Medicine and Health Sciences Commons^™

Pum1 Mediates The Posttranscriptional Regulation Of Human Fetal Hemoglobin, Yuncheng Man, Amma Owusu-Ansah, Omar Y. Mian, Umut A. Gurkan, Anton A. Komar, Merlin Nithya Gnanapragasam

Faculty Scholarship

The fetal-to-adult hemoglobin switching at about the time of birth involves a shift in expression from γ-globin to β-globin in erythroid cells. Effective re-expression of fetal γ-globin can ameliorate sickle cell anemia and β-thalassemia. Despite the physiological and clinical relevance of this switch, its posttranscriptional regulation is poorly understood. Here, we identify Pumilo 1 (PUM1), an RNA-binding protein with no previously reported functions in erythropoiesis, as a direct posttranscriptional regulator of β-globin switching. PUM1, whose expression is regulated by the erythroid master transcription factor erythroid Krüppel-like factor (EKLF/KLF1), peaks during erythroid differentiation, binds γ-globin messenger RNA (mRNA), and reduces γ-globin …

Detection Of Progression Or Regression Of Breast Cancer By Circulating Tumor Dna (Ctdna), Ujjwal Karki, Bipin Ghimire, Emma Herrman, Siddhartha Yadav, Mohammad Muhsin Chisti

Conference Presentation Abstracts

Circulating tumor DNA (ctDNA) are short DNA sequences shed by tumor cells into the systemic circulation. Studies have shown potential utility of the test to predict relapse or recurrence following treatment in solid tumors, but sensitivity and specificity have varied widely, ranging from 19-100% and 80-100% respectively, in breast cancer specifically. Moreover, literature describing the utility of monitoring dynamic changes in ctDNA trends is limited. We aim to evaluate the correlation between ctDNA test, both single test as well as dynamic trends in value over time, with imaging findings.

Multispectral Imaging For Microchip Electrophoresis Enables Point-Of-Care Newborn Hemoglobin Variant Screening, Ran An, Yuning Huang, Anne Rocheleau, Qiaochu Zhang, Yuncheng Man, Zoe Sekyonda, Amma Owusu-Ansah, Umut A. Gurkan

Faculty Scholarship

Hemoglobin (Hb) disorders affect nearly 7% of the world's population. Globally, around 400,000 babies are born annually with sickle cell disease (SCD), primarily in sub-Saharan Africa where morbidity and mortality rates are high. Screening, early diagnosis, and monitoring are not widely accessible due to technical challenges and cost. We hypothesized that multispectral imaging will allow sensitive hemoglobin variant identification in existing affordable paper-based Hb electrophoresis. To test this hypothesis, we developed the first integrated point-of-care multispectral Hb variant test: Gazelle-Multispectral. Here, we evaluated the accuracy of Gazelle-Multispectral for Hb variant newborn screening in 265 newborns with known hemoglobin variants including …

Luspatercept In Low-Risk Myelodysplastic Syndrome: A Real-World Single Institution Case Series, Shamis Khan, Sara Taveras Alam, Rosa Torres Ramos, John Etumbani Mbue, Effrosyni Apostolidou, Gustavo A Rivero, Sarvari Venkata Yellapragada

Journal Articles

No abstract provided.

Sociodemographic Determinants Of Oral Anticoagulant Prescription In Patients With Atrial Fibrillations: Findings From The Pinnacle Registry Using Machine Learning, Zahra Azizi, Andrew T. Ward, Donghyun J. Lee, Sanchit S. Gad, Kanchan Bhasin, Robert J. Beetel, Tiago Ferreira, Sushant Shankar, John S. Rumsfeld, Salim S. Virani

Office of the Provost

Background: Current risk scores that are solely based on clinical factors have shown modest predictive ability for understanding of factors associated with gaps in real-world prescription of oral anticoagulation (OAC) in patients with atrial fibrillation (AF).
Objective: In this study, we sought to identify the role of social and geographic determinants, beyond clinical factors associated with variation in OAC prescriptions using a large national registry of ambulatory patients with AF.
Methods: Between January 2017 and June 2018, we identified patients with AF from the American College of Cardiology PINNACLE (Practice Innovation and Clinical Excellence) Registry. We examined associations between patient …

Pathogenicity And Impact Of Hla Class I Alleles In Aplastic Anemia Patients Of Different Ethnicities, Timothy S Olson, Benjamin F Frost, Jamie L Duke, Marian Dribus, Hongbo M Xie, Zachary D Prudowsky, Elissa Furutani, Jonas Gudera, Yash B Shah, Deborah Ferriola, Amalia Dinou, Ioanna Pagkrati, Soyoung Kim, Yixi Xu, Meilun He, Shannon Zheng, Sally Nijim, Ping Lin, Chong Xu, Taizo A Nakano, Joseph H Oved, Beatriz M Carreno, Yung-Tsi Bolon, Shahinaz M Gadalla, Steven Ge Marsh, Sophie Paczesny, Stephanie J Lee, Dimitrios S Monos, Akiko Shimamura, Alison A Bertuch, Loren Gragert, Stephen R Spellman, Daria V Babushok

Department of Medicine Faculty Papers

Acquired aplastic anemia (AA) is caused by autoreactive T cell-mediated destruction of early hematopoietic cells. Somatic loss of human leukocyte antigen (HLA) class I alleles was identified as a mechanism of immune escape in surviving hematopoietic cells of some patients with AA. However, pathogenicity, structural characteristics, and clinical impact of specific HLA alleles in AA remain poorly understood. Here, we evaluated somatic HLA loss in 505 patients with AA from 2 multi-institutional cohorts. Using a combination of HLA mutation frequencies, peptide-binding structures, and association with AA in an independent cohort of 6,323 patients from the National Marrow Donor Program, we …

Catch Bonds In Sickle Cell Disease: Shear-Enhanced Adhesion Of Red Blood Cells To Laminin, Utku Goreke, Shamreen Iram, Gundeep Singh, Sergio Domínguez-Medina, Yuncheng Man, Allison Bode, Ran An, Jane A. Little, Christopher L. Wirth, Michael Hinczewski, Umut A. Gurkan

Faculty Scholarship

Could the phenomenon of catch bonding—force-strengthened cellular adhesion—play a role in sickle cell disease, where abnormal red blood cell (RBC) adhesion obstructs blood flow? Here we investigate the dynamics of sickle RBCs adhering to a surface functionalized with the protein laminin (a component of the extracellular matrix around blood vessels) under physiologically relevant micro-scale flow. First, using total internal reflectance microscopy we characterize the spatial fluctuations of the RBC membrane above the laminin surface before detachment. The complex dynamics we observe suggest the possibility of catch bonding, where the mean detachment time of the cell from the surface initially increases …

Simultaneous Onset Of Haematological Malignancy And Covid: An Epicovideha Survey, Chiara Cattaneo, Jon Salmanton-García, Francesco Marchesi, Shaimaa El-Ashwah, Federico Itri, Barbora Weinbergerová, Maria Gomes Da Silva, Michelina Dargenio, Julio Dávila-Valls, Natasha Ali

Department of Pathology and Laboratory Medicine

Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines.
Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022.
Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients …

Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R. Deshotels, Caroline Sun, Vijay Nambi, Salim S. Virani, Kunihiro Matsushita, Bing Yu, Christie . M. Ballantyne, Ron C. Hoogeveen

Office of the Provost

Background: Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person's life is sufficient for cardiovascular risk assessment in all adults.
Methods and Results: Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline …

Trends, Predictors, And Outcomes Of Transcatheter Aortic Valve Implantation In Patients With Bicuspid Aortic Valve Related Disease: Insights From The Nationwide Inpatient Sample And Nationwide Readmission Database, Waqas Ullah, Salman Zahid, Hamza Muhammadzai, Fouad Khalil, Arnav Kumar, Abdul Mannan Khan Minhas, Muhammad Zia Khan, Salim S. Virani, David L. Fischman, Pinak Shah

Office of the Provost

Background: Transcatheter aortic valve implantation (TAVI) has increasingly been utilized in patients with bicuspid aortic valve (BAV) related aortic stenosis (AS) with insufficient large-scale data on its safety.
Methods: The Nationwide Inpatient Sample and Nationwide Readmission Database (2011-2018) were queried to identify patients undergoing TAVI for BAV versus trileaflet aortic valve (TAV) associated AS. The in-hospital, 30- and 180-day odds of outcomes were assessed using a propensity-matched analysis (PSM) to calculate adjusted odds ratios (aOR) with its 95% confidence interval (CI).
Results: A total of 216,723 TAVI (TAV: 214,050 and BAV: 2,673) crude and 5,347 matched population (TAV: 2,674 and …

Chronic Red Cell Exchange In Sickle Cell Patients With Iron Overload May Not Affect Mortality, Yi Yuan Zhou, Hollie M. Reeves, Robert W. Maitta

Faculty Scholarship

Sickle cell disease (SCD) is an inherited blood disorder that affects ~100,000 Americans (1, 2). In SCD, red blood cells (RBC) containing aberrant sickle hemoglobin (HgbS) become sickle-shaped at low oxygen tension and stick together leading to obstructed blood flow. The resulting decrease in tissue oxygenation causes chronic complications such as vasculo-occlusive pain crises among others that require frequent hospitalizations (3). Chronic RBC transfusions play a prominent role in the treatment of this disease by improving oxygenation through addition of normal RBC and dilution of RBC containing HgbS (4, 5). However, the major disadvantage of management with simple transfusion is …

Sickle Cell Disease Chronic Joint Pain: Clinical Assessment Based On Maladaptive Central Nervous System Plasticity, Tiago Da Silva Lopes, Samir K. Ballas, Jamille Evelyn Rodrigues Souza Santana, Pedro De Melo-Carneiro, Lilian Becerra De Oliveira, Katia Nunes Sá, Larissa Conceição Dias Lopes, Wellington Dos Santos Silva, Rita Lucena, Abrahão Fontes Baptista

Department of Medicine Faculty Papers

Chronic joint pain (CJP) is among the significant musculoskeletal comorbidities in sickle cell disease (SCD) individuals. However, many healthcare professionals have difficulties in understanding and evaluating it. In addition, most musculoskeletal evaluation procedures do not consider central nervous system (CNS) plasticity associated with CJP, which is frequently maladaptive. This review study highlights the potential mechanisms of CNS maladaptive plasticity related to CJP in SCD and proposes reliable instruments and methods for musculoskeletal assessment adapted to those patients. A review was carried out in the PubMed and SciELO databases, searching for information that could help in the understanding of the mechanisms …

Defective Rab31-Mediated Megakaryocytic Early Endosomal Trafficking Of Vwf, Egfr, And M6pr In Runx1 Deficiency, Gauthami Jalagadugula, Guangfen Mao, Lawrence E Goldfinger, Jeremy Wurtzel, Fabiola Del Carpio-Cano, Michele P Lambert, Brian Estevez, Deborah L French, Mortimer Poncz, A Koneti Rao

Cardeza Foundation for Hematologic Research

Transcription factor RUNX1 is a master regulator of hematopoiesis and megakaryopoiesis. RUNX1 haplodeficiency (RHD) is associated with thrombocytopenia and platelet granule deficiencies and dysfunction. Platelet profiling of our study patient with RHD showed decreased expression of RAB31, a small GTPase whose cell biology in megakaryocytes (MKs)/platelets is unknown. Platelet RAB31 messenger RNA was decreased in the index patient and in 2 additional patients with RHD. Promoter-reporter studies using phorbol 12-myristate 13-acetate-treated megakaryocytic human erythroleukemia cells revealed that RUNX1 regulates RAB31 via binding to its promoter. We investigated RUNX1 and RAB31 roles in endosomal dynamics using immunofluorescence staining for markers of …

Covid-19 And Blood Clots: A Report Of Massive Pulmonary Embolism In Covid-19 Patient Supported On Veno-Venous Ecmo And The Utility Of Thrombolysis, Bindu Akkanti, Joseph Zwischenberger, Mark T Warner, Kha Dinh, Rahat Hussain, Farah Kazzaz, Pascal Kingah, Lisa M Janowiak, Biswajit Kar, Igor D Gregoric

Journal Articles

COVID-19 morbidity and mortality are not equivalent to other etiologies of acute respiratory distress syndrome (ARDS) as fulminant activation of coagulation can occur, thereby resulting in widespread microvascular thrombosis and consumption of coagulation factors. A 53-year-old female presented to an emergency center on two occasions with progressive gastrointestinal and respiratory symptoms. She was diagnosed with COVID-19 pneumonia and admitted to a satellite intensive care unit with hypoxemic respiratory failure. She was intubated and mechanically ventilated, but her ARDS progressed over the next 48 hours. The patient was emergently cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO) and transferred to our …

Unreliable Automated Complete Blood Count Results: Causes, Recognition, And Resolution, Gene Gulati, Guldeep Uppal, Jerald Z. Gong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Automated hematology analyzers generate accurate complete blood counts (CBC) results on nearly all specimens. However, every laboratory encounters, at times, some specimens that yield no or inaccurate result(s) for one or more CBC parameters even when the analyzer is functioning properly and the manufacturer's instructions are followed to the letter. Inaccurate results, which may adversely affect patient care, are clinically unreliable and require the attention of laboratory professionals. Laboratory professionals must recognize unreliable results, determine the possible cause(s), and be acquainted with the ways to obtain reliable results on such specimens. We present a concise overview of the known causes …

Occlusionchip: A Functional Microcapillary Occlusion Assay Complementary To Ektacytometry For Detection Of Small-Fraction Red Blood Cells With Abnormal Deformability, Yuncheng Man, Ran An, Karamoja Monchamp, Zoe Sekyonda, Erdem Kucukal, Chiara Federici, William J. Wulftange, Utku Goreke, Allison Bode, Umut A. Gurkan

Faculty Scholarship

Red blood cell (RBC) deformability is a valuable hemorheological biomarker that can be used to assess the clinical status and response to therapy of individuals with sickle cell disease (SCD). RBC deformability has been measured by ektacytometry for decades, which uses shear or osmolar stress. However, ektacytometry is a population based measurement that does not detect small-fractions of abnormal RBCs. A single cell-based, functional RBC deformability assay would complement ektacytometry and provide additional information. Here, we tested the relative merits of the OcclusionChip, which measures RBC deformability by microcapillary occlusion, and ektacytometry. We tested samples containing glutaraldehyde-stiffened RBCs for up …

Grk2 Regulates Adp Signaling In Platelets Via P2y1 And P2y12., Xuefei Zhao, Matthew Cooper, James V Michael, Yanki Yarman, Aiden Baltz, J Kurt Chuprun, Walter J Koch, Steven E. Mckenzie, Maurizio Tomaiuolo, Timothy J Stalker, Li Zhu, Peisong Ma

Department of Medicine Faculty Papers

The critical role of G protein-coupled receptor kinase 2 (GRK2) in regulating cardiac function has been well documented for >3 decades. Targeting GRK2 has therefore been extensively studied as a novel approach to treating cardiovascular disease. However, little is known about its role in hemostasis and thrombosis. We provide here the first evidence that GRK2 limits platelet activation and regulates the hemostatic response to injury. Deletion of GRK2 in mouse platelets causes increased platelet accumulation after laser-induced injury in the cremaster muscle arterioles, shortens tail bleeding time, and enhances thrombosis in adenosine 5'-diphosphate (ADP)-induced pulmonary thromboembolism and in FeCl3-induced carotid …

Safety And Efficacy Of Voxelotor In Pediatric Patients With Sickle Cell Disease Aged 4 To 11 Years., Jeremie H. Estepp, Ram Kalpatthi, Gerald Woods, Sara Trompeter, Robert I. Liem, Kacie Sims, Adlette Inati, Baba P D Inusa, Andrew Campbell, Connie Piccone, Miguel R. Abboud, Kim Smith-Whitley, Sandra Dixon, Margaret Tonda, Carla Washington, Noelle M. Griffin, Clark Brown

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sickle cell disease (SCD) is a devastating, multisystemic disorder that affects millions of people worldwide. The earliest clinical manifestations of SCD can affect infants as young as 6 months of age, and pediatric patients are at risk for acute and life-threatening complications. Early intervention with treatments that target the underlying pathophysiological mechanism of SCD, sickle hemoglobin (HbS) polymerization, are expected to slow disease progression and circumvent disease-associated morbidity and mortality.

PROCEDURE: The HOPE-KIDS 1 trial (NCT02850406) is an ongoing four-part, phase 2a, open-label, single- and multiple-dose study to evaluate the pharmacokinetics, efficacy, and safety of voxelotor-a first-in-class HbS polymerization …

Predictive Factors And Outcomes For Ibrutinib In Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter Cohort Study, Narendranath Epperla, Qiuhong Zhao, Sayan Mullick Chowdhury, Lauren Shea, Tamara K Moyo, Nishitha Reddy, Julia Sheets, David M Weiner, Praveen Ramakrishnan Geethakumari, Malathi Kandarpa, Ximena Jordan Bruno, Colin Thomas, Michael C Churnetski, Andrew Hsu, Luke Zurbriggen, Cherie Tan, Kathryn Lindsey, Joseph Maakaron, Paolo F Caimi, Pallawi Torka, Celeste Bello, Sabarish Ayyappan, Reem Karmali, Seo-Hyun Kim, Anna Kress, Shalin Kothari, Yazeed Sawalha, Beth Christian, Kevin A David, Irl Brian Greenwell, Murali Janakiram, Vaishalee P Kenkre, Adam J Olszewski, Jonathon B Cohen, Neil D. Palmisiano, Elvira Umyarova, Ryan A Wilcox, Farrukh T Awan, Juan Pablo Alderuccio, Stefan K Barta, Natalie S Grover, Nilanjan Ghosh, Nancy L Bartlett, Alex F Herrera, Geoffrey Shouse

Department of Medicine Faculty Papers

Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% …

Antithrombin-Iii Mitigates Thrombin-Mediated Endothelial Cell Contraction And Sickle Red Blood Cell Adhesion In Microscale Flow, William J. Wulftange, Erdem Kucukal, Yuncheng Man, Ran An, Karamoja Monchamp, Charlotte D. Sevrain, Himanshu R. Dashora, Allison Bode, Jane A. Little, Umut A. Gurkan

Faculty Scholarship

Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III (ATIII), an endogenous serine protease inhibitor, inhibits several enzymes in the coagulation cascade, including thrombin. Here, we utilize a biomimetic microfluidic device to model the morphology and adhesive properties of endothelial cells (ECs) activated by thrombin and examine the efficacy of ATIII in mitigating the adhesion of SCD patient-derived red blood cells (RBCs) and EC retraction. Microfluidic devices were fabricated, seeded with ECs, and incubated under physiological shear stress. Cells were then activated with thrombin with or without an ATIII …

Global Think Tank On The Clinical Considerations And Management Of Lipoprotein(A): The Top Questions And Answers Regarding What Clinicians Need To Know, Salim S. Virani, Marlys L. Koschinsky, Lisa Maher, Anurag Mehta, Carl E. Orringer, Raul D. Santos, Michael D. Shapiro, Joseph J. Saseen

Office of the Provost

Evidence from Mendelian randomization studies suggest that lipoprotein(a) (Lp(a)) has a causal role in the development of atherosclerotic cardiovascular disease risk. However, guidelines and consensus statement recommendations vary regarding how clinicians should incorporate Lp(a) into patient care. To provide practical answers to key questions pertaining to Lp(a) that clinicians will find useful when assessing and treating patients, a global think tank was convened. Representatives from seven national and international stakeholder organizations answered questions that were focused on: Lp(a) measurement; ethnic, gender, and age considerations; factoring Lp(a) into risk assessment; and current and emerging treatment options for elevated Lp(a). This manuscript …

Characterization And Assessment Of Barriers And Facilitators To The Decision-Making Process For Blood And Blood Donor Safety In The United States: A Collective Case Study, Lauren A. Crowder

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Over 16 million blood components are transfused to patients in need every year in the United States (Jones et al., 2021). Because of the reliance on human blood donors, the donation and transfusion of blood will always be associated with some level of risk for both donors and recipients; the tolerability of these risks may vary from stakeholder to stakeholder. While the U.S. Food and Drug Administration (FDA) concedes that attaining a blood supply with zero risk for transmission of infectious diseases may be unattainable (U.S. Food and Drug Administration, 2019), they continue to strive for the lowest …

A Pilot Phase Ib/Ii Study Of Whole-Lung Low Dose Radiation Therapy (Ldrt) For The Treatment Of Severe Covid-19 Pneumonia: First Experience From Africa, Mansoor Saleh, Karishma Sharma, Jasmit Shah, Farrok Karsan, Angela Waweru, Martin Musumbi, Reena Shah, Shahin Sayed, Innocent Abayo, Noureen Karimi, Stacey Gondi, Sehrish Rupani, Grace Kirathe, Heldah Amariati

Internal Medicine, East Africa

Background: Low dose radiation therapy (LDRT) has been used for non-malignant conditions since early 1900s based on the ability of single fractions between 50–150 cGy to inhibit cellular proliferation. Given scarcity of resources, poor access to vaccines and medical therapies within low and middle income countries, there is an urgent need to identify other cost-effective alternatives in management of COVID-19 pneumonia. We conducted a pilot phase Ib/II investigator-initiated clinical trial to assess the safety, feasibility, and toxicity of LDRT in patients with severe COVID-19 pneumonia at the Aga Khan University Hospital in Nairobi, Kenya. Additionally, we also assessed clinical …

Hepatoid Adenocarcinoma Of Lung: A Rare And Challenging Tumor, Bipin Ghimire, Ashbina Pokharel, Samiksha Pandey, Ujjwal Jung Karki, Can Wang, Michael Stender

Conference Presentation Abstracts

Hepatoid adenocarcinoma (HAC) is an extremely rare extra-hepatic malignant tumor having hepatic features on pathology. Stomach is the most common site, and hepatoid adenocarcinoma of lung (HAL) accounts for 2.3 – 5% of all HACs. Less than 100 cases of HAL have been reported worldwide since its concept was put forward in 1990. A 63-year-old female presented to the ED with back pain. Initial evaluation revealed anemia (hemoglobin 6.7), hypercalcemia (12.1 mg/dl), GFR 54 mL/min. X-ray thoracic spine and chest showed two vertebral compression deformities and lytic lesions on multiple ribs. Initially, multiple myeloma was considered likely but further evaluation …

Merkle Cell Carcinoma While On Rituximab - Is It A Coincidence?, Bana Antonios, Emma Herrman, Mohammad Muhsin Chisti

Conference Presentation Abstracts

A 79-year old woman with history of relapsed Stage II, grade III follicular lymphoma was treated with four cycles of rituximab and bendamustine with an excellent response. She was subsequently placed on maintenance rituximab infusions every eight weeks. Six months later, she presented to the dermatology clinic with a newly raised erythematous papule on her left cheek. Excisional biopsy confirmed a diagnosis of Merkel cell carcinoma which was resected with wide margins. Merkel cell carcinoma (MCC) is a rare aggressive skin malignancy, with a dramatic increase in incidence in the past few decades. It grows and metastasizes rapidly and diagnosis …

Hemophilia A: Strategies For Improving Long-Term Holistic Management, Adherence, And Quality Of Life, Miguel A Escobar, Cindy Leissinger, Guy Young

Journal Articles

Hemophilia A is a rare inherited bleeding disorder characterized by a deficiency in factor VIII. The evolution of currently approved prophylaxis therapy in hemophilia A will be reviewed, including the clinical value of prophylaxis, real-world experience with prophylaxis, and patient quality-of-life factors that must be considered when choosing treatment options for these patients.

Anti‐Cd20 Therapeutic Options In Immune‐Mediated Thrombotic Thrombocytopenic Purpura, Robert W. Maitta

Faculty Scholarship

Immunosuppression with rituximab in immune-mediated thrombotic thrombocytopenic purpura helps decrease production of autoantibody mediating ADAMTS13 clearance from circulation. Failure to respond to rituximab in a satisfactory way or made difficult by adverse events to the medication does not represent a reason to stop considering anti-CD20 therapies to control antibody production. Therefore, both of atumumab and obinutuzumab with specificity to CD20, represent potentially valuable therapeutic tools in patients who are not candidates for rituximab. Commentary on: Doyle et al. The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura. Br J Haematol. 2022;198:391-396.1.

Role Of Extracellular Vesicles In Glia-Neuron Intercellular Communication, Shahzad Ahmad, Rohit K Srivastava, Pratibha Singh, Ulhas P. Naik, Amit K Srivastava

Department of Medicine Faculty Papers

Cross talk between glia and neurons is crucial for a variety of biological functions, ranging from nervous system development, axonal conduction, synaptic transmission, neural circuit maturation, to homeostasis maintenance. Extracellular vesicles (EVs), which were initially described as cellular debris and were devoid of biological function, are now recognized as key components in cell-cell communication and play a critical role in glia-neuron communication. EVs transport the proteins, lipids, and nucleic acid cargo in intercellular communication, which alters target cells structurally and functionally. A better understanding of the roles of EVs in glia-neuron communication, both in physiological and pathological conditions, can aid …

G Protein-Coupled Receptor Kinase 5 Regulates Thrombin Signaling In Platelets Via Par-1., Kate Downes, Xuefei Zhao, Nicholas S Gleadall, Harriet Mckinney, Carly Kempster, Joana Batista, Patrick L Thomas, Matthew Cooper, James V Michael, Roman Kreuzhuber, Katherine Wedderburn, Kathryn Waller, Bianca Varney, Hippolyte Verdier, Neline Kriek, Sofie E Ashford, Kathleen E Stirrups, Joanne L Dunster, Steven E Mckenzie, Willem H Ouwehand, Jonathan M Gibbins, Jing Yang, William J Astle, Peisong Ma

Cardeza Foundation for Hematologic Research

The interindividual variation in the functional response of platelets to activation by agonists is heritable. Genome-wide association studies (GWASs) of quantitative measures of platelet function have identified fewer than 20 distinctly associated variants, some with unknown mechanisms. Here, we report GWASs of pathway-specific functional responses to agonism by adenosine 5'-diphosphate, a glycoprotein VI-specific collagen mimetic, and thrombin receptor-agonist peptides, each specific to 1 of the G protein-coupled receptors PAR-1 and PAR-4, in subsets of 1562 individuals. We identified an association (P = 2.75 × 10-40) between a common intronic variant, rs10886430, in the G protein-coupled receptor kinase 5 gene (GRK5) …

The Efficacy And Safety Of Roxadustat For The Treatment Of Anemia In Non-Dialysis Dependent Chronic Kidney Disease Patients: An Updated Systematic Review And Meta-Analysis Of Randomized Clinical Trials, Basel Abdelazeem, Joseph Shehata, Kirellos Said Abbas, Nahla Ahmed El-Shahat, Bilal Malik, Pramod Savarapu, Mostafa Eltobgy, Arvind Kunadi

School of Medicine Faculty Publications

Background Roxadustat (ROX) is a new medication for anemia as a complication of chronic kidney disease (CKD). Our meta-analysis aims to evaluate the efficacy and safety of ROX, especially on the cardiovascular risks, for anemia in NDD-CKD patients. Methods Electronic databases were searched systematically from inception to July 2021 to look for randomized control trials (RCTs) that evaluated ROX NDD-CKD patients. Hemoglobin level and iron utilization parameters, including ferritin, serum iron, transferrin saturation (TSAT), total iron-binding capacity (TIBC), transferrin, and hepcidin were analyzed for efficacy. Pooled risk ratios (RRs) and standardized mean differences (SMDs) were calculated and presented with their …