Hematology Commons^™

All Three Supersystems-Nervous, Vascular, And Immune-Contribute To The Cortical Infarcts After Subarachnoid Hemorrhage, Jens P Dreier, Alexander Joerk, Hiroki Uchikawa, Viktor Horst, Coline L Lemale, Helena Radbruch, Devin W Mcbride, Peter Vajkoczy, Ulf C Schneider, Ran Xu

Faculty, Staff and Student Publications

The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical …

Coronavirus Disease 2019 (Covid-19) Real World Data Infrastructure: A Big-Data Resource For Study Of The Impact Of Covid-19 In Patient Populations With Immunocompromising Conditions, James M. Crawford, Lynne Penberthy, Ligia A. Pinto, Keri N. Althoff, Magdalene M. Assimon, Oren Cohen, Laura Gillim, Tracy L. Hammonds, Shilpa Kapur, Harvey W. Kaufman, David Kwasny, Jean W. Liew, William A. Meyer 3rd, Shannon L. Reynolds, Cheryl B. Schleicher, Suki Subbiah, Catherine Theruviparampil, Zachary S. Wallace, Jeremy L. Warner, Suhyeon Yoon, Yonah C. Ziemba

School of Medicine Faculty Publications

Background. We developed a United States–based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials. Methods. The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and …

Transcription Factor Runx1 Regulates Coagulation Factor Xiii-A (F13a1): Decreased Platelet-Megakaryocyte F13a1 Expression And Clot Contraction In Runx1 Haplodeficiency, Fabiola Del Carpio-Cano, Natthapol Songdej, Liying Guan, Guangfen Mao, Lawrence E. Goldfinger, Jeremy G.T. Wurtzel, Kiwon Lee, Michele P. Lambert, Mortimer Poncz, A. Koneti Rao

Cardeza Foundation for Hematologic Research

BACKGROUND: Germline RUNX1 haplodeficiency (RHD) is associated with thrombocy- topenia, platelet dysfunction, and predisposition to myeloid malignancies. Platelet expression profiling of an RHD patient showed decreased F13A1, encoding for the A subunit of factor (F)XIII, a transglutaminase that cross-links fibrin and induces clot stabilization. FXIII-A is synthesized by hematopoietic cells, megakaryocytes, and monocytes.

OBJECTIVES: o understand RUNX1 regulation of F13A1 expression in platelets/mega- karyocytes and the mechanisms and consequences of decreased F13A1 in RHD.

METHODS: We performed studies in platelets, human erythroleukemia (HEL) cells, and human CD34+ cell-derived megakaryocytes including on clot contraction in cells following small inhibitor RNA knockdown …

Hyperleukocytosis In A Neuroblastoma Patient After Treatment With Natural Killer T Cells Expressing A Gd2-Specific Chimeric Antigen Receptor And Il-15, Gengwen Tian, Amy N Courtney, Hangjin Yu, Saleh Bhar, Xin Xu, Gabriel A Barragán, Claudia Martinez Amador, Nisha Ghatwai, Michael S Wood, Deborah Schady, Antonino Montalbano, Shantan Reddy, Aoife M Roche, David De La Cerda, Donald Williams Parsons, Erica J Di Pierro, Frederic D Bushman, Andras Heczey, Leonid S Metelitsa

Faculty, Staff and Students Publications

The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15). This patient was the first to be treated on dose level (DL) 5 and the first patient whose product was restimulated with K562-derived artificial antigen-presenting cells (aAPCs) instead of autologous peripheral blood mononuclear cells …

Enhancing Clinical Trial Matching In Molecular Diagnostics: Using Natural Language Processing And Clustering Approaches In Hematological Malignancies, Gillian Fanning

Theses and Dissertations

Clinical trial matching is a critical component of personalized medicine, particularly in the management of hematologic malignancies. At Virginia Commonwealth University (VCU) Health, the Molecular Diagnostics (MDX) Lab produces somatic variant reports and recommends clinical trials based on the presence of clinically significant mutations. However, the current manual trial recommendation process is time-intensive and lacks scalability.

This study introduces a computational framework to streamline and standardize clinical trial matching using natural language processing (NLP) and unsupervised clustering. Trial brief descriptions were analyzed to extract frequent terms, and trials were grouped based on term similarity using joint dimensionality reduction and clustering. …

Comparative Effectiveness Of High-Intensity Interval Training And Moderate-Intensity Continuous Training On Cardiometabolic Health In Patients With Diabesity: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Sameer Badri Al-Mhanna, Eric Tsz-Chun Poon, Barry A. Franklin, Mark A. Tarnopolsky, John A. Hawley, John M. Jakicic, Emmanuel Stamatakis, Jonathan P. Little, Linda S. Pescatello, Deborah Riebe, Walter R. Thompon, James S. Skinner, Sheri R. Colberg, Jonathan K. Ehrman, George S. Metsios, Helen T. Douda, Norsuhana Omar, Abdullah F. Alghannam, Alexios Batrakoulis

Human Movement Studies & Special Education Faculty Publications

Objective

To evaluate the effects of high-intensity interval training (HIIT) on cardiometabolic health-related outcomes in patients with type 2 diabetes mellitus and concurrent overweight/obesity (diabesity).

Design

Systematic review and meta-analysis of randomized controlled trials (RCTs).

Data sources

PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Google Scholar databases were searched from inception up to January 31, 2025.

Eligibility criteria for selected studies

RCTs comparing HIIT alone ≥ 2 weeks in duration with moderate-intensity continuous training (MICT). Participants were adults with diabesity.

Results

A total of 26 RCTs qualified, involving 790 patients (50/50 female/male ratio; age: 59.8 ± 12.9 …

Investigating The Role Of Prostasin In Angiogenesis: A Chorioallantoic Membrane Model Approach, Zaima Aline

Honors Undergraduate Theses

Prostasin, also known as PRSS8 or CAP1, is a glycosylphosphatidylinositol (GPI)-anchored extracellular serine protease involved in various physiological and pathophysiological processes. Prostasin expression is observed during key phases of trophoblast invasion and placental development, critical steps in embryo implantation in Rhesus monkeys. This suggests a role for prostasin in extracellular matrix remodeling and tissue invasion, both essential for a healthy pregnancy. Moreover, prostasin appears vital for development as studies in mice show that a germline knockout of the gene leads to significant placental defects and eventual embryonic death, highlighting its importance in vascular and structural development within the placenta.

Building …

Recombinant Factor Viia: New Insights Into The Mechanism Of Action Through Product Innovation, Miguel A Escobar, Maureane Hoffman, Giancarlo Castaman, Cedric Hermans, Johnny Mahlangu, Johannes Oldenburg, Charles L Percy, Mark T Reding, Amy D Shapiro, Steven W Pipe

Faculty, Staff and Student Publications

Management of bleeding in persons with hemophilia and inhibitors involves treatment with bypassing agents, including recombinant activated factor VII (rFVIIa). Two rFVIIa products are commercially approved for use in the United States and the European Union. Eptacog alfa and eptacog beta share the same amino acid sequence but differ in posttranslational modifications. Although rFVIIa has been used to manage bleeding in persons with hemophilia and inhibitors for over 30 years, its mechanisms of action is still being studied. In vitro and in vivo studies have suggested that rFVIIa could promote hemostasis by (1) increasing tissue factor-dependent activation of factor (F)X …

Cooperative Role Of Distinctive Tp53 And Pten Combined Loss In The Peripheral T Cell Lymphoma-Gata3 Molecular Subgroup, Waseem G. Lone, Jiayu Yu, Xuxiang Liu, Dylan T. Jochum, Alyssa Bouska, Kunal Shetty, Tyler Herek, Sunandini Sharma, Chengfeng Bi, Rauf Shah, Zaina W. Nasser, Catalina Amador, Aiza Arif, Abdul Rouf Mir, Yuping Li, Tayla B. Heavican-Foral, Jacob Robinson, R. Katherine Hyde, Mamiko Sakata-Yanagimoto, Satyanarayana Rachagani, Timothy W. Mckeithan, David W. Scott, Louis M. Staudt, Giorgio Inghirami, Andrew Feldman, Timothy Greiner, Julie M. Vose, Lisa Rimsza, Joseph Khoury, Wing C. Chan, Javeed Iqbal, Lymphoma/Leukemia Molecular Profiling Project (Llmpp)

Journal Articles: Oncology and Hematology

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of postthymic T cell neoplasms, with ~40% classified as PTCL-not otherwise specified (PTCL-NOS). PTCL-GATA3, a molecularly defined subtype, associated with T helper 2 (T_H2)-like differentiation and poor prognosis, has frequent co-occurrence of TP53 loss/mutation and heterozygous PTEN loss. CD4+ T cell conditional mouse models with Trp53 mutation/deletion and Pten loss demonstrated mature T cell lymphomas (mTCLs) with T_H2-like transcriptomic and immunophenotypic profiles. Molecular studies revealed that codeletion of Trp53/Pten induced T cell receptor and Janus kinase-signal transducer and activator of transcription signaling, promoting T_H2 differentiation …

Integrative Genomic And Transcriptomic Analysis Reveals Targetable Vulnerabilities In Angioimmunoblastic T-Cell Lymphoma, Alyssa Bouska, Weiwei Zhang, Sunandini Sharma, Harald Holte, Rauf Shah, Waseem G. Lone, Mahfuza Afroz Soma, Ruimeng Yang, Xuxiang Liu, Syed Mehmood, Ravneet Singh Chawla, Luca Vincenzo Cappelli, Danilo Fiore, Qiang Gong, Tayla B. Heavican-Foral, Jeffrey J. Cannatella, Catalina Amador, Aiza Arif, Lynette M. Smith, Soon Thye Lim, Choon Kiat Ong, Andrew L. Feldman, Ming-Qing Du, Anamarija M. Perry, Laurence De Leval, Timothy C. Greiner, Kai Fu, Gunhild Trøen, Daniel Vodák, Sigve Nakken, Jan Delabie, David Weinstock, Stefano Pileri, Antonella Laginestra, Kyeongjin Kim, Utpal Pajvani, Julie M. Vose, Dennis D. Weisenburger, Steven M. Horwitz, Sandeep Dave, Joseph Khoury, Giorgio Inghirami, Wing C. Chan, Javeed Iqbal

Journal Articles: Oncology and Hematology

Nodal follicular helper T-cell (T_FH) lymphoma of the angioimmunoblastic (AITL) subtype has a dismal prognosis. Using whole-exome sequencing (n = 124), transcriptomic (n = 78), and methylation (n = 40) analysis, we identified recurrent mutations in known epigenetic drivers (TET2, DNMT3A, IDH2^R172) and novel ones (TET3, KMT2D). TET2, IDH2^R172, DNMT3A co-mutated AITLs had poor prognosis (p < 0.0001). Genes regulating T-cell receptor (TCR) signaling (CD28, PLCG1, VAV1, FYN) or activation (RHOA^G17V) or regulators of the PI3K-pathway (PIK(3)C members, PTEN, PHLPP1, PHLPP2) were mutated. CD28 mutation/fusion was associated with poor prognosis (p = 0.02). WES of purified, neoplastic T-cell (CD3⁺PD1⁺) demonstrated high concordance with …

Serglycin Controls Megakaryocyte Retention Of Platelet Factor 4 And Influences Megakaryocyte Fate In Bone Marrow, Joshua Lykins, Isabelle C. Becker, Virginia Camacho, Hammodah Rawhi Hammodah Alfar, Joonwoo Park, Joseph Italiano, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Megakaryocytes (MKs) produce platelets, and similar to other hematopoietic progenitors, they are involved in homeostatic aspects of their bone marrow niche. MKs release and endocytose various factors, such as platelet factor 4 (PF4)/CXCL4. Here, we show that the intra-α-granular proteoglycan, serglycin (SRGN), plays a key role in this process by retaining PF4, and perhaps other factors, during MK maturation. Immature, SRGN–/– MKs released ~80% of their PF4, and conditioned media from these cells negatively affected wild-type MK differentiation in vitro. This was replicated in wild-type MKs by treatment with the polycation surfen, a known inhibitor of glycosaminoglycan (GAG)/protein interactions. In …

Contact Pathway Factors As Potential Modifiers Of Bleeding Related To Factor Xi Deficiency, Ivy R. Han, Leah Rosenfeldt, Courtney Young, Bal Krishan Phd, Rachel Cantrell Phd, Cassie Sprague, Mousa Kharnaf, William Abplanalp, Joseph Palumbo Md

Williams Honors College, Honors Research Projects

Factor XI (FXI) deficiency, also known as Hemophilia C, is characterized by mild to moderate bleeding symptoms. However, the factors that modify bleeding severity in FXI deficiency are not fully understood. In this study, we investigated whether components of the contact activation pathway can act as modifiers of bleeding in the context of FXI deficiency. Using a tail vein transection (TVT) model in rats, we assessed bleeding in four experimental groups: wild-type Sprague-Dawley rats, Prekallikrein knockout (PKK^-/-) rats, rats treated with a FXI-inhibiting antibody, and PKK-/- rats treated with the FXI antibody.

Under anesthesia, each rat underwent a …

Longitudinal Assessment Of Intravillous Arterioles In Normal Pregnancy Using Superb Microvascular Imaging, R. Horgan, E. Sinkovskaya, G. Saade, E. Kalafat, A. Heeze, A. Abuhamad

Department of Obstetrics & Gynecology Faculty Publications

Objective

To use superb microvascular imaging (SMI) to longitudinally evaluate blood flow in intravillous arterioles (IVA) in pregnancy, and to develop reference ranges for IVA pulsatility index (PI) and peak systolic velocity (PSV) from 12 to 38 weeks' gestation.

Methods

The data for this study were obtained from the National Institutes of Health-funded Human Placenta Project. Eligible for inclusion were women aged 18-35 years, with a body mass index of <  30 kg/m², without comorbidities, with a singleton pregnancy conceived spontaneously and a gestational age of ≤ 13 + 6 weeks. Exclusion criteria were maternal or neonatal complications, fetal or umbilical cord anomalies, abnormal placental implantation and delivery <  37 weeks. Each participant underwent eight ultrasound examinations during pregnancy. Using SMI technology, the total number of IVA identified was recorded in a sagittal placental section at the level of cord insertion. The PI and PSV were measured in a total of six IVA (two in the central portion of the placenta, two peripherally towards the uterine fundal portion and two peripherally towards the lower uterine segment). Umbilical artery (UA)-PI was also obtained. Multilevel regression models were used to create reference ranges for IVA-PI and IVA-PSV at 12-38 weeks' gestation.

Results

A total of 90 women fulfilled the study criteria. IVA-PI decreased throughout pregnancy from a mean ± SD of 1.04 ± 0.23 in the first trimester (at 12-13 weeks) …

The Effect Of Inelastic Compression Wraps On The Quality Of Life Of People With Chronic Venous Insufficiency: A Single-Center, Single-Arm Prospective Study, Abby Hargis Smits, Marita Yaghi, Narges Maskan Bermudez, Hadar Lev-Tov

Department of Medicine Faculty Publications

Background/Objectives: First line therapy for all manifestations of chronic venous insufficiency (CVI) is compression. However, patients frequently report dissatisfaction with compression stockings. Therefore, there is a need to find alternative therapeutic options that can promote compliance. Here, we investigate the impact of the novel, inelastic compression wrap device on quality of life (QoL) in patients with CVI who have failed therapy with compression stockings in the past. Methods: We conducted a six-week, open-label, single-center, non-blinded, prospective cohort study. The primary endpoint was the change in QoL over 6 weeks as measured by the Chronic Venous Disease Quality of Life Questionnaire …

Emergent Transcatheter Tricuspid Edge-To-Edge Repair For Right Ventricular Shock From Tricuspid Regurgitation In Hypertrophic Cardiomyopathy, Nicholas J. Valle, Amin Yehya, Animesh Rathore, Erich L. Kiehl, Matthew R. Summers

Department of Medicine Faculty Publications

Background

Transcatheter tricuspid edge-to-edge repair (T-TEER) is an emerging technology used to treat severe tricuspid regurgitation (TR). The pivotal trials demonstrating the safety and efficacy of T-TEER exclude patients with severely reduced left ventricular function (≤20%).

Case Summary

We demonstrate the use of T-TEER in a patient with end-stage hypertrophic cardiomyopathy who suffered acute, torrential TR and subsequently developed cardiogenic shock as a complication of high-risk transvenous lead extraction. Why Beyond the Guidelines Currently, there are no guidelines addressing the nonsurgical emergent management of acute TR.

Discussion

The TriClip system (Abbott) may have certain advantages when used in managing acute …

Association Between Neighborhood-Level Social Vulnerability And Hypertension Outcomes, John E. Brush Jr., Chungsoo Kim, Yuntian Liu, Xin Xin, Chenxi Huang, Iris J. Lundy, Jordan R. Asher, Mitsuaki Sawano, Patrick Young, Jacob Mcpadden, Mark Anderson, John S. Burrows, Harlan M. Krumholz, Yuan Lu

Department of Medicine Faculty Publications

Background

Neighborhood-level social vulnerability is associated with hypertension prevalence and severity and with cardiovascular complications in conditions other than hypertension, but its association with cardiovascular complications in patients with hypertension is understudied.

Objectives

The aim of the study was to examine how the neighborhood-level social vulnerability index (SVI) influences cardiovascular outcomes in a large, diverse cohort of patients with hypertension.

Methods

We used electronic health data to examine the association between census tract-level rankings for the SVI with a composite endpoint of incident myocardial infarction, congestive heart failure, or stroke.

Results

In a longitudinal cohort of 330,972 patients with hypertension …

Anemia In Pregnant Women: Findings From Kuwait Birth Cohort Study, Abdullah Al-Taiar, Ali H. Ziyab, Majeda S. Hammoud, Reem Al-Sabah, Saeed Akhtar

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Background Anemia is the most common hematologic disorder in pregnancy, affecting over one-third of pregnant women globally. This study aimed to assess the prevalence of anemia in pregnant women and its associated factors in the Kuwait Birth Cohort study.

Methods The Kuwait birth cohort (n = 1,108) was a prospective study in which pregnant women were recruited during their second or third trimester. Data were collected through personal interviews during antenatal care visits, including data on sociodemographic and lifestyle factors. Blood samples were analyzed under strict quality control to measure various laboratory indicators. Anemia was defined as hemoglobin (Hb) < 110 g/L. Predictors of anemia were categorized as underlying or direct factors, and logistic regression models were used to investigate their association with anemia.

Results …

Tagraxofusp Maintenance Post-Hematopoietic Stem Cell Transplantation Provides Long-Term Survival And Manageable Safety For A Patient With Blastic Plasmacytoid Dendritic Cell Neoplasm, Qaiser Bashir, Marina Konopleva, Glorette Abueg, Jeremy Ramdial, Chitra Hosing, Samer A Srour, Amin Alousi, Uday R Popat, Yago Nieto, Gheath Alatrash, Richard E Champlin, Elizabeth J Shpall, Muzaffar Qazilbash, Naveen Pemmaraju

Faculty, Staff and Student Publications

Presented here is the case of a 68-year-old woman with blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with tagraxofusp (TAG) maintenance therapy post-allogeneic hematopoietic stem cell transplantation (allo-HCT). Prior to allo-HCT, the patient was treated with hydroxyurea and mini-CVD (cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate (Methotrexate) and cytarabine) + venetoclax + TAG for 5 cycles, which induced morphologic complete remission with minimal residual disease. After allo-HCT, the patient had persistent cytogenic abnormalities 45,XX,der(7)add(7)(p13)del(7)(q11.2q22)add(7)(q32),add(12)(p13),-15,del(16)(q23),-17,+22,+2mar[1]/46,XX[19], and was then treated with TAG maintenance therapy at 9 mg/kg on a 28-day cycle for 16 cycles. At mid-treatment (cycle 6 of 16 cycles of …

Management Of Hemolytic Transfusion Reactions In A Patient With Chronic Myelomonocytic Leukemia And Rare Antibodies: A Case Report, Grace S Park, Himachandana Atluri, Courtney D Dinardo, Bryan Guillroy, Jean Horak, Effrosyni Apostolidou, Maryam Buni, Guillermo Montalban Bravo, Naveen Pemmaraju

Faculty, Staff and Student Publications

Delayed hemolytic transfusion reaction (DHTR) poses a significant challenge in patients receiving blood transfusions. This case report highlights the complexities of managing DHTR in a newly diagnosed chronic myelomonocytic leukemia (CMML) patient with clinically significant JKa and little c antibodies during induction chemotherapy. A 46-year-old woman with CMML-2 who presented for induction chemotherapy was found to have hemolytic anemia. Due to presence of JKa and little c antibodies, she required intensive monitoring and supportive care measures. The coexistence of JKa and little c antibodies complicates transfusion management and chemotherapy tolerance in CMML patients.

Deep Dive Into Targeted Therapies: Understanding Idh1-Mutant Aml Treatments [Podcast], Amer M Zeidan, Courtney Dinardo

Faculty, Staff and Student Publications

This podcast episode reviews recent advances in the treatment of IDH1-mutant acute myeloid leukemia (AML), focusing on the mechanisms, efficacy, and safety profiles of approved IDH1 inhibitors. The purpose is to present expert insights and clinical data from key trials that underscore the clinical benefits of these targeted therapies. Through discussion of key findings from pivotal clinical trial studies, including data supporting the use of these agents in both newly diagnosed and relapsed or refractory (R/R) settings, the episode highlights significant outcomes such as increased overall response and prolonged duration of remission in patients treated with IDH1 inhibitors. The analysis …