymphedema; the pathophysiology of both conditions is similar. Lymphedema can be a chronic, acute, or transient alteration, which can eventually lead to keratinization of the skin. An increase in the incidence of lymphedema has also been observed with increase in levels of obesity.

Ponatinib-Induced Adverse Effects: Thrombocytopenia, Pancreatitis And Hepatoxicity-- A Case Report, Saba Hasan, Crystal Fedorkiv, Naba Rahman, Jennifer Andres

Research Day

Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disease that generates from malignant transformation of pluripotent hematopoietic stem cells. First line treatment for CML is the tyrosine kinase inhibitor (TKI), imatinib. For patients resistant or intolerant to imatinib, other TKIs, dasatinib, nilotinib, and ponatinib, are approved treatments. Patients who are resistant or intolerant to other agents are started on ponatinib as a last line option. Common adverse events of ponatinib are hypertension, dry skin, rash, abdominal pain, constipation, and nausea. More serious adverse effects include cardiovascular effects, fluid retention, pancreatitis, severe myelosuppression, and hepatotoxicity. Treatment for these adverse effects can …

Concurrent Non-Ketotic Hyperglycinemia And Propionic Acidemia In An Eight Year Old Boy, Paul Kruszka, Brian Kirmse, Dina Zand, Kristina Cusmano-Ozog, Elaine Spector, John Hove, Kimberly A. Chapman

Pathology Faculty Publications

This is the first reported case of a patient with both non-ketotic hyperglycinemia and propionic acidemia. At 2 years of age, the patient was diagnosed with non-ketotic hyperglycinemia by elevated glycine levels and mutations in the GLDC gene (paternal allele: c.1576_1577insC delT and c.1580delGinsCAA; p.S527Tfs*13, and maternal allele: c.1819G>A; p.G607S). At 8 years of age after having been placed on ketogenic diet, he became lethargic and had severe metabolic acidosis with ketonuria. Urine organic acid analysis and plasma acylcarnitine profile were consistent with propionic acidemia. He was found to have an apparently homozygous mutation in the PCCB gene: c.49C …

Scanned Ion Beam Therapy For Thoracic Tumors, John Gordon Eley

Dissertations and Theses (Open Access)

Although frequently cured of Hodgkin lymphoma, adolescents and young adults can develop radiation induced second cancers. These patients could potentially benefit from scanned ion radiotherapy yet likely would require motion mitigation strategies. In theory, four-dimensional (4D) optimization of ion beam fields for individual motion states of respiration can enable superior sparing of healthy tissue near moving targets, compared to other motion mitigation strategies. Furthermore, carbon-ion therapy can sometimes provide greater relative biological effectiveness (RBE) for cell sterilization in a target but nearly equivalent RBE in tissue upstream of the target, compared to proton therapy. Thus, we expected that for some …

High Hiv Incidence Among Persons Who Inject Drugs In Pakistan: Greater Risk With Needle Sharing And Injecting Frequently Among The Homeless., Rab Nawaz Samo, Arshad Altaf, Ajmal Agha, Omrana Pasha, Shafquat Rozi, Ashraf Memon, Saleem Azam, Meridith Blevins, Sten Vermund, Sharaf Ali Shah

Community Health Sciences

BACKGROUND:

The incidence of HIV among persons who inject drugs (PWIDU) has fallen in many nations, likely due to successes of clean needle/syringe exchange and substance abuse treatment and service programs. However in Pakistan, prevalence rates for PWID have risen dramatically. In several cities, prevalence exceeded 20% by 2009 compared to a 2003 baseline of just 0.5%. However, no cohort study of PWID has ever been conducted.

METHODS:

We enrolled a cohort of 636 HIV seronegative PWID registered with three drop-in centers that focus on risk reduction and basic social services in Karachi. Recruitment began in 2009 (March to June) …

Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley

Dissertations and Theses (Open Access)

Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …

Identifying The Relationship Between Benzene Exposure And The Development Of Acute Myeloid Leukemia, Jacqueline G. Tally

Senior Honors Projects

My interest in epigenetic carcinogenesis-related research stems from both academic and personal experiences. I have come to recognize the significance of environmental chemical exposures in the development of cancer through my studies in nursing, and nutrition and food science. I am particularly interested in the epigenetics of acute myeloid leukemia (AML) because I am an AML survivor.

AML is a rare and highly malignant cancer. It is estimated 13,780 new cases of AML will be identified in theUnited Statesthis year with a 74% mortality rate (calculated 10,200 deaths/13,780 new cases). AML develops from alterations in the survival and proliferation of …