Hematology Commons^™

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) …

Effectiveness And Safety Of Intravenous Iron Therapy In Outpatient Obstetrical Clinic For Treatment Of Iron-Deficiency Anemia During Pregnancy, Ellen M. Murrin, Olivia S. Lebeau, Lillian Singer, Mark A. Kassab, Peyton Kalan, Julie Costanzo, Scott A. Sullivan, George L. Maxwell, George R. Saade, Antonio F. Saad

Department of Obstetrics & Gynecology Faculty Publications

Background

Iron-deficiency anemia (IDA) affects over one-third of pregnant patients globally, contributing to severe maternal morbidity and adverse neonatal outcomes. Oral iron supplementation, while cost-effective, is limited by poor absorption, significant gastrointestinal side effects, and poor adherence. The use of intravenous (IV) iron addresses many of these concerns, including eliminating GI side effects and the need for daily therapy. However, administration of IV iron in pregnant patients is typically restricted to specialized infusion centers or hospitals due to concerns about acute side effects, cost, resource utilization, the need for fetal heart rate monitoring, and extended infusion times.

Methods

This descriptive …

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 …

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 …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

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 …

Lp-118 Is A Novel B-Cell Lymphoma 2 / Extra-Large Inhibitor That Demonstrates Efficacy In Models Of Venetoclaxresistant Chronic Lymphocytic Leukemia, Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, Kerrya Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis …

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.

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 …

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 …

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 …

Hemophagocytic Lymphohistiocytosis In A Critically Ill Patient: A Case Report Of A Potentially Fatal Entity, Ali Khreisat, Inna Mikaella Sta Maria, Giovi Grasso-Knight, Meghan Mansour

HCA Healthcare Journal of Medicine

Background

Hemophagocytic lymphohistiocytosis (HLH) is a non-neoplastic proliferation and macrophage activation that induces cytokine-mediated bone marrow suppression and features of intense phagocytosis in the bone marrow and liver, leading to multi-organ dysfunction and ultimate failure. The diagnosis of HLH in an intensive care setting is challenging, and it is associated with high morbidity and mortality. HLH-94 is the standard protocol for treatment, consisting of dexamethasone and chemotherapy like etoposide.

Case Presentation

We present the case of a 73-year-old woman who had a prolonged hospitalization for vomiting, diarrhea, and dehydration. Her conditions were complicated by acute refractory pancytopenia on the 12th …

Hemophagocytic Lymphohistiocytosis Due To Ehrlichiosis: A Case Series, Ajay Iyer, Mattias D'Anna, Shruti Verma, Thomas Pritchard, Vladimir Begilman, Himal Bajracharya, Kaveh Naemi

HCA Healthcare Journal of Medicine

Background

Hemophagocytic lymphohistiocytosis (HLH) is an immunologic syndrome characterized by excessive inflammation and tissue injury due to uncontrolled activation of the phagocytic system. The underlying mechanism is a lack of downregulation of activated macrophages and lymphocytes by natural killer and T cells. Unfortunately, the diagnosis is often delayed or missed due to the rarity of the disease, decreased awareness, and clinical picture variability. Ehrlichiosis is becoming a more prevalent tick-borne illness in endemic regions and a relatively uncommon but increasingly considered cause of HLH.

Case Presentation

We describe the cases of 2 patients diagnosed with secondary HLH as per the …

Investigating The Effects Of Nosocomial Clostridioides Difficile Infection Among Acute Leukemia Patients: Insights From The 2020 National Inpatient Sample, Zubair Hassan Bodla, Mariam Hashmi, Fatima Niaz, Umer Farooq, Muhammad Jahanzeb Khalil, Farhan Khalid, Kipson Charles, Christopher L. Bray

HCA Healthcare Journal of Medicine

Background

Rising nosocomial Clostridioides difficile infections pose high risks, especially for immunocompromised leukemia patients, necessitating targeted research to enhance patient care and outcomes.

The objective of this study was to investigate the impact of nosocomial Clostridioides difficile infections (CDI) on patients hospitalized with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

Methods

Our study was a retrospective analysis of adult patients hospitalized with a primary diagnosis of ALL or AML, using the Nationwide Inpatient Sample (NIS) database for 2020. Primary outcomes included the incidence of nosocomial CDI and all-cause inpatient mortality. Secondary outcomes included hospital length of stay, resource …

Navigating Rarity: A Case Report On Primary Splenic Lymphoma, Santosh Pv Rai, Skand Rastogi, Anshuman Senapati, Jyoti Kini, Salama Yasmeen

Manipal Journal of Medical Sciences

Primary Splenic Lymphoma (PSL) is a rare condition, which complicates its understanding and definition. The rarity of PSL has led to varied definitions: some consider it primary only if splenomegaly is predominant, while others include spleen involvement with hilar lymph nodes. Documentation on PSL is sparse in Indian literature. This case report of a 48-year-old woman, presenting with fever, weight loss, and left hypochondrium pain, and diagnosed with PSL through CECT abdomen and USG-guided biopsy, contributes to better understanding of the condition.

Digital Cognitive Behavioral Therapy Vs Education For Pain In Adults With Sickle Cell Disease, Charles R. Jonassaint, Christina M. Lalama, C. Patrick Carroll, Sherif M. Badawy, Megan E. Hamm, Jennifer N. Stinson, Chitra Lalloo, Santosh L. Saraf, Victor R. Gordeuk, Robert M. Cronin, Nirmish Shah, Sophie M. Lanzkron, Darla Liles, Julia A. O'Brien, Cassandra Trimnell, Lakiea Bailey, Raymona H. Lawrence, Leshana Saint Jean, Michael Debaun, Laura M. De Castro, Tonya M. Palermo, Kaleab Z. Abebe

Department of Medicine Faculty Papers

Despite the burden of chronic pain in sickle cell disease (SCD), nonpharmacological approaches remain limited. This multisite, randomized trial compared digital cognitive behavioral therapy (CBT) with a digital pain/SCD education program ("Education") for managing pain and related symptoms. Participants were recruited virtually from seven SCD centers and community organizations in the United States. Adults (aged ≥18 years) with SCD-related chronic pain and/or daily opioid use were assigned to receive either CBT or Education for 12 weeks. Both groups used an app with interactive chatbot lessons and received personalized health coach support. The primary outcome was the change in pain interference …

Influence Of Antibody–Drug Conjugate Cleavability, Drug-To-Antibody Ratio, And Free Payload Concentration On Systemic Toxicities: A Systematic Review And Meta-Analysis, Shou Ching Tang, Carrie Wynn, Tran Le, Martin Mccandless, Yunxi Zhang, Ritesh Patel, Nita Maihle, William Hillegass

School of Medicine Faculty Publications

While in theory antibody drug conjugates (ADCs) deliver high-dose chemotherapy directly to target cells, numerous side effects are observed in clinical practice. We sought to determine the effect of linker design (cleavable versus non-cleavable), drug-to-antibody ratio (DAR), and free payload concentration on systemic toxicity. Two systematic reviews were performed via PubMed search of clinical trials published between January 1998—July 2022. Eligible studies: (1) clinical trial for cancer therapy in adults, (2) ≥ 1 study arm included a single-agent ADC, (3) ADC used was commercially available/FDA-approved. Data was extracted and pooled using generalized linear mixed effects logistic models. 40 clinical trials …

Transcriptomic Clustering Of Chronic Lymphocytic Leukemia: Molecular Subtypes Based On Bruton’S Tyrosine Kinase Expression Levels, Gorkem Kismali, Ganiraju Manyam, Nitin Jain, Cristina Ivan, Betty Lamothe, Mary L Ayres, Lakesla R Iles, William G Wierda, Varsha Gandhi

Faculty, Staff and Student Publications

Historically, CLL prognostication relied on disease burden, reflected in clinical stage. Later, chromosome abnormalities and genomics suggested several CLL subtypes which were aligned with response to therapy. Gene expression profiling data identified pathways associated with CLL progression. We hypothesized that transcriptome and proteome may identify functional omics associated with CLL nosology. As a test cohort, we utilized publicly available treatment-naïve CLL transcriptomics data (n = 130) and did consensus clustering that identified BTK-expression-based clusters. The BTK-High and BTK-Low clusters were validated in public and our in-house databases (n = >550 CLL patients). To associate with functional relevance, we took samples …

The Revised Cdc Chronic Pain Guidelines And Payer Opioid Analgesic Policies In Michigan, Victoria Tutag Lehr, Cynthia L. Arfken

Michigan Journal of Public Health

Abstract

The 2016 publication of A Guideline for Prescribing Opioids for Chronic Pain by the Centers for Disease Control and Prevention motivated commercial and Medicaid payers to restrict their opioid prescribing policies including the imposition of hard limits on opioid daily dosages and duration. One result of these policies was an increase in abrupt opioid discontinuation and rapid tapering events for patients receiving long-term opioid therapy. Responding to this misapplication of the 2016 guideline, the 2022 revised guidelines emphasized individualized opioid therapy and exclusion of certain chronic diseases. However, it is not known if the payers changed their policies to …