Antithrombotic Efficacy And Bleeding Risks Of Vaccine-Induced Immune Thrombotic Thrombocytopenia Treatments,
2024
Thomas Jefferson University
Antithrombotic Efficacy And Bleeding Risks Of Vaccine-Induced Immune Thrombotic Thrombocytopenia Treatments, Halina H.L. Leung, Zohra Ahmadi, Brendan Lee, John Casey, Sumita Ratnasingam, Steven E. Mckenzie, Jose Perdomo, Beng H. Chong
Cardeza Foundation for Hematologic Research
Current guidelines for treating vaccine-induced immune thrombotic thrombocytopenia (VITT) recommend nonheparin anticoagulants and IV immunoglobulin (IVIg). However, the efficacy of these treatments remains uncertain due to case studies involving small patient numbers, confounding factors (eg, concurrent treatments), and a lack of animal studies. A recent study proposed danaparoid and heparin as potential VITT therapies because of their ability to disrupt VITT IgG-platelet factor 4 (PF4) binding. Here, we examined the effects of various anticoagulants (including unfractionated [UF] heparin, danaparoid, bivalirudin, fondaparinux, and argatroban), IVIg, and the FcγRIIa receptor-blocking antibody, IV.3. Our investigation focused on VITT IgG-PF4 binding, platelet activation, thrombocytopenia, …
The Role Of Microrna-155 As A Biomarker In Diffuse Large B-Cell Lymphoma,
2024
Thomas Jefferson University
The Role Of Microrna-155 As A Biomarker In Diffuse Large B-Cell Lymphoma, Epameinondas Koumpis, Vasileios Georgoulis, Konstantina Papathanasiou, Alexandra Papoudou-Bai, Panagiotis Kanavaros, Evangelos Kolettas, Eleftheria Hatzimichael
Computational Medicine Center Faculty Papers
Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL). Despite the use of newer agents, such as polatuzumab vedotin, more than one-third of patients have ultimately relapsed or experienced refractory disease. MiRNAs are single-stranded, ~22-nucleotide-long RNAs that interact with their target RNA. They are significant regulators of post-transcriptional gene expression. One significant miRNA, miR-155, is involved in the pathophysiology of DLBCL and it is a critical modulator of hematopoiesis, inflammation, and immune responses. Targets of miR-155, such as histone deacetylase 4 (HDAC4), suppressor of cytokine signaling-1 (SOCS1) and immune cells, play a crucial role in DLBCL …
Genetic Risk Stratification And Outcomes Among Treatment-Naive Patients With Aml Treated With Venetoclax And Azacitidine,
2024
The Texas Medical Center Library
Genetic Risk Stratification And Outcomes Among Treatment-Naive Patients With Aml Treated With Venetoclax And Azacitidine, Hartmut Döhner, Keith W Pratz, Courtney D Dinardo, Andrew H Wei, Brian A Jonas, Vinod A Pullarkat, Michael J Thirman, Christian Récher, Andre C Schuh, Sunil Babu, Xiaotong Li, Grace Ku, Zihuan Liu, Yan Sun, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea
Faculty, Staff and Student Publications
The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most …
Frontline Ph-Negative B-Cell Precursor Acute Lymphoblastic Leukemia Treatment And The Emerging Role Of Blinatumomab,
2024
The Texas Medical Center Library
Frontline Ph-Negative B-Cell Precursor Acute Lymphoblastic Leukemia Treatment And The Emerging Role Of Blinatumomab, Elias J Jabbour, Hagop M Kantarjian, Nicola Goekbuget, Bijal D Shah, Sabina Chiaretti, Jae H Park, Anita W Rijneveld, Lia Gore, Shaun Fleming, Aaron C Logan, Josep M Ribera, Tobias F Menne, Khalid Mezzi, Faraz Zaman, Kelly Velasco, Nicolas Boissel
Faculty, Staff and Student Publications
This narrative review seeks to summarize chemotherapeutic regimens commonly used for patients with newly diagnosed Philadelphia (Ph) chromosome-negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in the frontline setting and to describe the latest clinical research using the bispecific T-cell-engaging immunotherapy blinatumomab in the first-line treatment setting. Current standard-of-care chemotherapeutic backbones for newly diagnosed Ph-negative BCP-ALL are based on the same overarching treatment principle: to reduce disease burden to undetectable levels and maintain lasting remission. The adult treatment landscape has progressively evolved following the adoption of pediatric-inspired regimens. However, these intense regimens are not tolerated by all, and high-risk patients still …
Assessing The Impact Of Obesity On Postoperative Outcomes In Rcc Using Machine Learning,
2024
Corewell Health East Resident
Assessing The Impact Of Obesity On Postoperative Outcomes In Rcc Using Machine Learning, Atulya A. Khosla, Manas Pustake, Sufal Chhabra, Yanjia Zhang, Mukesh Roy, Muni Rubens, Venkataraghavan Ramamoorthy, Anshul Saxena, Ishmael A. Jaiyesimi
Conference Presentation Abstracts
Introduction Obesity is associated with an increased risk of developing renal cell carcinoma (RCC) but paradoxically correlates with improved outcomes in metastatic cases. Moreover, the data on the relationship between obesity and postoperative outcomes following nephrectomy are inconsistent. Accurate prediction of postoperative outcomes, including complications, 30-day readmissions, and mortality, is essential for improving patient outcomes in surgical procedures. In this study, we utilized ML models to predict such outcomes in RCC patients undergoing nephroureterectomy, radical nephrectomy, partial nephrectomy, and other excision procedures on the kidney using data from the National Surgical Quality Improvement Program (NSQIP; 2016- 2021). Methods A gradient-boosted …
Nosebleed No More: Recognizing And Diagnosing Factor Viii Inhibitor,
2024
HCA Florida Kendall Hospital
Nosebleed No More: Recognizing And Diagnosing Factor Viii Inhibitor, Salam Harb, Leidy Huie Martinez Md, Jose Alvarado Md, Ajit Koli Do, Hazem Nasef Ms4
HCA-NSU MD Research Day
Acquired hemophilia is a condition characterized by the unexpected onset of severe bleeding due to an issue with coagulation factors. Typically, this disorder results from the production of autoantibodies against the Factor VIII coagulation factor. Although acquired hemophilia is an extremely rare condition, with an annual incidence of just 1.5 cases per million, it is crucial to recognize and understand it. This is because diagnosing this disorder is intricate, and if left undiagnosed and untreated, it can lead to high levels of morbidity and mortality. This case stands out as the condition typically targets older adults, with around 80% of …
Genetically Determined Telomere Length In Monoclonal Gammopathy Of Undetermined Significance, Multiple Myeloma Risk And Outcome,
2024
The Texas Medical Center Library
Genetically Determined Telomere Length In Monoclonal Gammopathy Of Undetermined Significance, Multiple Myeloma Risk And Outcome, Matteo Giaccherini, Alyssa I Clay-Gilmour, Romano Liotti, Angelica Macauda, Manuel Gentiluomo, Elizabeth E Brown, Mitchell J Machiela, Stephen J Chanock, Michelle A T Hildebrandt, Aaron D Norman, Elisabet Manasanch, S Vincent Rajkumar, Jonathan N Hofmann, Sonja I Berndt, Parveen Bhatti, Graham G Giles, Elad Ziv, Shaji K Kumar, Nicola J Camp, Wendy Cozen, Susan L Slager, Federico Canzian, Federica Gemignani, Celine M Vachon, Daniele Campa
Faculty, Staff and Student Publications
No abstract provided.
How Did Dat Happen? A Coombs Negative Delayed Hemolytic Transfusion Reaction In A Patient With Myelodysplastic Syndrome: A Case Report,
2024
Rochester General Hospital
How Did Dat Happen? A Coombs Negative Delayed Hemolytic Transfusion Reaction In A Patient With Myelodysplastic Syndrome: A Case Report, Aniket Vijay Rao Dr, Aditya Sanjeevi, Daniel Jose Idoate, Nagesh Jadhav, Basil Verghese, Himal Kharel
Advances in Clinical Medical Research and Healthcare Delivery
Delayed hemolytic transfusion reactions (DHTRs) present significant challenges in diagnosis and management despite advancements in pre-transfusion testing. We report a case of a 76-year-old female with myelodysplastic syndrome (MDS) who developed severe hemolytic anemia following a seemingly compatible blood transfusion and appropriate pretransfusion testing. Evaluation revealed characteristics consistent with DHTR. Diagnostic uncertainty arose due to a negative Direct Antiglobulin Test (DAT) in the setting of a concomitant Vitamin B-12 deficiency. She was supported with prednisone and B12 supplementation. We discuss challenges in diagnosis, including the limitation of DAT, and propose strategies for comprehensive antibody identification. The case underscores the importance …
Recurrent Deep Vein Thrombosis In May Thurner Syndrome Precipitated By Heparin Induced Thrombocytopenia: A Case Report And Review Of Literature,
2024
Rochester Regional Health
Recurrent Deep Vein Thrombosis In May Thurner Syndrome Precipitated By Heparin Induced Thrombocytopenia: A Case Report And Review Of Literature, Abhishek Bhandari, Chengu Niu
Advances in Clinical Medical Research and Healthcare Delivery
May Thurner Syndrome involves the extrinsic compression of the left common iliac vein by the right common iliac artery, which predisposes to venous thrombosis. This case report and review of literature details a complex instance of recurrent Deep Vein Thrombosis (DVT) in a 58-year-old female patient with May Thurner Syndrome (MTS), exacerbated by Heparin-Induced Thrombocytopenia (HIT). The patient, post Coronary Artery Bypass Graft surgery, developed leg symptoms leading to the discovery of an extensive DVT from the calf veins to the external iliac vein. She was initially treated with heparin, which was switched to bivalirudin following a significant drop in …
Tak1 Blockade Plus Azacitidine Induces Apoptosis, Augments Cytarabine, And Ablates Clonogenicity In Mll-Af9+ Human Aml Cell Lines,
2024
Loyola University Chicago
Tak1 Blockade Plus Azacitidine Induces Apoptosis, Augments Cytarabine, And Ablates Clonogenicity In Mll-Af9+ Human Aml Cell Lines, Austin P. Runde, Cameron Lewis, Peter Breslin Sj, Jiwang Zhang
School of Medicine
Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow [1]. Aside from the PML-RARA+ subtype, AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a two-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine; etoposide may also be added in select regimens. Despite 60-70% of patients achieving complete remission (CR), …
Prognostic Stratification In Dlbcl Patients With Aberrant Myc Gene,
2024
The Texas Medical Center Library
Prognostic Stratification In Dlbcl Patients With Aberrant Myc Gene, Jian-Rong Li, Vikram R Shaw, Abi Parthasarathy, Yong Li, Christopher I Amos, Chao Cheng
Faculty, Staff and Students Publications
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a subset of patients who exhibit treatment resistance and poor prognoses. Genomic assays have been widely employed to identify high-risk individuals characterized by rearrangements in the MYC, BCL2 and BCL6 genes. These patients typically undergo more aggressive therapeutic treatments; however, there remains a significant variation in their treatment outcomes. This study introduces an MYC signature score (MYCSS) derived from gene expression profiles, specifically designed to evaluate MYC overactivation in DLBCL patients. MYCSS was validated across several independent cohorts to assess its ability to stratify patients based on MYC-related genetic …
Outcomes And Genetic Dynamics Of Acute Myeloid Leukemia At First Relapse,
2024
The Texas Medical Center Library
Outcomes And Genetic Dynamics Of Acute Myeloid Leukemia At First Relapse, Alex Bataller, Hagop Kantarjian, Alexandre Bazinet, Tapan Kadia, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Ghayas C Issa, Yesid Alvarado, Guillermo Montalban-Bravo, Abhishek Maiti, Hussein A Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi
Faculty, Staff and Student Publications
Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. At relapse, mutations in genes involved in pathway signaling tended …
Vertical Targeting Of The Pi3k/Akt Pathway At Multiple Points Is Synergistic And Effective For Non-Hodgkin Lymphoma,
2024
The Texas Medical Center Library
Vertical Targeting Of The Pi3k/Akt Pathway At Multiple Points Is Synergistic And Effective For Non-Hodgkin Lymphoma, Kristyna Kupcova, Jana Senavova, Filip Jura, Vaclav Herman, Anezka Rajmonova, Mariana Pacheco-Blanco, Tereza Chrbolkova, Iva Hamova, R Eric Davis, Ondrej Havranek
Faculty, Staff and Student Publications
The phosphatidylinositol 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway is critically active in many cell types, both normal and neoplastic. Many small-molecule inhibitors targeting different levels of the PI3K/AKT pathway have been developed for cancer therapy, but their efficacy is reduced by compensatory pathway re-activation mechanisms, and their tolerability by toxic side effects. We studied this problem using cell lines representing diffuse large B-cell lymphoma (SUDHL-4 and OCI-Ly7), a genetically-encoded live-cell reporter of AKT activity, and 3 small-molecule inhibitors targeting different levels of the pathway: idelalisib (PI3Kδ), GSK2334470 (PDPK1), and ipatasertib (AKT). Half-maximal (IC50) concentrations of these inhibitors for AKT activity …
Optimal Infused Cd34+ Cell Dose In Multiple Myeloma Patients Undergoing Upfront Autologous Hematopoietic Stem Cell Transplantation,
2024
The Texas Medical Center Library
Optimal Infused Cd34+ Cell Dose In Multiple Myeloma Patients Undergoing Upfront Autologous Hematopoietic Stem Cell Transplantation, Oren Pasvolsky, Curtis Marcoux, Denái R Milton, Babar Pal, Mark R Tanner, Qaiser Bashir, Samer Srour, Jaehyun Lee, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Yosra Aljawai, Partow Kebriaei, Melody R Becnel, Hans C Lee, Krina K Patel, Sheeba K Thomas, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash
Faculty, Staff and Student Publications
Autologous transplantation remains the standard of care for eligible multiple myeloma (MM) patients, yet optimal CD34+ cell dose remains unclear. We conducted a retrospective study on MM patients undergoing upfront transplant between 2005 and 2021 and divided them into low (≤2.5 × 106 cells/kg) and high (>2.5 × 106 cells/kg) CD34+ dose groups. We included 2479 patients, 95 in the low CD34+ group and 2384 in the high CD34+ group. Patients in the low CD34+ group were older (63.2 vs 61.1 years, p = 0.013), more often had R-ISS III (19% vs 9%, p = 0.014), received plerixafor (60% …
Biomarker Potential Of Nuclear Nrf2 Activation In The Abc Subtype Of Diffuse Large B‑Cell Lymphoma,
2024
Thomas Jefferson University
Biomarker Potential Of Nuclear Nrf2 Activation In The Abc Subtype Of Diffuse Large B‑Cell Lymphoma, Chin-Mu Hsu, Shih-Yu Kao, Chia-Hung Yen, Chi-En Hsiao, Shih-Feng Cho, Hui-Ching Wang, Tsung-Jang Yeh, Jeng-Shiun Du, Min-Hong Wang, Tzu-Yu Hsieh, Samuel Yien Hsiao, Yuhsin Tsai, Li-Chuan Hung, Yi-Chang Liu, Kung-Chao Chang, Hui-Hua Hsiao
SKMC Student Presentations and Publications
Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma characterized by distinct subtypes and heterogeneous treatment outcomes. Oxidative stress and the dysregulation of related regulatory genes are prevalent in DLBCL, prompting an investigation into the nuclear factor erythroid 2-related factor 2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) signaling pathway and associated genes. The present study assessed pathological specimens and clinical data from 43 newly diagnosed patients with DLBCL, comparing the associations and correlations between the expression of Nrf2, Keap1, microtubule-associated protein 1 light chain 3β (LC3B) and nitrotyrosine and the activated B-cell (ABC) and germinal center B-cell (GCB) subtypes of …
The Dleu2/Mir-15a/Mir-16-1 Cluster Shapes The Immune Microenvironment Of Chronic Lymphocytic Leukemia,
2024
The Texas Medical Center Library
The Dleu2/Mir-15a/Mir-16-1 Cluster Shapes The Immune Microenvironment Of Chronic Lymphocytic Leukemia, Ronghua Zhang, Priyanka Khare, Priyanka Banerjee, Cristina Ivan, Sarah Schneider, Federica Barbaglio, Karen Clise-Dwyer, Vanessa Behrana Jensen, Erika Thompson, Marisela Mendoza, Nicholas Chiorazzi, Shih-Shih Chen, Xiao-Jie Joy Yan, Nitin Jain, Paolo Ghia, Federico Caligaris-Cappio, Rima Mendonsa, Sashi Kasimsetty, Ryan Swoboda, Recep Bayraktar, William Wierda, Varsha Gandhi, George A Calin, Michael J Keating, Maria Teresa Sabrina Bertilaccio
Faculty, Staff and Student Publications
The development and progression of chronic lymphocytic leukemia (CLL) depend on genetic abnormalities and on the immunosuppressive microenvironment. We have explored the possibility that genetic drivers might be responsible for the immune cell dysregulation that shapes the protumor microenvironment. We performed a transcriptome analysis of coding and non-coding RNAs (ncRNAs) during leukemia progression in the Rag2-/-γc-/- MEC1-based xenotransplantation model. The DLEU2/miR-16 locus was found downmodulated in monocytes/macrophages of leukemic mice. To validate the role of this cluster in the tumor immune microenvironment, we generated a mouse model that simultaneously mimics the overexpression of hTCL1 and the germline deletion of the …
Nutritional Intervention As Adjuvant Therapy For T-Cell Acute Lymphoblastic Leukemia,
2024
The Texas Medical Center Library
Nutritional Intervention As Adjuvant Therapy For T-Cell Acute Lymphoblastic Leukemia, Miriam B Garcia, Palaniraja Thandapani
Faculty, Staff and Student Publications
No abstract provided.
Evaluation Of Ki-67 Expression And Large Cell Content As Prognostic Markers In Mzl: A Multicenter Cohort Study,
2024
Thomas Jefferson University
Evaluation Of Ki-67 Expression And Large Cell Content As Prognostic Markers In Mzl: A Multicenter Cohort Study, Natalie S. Grover, Kaitlin Annunzio, Marcus Watkins, Pallawi Torka, Reem Karmali, Andrea Anampa-Guzmán, Timothy S. Oh, Heather Reves, Montreh Tavakkoli, Emily Hansinger, Beth Christian, Colin Thomas, Stefan K. Barta, Praveen Ramakrishnan Geethakumari, Nancy L. Bartlett, Geoffrey Shouse, Adam J. Olszewski, Narendranath Epperla
Department of Medicine Faculty Papers
Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among …
Alliance A061202: Ixazomib, Pomalidomide, And Dexamethasone For Patients With Lenalidomide-Refractory Mm In First Relapse.,
2024
OhioHealth
Alliance A061202: Ixazomib, Pomalidomide, And Dexamethasone For Patients With Lenalidomide-Refractory Mm In First Relapse., Peter Voorhees, Vera Suman, Yvonne Efebera, Noopur Raje, Sascha Tuchman, Cesar Rodriguez, Jacob Laubach, Misty Bova-Solem, Destin Carlisle, Saad Usmani, Philip Mccarthy, Paul G Richardson
Oncology Articles
Optimal therapy for the growing number of patients with lenalidomide (LEN)-refractory multiple myeloma in their first relapse remains poorly defined. We therefore undertook a randomized phase 2 study to evaluate the efficacy and safety of combining the oral proteasome inhibitor ixazomib (IXA) with pomalidomide (POM) and dexamethasone (DEX) in this patient population. The overall response rate (ORR) for POM-DEX was 43.6%, and for IXA-POM-DEX, it was 63.2%. The depth of response, measured by the attainment of at least a very good partial response, favored triplet therapy over doublet therapy (28.9% vs 5.1%; P = .0063). A preplanned interim analysis after …
Physician Perspectives About The Diagnosis And Management Of Acute Chest Syndrome,
2024
UCSF Benioff Children's Hospital Oakland
Physician Perspectives About The Diagnosis And Management Of Acute Chest Syndrome, Neha Bhasin, Dana Marie Leblanc, Sean Yates, Quentin Eichbaum, An Pham, Deva Sharma, Li Zhang, Elliott P. Vichinsky, Ravi Sarode
School of Medicine Faculty Publications
Background: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). There is a lack of evidence-based laboratory and clinical risk stratification guidelines for the diagnosis and management of ACS. Study Design and Methods: To better understand physician practices for the management of ACS in the United States, we created an ACS Working Group including hematology and transfusion medicine physicians from four different SCD treatment centers in the United States. The working group created a physician survey that included physician demographics and ACS diagnostic criteria that they …
