Hematology Commons^™

Platelet Glycogenolysis Is Important For Energy Production And Function, Kanakanagavalli Shravani Prakhya, Hemendra J. Vekaria, Daniёlle M. Coenen, Linda Omali, Joshua Lykins, Smita Joshi, Hammodah Rawhi Hammodah Alfar, Qing Jun Wang, Patrick G. Sullivan, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Although the presence of glycogen in platelets was established in the 1960s, its importance to specific functions (i.e., activation, secretion, aggregation, and clot contraction) remains unclear. Patients with glycogen storage disease often present with increased bleeding and glycogen phosphorylase (GP) inhibitors, when used as treatments for diabetes, induce bleeding in preclinical studies suggesting some role for this form of glucose in hemostasis. In the present work, we examined how glycogen mobilization affects platelet function using GP inhibitors (CP316819 and CP91149) and a battery of ex vivo assays. Blocking GP activity increased glycogen levels in resting and thrombin-activated platelets and inhibited …

The Complementary Roles Of Vamp-2, -3, And -7 In Platelet Secretion And Function, Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N. Smith, Harry Chanzu, Ming Zhang, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/ VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis. To address the importance of VAMP-7 (V7), we analyzed mice with global deletions of V3 and V7 together or platelet-specific deletions of V2, V3, and global deletion of V7. We measured the kinetics of cargo release, and its effects on three injury models to define the context-specific roles of these VAMPs. Loss of V7 minimally affected dense and α …

Deep Learning, 3d Ultrastructural Analysis Reveals Quantitative Differences In Platelet And Organelle Packing In Covid-19/Sarscov2 Patient-Derived Platelets, Sagar S. Matharu, Cassidy S. Nordmann, Kurtis R. Ottman, Rahul Akkem, Douglas Palumbo, Denzel R. D. Cruz, Kenneth Campbell, Gail Sievert, Jamie L. Sturgill, James Zachary Porterfield, Smita Joshi, Hammodah Rawhi Hammodah Alfar, Chi Peng, Irina D. Pokrovskaya, Jeffrey A. Kamykowski, Jeremy P. Wood, Beth A. Garvy, Maria A. Aronova, Sidney W. Whiteheart, Richard D. Leapman, Brian Storrie

Saha Cardiovascular Research Center Faculty Publications

Platelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients. Statistical analysis reveals that the α-granule/ mitochondrion-to-plateletvolume ratio …

An Analytical Study Of The Risk Factors Affecting The Platelet Aggregation In Patients With Sepsis, Vishnu Priya, Jitender M. Khunger, Anupma Arora

Journal of Medicine in Scientific Research

Objectives (a) To determine the correlation of platelet count and aggregation with sepsis severity and (b) to find the risk factors affecting the platelet aggregation in sepsis. Patients and methods The present observational cross-sectional study was conducted on 30 patients of sepsis over a period of 18 months. All patients underwent complete blood counts, and platelet aggregation to ADP. Pearson correlation coefficient was used to assess the association of Sequential Organ Failure Assessment (SOFA) score and aggregation to ADP and platelet. Linear regression was done to determine the risk factors affecting platelet aggregation in sepsis. A P value of less …

Acute Myeloid Leukemia With Concurrent Npm1 And Runx1 Mutations, Zhuang Zuo, L Jeffrey Medeiros, C Cameron Yin

Faculty, Staff and Student Publications

NPM1 mutation, as a founding genetic event, cooperates with other gene mutations, such as DNMT3A and FLT3, to promote the development of acute myeloid leukemia. NPM1 mutation, however, has been reported to be mutually exclusive with RUNX1 mutation in acute myeloid leukemia cases. In this study, we analyzed mutation panel testing data from a relatively large cohort of rare AML cases with both NPM1 and RUNX1 mutations. We describe the dynamic process of the emergence of these mutations, as well as molecular genetic features and clinical outcome of these patients. We show that concurrence of both mutations in acute …

Integrated Clinical Genotype-Phenotype Characteristics Of Early T-Cell Precursor Acute Lymphoblastic Leukemia, Matthew T Ye, Yi Wang, Zhuang Zuo, Steliana Calin, Hua He, Zhenya Tang, Elias J Jabbour, Gautam Borthakur, Yizhuo Zhang, Yaling Yang, M James You

Faculty, Staff and Student Publications

Background: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a unique immunophenotype and high treatment failure rate. The molecular genetic abnormalities and their prognostic impact in ETP-ALL patients are poorly understood.

Methods: The authors performed systematic analyses of the clinicopathologic features with an emphasis on molecular genetic aspects of 32 patients with ETP-ALL.

Results: The median age was 43 years (range, 16-71). The blasts were positive for cytoplasmic CD3 and CD7 and negative for CD1a and CD8. Other markers expressed included CD34 (88%), CD33 (72%), CD117 (68%), CD13 (58%), CD5 (partial, 56%), CD2 (38%), …

Women In Lymphoma: A 4-Year Journey In Promoting Gender Equity, Judith Trotman, Ann Lacasce, Wendy Osborne, Anna Steiner, Eliza Hawkes, Carla Casulo, Florence Broussais, Kate Cwynarski, Paola Ghione, Justine Kahn, Sharyn Kurtz, Kim Linton, Carolina Mahuad, Monique Minnema, Loretta Nastoupil, Wendy Osborne, Astrid Pavolvsky, Michelle Poon, Clementine Sarkozy, Laurie Sehn, Soni Smith, Anna Sureda, Carrie Thompson, Judith Trotman, Julie M. Vose

Journal Articles: Oncology and Hematology

No abstract provided.

The Salento Prognostic Model For Limited-Stage Peripheral T-Cell Lymphoma From The International T-Cell Project Network, Greg Hapgood, Monica Civallero, Yana Stepanishyna, Julie M. Vose, Monica Elena Cabrera, Ranjana H Advani, Stefano A. Pileri, Martina Manni, Steven M. Horwitz, Francine M. Foss, Felicitas Hitz, John Radford, Ivan Dlouhy, Carlos Chiattone, Won Seog Kim, Tetiana Skrypets, Arnon Nagler, Judith Trotman, Stefano Luminari, Massimo Federico

Journal Articles: Oncology and Hematology

The natural history of limited-stage peripheral T-cell lymphomas (PTCLs) remains poorly defined. We investigated outcomes and prognostic variables in patients registered in the T-Cell Project (TCP) (#NCT01142674) to develop a model to predict overall survival (OS) for the common nodal PTCL subtypes (PTCL-NOS, AITL, ALCL). The model was validated in an independent data set from Australian and Brazilian registries. 211 patients registered in the TCP between 2006-2018 were studied. The median age was 59 years (range 18-88) and median follow-up was 49 months. One hundred twenty-seven patients (78%) received anthracycline-based regimens, 5 patients (3%) radiotherapy alone (RT), 24 patients (15%) …

Protein S In Coagulation And Inflammation, Martha Mega Silvia Sim

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein S (PS) is a key regulator, which links inflammation and coagulation and performs multiple proposed functions in both processes. PS exists in the blood as a free soluble form (~40%), bound to complement component 4b-binding protein/ C4BP (~60%), and packaged in platelet α-granules (~2.5%). Subendothelial tissue factor (TF), upon exposure to blood, initiates coagulation, a proteolytic cascade which results in the activation of thrombin, the enzyme responsible for formation of a fibrin clot. PS is a critical anticoagulant that inhibits multiple steps of this process. Only the free fraction of PS has full anticoagulant properties, as C4BP blocks this …

Glycolytic Regulation Of Intestinal Stem Cell Self-Renewal And Differentiation, Chang Li, Yuning Zhou, Ruozheng Wei, Dana L. Napier, Tomoko Sengoku, Michael Alstott, Jinpeng Liu, Chi Wang, Yekaterina Y. Zaytseva, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

BACKGROUND AND AIMS: The intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis. An imbalance in this highly regimented process within the intestinal crypts is associated with several intestinal pathologies. Although metabolic changes are known to play a pivotal role in cell proliferation and differentiation, how glycolysis contributes to intestinal epithelial homeostasis remains to be defined.

METHODS: Small intestines were harvested from mice with specific hexokinase 2 (HK2) deletion in the intestinal epithelium or LGR5þ stem cells. Glycolysis was measured using the Seahorse XFe96 analyzer. Expression of phospho-p38 mitogen- activated protein kinase, the transcription factor atonal homolog 1, …

Positron Emission Tomography Derived Metrics In Relapsed Or Refractory Large B-Cell Lymphoma With Residual Disease Before Autologous Stem Cell Transplant, Hua-Jay J Cherng, Guofan Xu, Lei Feng, Raphael Steiner, Luis Fayad, Paolo Strati, Ranjit Nair, Loretta J Nastoupil, Hun Ju Lee, Sattva S Neelapu, Christopher R Flowers, Maria Rodriguez, Michael Wang, Fredrick Hagemeister, Chelsea C Pinnix, Jeremy Ramdial, Samer Srour, Yago Nieto, Katayoun Rezvani, Richard Champlin, Partow Kebriaei, Jason Westin, Homer A Macapinlac, Elizabeth Shpall, Sairah Ahmed

Faculty, Staff and Student Publications

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, …

Ultrasensitive Tapered Optical Fiber Refractive Index, Erem Ujah, Meimei Lai, Gymama Slaughter

Electrical & Computer Engineering Faculty Publications

Refractive index (RI) sensors are of great interest for label-free optical biosensing. A tapered optical fiber (TOF) RI sensor with micron-sized waist diameters can dramatically enhance sensor sensitivity by reducing the mode volume over a long distance. Here, a simple and fast method is used to fabricate highly sensitive refractive index sensors based on localized surface plasmon resonance (LSPR). Two TOFs (l = 5 mm) with waist diameters of 5 µm and 12 µm demonstrated sensitivity enhancement at λ = 1559 nm for glucose sensing (5-45 wt%) at room temperature. The optical power transmission decreased with increasing glucose concentration due …

Improved Outcomes With “7+3” Induction Chemotherapy For Acute Myeloid Leukemia Over The Past Four Decades: Analysis Of Swog Trial Data, Megan Othus, Guillermo Garcia-Manero, John E Godwin, James K Weick, Frederick R Appelbaum, Harry P Erba, Elihu H Estey

Faculty, Staff and Student Publications

We have previously shown that complete response (CR) rates and overall survival of patients with acute myeloid leukemia have improved since the 1980s. However, we have not previously evaluated how the length of first CR (CR1) has changed over this time period. To address this, we analyzed 1,247 patients aged 65 or younger randomized to "7+3" arms from five SWOG studies: S8600 (n=530), S9031 (n=98), S9333 (n=57), S0106 (n=301), and S1203 (n=261). We evaluated length of CR1 and survival after relapse from CR1 over the four decades that these studies represent. Both length of CR1 and survival after relapse from …

Development And Validation Of Early Death Risk Score Model For Emergency Status Prediction In Very Severe Aplastic Anemia, Xu Liu, Wenrui Yang, Li Zhang, Liping Jing, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Xin Zhao, Fengkui Zhang

Faculty, Staff and Student Publications

This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×109/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation …

The History Of Oral Decitabine/Cedazuridine And Its Potential Role In Acute Myeloid Leukemia, Robert Briski, Guillermo Garcia-Manero, Hagop Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Decitabine, a member of the 5-azanucleosides, has a dose-dependent mechanism of action in vitro: termination of DNA replication at high doses, and inhibition of DNA methyltransferase at low doses. The alteration of DNA methylation patterns by low-dose decitabine is hypothesized to upregulate genes, which promote myeloblast differentiation. In a phase III clinical trial, low-dose decitabine achieved a superior overall response rate (ORR) when compared with 'treatment choice' [consisting of low-dose cytarabine (80%) and supportive care (20%)] as a frontline treatment for elderly patients with acute myeloid leukemia (AML). Despite an improved ORR, the median overall survival (OS) for elderly …

Survival Outcomes In Patients With Relapsed/Refractory Or Mrd-Positive B-Cell Acute Lymphoblastic Leukemia Treated With Blinatumomab, Hagop M Kantarjian, Aaron C Logan, Faraz Zaman, Nicola Gökbuget, Ralf C Bargou, Yi Zeng, Gerhard Zugmaier, Franco Locatelli

Faculty, Staff and Student Publications

Blinatumomab has demonstrated significant efficacy in adult and pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-cell ALL) and patients with measurable residual disease (MRD). This review aimed to compare median relapse-free survival (RFS) and median overall survival (OS) in adult and pediatric patients with R/R or MRD-positive B-cell ALL from pivotal studies [MT-103-211 and TOWER for adults with Philadelphia chromosome (Ph)-negative R/R B-cell ALL, ALCANTARA for adults with Ph-positive R/R B-cell ALL, MT-103-203 for adults with MRD-positive B-cell ALL, and MT-103-205 for pediatric patients with R/R B-cell ALL], with the median RFS and OS from retrospective analyses, country …

การศึกษาลักษณะกลายพันธุ์ของยีนที่ถอดรหัสเป็นโปรตีนในเยื่อหุ้มเซลล์เม็ดเลือดแดงในผู้ป่วยกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติ, จารุวรรณ ปานาราช

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติเป็นโรคโลหิตจางตั้งแต่กำเนิดเกิดจากการกลายพันธุ์ของยีนที่กำหนดการสร้างโปรตีนไซโทสเกเลตอนซึ่งเป็นโครงสร้างของเยื่อหุ้มเซลล์เม็ดเลือดแดงเพื่อให้เซลล์เม็ดเลือดแดงมีความยืดหยุ่นและรักษารูปร่างได้โดยยีนที่เกี่ยวข้องได้แก่ ANK1, SPTA1, SPTB, EPB42 และ SLC4A1 งานวิจัยนี้ทำการศึกษาการกลายพันธุ์โดยใช้ Whole exome sequence (WES) และตรวจยืนยันผลด้วยเทคนิค Sanger sequencing ซึ่งงานวิจัยนี้พบการกลายพันธุ์ตำแหน่งใหม่ที่เป็นสาเหตุทำให้เกิดโรคเม็ดเลือดแดงป่องพันธุกรรมจำนวน 3 ตำแหน่งและพบการกลายพันธุ์ในผู้ป่วย hereditary pyropoikilocytosis (HPP) 1 ตำแหน่ง การกลายพันธุ์ตำแหน่งใหม่ประกอบด้วยการกลายพันธุ์ในยีน SPTB ตำแหน่ง c.5692C>T และ c.3823delG และในยีน ANK1 c.1994C>A ผลการศึกษาผลของการกลายพันธุ์ในระดับอาร์เอ็นเอพบว่าการกลายพันธุ์ตำแหน่ง c.5692C>T และ c.3823delG ในยีน SPTB และ c.1994C>A ในยีน ANK1 ส่งผลให้เกิด premature stop codon และพบว่าการกลายพันธุ์ตำแหน่ง c.5692C>T และ c.3823delG ในยีน SPTB ส่งผลให้ระดับการแสดงออกของยีนลดลงเมื่อเทียบกับคนปกติซึ่งอาจเกิดจากกระบวนการ nonsense-mediated mRNA degradation ทำให้ mRNA ที่ผิดปกติถูกทำลาย ผลจากการเพาะเลี้ยงเซลล์เม็ดเลือดตัวอ่อนพบว่าผู้ป่วยเม็ดเลือดแดงป่องพันธุกรรมมีอัตราการเพิ่มจำนวนเซลล์เม็ดเลือดแดงตัวอ่อนมากกว่าคนปกติ แต่มีการเจริญเติบโตและพัฒนาช้ากว่าคนปกติ จากการวัดปริมาณไมโครพาติเคิลด้วยเทคนิคโฟลไซโทเมทรีพบว่าในผู้ป่วยกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติมีปริมาณไมโครพาติเคิลที่สูงกว่าคนปกติ องค์ความรู้ที่ได้จากงานวิจัยนี้ทำให้ทราบกลไกการเกิดความผิดที่เกิดจากการกลายพันธุ์ของยีน SPTB และ ANK1 ในเซลล์เม็ดเลือดแดงผู้ป่วยกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติเพิ่มขึ้น

Hyperviscosity Syndrome Induced Bilateral Visual And Auditory Impairment In Therapy Resistant Waldenström Macroglobulinemia With Myd88 And Cxcr4 Mutations, Marie M Plante, Erinmarie O Kimbrough, Amit K Agarwal, Liuyan Jiang, Kirk Bourgeois, Greta C Stamper, Michael W Stewart, Han W Tun

Faculty, Staff and Student Publications

Hyperviscosity syndrome (HVS) is an emergent complication of Waldenström macroglobulinemia (WM) characterized by visual, neurologic, and rarely auditory impairment. We report a 69-year-old female with MYD88 and CXCR4-mutant WM who developed HVS resulting in bilateral blindness and deafness associated with neurologic manifestations including confusion, severe generalized weakness, and imbalance. Ophthalmologic evaluation revealed bilateral central retinal vein occlusion (CRVO), diffuse retinal hemorrhages, macular edema, and serous macular detachments (SMD). Magnetic resonance imaging of the brain showed bleeding in the inner ears. Management was challenging as her WM was resistant to systemic therapies including bendamustine + rituximab (BR) and rituximab + bortezomib …

Quadricuspid Aortic Valve With Guarded Left Coronary Artery Ostium In An Infant With Myocardial Infarction, Anne Aurelie Tedga, Frank Pigula, Latasha Lewis, Thomas Richard Kimball

Faculty, Staff and Student Publications

• Anatomical variations of the aortic valve include unicuspid, bicuspid, and quadricuspid.
• The bicuspid aortic valve is most common and affects 1%-2% of the general population.
• QAV is generally an isolated malformation, and adults most commonly present with AR.
• Coronary anomalies have been reported in up to 10% of patients with QAV.
• Prompt and accurate imaging will lead to corrective surgery.

Antithrombin Activity Is Associated With Persistent Thromboinflammation And Mortality In Patients With Severe Covid-19 Illness, Amber Chen-Goodspeed, Goutham Dronavalli, Xu Zhang, Jeanette M Podbielski, Bela Patel, Katalin Modis, Bryan A Cotton, Charles E Wade, Jessica C Cardenas

Faculty, Staff and Student Publications

Introduction: Severe COVID-19 illness can lead to thrombotic complications, organ failure, and death. Antithrombin (AT) regulates thromboinflammation and is a key component of chemical thromboprophylaxis. Our goal was to examine the link between AT activity and responsiveness to thromboprophylaxis, markers of hypercoagulability, and inflammation among severe COVID-19 patients.

Methods: This was a single-center, prospective observational study enrolling SARS-CoV-2-positive patients admitted to the intensive care unit on prophylactic enoxaparin. Blood was collected daily for 7 days to assess AT activity and anti-factor Xa levels. Patient demographics, outcomes, and hospital laboratory results were collected. Continuous variables were compared using Mann-Whitney tests, and …

Addition Of Aspirin To Venous Thromboembolism Chemoprophylaxis Safely Decreases Venous Thromboembolism Rates In Trauma Patients, Daniel Lammers, Michelle Scerbo, Annamaria Davidson, Matthew Pommerening, Jeffrey Tomasek, Charles E Wade, Jessica Cardenas, Jan Jansen, Charles C Miller, John B Holcomb

Faculty, Staff and Student Publications

Background: Trauma patients exhibit a multifactorial hypercoagulable state and have increased risk of venous thromboembolism (VTE). Despite early and aggressive chemoprophylaxis (CP) with various heparin compounds ("standard" CP; sCP), VTE rates remain high. In high-quality studies, aspirin has been shown to decrease VTE in postoperative elective surgical and orthopedic trauma patients. We hypothesized that inhibiting platelet function with aspirin as an adjunct to sCP would reduce the risk of VTE in trauma patients.

Methods: We performed a retrospective observational study of prospectively collected data from all adult patients admitted to an American College of Surgeons Level I Trauma center from …

Not Just A Pain: A Medical Simulation Case About Biased Communication And Osteomyelitis In Pediatric Sickle Cell Anemia, Adeola A Kosoko, Yakira R Alford, Karl A Upplegger, Gowri S Stevens

Faculty, Staff and Student Publications

Introduction

Biases in communication can be harmful to patient perceptions of care and the medical team's decision-making. Optimal communication must be taught and practiced similarly to the optimal management of the complex medical conditions associated with sickle cell disease (SCD). This simulation is designed to teach about biases, optimizing communication to and about a patient with SCD, and appropriately diagnosing and managing pediatric osteomyelitis as a complication of SCD.

Methods

We designed and implemented a simulation case targeting emergency medicine residents and fellows to raise awareness about biases associated with SCD care and the complication of osteomyelitis in children with …

Recurrent Strokes In A Woman With A History Of Thrombotic Thrombocytopenic Purpura, Ijele Adimora, Bingnan Zhang, Modupe Idowu

Faculty, Staff and Student Publications

Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy characterized by mechanical hemolytic anemia, resulting in end-organ damage. We describe a case of TTP which presented as an ischemic stroke. The patient presented with stroke as the primary manifestation of TTP despite a normal platelet count and mildly elevated lactate dehydrogenase level (LDH). The patient underwent two transfusions of fresh frozen plasma (FFP), and ADAMTS13 levels confirmed the diagnosis of TTP after discharge. This case demonstrates the importance of maintaining a high index of suspicion for TTP in the setting of normal laboratory values and reveals the many atypical manifestations of TTP.

Investigation Of The Dyrk1a Regulation By Lzts2-Sipa1l1 Complex, Rebecca Gunnin, Austin Witt B.S., Larisa Litovchick M.D.,Ph.D.

UROP Posters

A region on chromosome 21, the Down Syndrome critical region (DSCR), is associated with major defects found in Down Syndrome, such as craniofacial malformations. DYRK1A is a gene found on chromosome 21 within the DSCR that encodes an enzyme, dual specificity tyrosine-phosphorylation-regulated kinase 1A. DYRK1A is known to phosphorylate many substrate proteins and is thought to be involved in tumor suppression, neurological development, cell cycle regulation, and aging. Recently, the Litovchick lab and others reported that DYRK1A also plays a role in the double-strand break repair of DNA, which could lead to mutations and tumorigenesis, if deregulated.

The Litovchick lab …

Treatment De-Escalation In Philadelphia Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia: The Emerging Role Of Chemotherapy-Free Regimens, Fadi G Haddad, Jacki Sawyers, Nicholas J Short

Faculty, Staff and Student Publications

The management of Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) has witnessed major progress over the past two decades. Initially, the incorporation of the first-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) imatinib into intensive chemotherapy regimens improved outcomes compared with chemotherapy alone. The combinations of chemotherapy with second- or third-generation TKIs further improved outcomes, with higher rates of complete molecular remission (CMR) and superior survival. The combination of ponatinib plus chemotherapy resulted in durable remissions and prolonged long-term survival, even in patients who did not receive allogeneic stem cell transplantation (SCT). The promising results seen with later-generation TKIs have caused many …

Strengthening Deep-Learning Models For Intracranial Hemorrhage Detection: Strongly Annotated Computed Tomography Images And Model Ensembles, Dong-Wan Kang, Gi-Hun Park, Wi-Sun Ryu, Dawid Schellingerhout, Museong Kim, Yong Soo Kim, Chan-Young Park, Keon-Joo Lee, Moon-Ku Han, Han-Gil Jeong, Dong-Eog Kim

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Multiple attempts at intracranial hemorrhage (ICH) detection using deep-learning techniques have been plagued by clinical failures. We aimed to compare the performance of a deep-learning algorithm for ICH detection trained on strongly and weakly annotated datasets, and to assess whether a weighted ensemble model that integrates separate models trained using datasets with different ICH improves performance.

METHODS: We used brain CT scans from the Radiological Society of North America (27,861 CT scans, 3,528 ICHs) and AI-Hub (53,045 CT scans, 7,013 ICHs) for training. DenseNet121, InceptionResNetV2, MobileNetV2, and VGG19 were trained on strongly and weakly annotated datasets and …

Case Report: Navigating The Challenges: Successful Mechanical Thrombectomy In A Case Of Persistent Primitive Hypoglossal Artery, Kamran Ahmed Khan, Irfan Amjad Lutfi, Jehangir Ali Shah, Salman Farooq, Shahnoor Ahmed, Bashir Ahmed Solangi, Ayan Ahmed Khan, Fazal Zaidi, Ali Ammar, Nadeem Qamar

Faculty, Staff and Student Publications

Persistent primitive hypoglossal artery (PPHA) is a highly uncommon abnormal connection between the internal carotid artery (ICA) and vertebral artery (VA), with reported incidences ranging from 0.027 to 0.26%. Attempting endovascular intervention in such cases presents a considerable challenge as it carries a higher risk of embolization and other procedure-related complications that may affect a wide area of the brain. We present a case study involving the utilization of mechanical thrombectomy (MT) to treat an ischemic stroke in the M1 segment of the middle cerebral artery (MCA) despite the presence of PPHA. Performing mechanical thrombectomy in an anomalous vascular connection …

Perioperative Outcomes Of Patients With Bleeding Disorders Undergoing Major Surgery At An Academic Hemophilia Treatment Center, Ruben Rhoades, Zachary French, Amy Yang, Karen Walsh, Douglass A. Drelich, Steven E. Mckenzie

Department of Medicine Faculty Papers

Persons with bleeding disorders (PwBD) are at high risk for bleeding with invasive procedures. However, the risk of bleeding in PwBD undergoing major surgery and outcomes of patients managed perioperatively at a hemophilia treatment center (HTC) are not well described. We performed a retrospective review of surgical outcomes among PwBD undergoing major surgery between January 1st, 2017 and December 31st, 2019 at the Cardeza Foundation Hemophilia and Thrombosis Center in Philadelphia, PA. The primary outcome was postoperative bleeding, assessed according to the ISTH-SSC's 2010 definition. Secondary outcomes included use of unplanned postoperative hemostatic therapy, LOS, and 30-day readmission rate. Results …

Pediatric Traumatic Hemorrhagic Shock Consensus Conference Research Priorities, Robert T Russell, Melania M Bembea, Matthew A Borgman, Randall S Burd, Barbara A Gaines, Mubeen Jafri, Cassandra D Josephson, Christine M Leeper, Julie C Leonard, Jennifer A Muszynski, Kathleen K Nicol, Daniel K Nishijima, Paul A Stricker, Adam M Vogel, Trisha E Wong, Philip C Spinella

Faculty, Staff and Students Publications

BACKGROUND: Traumatic injury is the leading cause of death in children and adolescents. Hemorrhagic shock remains a common and preventable cause of death in the pediatric trauma patients. A paucity of high-quality evidence is available to guide specific aspects of hemorrhage control in this population. We sought to identify high-priority research topics for the care of pediatric trauma patients in hemorrhagic shock.

METHODS: A panel of 16 consensus multidisciplinary committee members from the Pediatric Traumatic Hemorrhagic Shock Consensus Conference developed research priorities for addressing knowledge gaps in the care of injured children and adolescents in hemorrhagic shock. These ideas were …

Pediatric Traumatic Hemorrhagic Shock Consensus Conference Recommendations, Robert T Russell, Joseph R Esparaz, Michael A Beckwith, Peter J Abraham, Melania M Bembea, Matthew A Borgman, Randall S Burd, Barbara A Gaines, Mubeen Jafri, Cassandra D Josephson, Christine Leeper, Julie C Leonard, Jennifer A Muszynski, Kathleen K Nicol, Daniel K Nishijima, Paul A Stricker, Adam M Vogel, Trisha E Wong, Philip C Spinella

Faculty, Staff and Students Publications

Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization …